Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study.

Purpose: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC.

Patients And Methods: Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577).

Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer.

Aim: Locally advanced fixed T4 rectal cancer has a poor prognosis and no standard treatment strategy. The aim of this study was to investigate the safety and efficacy of neoadjuvant chemoradiotherapy using hypofractionated radiotherapy combined with local hyperthermia, capecitabine, oxaliplatin and metronidazole.

Method: Radiotherapy was given to a total dose of 40 Gy in 10 fractions.

Coexpression of two mRNA isoforms of insulin-like growth factor-1 gene and mRNA of YB-1 gene in patients with multiple myeloma.

Coexpression of two mRNA isoforms for insulin-like growth factor-1 (IGF-1A and IGF-1B) and expression of YB-1 mRNA were analyzed in the bone marrow aspirates from 19 patients with multiple myeloma. It was shown that mRNA isoforms for IGF-1A and IGF-1B were mainly expressed in samples with hyperexpression of YB-1 mRNA, and, on the contrary, practically were not expressed (except sporadic cases) in samples with low level of YB-1 mRNA expression. Coexpression of mRNA isoforms for IGF-1A and IGF-1B were observed in 80% patients with multiple myeloma.

PET/MR in oncology: an introduction with focus on MR and future perspectives for hybrid imaging.

After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology.

Matrix metalloproteinases 2, 7, and 9 in tumors and sera of patients with breast cancer.

Enzyme immunoassay showed that the content of matrix metalloproteinases (MMP) 2 and 7 in tumors was higher than in the adjacent histologically intact tissue in 91 and 76% patients with breast cancer, respectively, while MMP-9 levels in the tumor and intact tissue were virtually the same. Serum concentrations of MMP-2 and MMP-7 did not correlate with their levels in the tumors, were within the normal range, and virtually did not decrease after removal of the primary tumor. Serum levels of MMP-9 in patients were significantly lower than in the control and increased after surgery in 85% patients.

Possibility of microorganism elimination from the blood using modified coal hemosorbents.

We studied the possibility of using coal hemosorbents for elimination gram-positive and gram-negative microorganisms from the blood. After hemosorption, the number of S. aureus and K.

Granulosa cell tumors of the ovary and inhibin B.

We present the results of immunoenzyme detection of inhibin B in blood serum of patients with adult-type granulosa cell tumors of the ovary. Blood concentration of inhibin B at the end of menstrual cycle in patients with tumor relapse was significantly higher than in patients during remission and in virtually healthy women. The increase in inhibin B concentration preceded clinical manifestation of the disease relapse by 2-13 months, which demonstrates high diagnostic sensitivity of this marker and suggests that it can be recommended for the use in diagnostics and monitoring of granulosa cell tumors of the ovaries.

Cancer mortality among female and male workers occupationally exposed to inorganic lead in the printing industry.

Objective: Evaluation of the carcinogenicity of lead for humans has been based primarily on the results of studies on occupationally exposed men, although gender differences in lead metabolism have been reported. In addition, most of the previous studies have been limited by a failure to identify and control for co-exposures to other known occupational carcinogens. The present study follows an industrial cohort of workers, mostly women, with moderate lead exposure and no confounding by other occupational exposures.

Urokinase and tissue plasminogen activators and their PAI-1 inhibitor in tumors of patients with oral mucosal cancer: relationship with the main clinical morphological factors.

Enhanced activation of plasminogen by the urokinase pathway (uPA elevation) in patients with cancer of the oral mucosa paralleled by an increase of PAI-1 level in the tumor compared to the adjacent mucosa was shown by enzyme immunoassay. No statistically significant associations of the level of the studied proteins in the tumor with such prognostic factors as location, growth form, histological structure, differentiation degree, size, and dissemination of the primary tumor, involvement of the regional lymph nodes, and stage of the disease were detected.

Clinical significance of the content of biomolecular markers in invasive front of colon carcinomas.

We studied the expression of β-catenin, matrix metalloproteinase 9, collagen IV, and laminin in invasive front of primary colon adenocarcinomas and their metastases in lymph nodes and liver. Intensive expression of matrix metalloproteinase 9 in zones of invasive growth of the tumor was associated with enhanced accumulation of β-catenin in the nuclei of tumor cells in peripheral zones of 28% studied tumors. The presence of nuclear β-catenin and increased content of metalloproteinase 9 in the tumor were associated with abnormal accumulation of laminin in cell cytoplasm and with the absence of collagen IV-containing basal membranes.

Compaction principle and approaches to biopolymer structure deciphering.

On the basis of a principle of maximum compaction of biopolymer structure in a limited space derived from the concept about the existence of three different types of dimers in the studied structure, we propose a hypothesis according to which side groups in macromolecules (nitrogenous bases in nucleic acids or R-groups in proteins) are specifically distributed in different points depending on geometrical shape of dimer bending in the biopolymer chain backbone. The latter provides the possibility of complete deciphering of biopolymer structure.

The use of autologous peripheral blood stem cells as a hemopoietic support during polychemotherapy of children with soft tissue sarcomas.

Intensification of cycle polychemotherapy in disseminated tumors considerably improves the efficiency of complex treatment. Reinfusion of peripheral blood stem cells as a factor of replacement treatment during hemopoietic suppression or disorders is now becoming more and more promising.

Peculiarities of proliferation and differentiation of cambial and daughter cells of epidermal-dermal morphofunctional zone in normal epithelium and in cancer.

The cambial and daughter cells of normal epithelium function in the morphofunctional zone consisting of two subunits with 12 cambial cells in each. Daughter cells are differentiated in an electrical field created by 12 pairs of maternal and daughter cells, products of division of cambial cells located in the same subunit. The differentiation requires relaxation of the cortex of daughter cells via expression of SH3 domain of Src kinase by dermal daughter cells, which leads to a decrease in activity of RhoA in epidermal cells, their stretching, and activation of SH2 domain of Src responsible for differentiation.

In vitro effect of Knotolan, a new lignan from Abies sibirica, on the growth of hormone-dependent breast cancer cells.

Here we present antiestrogenic effects of Knotolan, a new dietary lignan from Abies sibirica raw material. Knotolan abolished growth-stimulating effects of 17β-estradiol on hormone-dependent MCF-7 cells.

Vascular endothelial growth factor and its type 2 receptor in hepatocellular carcinoma.

Histological analysis demonstrated an increase in the number of blood vessels and expression of CD34 and vascular endothelial growth factor in hepatocellular carcinoma tissue compared to adjacent liver tissue. Increased immunohistochemical expression of vascular endothelial growth factor and the content of this factor and its type 2 receptor correlated with the degree of histological differentiation and stage of the tumor.

Matrix metalloproteinases 2, 7, and 9 and tissue inhibitor of metalloproteinases-1 in tumors and serum of patients with ovarian neoplasms.

The content of matrix metalloproteinases 7 and 9 was significantly increased, while the content of metalloproteinase 2 was reduced in ovarian cancer tissue compared to benign tumors. In blood serum from patients with ovarian cancer, the concentrations of matrix metalloproteinases 7 and 9 and their type 1 tissue inhibitor were significantly elevated, while the concentration of matrix metalloproteinase 2 was reduced compared to the corresponding parameters in healthy women. After chemotherapy, tissue and serum concentrations of metalloproteinases and their inhibitor in patients practically returned to normal.

Squamous cell carcinoma of the esophagus: evaluation of the status of epidermal growth factor receptors (EGFR and HER-2) by immunohistochemistry and in situ hybridization.

We performed a parallel evaluation of the status of epidermal growth factor receptors EGFR and HER-2 in tumor samples from 31 patients with squamous cell carcinoma of the esophagus. Hyperexpression of proteins was detected by immunohistochemical methods and gene amplification and other chromosome abnormalities were studied using FISH reaction. Evaluation of EGFR status showed that amplification of EGFR gene was present in 25% cases and chromosome 7 polysomy was detected in 29.

Immunological peculiarities of CD-56-positive serous ovarian adenocarcinoma.

Here we present the results of evaluation of the expression of neural cell adhesion molecules CD56 (NCAM) in serous ovarian adenocarcinoma. The expression was detected in 48.5% cases.

The expression and DNA-binding activity of NF-κB nuclear transcription factor in the tumors of patients with breast cancer.

The content and DNA-binding activity of NF-κB nuclear transcription factor subunit p65 (NF-κBp65) were evaluated by quantitative enzyme immunoassay in tumors and histologically intact tissues of 119 patients with breast cancer. DNA-binding activity of NF-κBp65 in the tumors was higher than in adjacent tissue in 97% cases. This elevation was paralleled by an increase in total protein content in the majority of cases.

Insulin-like growth factor-1 and insulin inhibit caspase-3/7 activation initiated by interleukin-1β in the rat eye retinal neurons.

Proinflammatory cytokine IL-1β specifically stimulates caspase-3/7 in vitro in RGC-5 rat eye retinal neurons. Insulin and insulin-like growth factor-1 and their combination inhibit caspase-3/7 activation in these cells, induced by removal of the serum from culture medium and/or by IL-1β treatment.

Efficiency and tolerance of aranose combinations with cisplatin and gemcitabine in experimental lung cancer.

The efficiency of aranose combinations with gemcitabine and cisplatin was studied in experimental Lewis lung epidermoid carcinoma. Significant synergism of all the studied combinations and their satisfactory tolerance was demonstrated. The gemcitabine+cisplatin+aranose combination was significantly more effective than gemcitabine+cisplatin.

Comparative enzyme immunoassay of matrix metalloproteinases-2, -7, -9 and their tissue inhibitor-2 in tumors and plasma of patients with gastric cancer.

The content of matrix metalloproteinases (MMP) -2, -7, and -9 was significantly higher in tumors in comparison with the adjacent histologically intact gastric mucosa in 80, 70, and 72% patients with gastric cancer, respectively, the increase in the level of MMP tissue inhibitor-2 (TIMP-2) detected in 61% tumors was insignificant. Only plasma level of MMP-7 was elevated in primary patients in comparison with the control and positively correlated with the expression of this protein in the tumor. The concentration of MMP-7 was maximum in the blood of patients with tumor invasion in lymph vessels.

Cellular expression of INK4a gene in cells of bladder cancer associated with human papilloma virus-16.

Hyperexpression of p16(INK4a) protein is an early marker of cervical cancer. Hyperexpression of INK4a gene encoding this protein at the level of mRNA and p16(INK4a) was detected in tumor cells of some patients with bladder cancer associated with human papilloma virus-16. However, in contrast to cervical cancer, this phenomenon in urothelial carcinomas does not correlate with expression of human papilloma virus-16 oncogenes E6 and E7.

Matrix metalloproteinases 2, 7, 9 and tissue inhibitor of matrix metalloproteinase-1 in the sera of patients with bone tumors.

Comparative enzyme immunoassay of matrix metalloproteinases (MMP-2, -7, -9) and their tissue inhibitor-1 (TIMP-1) in the sera of 26 healthy individuals and 54 patients with primary osteal tumors before therapy revealed elevated TIMP-1 levels in the patients with classical central and periosteal osteosarcomas in comparison with the control. In patients, the level of MMP-9 significantly decreased compared to that in healthy individuals, while the levels of MMP-2 and MMP-7 remained unchanged. No differences in serum levels of MMP and TIMP-1 associated with gender, age, primary osteal tumor location and size were detected.

Clinical significance of levels of molecular biological markers in zones of invasive front-line of colorectal cancer.

The role of expression of markers (beta-catenin, matrix metalloproteinase 9, collagen IV, and laminin) in primary colorectal adenocarcinomas and their metastases in the liver and lymph nodes of patients with colorectal cancer was studied. High level of matrix metalloproteinase 9 expression in zones of invasive growth of colorectal cancer was associated with high accumulation of beta-catenin in cancer cell nuclei in the peripheral zones of 30% studied tumors. The presence of nuclear beta-catenin and high content of matrix metalloproteinase 9 in the tumor were associated with abnormal accumulation of laminin in the cytoplasm and with the absence of basal membranes containing collagen IV.