Tabernero J.,Autonomous University of Barcelona |
Garcia-Carbonero R.,University of Seville |
Cassidy J.,Beatson Laboratories |
Cassidy J.,Roche Holding AG |
And 17 more authors.
Clinical Cancer Research | Year: 2013
Purpose: This randomized, double-blind, placebo-controlled, phase IIb study evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC). Experimental Design: Patients were randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m2; levo-leucovorin 200 mg/m2; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion) every 14 days. Primary endpoint was progression-free survival (PFS). Target sample was 120 events in 180 patients for >85% power (two-sided α = 0.20) to detect an HR = 0.65. Results: Of 198 patients randomized, median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus 8.7 months for placebo plus mFOLFOX6 (HR = 0.88; 95% CI, 0.64-1.23; P = 0.46). There was no difference between treatment arms for overall survival. Subgroup analyses of PFS and overall survival showed no difference between treatment arms by KRAS or BRAF status (mutant and wild type). The most common grade 3/4 adverse events in the sorafenib and placebo arms were neutropenia (48% vs. 22%), peripheral neuropathy (16% vs. 21%), and grade 3 hand-foot skin reaction (20% vs. 0%). Treatment discontinuation because of adverse events was 9% and 6%, respectively. Generally, dose intensity (duration and cumulative doses) was lower in the sorafenib arm than in the placebo arm. Conclusion: This study did not detect a PFS benefit with the addition of sorafenib to first-line mFOLFOX6 for mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups were small. These results do not support further development of sorafenib in combination with mFOLFOX6 in molecularly unselected patients with mCRC. ©2013 AACR.
Uzdensky A.,Southern Federal University |
Demyanenko S.,Southern Federal University |
Bibov M.,Southern Federal University |
Sharifulina S.,Southern Federal University |
And 3 more authors.
Tumor Biology | Year: 2014
Epigenetic processes play a critical role in melanoma development. However, little is known about proteins responsible for epigenetic transformations in melanoma cells. The processes in the peritumoral skin within the excision margin are almost unstudied. We studied the changes in expression of 112 proteins involved in epigenetic regulation of gene expression in the human cutaneous melanoma and its peritumoral zone using “The Proteomic Antibody Microarrays” (GRAA2, Sigma-Aldrich). Dimethylated histone H3 at lysines 4 and 9 as well as proteins involved in the regulation of transcription (histone deacetylases HDAC-1 and HDAC-11, DNA methyl-binding protein Kaiso), cell cycle control (protein kinases Aurora-В and PKR, chromosome protein CENP-E, and phosphorylated and acetylated histone H3), DNA repair (phosphorylated histone H2AX), and nuclear protein import (importins α3 and α5/7) were over-expressed in the melanoma tissue as compared with normal skin. At the same time, HDAC-10 and proliferating cell nuclear antigen PCNA were downregulated. In the peritumoral skin, at the excision margin (1–2 cm from the melanoma edge), we observed similar changes in expression of these proteins and, additionally, over-expression of arginine methyltransferases PRMT5 and NAD-dependent histone deacetylase SIR2. Histone methyltransferase G9a and metastasis-associated protein 2 were downregulated. Therefore, epigenetic regulation that requires histone modifications and expression of some regulatory proteins is of importance for melanoma development and propagation. The observed changes in the peritumoral skin may indicate the epigenetic pre-tuning in this zone possibly involved in malignant transformation. These results can be potentially useful for melanoma diagnostics and targeted therapy. © 2014, International Society of Oncology and BioMarkers (ISOBM).
Kirichenko E.Yu.,Southern Federal University |
Zhukova G.V.,Rostov Research Institute of Oncology |
Grigorov S.V.,Rostov Research Institute of Oncology |
Grankina A.O.,Southern Federal University |
Atmachidi D.P.,Rostov Research Institute of Oncology
Arkhiv Patologii | Year: 2015
Objective: to reveal the expression of neuronal connexin 36 (Cx36) in gliomas and then to analyze the ratio of expression of Cx36 to that of neuroglial antigens (synaptophysin, neurofilaments, and glial fibrillary acidic protein). Material and methods. Varying grade human glioma samples and tumor-adjacent tissue fragments were used for immunohistochemical examination. Results. A procedure for immunohistochemical detection of Cx36 in brain tissue was tried out. It was shown that the decreased level of the examined neuronal proteins was accompanied by the impaired coexpression of synaptophysin/neurofilaments and Cx36 in the series of astrocytomas - anaplastic astrocytomas - glioblastomas. The immunohistochemical heterogeneity of glioblastomas was found. Conclusion. The findings suggest that it is promising to include anti-Cx36 antibodies in immunohistochemical panels when examining brain tumors. Data on the lower levels of the examined neuronal proteins, on the specific features of their distribution and impaired coexpression expand their idea on the pathogenesis of a brain tumor process and determine an area for further investigations.
Mikhailov N.Y.,Russian Academy of Sciences |
Garkavi L.H.,Rostov Research Institute of Oncology |
Mashchenko N.M.,Rostov Research Institute of Oncology |
Zhukova G.V.,Rostov Research Institute of Oncology
Biophysics | Year: 2012
High-frequency oscillations in a pulse wave signal in the range of 1-50 Hz and their relation to differential blood count leucocytes have been investigated. It is shown that the correlation coefficients grow in the frequency range of 1-12.5 Hz between high-frequency oscillations in a pulse wave signal and stab neutrophils, monocytes and segmented granulocytes. The procedure of smoothing the coefficients of harmonic variation has been proposed. © 2012 Pleiades Publishing, Ltd.
Zlatnik E.Yu.,Rostov Research Institute of Oncology |
Zakora G.I.,Rostov Research Institute of Oncology |
Nepomnyashchaya E.M.,Rostov Research Institute of Oncology
Medical News of North Caucasus | Year: 2016
The aim of the study was to assess the in vitro effects of biogenic metalsnanoparticles (NP Fe, NP Zn) on the activity of cells mediating innate and adaptive immunity in cancer patients. Immunologic methods (immunofluorescent, cytotoxic, ELISA, NBT tests) were used to find out any influence of incubation with NP on functional activity, receptorsexpression, production of monokines and lymphokines by blood mononuclear cells in patients with malignant tumors. No obvious injury of T-cells, NK-cells and phagocytes was noted. At the same time stimulation of monocytesHLA-DR expression and N?-cellscytotoxicity was observed after incubation with NP Fe, while incubation with both NP Fe and NP Zn induced modulating effect on TNF-α and IL-1α production. Incubation with NP Fe resulted in more active stimulation of phagocytes than incubation with NP Zn. Thus, we found positive in vitro effect of biogenic metals' nanoparticles on some phenotypic and functional properties of immune cells, i.e. modulation of neutrophils, monocytes and natural killers' activities.
Todorov S.S.,Rostov Research Institute of Oncology |
Kit O.I.,Rostov Research Institute of Oncology |
Bosenko E.S.,Rostov Research Institute of Oncology |
Kas'yanenko V.N.,Rostov Research Institute of Oncology |
And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2014
We performed a complex morphoimmunohistochemical study of synchronous bilateral breast cancer (diagnosed in 0.69% cases in women of the postproductive period after the age of 50). The molecular genetic characteristics of this cancer were detected and the algorithm of diagnostic studies was suggested. We have demonstrated that bilateral breast cancer was in 75% cases estrogen- and progesterone-positive, but androgen-negative. The HER-2/neu status of the tumor was negative in 75% cases, but expression of HER-2/neu was detected in the tumor of one mammary gland in 20% cases. Membrane expression of E-cadherin in infiltrative ductal cancer cells significantly decreased up to its complete disappearance with the decrease in tumor cell differentiation degree. The data provide new insight into prognostic value of the studied biomarkers and help to develop treatment protocol with consideration for the molecular biology of this group of tumors. © 2014, Springer Science+Business Media New York.
PubMed | Rostov Research Institute of Oncology
Type: Journal Article | Journal: Terapevticheskii arkhiv | Year: 2016
to define some clinical characteristics of synchronous and metachronous colorectal cancer (CRC).The investigation was concerned with the data of 150 patients with T1-4N0-2M0-1 multiple primary CRC. The clinical, biological, and morphological characteristics of synchronous and metachronous tumors were analyzed.Multiple primary tumors were 6.01% of all the cases of CRC. There was a preponderance of synchronous CRC (63.75%) with the tumor localized in the sigmoid colon and rectum. In women, synchronous colorectal tumors were more often concurrent with breast tumors; metachronous ones were detected after treatment for genital tumors. In men, synchronous colorectal tumors were more frequently concurrent with kidney cancer; metachronous ones were identified after treatment for gastric cancer.The found characteristics of multiple primary colorectal tumors may be taken in account in programs for both primary diagnosis and follow-up after treatment for malignant tumors, which will be able to improve the early detection of cancer patients and their treatment results.
PubMed | Rostov Research Institute of Oncology
Type: Journal Article | Journal: Biomeditsinskaia khimiia | Year: 2016
The use of metal nanoparticles (NPs) for cancer treatment requires careful examination of their biological effects. The aim of this study was to determine parameters of oxidative processes in the blood of tumor-bearing animals treated with metallic iron NPs only. The markers of antioxidant status and accumulation of lipid peroxidation products were measured in erythrocytes and blood plasma of rats with Pliss lymphosarcoma (PLS) and intact rats. PLS animals were treated eight times with iron NPs (at a dose of 1.25 mg/kg bw (main group), rats of the control group received saline (0.3 ml). In control animals, an increase in malondialdehyde (MDA) was observed in red blood cells (RBC) by 45%; this was accompanied by compensatory increase in reduced glutathione (GSH) and catalase by 24% and 14.3%, respectively (p<0.05). In plasma an increase in MDA by 167.4% (p<0.01) and a decrease in oxidase activity of ceruloplasmin (CP) by 36.8% (p<0.001) were found. In the main group there was a decrease of accumulation of lipid peroxidation products in the blood. Intensity of detected changes depended on the antitumor effect: rats with growing LSP showed a tendency to the decrease in the RBC MDA level and normalization of plasma MDA; in animals with LSP regression this marker did not differ from normal values. In all animals of the main group the CP content was basically the same as in intact rats while GSH increased in the group without therapeutic effect (by 218.6%) and in the group with the effect by 69% (versus normal values; p<0.01). SOD activity in the rats with LSP growth significantly increased (by 42%), in the rats with regression decreased (by 30%) with subsequent normalization. Thus, administration of iron NPs caused activation of the antioxidant system in blood and a significant decrease in the manifestations of oxidative stress associated with tumor growth.
PubMed | Rostov Research Institute of Oncology
Type: Journal Article | Journal: Bulletin of experimental biology and medicine | Year: 2014
We performed a complex morphoimmunohistochemical study of synchronous bilateral breast cancer (diagnosed in 0.69% cases in women of the postproductive period after the age of 50). The molecular genetic characteristics of this cancer were detected and the algorithm of diagnostic studies was suggested. We have demonstrated that bilateral breast cancer was in 75% cases estrogen- and progesterone-positive, but androgen-negative. The HER-2/neu status of the tumor was negative in 75% cases, but expression of HER-2/neu was detected in the tumor of one mammary gland in 20% cases. Membrane expression of E-cadherin in infiltrative ductal cancer cells significantly decreased up to its complete disappearance with the decrease in tumor cell differentiation degree. The data provide new insight into prognostic value of the studied biomarkers and help to develop treatment protocol with consideration for the molecular biology of this group of tumors.
PubMed | Rostov Research Institute of Oncology
Type: | Journal: Khirurgiia | Year: 2016
To study the types and early outcomes of combined interventions for locally advanced colorectal cancer.Since 2009 four hundreds and ninety eight patients underwent surgery in the Rostov Research Institute of Oncology for locally advanced colorectal cancer. Most cases of surgical procedures on adjacent organs included resection of small intestine (23.69%), supravaginal hysterectomy (16.47%), resection of bladder (12.25%), total hysterectomy (11.45%).Postoperative complications occurred in 178 (35.7%) patients. Their incidence was significantly lower in case of laparoscopic approach (12.5%). Functional-sparing interventions on bladder followed by its augmentation with enteric graft improves rehabilitation.Laparoscopic approach and functional-sparing surgery improve the results of locally advanced colorectal cancer management.