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Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity. RL2 inhibits the expression of the CXCL1 protein and apoptosis inhibitor A20 and enhances expression of IkB, NF-kB repressor. The ELISA method has been used to evaluate the antibody titer in the blood of mice, which received single and triple intravenous or intraperitoneal injections of RL2. The multiplex immunoassay of 23 cytokines in the mice blood has shown that the RL2 injections lead to a slight increase in the levels of systemic pro-inflammatory cytokine interleukin-5 (IL-5) and keratinocyte chemoattractant (KC), a homologue of human macrophage inflammatory protein-1 (MIP-1). These observations indicate the low immunogenicity of the recombinant lactaptin analog, which can be considered to be a potential molecular drug candidate for further clinical development.

Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.

The chemoinfusions (310) were carried out in celiac trunk in 167 patients with non-removed pancreas cancer at the period from 2000 to 2015. Locally advanced timorous process (stage III, n=79) was revealed in 79 patients and liver metastases (stage IV, n=88) were noted in 88 cases. The celiac axis infusion by Gemcitabine (1000 mg/m²) was applied for patients and GEMOX (Gemcitabine+Oxaliplatin 75 mg/m²) has been using since 2012. Symptomatic improvement such as decrease of pain, growth of body weight was noted in majority of patients. An average lifetime, median and one-year survival consisted of 7,6 months, 5,8 months and 10%. The patients (133) were treated by 1–2 cycles and after that by course of total body chemotherapeutics. There weren’t any serious complications. Toxic manifestations of chemotherapy weren’t higher than I–II degree and they were arrested by corrective therapy in 92 patients (55%). The celiac axis infusion is safe in patients with locally advanced and inoperable pancreas cancer. Symptomatic improvement showed the most patients. The objective response to the treatment had 20% patients and performance of repeated cycles led to increase of their survival.

Accumulation of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector pro- tein (recombinant third domain of alpha-fetoprotein - 3D-G2- Dox) in normal and tumor cells was studied in vitro within the framework of the development of selective transport system of anticancer drugs to the target cells. The objects of the study were cells of peripheral blood mononuclear fraction of healthy donors and cells of breast adenocarcinoma lines MCF-7 and MCF-7/MDR1, differing in chemosensitivity. G2-Dox and 3D-G2-Dox accumulated in tumor cells of the both lines better than free Dox (p<0,05). However removal of these drugs out of cells MCF-7 and MCF-7/MDR1 was significantly different: in the latter case all free Dox was excluded from the cells for 24 hours while Dox, accumulated in composition with dendrimers, still remained in the cells. It was important that 3D-G2-Dox (unlike the G2-Dox) accumulated in normal cells worse than free Dox (p<0.01). Thus, the results indicate that the use of 3D-G2-Dox is the most promising because it accumulates in tumor cells better and in normal cells worse than free Dox. Furthermore it can be assumed that the use of 3D-G2-Dox would be especially useful in cases of multi-drug resistance associated with the high expression of P-glycoprotein.

The anti-tumor activity of the binuclear form of dinitrosyl iron complexes with glutathione against Lewis lung carcinoma, found earlier upon intraperitoneal administration of the complexes, was also observed when this preparation was injected subcutaneously. A 100 μM/kg subcutaneous dose of the complex being used daily (as calculated per one iron atom in binuclear dinitrosyl iron complexes) for 10 or 15 days, inhibited the tumor growth by 43%. The effect was observed during the first two weeks after tumor transplantation. After that, the tumors began to grow at the rate equal to or even higher than that one for control animals. The mean survival time for treated mice exceeded the control values by 30%. Binuclear dinitrosyl iron complexes administered intraperitoneally was also effective against Ca-755 adenocarcinoma. However, in this case the mean survival time for treated animals increased only by 7%. The anti-tumor activity of S-nitrosoglutathione against Lewis lung carcinoma growth inhibition by 70% and Ca-755 adenocarcinoma growth inhibition by 90% was also shown. However, unlike binuclear dinitrosyl iron complexes the anti-tumor effect of S-nitrosoglutathione decreased when a daily dose of the compound increased (from 200 to 400 μM/kg) The initial anti-tumor effect of binuclear dinitrosyl iron complexes and S-nitrosoglutathione is suggested to be due to NO released from both compounds. A subsequent suppression of the effect is determined by the development of anti-nitrosative and anti-oxidant defense systems in tumors.

Antitumor activity of the novel for oncology compound, such as polysuccinimide, against some of experimental tumor models (Lewis lung carcinoma, Acatol adenocarcinoma, Ca-755 adenocarcinoma) has been established. This drug induced 60-80% tumor growth inhibition of these murine solid tumor strains. Polysuccinimide is also effective (60%) against development of metastatic process in lung (Lewis lung carcinoma). Polysuccinimide causes no changes in pH level in tumor tissue (P-388 leukemia, Acatol adenocarcinoma). This agent may be recommended for further profound preclinical study.

The purpose of this paper was to increase the effectiveness of radiation therapy (RT) of local recurrence of rectal cancer (MRRPK) by setting the preferred modes and dynamic medium dose fractionation irradiation MRRPK, assessing immediate outcomes, identifying the frequency and severity of early radiation reactions during radiation therapy. The study included 60 patients with a diagnosis of "local recurrence of rectal cancer." The median age was 67 years. Terms of recurrence after surgical treatment averaged 20 months. The histological structure of the tumor was presented adenocarcinoma in 57 (95%) patients. Radiation therapy (RT) was carried out in medium or dynamic fractionation. Chemotherapy used pelleted 5-fluorouracil. In group 1 (20 patients) received palliative radiotherapy course with a fractional dose of 3 Gy to 42 Gy SOD (SDeq 51 Gy). In group 2 (20 patients) underwent a course of radiotherapy using dynamic dose fractionation: fractional dose--4, 3 and 2 Gy to 51 Gy SDeq. In the third group (20 patients) underwent combined treatment using dynamic dose fractionation: fractional dose--4, 3 and 2 Gy to 56 Gy SDeq and chemotherapy--Xeloda or ftorafur. In group 1 complete regression was achieved in 1 patient, partial regression--15, stabilization--at 3, progression--at 1, that is clinical effect was observed in 19 of 20 patients. In group 2, complete regression of the tumor was diagnosed in 3 patients, partial regression--17, therefore, 100% of patients had received clinical effect. According to follow-up, 5 patients in this group were subsequently. In the third group of complete regression of the tumor was diagnosed in 7 patients, partial regression--13, ie, 100% of patients had received clinical effect. According to follow-up, 7 patients in this group were subsequently operated. Among the radiation reaction in group 1 nausea 1 tbsp. was observed in 3 patients, radiation Recto 1-2 degree--15, radiation epithelitis 1-2 degree--4 patients; in group 2, nausea 1 degree--At 7, radiation Recto 1-2 degree--At 7, radiation epithelitis 1-2 degree--In 6 patients and 6 reactions were observed; in the third group of nausea 1st. was observed in 7 patients, radiation Recto 1-2 degree--At 9, radiation epithelitis 1-2 degree--At 8 and 3 patients reactions were observed. Thus, when irradiated in the dynamic fractionation showed less pronounced dose response as beam during treatment, and after. Increasing the total dose with the addition radiomodification increases the frequency of complete responses with acceptable toxicity. As a result of treatment in all patients achieved a significant reduction in pain, relief of bleeding.

Fractions of water soluble and alkali soluble polysaccharides, as well as fucogalactan, a water soluble polysaccharide, and xylomannan, an alkali soluble polysaccharide, were isolated from the Ganoderma lucidum submerged mycelium. When administered orally, the polysaccharides showed antitumor activity in vivo on murine models of solid tumors. Xylomannan and fucogalactan showed the highest antitumor activity. Sensitivity to xylomannan was more pronounced in adenocarcinoma Ca755 as compared to the T-cell lymphocytic leukemia P388. The antitumor activity of the water soluble polysaccharides total fractions from the mycelium and fruiting bodies of the G. lucidum strain was almost identical. The maximum antitumor effect of the mycelium water soluble polysaccharides total fraction was observed with the use of the daily dose of 2 mg/kg.

This study presents the short-term outcomes of conformal external beam radiation therapy given in conjunction with hormone therapy to 110 patients with prostate cancer. We performed a comparative analysis of the rate and degree of radiation reactions and complications following delivery of a total dose of 70 Gy and 72-76 Gy to the tumor. In prostate cancer, a continuous course of dose-escalated conformal radiation therapy resulted in satisfactory tolerance and acceptable levels of late complications.

The antitumor activity of polyacrylates of the noble metals containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) has been studied using experimental murine solid tumor models (Lewis lung carcinoma and Acatol adenocarcinoma). It has been found that polyacrylates of the noble metals are capable of inhibiting tumor development by 50-90% compared to control. Auracryl that inhibites the growth of Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90%, respectively, compared to control is the most efficient among the tested compounds and can be recommended for the further profound preclinical studies.

Cytestrole acetate (CA), in the structure of which the steroidal antiestrogen component is associated with bis-β-cloroethylamino group, exhibits a strong cytotoxic activity against hormone-dependent cancer cell lines (CaOV, HeLa, MCF-7). In doxorubicin-resistant MCF-7 cells, CA potentiates the cytotoxic effect of etoposide and doxorubicin, and the IC50 for CA in these cells is 40 times lower than that for tamoxifen (TAM). In transplantable mice breast adenocarcinoma Ca-755, the therapeutic CA dose is 25 mg/kg when administered subcutaneously in oil solution for 5 days. On the DMBA-induced mammary tumors in rats, CA injected subcutaneously led to partial regressions 4 weeks after treatment in 75% of test rats, whereas TAM produced this effect in 43% of rats. Among various drug forms of CA, the most active were oil solution of CA in gelatin capsules for oral use and liposomal emulsion for intravenous administration, since these forms exhibited the highest values of Ca-755 tumor growth inhibition index (TGI = 97 - 98%).

Basing on the determined rate of early gastric cancer diagnosis it is possible to prognosticate the survival indices in patients, suffering gastric cancer after radical surgical intervention performance as well as the adjuvant chemotherapy efficacy. There were analyzed the data of their own, as well as such from Japan and Western Europe, concerning studying of the early gastric cancer incidence, the survival indices after conduction of D2 lymphodissection for gastric cancer and a rate of a synchronous macroscopically obvious remote metastases (SMVRM). There was established, that in gastric cancer patients the lesser is the early gastric cancer rate--the SMVRM rate is higher in any stage of the tumor; high rate of SMVRM in the patients, suffering gastric cancer coincide with a high rate of synchronous hided remote metastases in any stage of a tumor; the early gastric cancer rate correlates directly with a 5-year survival indices after radical surgical intervention for gastric cancer, in any resectable stage (I-III); the lesser early gastric cancer rate--the bigger necessity of adjuvant chemotherapy conduction for gastric cancer.

A prospective analysis of results of combined treatment of 22 patients with central stage II-III non-small cell lung cancer (NSCLC) was performed (the defeat of the main bronchi or lower parts of the trachea), which initially had been regarded as unresectable or inoperable (12 patients for functional reasons could not pass pneumonectomy, and in 10 patients a contraindication to primary surgery was the involvement of the distal trachea in tumor), but underwent surgery after preoperative treatment.Combination therapy included preoperative endobronchial photodynamic therapy (PDT) and chemotherapy followed by surgery and intraoperative PDT resection margins. PDT was carried out with the use of chlorine E6 (Radachlorin) and light wavelength of 662 nm. Overall response rate after neoadjuvant treatment was 82 %, endoscopic remission was observed in 21 of 22 patients (95%). 10 patients underwent pneumonectomy, 12--lobectomy. 19 surgical interventions were regarded as radical (R0--86%), 3--as microscopically non-radical (R1--14%). Degree of lymphatic metastasis spreading pN0 was detected in 6 patients (27 %), pN1--in 14 (64%) and pN2--in 2 patients (9%). Surgical lethality was 5%. In the late time of the whole observation period none of the patients developed local recurrence. One-year survival was 95%, 3-year--91%. PDT can play an important role in combination with surgical treatment for NSCLC and reduces the amount of resection in part of initially unresectable or inoperable patients.

We present the clinical observation of combined treatment of a patient with metastatic gastric cancer. The patient underwent combined chemotherapy for initially inoperable gastric cancer with metastases to the liver, paragastric lymph nodes, and peritoneal carcinomatosis with complete regression of distant metastases, which allowed radical surgery. The patient is currently under regular team observation without signs of disease. His present survival is 44 months.

Neoadjuvant treatment should not be given to grave cases of rectal cancer with concomitant perifocal inflammation, anemia and advanced age. To improve results, intraoperative intrapelvic chemotherapy in combination with hyperthermia was carried out at the Center's Clinic. Pre-clinical studies involved working out optimal cryo-temporal regimens to maximize cytotoxic effects of drugs and hyperthermia as well as establishing systemic influence of local hyperthermia and chemotherapy on the intraoperative intrapelvic one. Our optimal cryo-temporal regimens and intraoperative intrapelvic chemotherapy proved highly effective.

In the current study a technique for microencapsulation of human breast adenocarcinoma cells MCF-7 in alginate-chitosan microcapsules is used. Microencapsulation is proposed to generate multicellular tumor spheroids (MTS) based on these cells and to test them further as an in vitro model for anti-tumor drug screening. Cytotoxicity of methotrexate (MTX) was studied on the obtained MTS. A set of MTS with mean size of 150, 200 and 300 m was prepared in function of a cultivation time. After incubation of MTS in cultivation medium containing MTX at concentrations of 1, 2, 10, 50 and 100 nM for 48 hs cell viability was evaluated. MTS were shown to be more resistant to MTX than the monolayer culture, and the resistance to MTX was increased with enhancing a spheroid size. At MTX concentration of 100 nM a number of viable cells in MTS with the size of 300 m was 2.5-fold bigger than that one in monolayer culture. It is suggested that the cells in microencapsulated MTS can better mimic cell behavior in a small size solid tumor than the cells in a monolayer culture. In future microencapsulated MTS can be proposed as a novel in vitro model for anticancer drug screening.

Tumor regression was reported in 20-30% of patients with inoperable non-small-cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first-line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC.

Our experience of kalumide (bikalutamide) administration in patients with prostatic cancer agrees with the data of other investigators on a good effect of the drug on quality of life of patients with prostatic cancer.

Immediate results of 100 D2 lymphadenectomies, performed for gastric cancer, were analyzed. The combined treatment included preoperative radiotherapy (n=39), combinations of pre- and postoperative radiotherapy (n=18) and adjuvant chemotherapy (n=18). The majority of patients had tumors of the lower third of the stomach, histologically low- and non-differentiated adenocarcinomas. Gastrectomy was performed in majority of cases. Achieved results showed, that pre- and postoperative radiotherapy led neither to lethality nor to complication rate or to hospital stay time increase. Thus, D2 lymphadenectomy for surgical and combined treatment of the gastric cancer, is a safe procedure with an acceptable rate of postoperative complications. It does not prevent neo- and adjuvant chemo- or radiotherapy conduction. D2 lymphadenectomy allows a more thorough cancer staging, according both to international and Japanese classifications.

In the period from 1992 through 2006 transcatheter therapy was carried out in 46 patients with unresectable metastases of gastric cancer (MGC) into the liver. Repeated cycles of chemoinfusions in the hepatic artery (CIHA) with 5-fluorouracil, doxorubicine, mitomicine C and carboplatin were made to 35 patients. Chemioembolization of hepatic arteries (CEHA) using the same cytostatics and oil contrast agent was made toll patients. After CIHA a partial response to treatment and stabilization of the tumor growth was noted in 14 (40%) patients, progressing metastases in 21 (60%) patients. Mean survival period of 32 dead was 14.6 +/- 1.5 month and the indices of 1-, 2- and 3 years survival were 46, 15 and 5 % respectably. After CEHA a partial response and stabilization of the tumor growth were noted in 7 (63%) patients and in the rest 4 patients (37%) there was progressing. The mean survival period of 9 dead patients was 15.5 +/- 3.3 months; the indices of 1-, 2- and 3 years survival were 55, 18 and 10 % respectively (p(CINA-CEHA) > 0.01). The methods of interventional radiology are thought to be perspective for treatment of unresectable metastases into the liver.

Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

Lyzed epimastigotes of Trypanosoma cruzi clones P209-1, Gamba1, Sp104-1, MASu, Y7/1, MN12, Cl-Brener, 86/2036, Y7/2-1 inhibit the growth of Ehrlich adenocarcinoma in mice. the tumor decreased 1.5-3 times after 12 daily injections of lysates from 15 million epimastigotes. The protective effect progressed after the injections were discontinued and depended on the dose and lysate producer clone. Trypanosoma lysates in the studied doses were nontoxic.

The aim of our study was to evaluate the efficacy and safety of 3-drugs regimen: T 75 mg/m2 d2 + P 75 mg/m2 d2 + F 500 mg/m2 x 3h d 1-3 every 28 days. 31 patients (pts) with morphologically proven advanced gastric cancer of the age 29-77 years (median 61.0) have been treated with this regimen. They received 138 cycles (1-10, median 4.0 cycles per pt). The response rate was evaluated in pts received > or =2 cycles: CR 1/27 (3.7%), PR 12/27 (44.4%), SD 7/27 (25.9%), PD 7/27 (25.9%). The median duration of CR+PR--4.5 mon (1.1-9.9), of SD--6.8 mon (3.0-10.7). Median TTP--5.5 mon. Overall survival: median--11.5 mon, 1-year--46.6%. PS improvement was observed in 54.8%pts, symptomatic improvement--in 71% pts. Toxicity per pt (per cycle) was moderate. There were 11 elderly among these pts. We didn't receive any significant differences in efficacy and severe toxicity in this group compared to non-elderly pts. We observed 55.6% PR, 33.3% SD, 11.1% PD, TTP--4.6 mon, median OS-7.5 mon. in elderly and 5.6% CR, 38.9% PR, 22.2% SD, 33.3 % PD, TTP--6.1 mon, median OS-12.3 mon for non-elderly pts. But dose reduction was performed more frequently in the elderly then non-elderly: 63.6% vs 30.0% pts (p = 0.07) in 64.8% vs 19.1% cycles (p < 0.0001). We consider this regimen to be effective and well tolerated both for elderly and for non-elderly patients.

The bone marrow myelopeptide MP-2 (Leu-Val-Val-Tyr-Pro-Trp), exhibiting antitumor activity, and its retro-analogue (Trp-Pro-Tyr-Val-Val-Leu) were synthesized, and their properties were studied. The in vitro and in vivo activities of retro-MP-2 were comparable with those of MP-2. Both peptides equally restored the functional activity of T-lymphocytes inhibited by toxins released by HL-60 cells and inhibited by 70-82% the growth of various types of transplantable solid tumors: Ca-755 adenocarcinoma of the mammary gland, Lewis adenocarcinoma of the lung, and S180 sarcoma. The positions and intensities of the Cotton effects in CD spectra of the MP-2 peptide and its retro-analogue in various solvents are almost indistinguishable. The positions of extrema and integral intensities of the amide I and amide A bands in IR spectra of both peptides were practically identical. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.

Phophatidylinositol-3-kinase (PI3K) is a major intracellular protein that is responsible for the transmission of an antiapoptotic signal and controls the survival of tumor cells upon exposure to damaging agents. Experiments using different tumor cell cultures have shown that the resistance of cells to the antiproliferative action of dexamethasone, caused by their long cultivation with the hormone, is associated with the activation of PI3K and the transcription factor STATS. The activation of PI3K and STAT3 in the dexamethasone-resistant cells correlates with the increase in the total thyrosine kinase activity and with the decrease in the sensitivity of cells to exogenous proliferative agents, such as 17beta-estradiol. The long exposure of hormone-sensitive cells to nonhormonal factors that activate the PI3K/STAT3 signaling pathway, hypoxia in particular, has been shown to suffice to reduce the degree of hormonal tumor cell dependence. VEGF-A, an angiogenic peptide whose action was partially realizes through the PI3K-signalling pathway, has been demonstrated to be involved in the maintenance of cell growth, including the growth of hormone-independent cells. The findings suggest that complex changes in the antiapoptotic and mitogenic signaling pathways associated with PI3K, which ensures the autonomic, hormone-independent growth of tumor cells, may underlie the decreased hormonal dependence of tumor cells. Whether PI3K may be used to suppress the growth of hormone-independent tumors is discussed.

Biological effect of doxorubycin in standard (10(-3) mol/l) and ultra low doses (10(-5)-10(-20) mol/l) against some "signal" animal tumor systems--Lewis lung carcinoma, 755 adenocarcinoma, B-16 melanoma, Ehrlich carcinoma and L1210 leukemia was studied. The all models were very sensitive to the action of the drug in standard dose. Solid tumors' growth inhibition by 80-95% as well as increasing in life span of mice with L1210 leukemia by 86% in comparison with control and surviving of animals with Ehrlich carcinoma had been revealed. It had been shown that the drug in the area of ultra low doses occurred the following effects: inhibition of Lewis lung carcinoma growth by 80-95% compared to control after administration of the all tested ultra low doses; increasing of the life span of the animals with Ehrlich carcinoma and L1210 leukemia by 86-123% and 6-23%, correspondingly, upon the action of all tested ultra low doses; inhibition of B-16 melanoma growth by 50 and 70% after administration of the drug in doses 10(-20) mol/l and 10(-5) mol/l, correspondingly as well as deceleration of 755 carcinoma growth by 40% compared to control after action of the drug in the dose 10(-20) mol/l; stimulation of the B-16 melanoma growth by 20% relative to control after 10(-10) mol/l dose injection and enhancement of tumors sizes by 20-60% above control levels as a result of treatment of mice with 755 carcinoma by the drug in such ultra low doses as 10(-5) and 10(-15) mol/l. So, it was found that all tested tumor systems revealed certain sensitivity to the some ultra low doses of the drug. At the same time it was shown that doxorubycin in ultra low doses displayed alternative character of its biological effect, directivity of which varied according with the dose level and tumor strain.

The results of organ-sparing treatment of patients with cancers of the breast, uterine cervix, endometrium and ovary are described in the paper. A prospective randomized clinical study launched in 1995 at Petrov's Research Institute of Oncology comprised cases of above 700 patients with breast cancer, around 300 women with cancer in situ and with microinvasive cancer of the uterine cervix and 83 patients with initial endometrial cancer. The results of the above treatment (segment resection + axillar dissection + radiotherapy) were shown to be similar to those obtained after Petey-Dyson mastectomy (5-year survival of 86.7% versus 88.8%, p = 0.81). The risk of local recurrence was increasing in patients with the tumors' diameter of more than 1 cm who were not treated by radiotherapy. The total regression of tumors was registered in 70% of patients with initial endometrial cancer after hormone therapy by progestagens and antiestrogens; 20% of them maintained the reproductive function.

Based on an analysis of treatment of patients with colorectal cancer of the IV stage in two groups of patients by the method of cytoreductive technology (58 patients) compared with a group (64 patients) treated using palliate operations, the author makes a conclusion that cytoreductive operations are an alternative to palliative interventions since they give longer survival and save quality of life. The adjuvant immunochemotherapy is thought to be a necessary component of cytoreductive operations.

The study of the prognostic criteria of hormone-resistant prostatic cancer (PC) by specifying expression of androgen receptor protein as well as Bcl-2 and p53 proteins, apoptosis regulators, has demonstrated that tumor cells of hormone-sensitive and hormone-resistant PC forms have different variants of immunophenotype. Hormone-resistance is typical for tumors from urothelial, basal and neuroendocrine PC cells, glandular epithelium cells which lost androgen receptors (AR) and tumors consisting of cells which retain AR but simultaneously express Bcl-2 and/or p53 genes. The discovery of androgen-resistant cancer from glandular epithelium which has immunophenotype characteristics of a hormone-dependent tumor indicates the existence of other mechanisms of protection against apoptosis. The development of hormone-resistant cancer 2.5-3 years after hormonal therapy is associated with changes in immunophenotype of tumor cells. They become Bcl-2- and/or p53-positive while part of them lose AR. Thus, immunophenotype of tumor cells may serve a prognostic marker of hormonal resistance of the tumor and dictate the treatment policy.

Three-month treatment with casodex (150 mg/day) of untreated patients with locally advanced and/or advanced cancer of the prostate is well tolerated. The only side effect encountered in 9(60%) patients was temporary breast painfulness and swelling. Subjective effects consisted of higher activity (in 40% of patients), pain relief (in 33.3%), improved urination (in 80%). Objective effects comprise: reduction of prostate-specific antigen in 14(93.3%) patients by 150.4 ng/ml at the average; a rise in testosterone concentration in 12(80%) patients; regression of the tumor by more than 50% in 5(33.3%) patients; stabilization and partial regression of regional metastases (1 case); stabilization of distant metastases (3 of 4 cases). One patient showed progression of bone metastasizing in partial local regression of the tumor.

The data on clinical trials of newly-developed hormonotherapy of atypical hyperplasia (AH) and cervical adenocarcinoma (CAC) are presented. The study included 34 patients with histologically--confirmed AH and 86--CAC (stage I-II and III-IV). All patients were given preoperative "shock therapy" with a combination of progestins and anticoagulants: 500 mg, i.v., 10 days--(AH) and well-differentiated cell CAC; 20 days--moderately- and poorly-differentiated cell CAC. Total dose was 5 g and 10 g, respectively. Fibrolysin, pelentan and aspirin (antiaggregant of thrombocytes) were used as anticoagulants. For comparison, identical numbers of AH and CAC patients received similar preoperative progestin therapy without anticoagulants. The study was randomized. Hormonal pathomorphosis in tumor was identified after surgery and relevant characteristics of bioptical and resected material were compared. It was found that hormonotherapy used in conjunction with anticoagulants reinforced significantly all features of hormonal pathomorphosism both in AH and CAC stage I-II while, in well-differentiated cell adenocarcinoma, the difference from control was significant (p < 0.05).

Hematologic thrombopenia and leukopenia formation limits use of nitrullin as a toxic hazard. The drug showed moderate effect in treating inoperable non-small cell cancer of the lung and satisfactory end results. The treatment had marked symptomatic effect in patients with this cancer and, as a consequence, improved the quality of life. Nutrullin had immuno-modulating effect. Its application alone or in combination with VPN showed good results in the management of small-cell cancer of the lung.

Diagnosis and treatment of 228 patients with cancer of the buccal mucosa is analyzed. There were 130 women and 98 men aged 65 years on average. 218 were primary patients and 10 with relapses. Squamous-cell carcinomas with hornification predominated: 217 cases (95%). Adenocarcinoma was diagnosed in 8 (3.5%) and poorly differentiated cancer in 3 patients. Metastases to the regional lymph nodes were detected in 25% cases. For cosmetic reasons, radiotherapy (oral x-ray therapy, interstitial method, long-distance gamma beam therapy) was the method of choice.

Hemopoiesis was studied in 88 patients with lung cancer during antitumor chemotherapy and its combination with a dry SB extract. Administration of the plant preparation was accompanied with hemopoiesis stimulation, intensification of bone-marrow erythro- and granulocytopoiesis and increase in the content of circulating precursors of the type of erythroid and granulomonocytic colony-forming units.

Both intact mice and those with transplantable adenocarcinoma 755 were used in the investigation. The nitroxyl radical Tempol was shown to cut down the toxicity of 6-mercaptopurine and potentiate its antitumor effect to a certain degree. The study results suggest on the basis of an investigation of cytochrome P450 and some other evidence that said effect of Tempol might be due, at least, in part to antioxidant activity.

The results of the endolymphatic chemotherapy application in patients with metastatic cancer of stomach are presented. The low toxicity and high effectiveness were suggested. One-year survival was achieved in 42.2% of patients.

Preoperative intraarterial chemotherapy was administered to 69 patients with gastric cancer. In 34 patients the tumor was localized in the antral portion, in 27 in the body of the stomach involving the proximal portion, and in 8 total involvement of the stomach was revealed. Left gastric artery was catheterized in 42 patients, right gastric-omental artery in 27. An original method of "loop" catheterization of celiac artery branches was used permitting a selective probing of gastric arteries proper. For prolonged intraarterial chemotherapy of gastric cancer adriablastin or farmorubicin were used in single dose 30 mg/M2, 5-fluorouracil in dose 500 mg/M2; the cytostatics were infused in 2-3 sessions. Immediate results of intraarterial chemotherapy were assessed by angiography and other instrumental methods of investigation, as well as intraoperatively and by morphometric analysis. In 62.4% of patients significant or total destruction of the tumor was attained, the volumic share of a viable tumor component being 0 to 2.1%. Altogether 95% of patients survived the follow-up of 2 to 30 months.

The cycle of phospholipid turnover has been found to be under the negative control of hormonal cytostatics (progesterone) and under the positive control of proliferation stimulants (17 beta-estradiol, epidermal growth factor). Specific changes in the synthesis of phospholipids are shown when tamoxiphen, an antiestrogen and an inhibitor of protein kinase C, was used. The findings suggest that changes in the turnover rate of phospholipids are one of the key stages of steroid action on target cells and may be regarded as an additional criterion of tumor genetic sensibility.

The value of subrenal capsule assay for predicting individual chemoresistance of tumor was evaluated using samples from 32 lung carcinomas. Treatment with drugs which had proved effective in the test was followed by a recurrence-free period of 15.5 +/- 3.7 months, as compared to 8.0 +/- 1.0 months for patients receiving ineffective drugs.

The immunocorrective effect of indomethacin in the course of chemoradiation treatment for inoperable lung cancer was established in a group of 117 patients. It manifested itself in an increase in T-lymphocyte level, normalization of their membrane structure and improvement in immunoregulatory function mainly due to a rise in T-helper/inductor level. Blood plasma-circulating immune complex concentration returned to normal. The concomitant administration of indomethacin during chemoradiation therapy improved subjective status of patients and tumor response but failed to increase survival.