In this work there is considered the possibility of correction of therapy for weakness syndrome in incurable patients with the use of drugs affecting dopamine and serotonin exchanges. It is showed that the use of 100 mg of ladasten, 16 mg of ondansetron orally per day and 50 mg of agomelatine per night is more effective in therapy for fatigue/weakness syndrome in incurable cancer patients compared to standard therapy.

This article is about the possibilities of increasing effectiveness and reducing toxicity in standard chemotherapy for cancer. Three possibilities are described: mechanisms of and overcoming multidrug resistance, selective transportation and drug delivery using vectors and artificial vehicles, and individualization of anticancer therapy.

Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin's lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline--83% and 82%, 82% and 81% (p < 0.05). At the same time ABVD chemotherapy develops less toxicity (p < 0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin's lymphoma patients with extranodal lesions. Using more than 6 cycles doesn't seem to improve OS and DFS (the 5-year and 10-year DFS, OS estimates are 79% and 72%, 80% and 77% versus 88% and 87%, 90% and 89% (p < 0.05). Comparison of complications rate during chemotherapy with MOPP (919 cycles), ABVD (1300 cycles), BEACOPP-baseline (584 cycles), BEACOPP-escalated (140 cycles) reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p < 0.05).

Eribulin is a novel antimicrotubule drug, which is approved in the second line treatment of advanced breast cancer in patients who received anthracyclines and taxanes. The article presents the results of two huge phase III clinical trials (301, 305) and their pooled analysis. Eribulin monotherapy demonstates staistically significant improved overall survival compared to standart treatments (15.2 mnths vs 12.8 mnths, p = 0.03 in pooled analysis). Certain subgroups of patients--Her2-negative and triple-negative have the most survival benefit. According to own experience with Eribulin inside the clinical trials, presented in the article, the drug is effective and well tolerated even by older patients.

Endogenous intoxication and immune insufficiency accompany neoplastic process. Complex therapy for cancer worsens these pathologic conditions by its adverse effects (AE) and thus complicates treatment. Efferent therapy can provide continuity of antineoplastic therapy with normalization of hemostasis and decreasing the rate of AE and their intensity. Efferent therapy meaningfully increases patient's quality of life and decreases the needed drug support when used as a part of complex therapy. Proper use of efferent therapy can markedly increase efficacy of surgical treatment, radiation therapy and drug therapy.

New approach to synthesis of analogs of natural Combretastatin A-4 based on interaction of α-acetylenic ketones with secondary amines (diethyl amine, pyrrolidine, piperidine, morpholine) is offered. Unknown analogs of Combretastatin A-4 with β-aminovinylcarbonyl bridges are received earlier. Anti-inflammatory activity of the received connections is studied.

Binase--Bacillus pumilus RNase--endonuclease cleaves the phosphodiester bond between the 3'-guanylic residue and the 5'-OH residue of adjacent nucleotides with the formation of corresponding intermediate 2',3'-cGMP. Subsequent hydrolysis of 2',3'-cGMP into 3'-phosphate is highly specific and occurs slowly So the question arises about the existing time of that positional isomer during RNA catalytic cleavage by binase and about 2',3'-cGMP role in antitumor activity of the enzyme: In present work by means of enzyme-linked immunosorbent assay we established that during catalytic cleavage of RNA by binase 2',3'-cGMP is preserved in reaction mixture for an hour, at the same time phosphodiesterases activation doesn't lead to the total elimination of 2',3'-cGMP. The highest amount of 2',3'-cGMP was observed under the pH 8.5, it reaches nanomolar concentration at initial RNA concentration of 100-1000 μg/mL. Exogenous 2',3'-cGMP, like its positional isomer 3',5'-cGMP, doesn't trigger an apoptosis of human lung adenocarcinoma A549 cells, which are sensitive to binase apoptogenic action. Taking into account data about binase internalization and activation of mitochondrial pores opening by 2',3'-cyclic guanosine phosphates we may consider that 2',3'-cGMP can contribute to the apoptosis initiated by binase only when 2',3'-cGMP is generated intracellularly.

The objective of the present study was to elucidate the mechanisms underlying the ototoxic action of cisplatin after its single administration using an experimental model (white mice). Short latency acoustically evoked potentials (SAEP) and distortion-product otoacoustic emissions (DPOAE) were recorded for the purpose. The results of the study confirm the possibility of using the proposed model for the estimation of the cisplatin-induced loss of hearing. It was shown that a single cisplatin dose causes hearing impairment in the mice within 7 days after its administration; with the maximum effect becoming apparent on day 30.

Mitochondria play central roles in diverse physiological and pathological conditions associated with cell survival and death. Delocalized lipophilic cations, such as dequalinium (DQA), are accumulated in cancer cells attracted by the highly negative mitochondrial transmembrane potential of these cells. DQA showed a potent anticancer activity in cells from different malignancies. Here, we report the effect of DQA on PC-3 prostate cancer cells. Incubation with DQA at concentrations between 1.5 and 100 microM from 24 to 48 h decreases cell viability. The decrease in cell viability together with a loss of mitochondrial transmembrane potential induced an increase in reactive oxygen species production and cell death via caspase-3 dependent apoptotic pathway. QA was shown to cause moderate to strong cell death in a time and concentration dependent manner, causing a most advantageous effect at a concentration of 10 microM applied for a long 48 h time period, which might be a consequence of the kinetics of intracellular DQA accumulation in mitochondria, but also of the mechanisms of DQA-induced cell death. This data shows DQA as a promising agent against the human prostate cancer PC-3 cell line, activating the caspase-3 dependent apoptotic pathway. This fact might be beneficial for possible future applications in cancer therapy.

The effectiveness of the peptide immunomodulator molixan as a means of support and correction of chemoradiation therapy of oral mucositis have been studied in 36 patients with primary regional cancer of the oral mucosa and the oropharynx. Combined chemotherapy of patients with cisplatin and standard radiotherapy was associated with progression of oral mucositis and hematopoietic disorders which manifested themselves in the form of neutro-, lympho- and thrombocytopenia. Therapeutic intramuscular application of molixan at a dose of 60 mg once a day after a fraction of irradiation made it possible to reduce the severity of oral mucositis (from grade III-IV to grade I-II), as well as to maintain in patients a higher level of white blood cells and platelets in the blood, which made it possible to complete the planned course of chemoradiation therapy.

The spectral, fluorescent and functional properties of ferric oxide and ferric hydroxide nanoparticles loaded with doxorubicin and stabilized with citric acid or lysine were studied in comparison with free doxorubicin. Their effect on the opening of calcium-induced mitochondrial pore and the possibility of the controlled release of doxorubicin under the influence of redox stimuli were investigated. The data show that the effect of nanoparticles on mitochondria depends on the type of a stabilizer. The spectral and fluorescence methods used allow us to estimate the presence or absence of free doxorubicin in solution of nanoparticles and the:concentration of bound doxorubicin. It is shown that the dithiotreitol and glutathione increase the amplitude of absorption and fluorescence of doxorubicin during incubation with nanoparticles. It is assumed that this effect may be associated with the reduction of the oxidized iron by thiols with subsequent release of doxorubicin.

The anti-tumour dose-dependent effect of binuclear dinitrosyl iron complexes with glutathione as NO donors on solid tumour in the mouse Lewis lung carcinome was detected. The complexes being injected at the doses of 21, 42, 105 mg/kg daily during 10 days blocked completely the development of the tumour for the first week after tumour cell implantation into animals. After that, the part of tumour cells which remained in intact alive state began to grow at the rate equal to that for control animals. The effect was proposed to be caused via the formation of the anti-nitrosative defense system in the cells as a response to NO attack to cells. It was also hypothesized that this system can be inactivated by higher doses of dinitrosyl iron complexes. The data were obtained which were in line with the hypothesis.

to investigate intraocular pressure (IOP) and ocular blood flow (OBF) changes as well as the individual normal range of IOP in patients with age-related macular degeneration (AMD) with or without concomitant glaucoma after intravitreal anti-vascular endothelial growth factor (VEGF) therapy.

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.

Plant hormones play a key role in plant growth and differentiation. Many hormones are known as potential antitumor agents, yet others appear to affect the secretory activity and are produced by mammalian cells as pro-inflammatory cytokines. The goal of this research was to study the effect of abscisic and gibberellic acids on the secretory system of human cultured epidermoid carcinoma cells A431 and keratinocytes HaCat. Immunocytochemical and morphometric analysis demonstrated that subtoxic concentration of plant hormones induced the broadening of the ER network and increased the size of Golgi complex. Electron microscopy studies confirmed the hypertrophic changes of the Golgi apparatus, specifically, the swelling of cisternae in the trans-compartment of dictyosomes after exposure to abscisic acid, and swelling of cis- and trans-compartment of dictyosomes after exposure to abscisic acid, and swelling of cis- and trans-compartments of dictyosomes after exposure to gibberellic acid. Using of Click-iT technique allowed to detect the elevation of the total protein synthesis only in A431 cells exposed to abscisic acid. Cumulative data suggests that, under these conditions, the hypertrophy of Golgi apparatus may reflect the enhanced secretory activity of cells. In other experiments, the hypertrophy of Golgi is not related to increased protein synthesis and therefore may suggest the stress-related changes of ER and Golgi apparatus. Our results demonstrate that morphologically similar reaction of cellular organelles, such as hypertrophy of Golgi apparatus, is the result of different functional activities, and that molecular mechanisms underlying the changes induced in cells need further investigations.

Melanoma is one of the most malignant tumors, which leaves no chance of survival in the case of the "bang". There are various ways to treat tumors, however, recently in the field of cancer research, there are studies in which fungal metabolites have been used as antitumor agents. In this study we examined the effect of the culture fluid of the fungus Trichoderma asperellum 302 on the growth and development of melanoma B 16. We have shown that these culture fluid has anticancer properties, causing destruction of tumor tissue. Obtained data open new possibilities and prospects for the use of active substances derived from fungi in the complex therapy of cancer.

Some compound refering to the 3-hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones have been found to cause an increase in the number of mitotic cells and their subsequent death in vitro. This increased in the number of mitotic cells was not associated with increased cellular proliferative activity and was likely due to mitotic exit failure. Of note, the effect was more pronounced in the tumor cells when compared to human fibroblasts. Further studies are needed to investigate the molecular mechanisms of action of the compounds belonging to the class of 3-hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones.

Previously it was found that sodium fluoroacetate (SF) inhibited the growth of the Ehrlich cancer by means of monotherapy and enhanced the antitumor effect of cyclophosphamide (CP) in experiments with autochthonous subcutaneous tumors induced by benzo (a) pyrene. In this study a comparison of the antitumor activity of SF and metformin showed that both substances did not have significant effect in monotherapy but enhanced the effect of CP, increasing the percentage of tumors with the same or reduced volume. Besides, SF, unlike metformin increased the average duration of effect. The data obtained promoted further study of the mechanism of the antitumor effect of SF and the search effective combination with already known antitumor drugs.

This review presents data on the antitumor properties of antineoplastons--alternative means of treatment for cancer originally isolated from human blood and urine. It was assumed that antineoplastons (derivatives of peptides and amino acids) are natural regulators of cell differentiation. In experimental studies it was showed that synthetic antineoplastons (A10-3-phenyl-acetyl-amino-2,6-piperidinedione and AS2-1--a mixture of phenylacetic acid and phenylacetylglutamine) were able to prevent the introduction of glutamine into the cell, to block the action of Bcl-2, to activate p53 and p21, to inhibit histone deacetylase, to induce apoptosis. In experiments in vitro and in vivo in several studies it was registered antitumor activity, mainly on models of hepatocellular carcinoma and glioma. Clinical data are limited by reports of individual clinical cases or series of cases and the results of several clinical trials Phase I-II, indicating a possible antitumor activity.

Disbalance of bone homeostasis, associated with malfunctioning of RANK/RANKL/OPG system underlies the oncological processes such as the destruction of bone, metastasis development, tumor progression. Pathological activity of system was described in such conditions, as breast cancer, prostate cancer, multiple myeloma, squamous cell carcinoma, Hodgkin's disease, and also metastasis in bones from lung cancer and other malignant diseases. In the literature, there is evidence of involvement of RANK/RANKL/OPG system in the pathogenesis of bone tumors (osteosarcoma, giant cell tumor of bone, chondroblastoma). Experimental data show that RANKL inhibitors can play a role in reducing tumor-induced lesions of bone in multiple myeloma, breast cancer, prostate cancer and lung cancer. Also this review presents data from clinical studies of the drug efficacy targeted on RANK/RANKL/OPG system and results of authors' study of the levels of this system's components and proinflammatory cytokines in blood serum of primary bone sarcoma patients.