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.

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.

Fifty five patients with hormone-resistant prostate cancer were included in this retrospective controlled study. Chemotherapy with intravenous docetaxel (75 mg/m2 for 21 days) was performed in 30 patients, 25 patients received metronomic oral therapy with cyclophosphamide (50 mg/day). The central objective of this study was the comparison of overall survival in these groups. Pain management effectiveness, quality of life and PSA level were also compared. In docetaxel group the median overall survival was 15.9 +/- 1.7 months, in cyclophosphamide group 15.4 +/- 2.2 months (p = 0.5). Frequency of PSA level decrease was 76.7% and 44%, PSA response to therapy was observed in 46.7% and 12% of patients (p = 0.04 and p = 0.02). In docetaxel group pain reduction was achieved in 42.9% and in cyclophosphamide group in 31.3% of cases (p = 0.60). Grade III-IV hematological toxicity was observed only in docetaxel group (33% of patients), in 16.7% of patients receiving docetaxel the therapy had to be ceased due to adverse effect. Quality of live was improved in 26.7% of patients receiving docetaxel and in 16% of patients receiving cyclophosphamide.

Ninety-six patients with unresectable or metastatic colorectal cancer received first-line chemotherapy plus bevacizumab. The purpose of our study was to evaluate the safety and efficacy of the therapy. Median relapse-free survival lasted 10.4 months. Addition of bevacizumab was well tolerated and may be recommended for clinical use.

Dicarbamin-assisted mono- and combination chemotherapy (cyclophosphamide + carboplatin + cisplatin) for transplantable tumors born by linear or hybrid mice of both sexes was investigated. It was shown that long-term oral administration contributed to the effect of a range of cytostatic therapeutic dosage rather than adversely affected it. Our findings were used to make a case for clinical studies of dicarbamin for its potential of lowering hematological toxicity of antitumor therapy.

One hundred and twenty SHR male mice were randomly divided into 4 groups. Their clean-shaven backs were painted with 0.2 ml of 0.05% acetone solution of benz(a)pyrene (BP) twice a week. Group 1 was in control and received no additional treatment. From beginning to end (6 months), the remaining mice received melatonin 2 mg/l with drinking water at nighttime (group 2), metformin 200 mg/l with drinking water during 24 hrs (group 3), melatonin and metformin as in groups 2 and 3 (group 4). There was a separate group of intact animals. Skin tumor frequency decreased: among melatonin/metformin-treated mice (groups 1-4) - 83.3%, 66.7%, 60%83 and 50%; squamous cell carcinoma - 56.73%, 36.7%, 20% and 20%. Treatment with melatonin and metformin and their combinations was followed by significantly lower tumor multiplicity and smaller size, longer latency period and survival of tumor-bearers. After BP, levels of malonic dialdehyde (MDA) and catalase rose in blood serum while concentrations of the latter in skin tumors were higher than in cutaneous homogenates in intact animals. Melatonin and metformin significantly lowered MDA content of blood serum as compared with group 1. Blood serum catalase fell after their joint administration whereas it was 2.6 times as high in cutaneous homogenates after metformin. However, it decreased after melatonin.

We studied the parameters of binding of 5,10,15,20-tetra-(N-methyl-3-pyridyl)porphyrin (TMPyP3) to the anti-parallel human telomeric G-quadruplex d(TTAGGG)4, the oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 that does not form a quadruplex structure, as well as to the double stranded d(AC)8 x d(GT) and single stranded d(AC)8 and d(GT)8 DNAs. The analysis of absorption revealed that the binding constants and the number of DNA binding sites for TMPyP3 were d(AC)8 < d(GT)8 < d(AC)8 x d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. We demonstrated for the first time that the binding constant of TMPyP3 with the non-quadruplex chain dTTAGGGTTAGAG(TTAGGG)2 (1.3 x 10(7) M(-1)) is approximately 3 times bigger than the binding constant with the quadruplex d(TTAGGG)4 (4.6 x 10(6) M(-1)). Binding of two TMPyP3 molecules to d(TTAGGG)4 led to a decrease of thermostability of the G-quadruplex (deltaT(m) = -8 degrees C). Circular dichroism spectra of TMPyP3:d(TTAGGG)4 complexes revealed a shift of DNA structure from the G-quadruplex to an irregular chain. We hypothesize that partial destabilization of the telomeric G-quadruplex by TMPyP3 might be a reason for relatively low potency of this ligand as a telomerase inhibitor, as well as its marginal cytotoxicity for cultured tumor cells.

In this study cytostatic and chemosensitizing actions of gestagens are described. Cytostatic mechanisms can be divided into estrogen-mediated and independent ones. The former include down-regulation of estrogen receptors, induction of 17?-hydroxysteroid dehydrogenase and estron sulfotransferase. The latter are MAP-kinase inhibition, induction of cell differentiation and apoptosis. Chemosensitization by gestagens is due to inhibition of P-glycoprotein, GST and MRP. Another putative chemosensitization mechanisms involves mitochondrial transition pore (MTP), at least for such gestagens as buterol and acetomepregenol. Elucidation of common mechanisms of MTP and MDR regulation and the possible role of MTP in chemosensitization is a new direction of investigations into the action of steroid hormones.

To improve the efficiency of anticancer drugs due to their delivery to intracellular targets a set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized. NLS was attached to the parent molecule via ε-amino group of D-Lysine in position 1 or 6 of peptide sequence using orthogonal protection strategy. The biological activity studies revealed that incorporation of NLS moiety significantly increases cytotoxic activity of palmitoyl-containing GnRH analogues in vitro. The influence of tested peptides on tumor cells does not accompanied by the destruction of cell membrane, as confirmed in experiments with normal fibroblasts, used as a control.

Shown antimicrotrubules activity of new 2,6-dinitroaniline compounds. Investigated their ability on apoptotic processes in a plant cell when used as a composition with inhibitors of acetyl-CoA carboxylase.

The review is summarizes current information on biological activity and search of the antineoplastic mechanism of action of alkyl glycerolipids. Special attention is paid to following problems: selective ability phosphorus alkyl glycerolipids, antineoplastic activity, cytostatic and cytotoxic effects of edelfosine and its analogues. The review contains set of the data known for today from the literature, on the possible mechanism cytoyoxic actions of such connections.

A novel approach is suggested to identify more homogenous subgroups involved in the follow-up of growth of spontaneous mammary tumors in mice (116, history-based analysis). That depends on subclinical period (preneoplastic and non-invasive stages of tumor growth) as well as rate of growth after clinical manifestation. An analysis of tumor growth rate versus survival of experimental and control animals after primary diagnosis and clinical manifestation of tumor showed that following a single peritumoral 2.5 x 10(6) IU IL-2 treatment tumor growth slowed down (n = 29; p < or = 0.05) while survival tended to improve. Originally fast-growing tumors without significant subclinical stage continued to grow but slowly. Females with such tumors survived longer than untreated controls without showing, however, any improvement on that parameter.

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.

Clinical data are reported upon the examination of a group of 160 women aged 18-55, suffering of a breast cancer and subjected to polychemotherapy using various cytostatic schemes: (I) standard CAF scheme, course repetition each 4 weeks; (II) alternating CAF and AVCFM schemes (intermittent introductions), a total of 4 courses. For the reduction of the cardiotoxic effects of anthracyclines, one part of patients was given an antioxidant preparation of amber acid--Reamberin--whose administration substantially decreased both the frequency of cardial complaints and the expression of clinical manifestations of the astheno-neurotic syndrome and prevented the occurrence of systolic and diastolic dysfunction of myocardium and the heart rhythm and conductivity disturbances.

According to some existing data, unlike sulphonylurea (SU) and insulin derivatives, treatment with biguanide metformin, for reasons still unknown, may diminish breast cancer (BC) morbidity in diabetic females. For its part, diabetes is known to worsen survival of BC patients although there is no evidence of a pathway by which antidiabetic therapy might influence the key prognostic feature of BC tissue--the tumor receptor phenotype. Combination of BC and diabetes (n=90) was studied. SU drugs were received for at least 12 months by 22 patients, biguanide metformin alone or in conjunction with SU by 15, insulin by 5, and dietary treatment alone--by 48 pts. Percentage of estrogen receptor-positive tumors did not vary significantly from group to group. However, progesterone receptor-positive (PR+) tumors in metformin-treated patients were revealed more often than in those receiving SU alone (p = 0.43) or with insulin (p = 0.041), respectively. Hence, previous treatment with metformin is expected lead to higher incidence of PR+ tumors which in turn may stimulate efficiency of hormonal therapy only in relevant group of diabetic BC patients.

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

Gemicitabine (2',2'-difluorodesoxycitidine) is a relatively new medicinal product from the group of anti-metabolites used as the first line therapy of pancreatic cancer, non-pulmonary cancer, and breast cancer. However, analysis of its toxicity spectrum revealed a large number of adverse events associated with the clinical application of this product. This fact is ascribed to the narrow range of therapeutic usages of this cytostatic preparation (from 25 mg/kg to 27 mg/kg). This paper is designed to summarize the available data on hematological, gastrointestinal, pulmonary, and cardiotoxicity of gemcitabine. They may be useful for the improvement of control over gemcitabine toxicity, correction of its dosage regime, and efficacious prevention of the most serious side effects.