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Vol 16, No 1 (2017)

REVIEWS

TECHNOLOGICAL APPROACHES TO IMPROVING THE PROCESS LYOPHILIZATION OF PROTEIN AND PEPTIDE DRUGS

Blynskaya E.V., Tishkov S.V., Alekseev K.V.

Abstract

Lyophilization of protein and peptide anticancer drugs is a promising method to create a stable and effective parenteral dosage forms. This article reviews the main problems encountered during lyophilization of protein and peptide drugs, and describes the best practices for solving these problems. The ways of optimization and improvement of the freeze-drying are given. Temperatures to improve the properties and prevent the destruction of the cake lyophilizatiе are suggested.
Russian Journal of Biotherapy. 2017;16(1):6-11
pages 6-11 views

IMPACT OF TUMOR-DERIVED FACTORS ON DENDRITIC CELLS IN CANCER

Keskinov A.A., Shurin M.R., Bukhman V.M., Shprakh Z.S.

Abstract

Dendritic cells play key role during tumorigenesis and immune response to it. They are able to uptake and present antigens to T cells, resulting in specific T cell mediated immune response. Furthermore, interaction between dendritic cells and other types of immune cells may boost cell-mediated and humoral immune response to cancer. Contrary to that, numerous tumor-derived factors may attract dendritic cells to neoplastic sites, causing impairment of their maturation, differentiation, and functional activity, resulting in deficiency of anti-tumor immune response or dendritic cell-mediated tolerance. Various factors within tumor microenvironment may either stimulate or inhibit dendritic cells and therefore need to be determined for improving efficacy of biotherapy utilizing dendritic cells. Meanwhile, recovery of dendritic cells functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-derived factors and their impact on dendritic cells in cancer.
Russian Journal of Biotherapy. 2017;16(1):12-23
pages 12-23 views

ORIGINAL REPORTS

COMPARISON IMMUNOCHEMOTHERAPY AND CHEMOTHERAPY EFFICASY IN FOLLICULAR LYMPHOMA

Falaleeva N.A.

Abstract

Russian Journal of Biotherapy. 2017;16(1):24-31
pages 24-31 views

PROGNOSTIC VALUE OF EXPRESSION OF ANDROGENETIC RECEPTORS IN DIFFERENT MOLECULAR TYPES OF BREAST CANCER

Ryabchikov D.A., Vorotnikov I.K., Kozlov N.A., Chkhikvadze N.V., Titov K.S., Shusharin A.S.

Abstract

Introduction. So far in the literature there is no consensus on the relationship between the level of androgens and their metabolites in various biological fluids and tissues with the development of breast cancer. As suggested by many researchers, determining the level of androgenetic receptors (AR) in the tumor in patients with breast cancer are able to access a number of promising directions in the study of prognosis of the disease and the search for new approaches to endocrine therapy of different molecular subtypes of breast cancer. Objective. To evaluate the clinical and prognostic significance of the immunohistochemical expression of AR in different molecular types of breast cancer. Materials and methods. In the present work we have studied the expression of AR in tumor tissue in patients of different molecular types of breast cancer. Results. The risk of death in patients with AR-positive breast cancer is 88 % lower than in patients with AR-negative tumors. Conclusion. It was concluded that the study of the expression of AR, is a promising direction not only in the assessment of the prognosis of the disease, but when searching for additional approaches to the treatment of breast cancer.
Russian Journal of Biotherapy. 2017;16(1):32-37
pages 32-37 views

PROGNOSTIC FACTORS OF THE EFFICACY OF ARANOZA-BAZED THERAPY IN NEUROENDOCRINE NEOPLASMS

Polozkova S.A., Gorbunova V.A., Delektorskaya V.V., Orel N.F., Kozlov N.N., Kuzminov A.E., Markovich A.A., Odintsova A.S., Emelyanova G.S.

Abstract

Introduction. In patients with neuroendocrine neoplasms it is necessary to search for new prognostic factors to identify a subgroup of patients who will benefit from drug treatment. Aim. The aim of the study was an optimization of Aranoza-based therapy in patients with neuroendocrine neoplasms by using both morphological and clinical factors as predictors of the treatment efficacy. Materials and methods. A total of 122 patients were enrolled and assessed for radiological response (RECIST 1.0) and progression-free survival. Results. Aranoza and its combinations had similar efficacy. The localization of metastases only in the liver, less than 3 metastatic zones, more than 6 courses of Aranoza-bazed chemotherapy, well-differentiated tumors, absence of doses reduction of Aranoza and temozolomide in anamnesis were predictors of the disease control rate. Progression-free survival was higher in patients with disease control rate (objective response + stabilization more than 6 months), Ki-67 < 20 %, well-differentiated tumors, more than 6 courses of Arano-za-based chemotherapy, objective biochemical response, less than 3 metastatic zones and absence of O6-alkylguanine-DNA alkyl-transferase expression. Conclusion. Future analysis of prognostic factors in patients treated with alkylating agents is needed.
Russian Journal of Biotherapy. 2017;16(1):38-46
pages 38-46 views

THE CHARACTERISTIC OF BONE MARROW STEM CELLS OF PATIENTS WITH THE COMPLICATED DIABETES

Nikolaeva L.P., Cherdantsev D.V., Titov K.S.

Abstract

Introduction. An increase in patients with diabetes and a large number of amputations of limbs make the search for new treatments for these patients. Materials and methods. The study included 17 patients with complicated forms of diabetes. Patients were studied in the bone marrow immediately after surgery - the amputation of the limb. The number of hematopoietic stem cells and mesenchymal stem cells using specific markers were determined in the laboratory. The immunohistochemical characteristics of bone marrow were carried out for all samples. Results and conclusion. The obtained results indicate the biological value of bone marrow removed with amputation of the lower limb of the patient with complicated diabetes mellitus. The ease of obtaining bone marrow makes the procedure approachable in surgical practice. The presence of hematopoietic and mesenchymal stem cells provides the opportunity to use them in autologous cell therapy for patient.
Russian Journal of Biotherapy. 2017;16(1):47-50
pages 47-50 views

MODELING OF ORTHOTOPICAL GROWTH OF HUMAN KIDNEY CANCER WITH SUBCUTANEOUS XENOGRAFTS RPOCH1 ON IMMUNODEFICIENT MICE

Andronova N.V., Sitdikova S.M., Morozova L.F., Raichlin N.T., Bukaeva I.A., Shubina I.Z., Kiselevsky M.V., Treshalina H.M.

Abstract

Russian Journal of Biotherapy. 2017;16(1):51-60
pages 51-60 views

ANTI-TUMOR EFFECT OF CPDA ENANTIOMERS IN VITRO IN THE MODEL OF ACUTE LYMPHOBLASTIC LEUKEMIA

Savinkova A.V., Tilova L.R., Borisova O.I., Zhidkova E.M., Kuzin K.A., Kirsanov K.I., Belitsky G.A., Budunova I.V., Yakubovskaya M.G., Lesovaya E.A.

Abstract

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.
Russian Journal of Biotherapy. 2017;16(1):61-69
pages 61-69 views

THE STUDY OF ANTITUMOR ACTIVITY OF PHENYLBUTYRATE IN COMBINATION WITH 5-FLUOROURACIL ON MODEL OF EHRLICH CARCINOMA

Fadeev N.P., Kharisov R.I., Kovan’Ko E.G., Pustovalov Y.I., Fadeeva V.L.

Abstract

Russian Journal of Biotherapy. 2017;16(1):70-75
pages 70-75 views

MULTIPHYTOADAPTOGENE ADMINISTRATION IN EARLY POSTNATAL ONTOGENESIS IMPROVE LIFE-SPAN AND PHYSICAL STATUS OF HIGH-CANCER MICE

Bocharov E.V., Karpova R.V., Bocharova O.A., Kucheryanu V.G., Shprakh Z.S.

Abstract

The aim of this investigation was to evaluate the life-span and physical status (weight, hair character, motor activity) of CBA inbred mice with high frequency of spontaneous hepatocarcinomas using multiphytoadaptogene complex (MPAC) preventive administration in early postnatal ontogenesis. Materials and method. MPAC is a herbal formula composed of forty plants water-ethanol extracts components including adaptogenes Panax ginseng, Eleutheroccosus senticosus, Rhodiola rosea. Anti-tumour, anti-oxidant, anti-mutagenic, immunomodifying activities of MPAC was demonstrated in previous studies. The study was carried out on 131 males of CBA mouse strain. The experimental mice received 10 % MPAC solution in drinking water during the first month of life including the final time period of liver differentiation. Motor activity was determined by a test of the «open field» automatically using Opto-Varimex-3 (Columbus Instruments, USA). The average lifespan was evaluated. Statistical analysis was performed with the program STATISTICA 6.0. Survival median was determined by the Kaplan-Meier method. Results. MPAC preventive use in early postnatal ontogenesis promotes mouse longevity increase for 17,1 % (p < 0,001), longevity median -for 25,6 % (p < 0,001). Physical status of experimental animals using MPAC administration had an advantage over control mice. Conclusion. So, data obtained demonstrate nontoxic MPAC administration in early ontogenesis promotes significant life-span increase, keeps the body weight, good coat state, motor activity as well as prevents hepatocarcinomas formation.
Russian Journal of Biotherapy. 2017;16(1):76-81
pages 76-81 views

FUCOIDAN FROM BROWN ALGAE FUCUS EVANESCENS: NEW PERSPECTIVES IN THE TREATMENT OF ATHEROSCLEROSIS

Krizshanovsky S.P., Kuznetsova T.A., Geltser B.I., Zaporozhets T.S., Ermakova S.P., Besednova N.N.

Abstract

Objective. The purpose of the research is the experimental study of the possibility of correction of disorders of lipid metabolism, lipid peroxidation and antioxidant protection (POL-AOP), liver structure on the model of alimentary hyperlipidemia in mice. Materials and methods. Fucoidan, a sulfated polysaccharide with a molecular weight of 160 kDa, derived from brown algae Fucus evanescens. The alimentary hyperlipidemia model was reproduced in mice. The biochemical parameters of lipid metabolism, state of POL-AOP system and the liver structure by MRT were studied. Results. We revealed the ability of fucoidan at per os administration to animals to normalize the key parameters of lipid metabolism, indicators of POL-AOP system, liver anatomic-topographic structure. Conclusion. The ability of fucoidan to correct these parameters allows us to consider it as a basis for the development of new biological medicines for the treatment of atherosclerotic disorders.
Russian Journal of Biotherapy. 2017;16(1):82-87
pages 82-87 views