Vol 22, No 3 (2017)

Articles

RAMUCIRUMAB THERAPY IN PATIENTS WITH ADVANCED GASTRIC AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA: A SYSTEMATIC REVIEW

Gorbounova V.A., Besova N.S., Bychkov M.B., Orlov S.V., Kogoniya L.M., Vozny E.K., Vladimirova L.U., Sakaeva D.D., Sholokhova E.A., Minasyan A.A., Gurochkin A.B., Cheng R., Orlando M.

Abstract

Objective. Gastric cancer is the fifth most common malignancy and the third leading cause of the cancer mortality worldwide. It is most often diagnosed at a locally advanced or metastatic stage. Angiogenesis has become an important target in the treatment of solid tumors, and antiangiogenic agents are a promising approach to cancer therapy. In this review, we summarize the current literature on the treatment of gastric and gastroesophageal cancer with ramucirumab, an antiangiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). Material and methods. We conducted a systematic search in May 2016 of PubMed and relevant congress proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies were aimed to prospectively evaluate the efficacy and safety of ramucirumab in advanced gastric or gastroesophageal cancer. Results. Our search yielded 91 publications including 5 manuscripts and 6 congress abstracts meeting the predefined inclusion criteria. Included studies reported outcomes were related to ramucirumab in gastric cancer, published within the past 5 years. Conclusion. Second-line treatment with ramucirumab, either as monotherapy or in combination with paclitaxel, significantly improves the survival of patients with advanced gastric cancer. Ramucirumab is well tolerated and has an acceptable safety profile. Furthermore, the patient quality of life is maintained with delayed both symptom worsening and deterioration of the functional status. Studies are required to identify potential predictive biomarkers of ramucirumab efficacy.
Russian Journal of Oncology. 2017;22(3):116-121
pages 116-121 views

TRANSDERMAL FENTANYL: PHARMACOLOGICAL ASPECTS OF THERAPY IN CANCER PATIENTS. PART 1. FROM THE DEVELOPMENT OF TRANSDERMAL FENTANYL FORMULATIONS TILL META-ANALYSES OF CLINICAL TRIALS

Sidorov A.V.

Abstract

There was given a review of data on pharmacology of fentanyl with focus on transdermal formulation. In the first part of the article improvements in technology of fentanyl transdermal patches were reviewed and advantages of the membrane-matrix system that are of practical use were highlighted. The results obtained from bioequivalence and therapeutic equivalence studies of traditional and improved transdermal fentanyl systems were given. Clinical trials with fentanyl transdermal patches as well as systematic reviews and meta-analyses on the efficacy and safety of transdermal fentanyl were summarized. The second part of the article will focus on factors contributing to the variability in pharmacokinetics and pharmacodynamics of fentanyl including pharmacogenetics; the taking into account the whole spectrum of these factors would allow to escaped the majority of errors during the administration of the drug e.g. transdermally. A special attention will be paid to basic principles and issues of the application of fentanyl transdermal therapeutic systems.
Russian Journal of Oncology. 2017;22(3):122-130
pages 122-130 views

ANALYSIS OF THE INTERRELATION OF THE VASCULAR ENDOTHELIAL GROWTH FACTOR WITH PITUITARY ADENOMAS COMPLICATED BY PITUITARY APOPLEXY

Makhkamov K.E., Azizov M.M., Vervekina T.A., Nishonov D.A.

Abstract

Aim. Despite the fact that the pituitary adenoma is a relatively benign tumor, sometimes the course of the disease is complicated by intramedullary hemorrhage. In the world literature there are single data on the molecular mechanism of hemorrhage in the adenomas of the pituitary gland. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and permeability of the endothelium in various brain tumors. There was made an analysis of the relationship between pituitary apoplexy and VEGF expression in pituitary adenomas. Material and methods. Immunohistochemical investigation of the level of expression of the molecular-biological marker - VEGF was performed with the use of monoclonal antibodies with the method of semiquantitative analysis in 30 pituitary adenoma patients. In the clinical study data about the age, gender, hormonal activity and X-ray study were studied. There was executed a statistical analysis of the relationship between clinical diagnostic data and VEGF expression. Results. Hormonal active tumors were detected in 12 (40%) cases, intratumoral hemorrhage - in 16 (53.3%), adenomas with cystic component - in 7 (23.3%) and invasion of cavernous sinus - in 22 (73.3%) of cases. Expression of VEGF was observed in 11 cases (36.6%). Based on the analysis the expression of VEGF was found to be closely related to pituitary apoplexy (PA) in pituitary adenomas (p < 0.001). However, there was no statistically significant relationship between VEGF and age, sex, tumor size, hormonal activity, cystic component presence, invasive tumor growth (p > 0.05). Conclusion. It was found that immunohistochemical examination of the level of expression of a molecular biological marker VEGF can be used in the evaluation of the prognosis of the disease or the identification of a risk group with a high probability of the development of pituitary apoplexy and recurrence of tumor growth.
Russian Journal of Oncology. 2017;22(3):131-135
pages 131-135 views

STUDY OF THE EFFECTIVENESS OF TARGETED THERAPY IN METASTATIC RENAL CELL CARCINOMA PATIENTS

Alekseeva G.N., Gurina L.I., Volkov M.V., Evtuchenko E.V.

Abstract

Objective. To study the relapse-free overall survival in metastatic renal cell carcinoma (mRCC) patients after the targeted therapy and to develop optimal approach to the treatment shedule. Material and methods. The research included 88 mRCC patients of mean age of 55.5 + 9.6 years, 63 (71.6%) men and 25 (28.4%) women. 42.0% patients had a favorable prognosis, 52.3% - intermediate one and 5.7% of the cases had poor prognosis. First line targeted therapy was carried out in 88 patients, the second line - in 26 patients, and the third line - in 7 patients. Results. The one or several lines of targeted therapy allowed to achieve 20 months of a median in survival without progression of the disease. Several lines of treatment increased a median of general survival up to 42 months in comparison with the patients who were involved in the one line of treatment (a median = 30 months), p = 0.001. Side effects of targeted therapy were reversible. In the first line targeted therapy the preference was given to sunitinib, in the second line - to sorafenib. Sorafenib had an advantage in case of not light-cellular forms of renal carcinoma. In cases with favorable prognosis factors, metastases into organ parenchyma, targeted therapy with bevacizumab was carried out.
Russian Journal of Oncology. 2017;22(3):136-141
pages 136-141 views

EFFECT OF INTRAVESICAL CHEMOTHERAPY, MODIFIED BY ELECTROMAGNETIC FIELD IN THE SCANNING MODE, ON THE LEVEL OF ENDOTOXEMIA AND OXIDATIVE PROCESSES IN THE BLOOD IN PATIENTS WITH BLADDER CANCER

Goroshinskaya I.A., Shevchenko A.N., Filatova E.V., Kachesova P.S., Nemashkalova L.A., Chudilova A.V.

Abstract

Muscle-non-invasive bladder cancer (MNIBC) accounts of 70% of malignant lesions of this localization and has a high rate of recurrence and complications after treatment that requires improvement of the management of such patients. The developed modification of adjuvant intravesical chemotherapy (IVCT) necessitates the evaluation of endotoxemia and the adequacy of antioxidant protection of patients. The purpose of the study is the assessment of indices that reflect the functional state of albumin, the severity of endogenous intoxication (EI) and the state of free radical oxidation in the blood of MNIBC patients receiving adjuvant IVCT modified by the influence of scanning electromagnetic field. Material and methods. Endogenous intoxication indices, the light sum of peroxide induced luminol dependent chemiluminescence, malondialdehyde (MDA) content, activity of superoxide dismutase, catalase and glutathione system were investigated in the blood of MNIBC 30patients receiving chemotherapy under the impact of electromagnetic field during the process of dynamic monitoring of patients in comparison with a group of healthy persons. Results. Before treatment, MNIBC patients were characterized by the increased content of medium mass molecules (MMM) by 34-80% and decreased albumin binding capacity by 20%, that leading to an increase of EI coefficient by 81%, indicating to the presence of EI. The observed increase in the intensity, accumulation of molecular products of lipid peroxidation and the low level of activity of the main antioxidant enzymes indicated to the contribution of free radical processes in the metabolic state of these patients. After completion of adjuvant IVCT under simultaneous exposure to the local scanning electromagnetic field the decrease of main markers of endotoxemia - MMM254 and MMM280 was revealed. Full restoration of the albumin binding capacity and balanced operation of the antioxidant system was observed 9 months after the surgery. Conclusion. Biochemical data are consistent with the clinical efficacy of adjuvant IVCT combined with the scanning magnetic field, which allows to improve indices of 2-year disease-free survival to 94% and to double the latency period of relapse.
Russian Journal of Oncology. 2017;22(3):142-148
pages 142-148 views

TISSUE GROWTH FACTORS OF VEGF FAMILY IN DYNAMICS OF THE DEVELOPMENT OF OVARIAN CANCER

Kit O.I., Frantsiyants E.M., Moiseenko T.I., Verenikina E.V., Cheryarina N.D., Kozlova L.S., Pogorelova Y.A., Rosenko L.Y.

Abstract

Ovarian carcinoma is the leading cause of death from gynecological cancer. Aim of the study is to reveal the role of VEGF-C comparing to VEGF-А in the progression of ovarian cancer. Material and methods. Tissue samples obtained from 76 patients with epithelial ovarian cancer (serous cystadenocarcinoma: T1N0M0; T2N0M0; T3NxM0; T4Nx-1M0) and 47 patients with cystadenoma were studied. Histological control was performed in all cases. Ovaries of 20 patients obtained during the surgery for uterine myoma were used as the intact tissue. All patients were 50.9 ± 2.9 years old. Levels of the growth factor as VEGF-A and its receptor VEGF-R1, as well VEGF-С and its receptor sVEGF-R3 - were measured by ELISA with the use of standard test systems. Results. VEGF-А levels in cystadenomas and intact tissue were similar, while in cystadenocarcinomas VEGF-А was significantly higher at all stages of the tumor development. sVEGF-R1 receptor in cystadenomas was lower in comparison with the intact tissue, in the contralateral ovary in T1N0M0 and in the tumorous ovary in T4Nx-1M0. VEGF-С level was higher significantly in all tumors, in cystadenocarcinomas it was higher if compared to cystadenomas. Its increase in the contralateral ovary in T1N0M0 differed from other tissue values being average. sVEGF-R3 receptor increased significantly at the later stages of ovarian cancer - T3NxM0 and T4Nx-1M0; its level was low only in the contralateral ovary in T1N0M0, and the values in other tissues were similar to the intact ones. Conclusion. The results show a high rate of lymphatic vessel formation in benign tumors at all stages of the development of the malignant tumor. The significant increase in VEGF-C level in the contralateral (non-tumorous) ovaries, compared to the intact tissue, allows considering VEGF-C, along with VEGF-А, as a pathogenetic factor of ovarian tumor development.
Russian Journal of Oncology. 2017;22(3):149-152
pages 149-152 views

EXPRESSION OF MARKERS OF APOPTOSIS (P53, BCL-2, BAX) AND PROLIFERATION (KI-67, TOPOISOMERASE IIA, ARGYROPHILIC PROTEINS OF NUCLEOLAR ORGANIZER REGIONS) IN HEALTHY PERSONS AND NON-SMALL CELL LUNG CANCER PATIENTS AND THEIR RELATIONSHIP WITH SOME CLINICAL AND MORPHOLOGICAL PARAMETERS

Panasyan A.U., Kobyakov D.S., Avdalyan A.M., Ivanov A.A., Lushnikova E.L., Bakarev M.A., Lazarev A.F.

Abstract

Study of markers of apoptosis and proliferation in relation to clinical and morphological parameters in non-small cell cancer (NSCLC) patients and healthy persons. There were investigated 237 surgery samples of NSCLC and 10 cases of normal lung tissues. p53, bcl-2, bax, Ki-67, topoisomerase IIα (ТороIIα) levels were determined by immunohistochemical method. Argyrophilic proteins associated with nucleolar organizer regions (AgNOR) were detected with silver nitrate. In NSCLC expression of p53, bcl-2, Ki-67, TopoIIα, AgNOR increased and expression of bax was lower if compared with the normal tissue. Expression of apoptotic markers (p53, bcl-2, bax) correlated with clinical and morphological parameters of NSCLC: histogenesis, N index and the stage (for bcl-2), gender (for bax). Expression of Ki-67 and TopoIIα correlated with gender, largest size of the tumor, histogenesis and differentiation. AgNOR proteins were interrelated with the gender, T and N indices, largest tumor dimension, stage, histogenesis and differentiation. In NSCLC cases the expression of apoptotic markers correlated with proliferation: in p53 positive tumors - high level of proliferation (Ki-67, TopoIIα, AgNOR), in bcl-2 positive tumors - low AgNOR, in bax positive tumors - low proliferative activity (Ki-67, TopoIIα). In NSCLC there is observed the change in expression of apoptotic markers (p53, bcl-2, bax) and proliferation (Ki-67, TopoIIα, AgNOR) in conjunction with normal tissue and clinical and morphological parameters of tumor.
Russian Journal of Oncology. 2017;22(3):153-157
pages 153-157 views

SENSITIVITY OF THE TRANSPLANTED HUMAN NEUROBLASTOMA TO ONCOLYTIC СOXSACKIE A7 VIRUS

Sosnovtceva A.O., Karshieva S.S., Smirnova G.B., Borisova Y.A., Lebedinskaya O.V., Shubina I.Z., Treshalina H.M., Chumakov P.M., Chekhonin V.P.

Abstract

Oncolytic viral therapy is a promising approach to targeted therapy of malignant tumors. In this article we consider the therapeutic potential of a non-pathogenic Coxsackie A7 virus (CA7V) with neurotropic properties on a model of human neuroblastoma. Purpose to study in vitro/in vivo sensitivity of human neuroblastoma HNB (from cell line JMR-32) to Coxsackie virus A7 (CA7V). Objectives: еvaluation of cytolytic activity in vitro on NB cells verified by cytomorphology and assessment of dynamics of the growth of subcutaneous neuroblastoma xenografts in Balb/c nude male mice exposed to CA7V multiple i.v. injections. Material and methods. CA7V was produced in the cells of line-producer С-33А. Cell culture and the strain of transplanted NB (JMR-32) were obtained from the Collection of N.N. Blokhin Russian Cancer Research Center. Cytomorphologic verification of neuroblastoma and CA7V cytolytic activity were executed with the use of standard cultural methods, TCID50 and IC50 criteria. Experiments «in vivo» were performed on immunodeficient Balb/c nude male mice bred and reared in the N.N. Blokhin Russian Cancer Research Center. The experiments were made at day 6 when neuroblastoma subcutaneous xenografts developed to the Vmean = 79-82 mm3 by day 6. The treatment with CA7V at the i.v. single dose of 1×108 cells per mouse was performed 3 times with 72-hours intervals; evaluation of the efficacy was made according to standard criterion Т/С ≤ 42%; and control of the tumor growth rate (Vt/V0) in the dynamics. Statistical assessment was made with the software Excel for Windows 2007 with the use of T-test under p ≤ 0.05. Results. Cytolytic effect of CA7V on neuroblastoma cells was registered similar to basic parameters of the original line-producer С-33А: TCID50 = 0.99×10-4 pfu/cell, and IC50 = 1.11×10-4 pfu/cell; 48 and 72 hours after virus reproduction in NB cells the rate was 2.0 and 1.5-fold higher than in the line-producer cells. СA7V inhibiting effect on the growth of large subcutaneous neuroblstoma xenografts is registered after the first i.v. injection at the minimal level of T/C = 67% (criterion ≤ 42%) with the 1.5-fold decrease of the tumor growth rate and cancellation of early mice death by day 22 vs day 15 in the control group of untreated mice (n = 8). Conclusion. The obtained results allow to consider human neuroblastoma (JMR-32) to possess the low sensitivity to oncolytic effect of in vitro/in vivo. In order to obtain significant effect in vivo the treatment should be started in mice with 2-fold smaller tumors and a higher initial dose of the oncolytic agent.
Russian Journal of Oncology. 2017;22(3):158-163
pages 158-163 views

PROPHYLAXIS AND TREATMENT OF SIDE EFFECTS OF ANTIANGIOGENIC THERAPY IN PATIENTS WITH METASTATIC COLORECTAL CARCINOMA

Meshcheryakov A.A.

Abstract

The review analyzed data from the literature and personal experience of the application of anti-angiogenic therapy in metastatic colorectal cancer. There are presented practical advices on prevention and treatment of the most common side effects of anti-angiogenic therapy.
Russian Journal of Oncology. 2017;22(3):164-168
pages 164-168 views

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