Deregulation mechanisms and therapeutic opportunities of p53-responsive microRNAs in diffuse large B-cell lymphoma.

Here, we have discussed the molecular mechanisms of p53-responsive microRNAs dysregulation in response to genotoxic stress in diffuse large B-cell lymphoma (DLBCL) patients. The role of micro ribonucleic acids (microRNAs) in p53-signaling cellular stress has been studied. MicroRNAs are the small non-coding RNAs, which regulate genes expression at post-transcriptional level.

Multiple Myeloma: Genetic and Epigenetic Biomarkers with Clinical Potential.

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics.

MicroRNA Expression Profile in Bone Marrow and Lymph Nodes in B-Cell Lymphomas.

Hodgkin's lymphomas (HL) and the majority of non-Hodgkin's lymphomas (NHL) derive from different stages of B-cell differentiation. MicroRNA (miRNA) expression profiles change during lymphopoiesis. Thus, miRNA expression analysis can be used as a reliable diagnostic tool to differentiate tumors.

Effective Prognostic Model for Therapy Response Prediction in Acute Myeloid Leukemia Patients.

Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by the malignant transformation of bone marrow-derived myeloid progenitor cells with extremely short survival. To select the optimal treatment options and predict the response to therapy, the stratification of AML patients into risk groups based on genetic factors along with clinical characteristics is carried out. Despite this thorough approach, the therapy response and disease outcome for a particular patient with AML depends on several patient- and tumor-associated factors.

[Endocrine disorders after combined chemoradiotherapy in Hodgkin Lymphoma survivors].

Background: Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of toxic effects leading to dysfunction of endocrine system. Hormonal disorders in HL and their relationships with the therapy used remain to be clarified.

The Methylation of the p53 Targets the Genes , , and in the Tumor Tissue of Diffuse Large B-Cell Lymphoma.

The regulation of oncogenes by microRNA is a focus of medical research. hsa-miR-203, hsa-mir-129, hsa-miR-34a, hsa-miR-34b and hsa-miR-34c are oncosuppressive microRNAs that mediate the antitumor activity of p53. We seek to evaluate the frequencies, co-occurrence and clinical significance of the methylation of the , , and genes in the tumor tissue of diffuse large B-cell lymphoma (DLBCL).

The Profile of MicroRNA Expression in Bone Marrow in Non-Hodgkin's Lymphomas.

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of malignant lymphomas that can occur in both lymph nodes and extranodal sites. Bone marrow (BM) is the most common site of extranodal involvement in NHL. The objective of this study is to determine the unique profile of miRNA expression in BM affected by NHL, with the possibility of a differential diagnosis of NHL from reactive BM changes and acute leukemia (AL).

Selection of reference genes for quantitative analysis of microRNA expression in three different types of cancer.

MicroRNAs (miRNAs) are promising biomarkers in cancer research. Quantitative PCR (qPCR), also known as real-time PCR, is the most frequently used technique for measuring miRNA expression levels. The use of this technique, however, requires that expression data be normalized against reference genes.

Approaches and Protocols to Analyze Autophagy and Its Role in Death of Apoptosis-Resistant Senescent Tumor Cells.

Anticancer therapy is complicated by the ability of malignant cells to activate cytoprotective autophagy that rescues treated cells. This protocol describes methods for analysis of autophagic process in apoptosis-resistant tumor cells treated with damaging agents. Induction of autophagy in these cells can activate apoptotic death.

MicroRNAs in the Myelodysplastic Syndrome.

The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development.

Drug responsiveness of leukemic cells detected in vitro at diagnosis correlates with therapy response and survival in patients with acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and chemotherapy remains the most commonly used treatment approach for this group of hematological disorders. Drug resistance is one of the predictors of unfavorable prognosis for leukemia patients.

Aim: The purpose of this study was to perform a retrospective analysis of the survival rate in AML patients according to age, tumor status, and chemotherapy regimen received and to analyze the therapy response of AML patients depending on the treatment received, initial responsiveness of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis and expression of immunological markers.

Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions.

Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems.

The miRNA Profile in Non-Hodgkin's Lymphoma Patients with Secondary Myelodysplasia.

Myelodysplastic syndromes are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, genetic instability and a risk of transformation to acute myeloid leukemia. Some patients with non-Hodgkin lymphomas (NHLs) may have developed secondary myelodysplasia before therapy. Bone marrow (BM) hematopoiesis is regulated by a spectrum of epigenetic factors, among which microRNAs (miRNAs) are special.

Prognostic Markers of Myelodysplastic Syndromes.

Myelodysplastic syndrome (MDS) is a clonal disease characterized by multilineage dysplasia, peripheral blood cytopenias, and a high risk of transformation to acute myeloid leukemia. In theory, from clonal hematopoiesis of indeterminate potential to hematologic malignancies, there is a complex interplay between genetic and epigenetic factors, including miRNA. In practice, karyotype analysis assigns patients to different prognostic groups, and mutations are often associated with a particular disease phenotype.

Clinical and Prognostic Significance of Cell Sensitivity to Chemotherapy Detected in vitro on Treatment Response and Survival of Leukemia Patients.

Multidrug resistance (MDR) is a major challenge in leukemia treatment. The objective of this study was to identity predictors of MDR to allow for rapid and economical assessment of the efficacy of planned antitumor therapy for leukemia patients. The study included 113 patients with acute and chronic leukemias.

Suppression of mTORC1 activity in senescent Ras-transformed cells neither restores autophagy nor abrogates apoptotic death caused by inhibition of MEK/ERK kinases.

Autophagy is conservative catabolic process that degrades organelles, in particular, mitochondria, and misfolded proteins within the lysosomes, thus maintaining cellular viability. Despite the close relationship between mitochondrial dysfunction and cellular senescence, it is unclear how mitochondria damage can induce autophagy in senescent cells. We show that MEK/ERK suppression induces mitochondria damage followed by apoptosis of senescent Ras-expressing cells.

Targeted elimination of senescent Ras-transformed cells by suppression of MEK/ERK pathway.

The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance.

[Frequency, spectrum, and functional significance of TP53 mutations in patients with diffuse large B-cell lymphoma].

A comparative analysis of oncogene mutations shows that variations in their frequency, spectrum, and hot-spot locations depends on the type of tumor and the ethnic origin of the population studied. The current version of the IARC TP53 Mutation Database lacks information about the frequency and spectrum of TP53 mutations in patients with DLBCL in Russia. The aim of this study was to assess the frequency and functional significance of TP53 mutations in patients with DLBCL in Novosibirsk.

Wip1 phosphatase: between p53 and MAPK kinases pathways.

Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment.

CHLOROQUINE DOES NOT CANCEL E1A+cHa-Ras TRANSFORMANTS’ DEATH INDUCED BY mTOR KINASE INHIBITOR pp242.

We have studied the dependence of cell viability on cell autophagy in control and senescent E1A+cHa-Ras transformed rat embryo fibroblasts. pp242, a TORC1/C2 kinase inhibitor, was used as a trigger of cell autophagy. Cell senescence was induced in the cells by sodium butyrate.

MEK/ERK-PATHWAY IS REQUIRED TO MAINTAIN CYTOPROTECTIVE AUTOPHAGY PROCESS IN IRRADIATED E1A+cHa-Ras TRANSFORMANTS.

Autophagy is a conservative process of misfolded protein and damaged organelle degradation that serves to support cellular viability. Autophagy is often induced in response to stress, DNA damage, retinoids, starvation and growth factor withdrawal. The aim of the present work was to study autophagic response of E1A+cHa-Ras-transformed cells to irradiation and to analyze the role of MEK/ERK pathway in regulation of autophagy induced by irradiation.