Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC.

Aim of the issue was to determine indications for intratecal chemotherapy drugs administration to prevent relapse of diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement.

The paper describes the results of 15 consecutive Russian clinical trials in the treatment of different types of acute leukemias, conducted by Russian cooperative group within the last 27-years and included more than 25 hundred patients. It was shown that the 5-years overall survival in AML younger than 60 years patients improved from 20 to 33%, in ALL - from 38 to 65%, in APL - from 0 to 95%. The cooperative work resulted in balanced clinical recommendations and protocols, reproducible in regional hospitals. Though till now there is a big difference in the long term outcome in acute leukemias patients treated in coordinating or regional centers mostly due to much higher early death rate: 7.5-9.5% vs 18-25%. This parameter should be used as criteria of the total efficacy of hematological service in each region of Russia. It became possible within the last years to integrate the minimal residual disease monitoring into clinical trials thus providing a clue parameter for choosing the further therapy - allogeneic stem cell transplantation. Non - chemotherapeutic approach with arsenic trioxide and all - trans retinoid acid had dramatically changed the toxicity and duration of treatment with very high efficacy. The Russian cooperative group was the first that started to include pregnant women with acute leukemias into clinical trials. This prospective and prolonged experience has shown that pregnancy in acute myeloid leukemia is an extremely poor prognostic factor, but it does not influence the outcome in acute lymphoblastic leukemia.

In proliferating normal and tumor cells, the telomere length (TL) is maintained by high telomerase activity (TA). In the absence of TA the TL maintenance involves a mechanism of alternative lengthening of telomeres (ALT). The aim of this study was to investigate the level of TA, the mTert expression and TL in cultured normal and transformed by γ- and γ,n-irradiation mesenchymal stem cells (MSCs) from mouse bone marrow, in sarcomas that developed after the transplantation of these cells into syngeneic mice, and in fibrosarcoma cell lines obtained from these tumors to find out the role of AT or ALT in maintaining TL in these cells. During prolonged cultivation of normal and transformed under the influence of γ- (1 Gy and 6 Gy) and γ,n-irradiation (0.05 Gy, 0.5 Gy, and 2 Gy) MSCs from mouse bone marrow, a decrease in TA was detected in irradiated cells. Even deeper decrease in TA was found in sarcomas developed after administration of transformed MSCs to syngeneic mice and in fibrosarcoma cell lines isolated from these tumors in which TA was either absent or was found to be at a very low level. TL in three of the four lines obtained was halved compared to the initial MSCs. With absent or low TA and reduced TL, the cells of all the obtained fibrosarcoma lines successfully proliferated without signs of a change in survival. The mechanism of telomere maintainance in fibrosarcoma cell lines in the absence of TA needs further investigation and it can be assumed that it is associated with the use of the ALT. The detected decrease or absence of TA in transformed under the action of irradiation MSCs with the preservation or even an increase in the telomerase gene expression may be associated with the formation of inactive splicing variants, and requires further study. The obtained lines of transformed MSCs and fibrosarcomas with TA and without the activity of this enzyme can be a useful model for studying the efficacy of TA and ALT inhibitors in vitro and in vivo.

Small bowel tumor causes gastrointestinal bleeding in 1-4% of cases. Gastrointestinal bleeding from metastases of renal cell carcinoma is a rare and little-known manifestation of this disease. We report a rare clinical case of a solitary metastasis of clear cell renal cell carcinoma into small bowel in 5 years after nephrectomy. The first symptom was intestinal bleeding. This example emphasizes the need for more thorough examination of patients with symptoms of latent and anamnestic blood loss.

To evaluate the long-term outcomes of surgical treatment of intrahepatic cholangiocarcinoma depending tumor dimensions, vascular invasion, lymph node metastases, cellular differentiation and quality of resection.

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits ("Cusabio", China). CNP caused a decrease in the total and free T by 1.5 times (p<0.05), E2 and P4 by 1.9 and 3 times, respectively, E3 by 1.6 times (p<0.05), as well as an increase in E1 by 1.4 times (p<0.05) as compared to the corresponding levels in the brain white matter of rats without CNP. CNP stimulated M1 sarcoma growth in both subcutaneous and intravenous transplantation. Regardless of the tumor site, the dynamics of total T, E2 and E3 in the brain had similar features, but the dynamics of free T, P4 and E1 differed. Thus, changes in the level of neurosteroids in the white matter of rat brain with CNP and tumor growth alone or associated with CNP are a reaction to stress.

Novel treatments for various types of malignant diseases are warranted. In this study, we evaluated JAK2 inhibitors (Janus kinase 2) for suppressing the growth of malignant neuroblastoma and glioblastoma cells as well as breast and non-small cell lung cancers. Neuroblastoma and glioblastoma cells are the most sensitive to the JAK2 inhibitor AG490. A study of the relative expression of receptors that can activate JAK2 suggests that cell line sensitivity to AG490 may be mediated by IL6-R, IL11-R and/or CSF1-R. AG490 enhances the effect of doxorubicin on neuroblastoma cells. Our findings suggest the possible relevance of JAK2 inhibitors for neuroblastoma therapy, especially in combination with doxorubicin.

The actin-binding proteins profilin, fascin, and ezrin were tested for involvement in metastasis of non-small cell lung cancer (NSCLC). The levels of the PFN1, FSCN1, and EZR mRNAs and respective proteins were determined by real-time PCR and Western blotting; tumor and adjacent normal lung tissue samples were obtained from 46 NSCLC patients. Patients with lymphatic metastasis had higher expression levels of the profilin, fascin, and ezrin mRNAs and the profilin and fascin proteins. Both mRNA and protein expression levels increased in patients with distant metastasis. The molecules may serve as predictors to evaluate the prognosis in NSCLC.

PARP10 is an intracellular mono-ADP ribosyltransferase and recent reports suggest that it regulates proliferation of some cell types. However, its effect on the proliferation of colorectal carcinoma cells has not yet been systematically reported. We explored the influence of PARP10 on the proliferation of several colorectal carcinoma cell types and carried out initial studies on the underlying mechanisms. Inhibition of the enzymatic activity of PARP10 led to significantly decreases in proliferative ability in LoVo cells and CT26 cells in vitro and suppressed growth of CT26 tumours in the subaxilliary region in Balb/c mice in vivo. Cell-cycle arrest accompanied these observations. Expression of the nuclear transfer factor β-catenin and it trans-location to the nucleus were also affected and the expression of its associated signal proteins Axin2 and c-Myb were increased and decreased, respectively. We demonstrate that PARP10 promotes proliferation of those colorectal carcinoma cells which express significant levels of PARP10. This promotion is suppressed when the enzymatic activity is inhibited. β-Catenin is likely to be the mediator of the antiproliferative effect.

We report surgical treatment of a 65-year-old patient with recurrent hemangioendothelioma of inferior and middle segment of inferior vena cava with spread to previously established prosthesis. Advanced resection of inferior vena cava and right-sided nephrectomy were not followed by complications and resulted R0 resection. Surgery time was 180 min. Inferior vena cava cross-clamping time was 30 min. Total blood loss was 300 ml. Hemangioendothelioma is a rare tumor with unpredictable potential for malignant transformation and obligatory indications for surgical treatment. Resection and reconstruction of inferior vena cava and renal veins with a synthetic conduit is effective and safe procedure.

Confocal laser endomicroscopy is an endoscopic diagnostic technique developed for real-time histological diagnosis of gastrointestinal diseases. This review is devoted to analysis of confocal laser endomicroscopy in diagnosis of gastrointestinal diseases, especially for screening or monitoring of gastrointestinal neoplasia.

To estimate the results of minimally invasive adrenalectomy in children and compare our data with worldwide results.

The purpose of the research is to clarify the diagnostic value of the ultrasound examination method in the diagnosis of tumors of the parotid gland. A clinical examination of 389 patients with tumors and tumor-like neoplasms of the parotid gland was performed. Based on the clinical examination of patients with tumors of the parotid glands, it can be concluded that the ultrasound examination method is highly informative and allows you to study in detail the structure of the tumor and the surrounding soft tissues, which significantly increases its diagnostic value. The use of a comprehensive diagnostic examination (ultrasound, CT, MRI) of patients with tumors of the parotid glands made it possible to increase the accuracy of the differential diagnosis of tumors to 98%.

Migration of cancer cells from the primary tumor site to nearby tissues is the starting point of the metastatic process. The invasive properties of cells are especially important for carcinomas, since tumor cells need to overcome the basement membrane and go beyond its boundaries to the underlying tissues. Substances that reduce the invasive ability of malignant cells are promising as antimetastatic agents. In the present work, the possibility of inhibiting the ability of different cancer cell lines to migrate under the influence of the Bacillus pumilus ribonuclease (binase) was analyzed using the scratch-wound assay. It was established that binase at non-toxic concentrations (10 μg/mL) reliably suppressed the migratory ability of HuTu 80 human duodenum adenocarcinoma cells incubated with RNase for 48-72 h. The antimetastatic potential of binase is confirmed by molecular modeling data demonstrating the ability of binase to inhibit cellular metalloproteinases that determine the migration of tumor cells.

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.

In hepatocellular carcinoma (HCC), the presence of cancer stem cells (CSCs) have been linked to drug resistance, epithelial-mesenchymal transition (EMT), and cancer relapse. This study investigates the expression profile of ZEB1, ZEB2, ABCG2 in HCC-CSCs, and the role of EMT promoter ZEB2 in cells treated with resveratrol. The expression of ZEB1, ZEB2 and ABCG2 transcripts were analyzed in CD133^(+)/CD44^(+) cells isolated from the PLC/PRF/5 cell line. ZEB2-dependent ABCG2 gene expression and the effects of resveratrol on proliferation, cell cycle and apoptosis were explored in SNU398 cell clones. An inverse correlation between ZEB1/ZEB2 and ABCG2 levels were observed both in CSCs and in ZEB2-knock-down cells. The resveratrol treatment significantly decreased cell viability, while promoting cell cycle arrest in ZEB2-independent manner. Interestingly, resveratrol-treated cells with low levels of ZEB2 were resistant to apoptosis. The interplay of expression levels of ABCG2 and ZEB family EMT transcription factors may play a role in establishing CSC-like phenotype in HCC cells resistant to resveratrol.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor prognosis and high mortality. The aberrant expression or alteration of microRNAs (miRNAs) contributes to the development and progression of cancer. Studies have shown that miR-455 plays a regulatory role in the development of HCC. Therefore, in the present study, the role of miR-455 was analyzed in HepG2 cells proliferation and apoptosis using MTT and flow cytometry methods. Binding sites were predicted by bioinformatics and luciferase assay was used to verify the target relationship between miR-455 and RhoC-encoding gene RHOC. After that, the effects of miR-455 on RHOC and its product RhoC, were explored by qPCR and Western blotting. As PTEN is a key tumor suppressor gene in HCC, and Bcl-2 and Caspase 3 are important indication of apoptosis, expression levels of PTEN, Bcl2 and Caspase 3 proteins were determined in cells overexpressing RhoC. We show that miR-455 promotes HepG2 cells apoptosis and inhibits proliferation. Bioinformatics analysis and luciferase assay indicate that specific recognition sites for miR-455 are within the RhoC 3'-UTR. Luciferase activity was significantly lower in the cells co-transfected with miR-455 mimics and RhoC-WT (p < 0.01) as compared to that in control cells, pointing that RHOC gene is, indeed, targeted by miR-455. RHOC mRNA was significantly reduced after miR-455 transfection in HepG2 cells. In addition, we show that RhoC could activate the HCC cells proliferation ability and inhibit apoptosis rate (p < 0.01), and decrease expression of PTEN and Caspase 3 (p < 0.01), while upregulating levels of Bcl2. In conclusion, our study indicates that miR-455 plays a suppressive role in HCC development by targeting RhoC-encoding mRNA.

PTTG1 (vertebrate securin) is a separation inhibitor and regulates DNA repair and transcription. The protein is predominantly expressed in the second half of the S phase and at the G2 stage. With the onset of anaphase, securin is ubiquitinated by the APC/C complex and degraded rapidly. Increased expression of PTTG1 is associated with enhanced tumor cell growth and metastasis. Recently, we found a short securin isoform lacking the main APC/C recognition site (D-box) and the DNA-binding domain encoded by exons 3 and 4. The mRNA level of the short isoform in unsynchronized cells is 0.4-2% of the full-length one. We reported earlier on the ability of the short PTTG1 isoform to activate some of the genes controlled by the full-length protein. In this work, groups of genes, whose expression is altered by the action of the short and complete securin isoforms, were determined using RNA sequencing. Groups of genes whose mRNA levels are regulated by both protein isoforms and only one of the isoforms were identified. For a more detailed study of the effect of securin isoforms on the transcriptional program of cells, the NFYB gene, encoding the NF-Y transcription regulator subunit, was chosen. Our data showed that with overexpression of the short isoform, the level of NFYB mRNA decreased 2.4 ± 0.7 times, while the complete isoform did not significantly affect the expression of NFYB. 2.2-fold suppression of the short isoform of securin led to an increase in the expression of NFYB mRNA by 2.7 ± 0.3 times. Moreover, the mRNA expression of full-length securin increased by 2.7 ± 0.4 times. Since NFYB is associated with the PTTG1 promoter region, we suggest that the short isoform may be involved in regulation of the expression of the main isoform of securin by changing the level of this transcription factor. Since NFYB and PTTG1 are involved in the development of tumors and the formation of drug resistance, we assume that the short isoform of securin may play an important role in these processes. Thus, we showed the functional significance of the minor short isoform of securin.

The article is devoted to the study of the diagnostic effectiveness of using magnifying chromoendoscopy when examining the oral cavity in patients with a gastroenterological profile with extra-esophageal manifestations of reflux disease. Pathologies of the oral cavity are often one of the additional symptoms, according to the Montreal Consensus and classification of gastroesophageal reflux disease (GERD). Barrett's esophagus is a serious complication of GERD, in which a cylindrical epithelium with intestinal metaplasia is found in the epithelial lining of the mucous membrane of the esophagus, which is a marker of this disease often in combination with dysplasia instead of squamous stratified non-keratinized epithelium. The relevance is due to the fact that this disease is considered as a precancerous condition and is associated with an increased risk of developing adenocarcinoma of the lower third of the esophagus. In this regard, timely diagnosis of Barrett's esophagus and monitoring of these patients will improve the prognosis of the disease and reduce the frequency of deaths.