
Vasily A YakovlevVirginia Commonwealth University | VCU · Department of Radiation Oncology
Vasily A Yakovlev
MD/Ph.D.
About
48
Publications
12,444
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Introduction
During the last 6 years, I investigated the mitigation effect of Sepiapterin, the precursor of NOS co-factor, on late post-irradiation heart and lung toxicities. Over the past 4 years, the main direction of my research has been studying the effect of exosomes and their contents on various intracellular processes and the use of exosomal microRNAs as a prognostic factor for various pathological conditions and side effects of anticancer therapy.
Additional affiliations
July 2018 - May 2024
July 2009 - May 2024
Education
September 1999 - July 2002
September 1997 - August 1999
September 1991 - July 1997
Publications
Publications (48)
Oral contraceptives (OCs) are approved for use after onset of menarche, which is well before brain maturation is complete. OC use may induce biochemical changes in the brain, especially during the neurobiologically dynamic adolescent/young adult years. MicroRNA cargo in L1CAM-associated extracellular vesicles was measured from serum samples collect...
While significant progress has been made in understanding various aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver following massive tissue loss or injury of liver remain unknown. As it was previously shown, the loss of liver mass affects putative hepatocyte‐sp...
While significant progress has been made in understanding different aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver after massive loss or injury of liver tissue remain unknown. The loss of liver mass affects tissue-specific mitogenic inhibitors in the blood, w...
Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles’ (EVs’) microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biolog...
Background
Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched exosomal microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology.
Methods...
Background
Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched exosomal microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology.
Methods...
The rectum is the primary dose limiting structure for radiation therapy (RT) in treating prostate cancer. Two clinical forms of rectal injury have been described: early and late. Early injury typically develops during RT and occurs to some degree in most patients. The condition is usually self-limiting, but can predispose patients to the developmen...
Increased levels of reactive oxygen/nitrogen species are one hallmark of chronic inflammation contributing to the activation of pro-inflammatory/proliferative pathways. In the cancers analyzed, the tetrahydrobiopterin:dihydrobiopterin ratio is lower than that of the corresponding normal tissue, leading to an uncoupled nitric oxide synthase activity...
Introduction
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA d...
After radiation exposure, endothelium-dependent vasorelaxation is impaired due to impaired nitric oxide production. Endothelial dysfunction is characterized by uncoupled endothelial nitric oxide synthase activity, oxidation of the reduced cofactor tetrahydrobiopterin to dihydrobiopterin as one well recognized mechanism. Oral treatment with sepiapte...
Introduction: A potential limiting feature for radiotherapy (RT) in the treatment of cancer is the toxicity that arises due to damage to normal tissues as a result of the radiation. This risk of toxicity is a particular concern in men with localized prostate cancer. Radiation-induced proctitis (RIP) is a common adverse effect of RT in treatment for...
Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA
Abstract:
Senescence represents a fundamental response to cancer therapy. Accumulating senescent cells contribute to the deleterious outcomes of cancer therapy including cancer relapse, effects that may be largely mediated by the Senescence-Associated Secretory Phenotype (...
Senescence represents a fundamental response to cancer therapy. Accumulating senescent cells contribute to the deleterious outcomes of cancer therapy including cancer relapse, effects that may be largely mediated by the Senescence-Associated Secretory Phenotype (SASP). In this work, we show that tumor cells induced into senescence by etoposide reta...
Introduction: A potential limiting feature for radiotherapy (RT) in the treatment of cancer is the toxicity that arises due to damage to normal tissues as a result of the radiation. This risk of toxicity is a particular concern in men with localized prostate cancer. Radiation-induced proctitis (RIP) is a common adverse effect of RT in treatment for...
Recently, clinical development of PARP inhibitors (PARPi) expanded from using them as a single agent to combining them with DNA-damaging therapy to derive additional therapeutic benefit from stimulated DNA damage. Furthermore, inhibiting PARP in cancers with BRCA1/2 mutations has been shown to be an effective synthetic lethality approach either as...
Human Dual-specificity tyrosine (Y) Regulated Kinase 1A (DYRK1A) is encoded by a dosage dependent gene whereby either trisomy or haploinsufficiency result in developmental abnormalities. However, the function and regulation of this important protein kinase are not fully understood. Here, we report proteomic analysis of DYRK1A in human cells that re...
H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when
enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cell size, and a senescence-associ...
While cellular senescence has long been recognized as an irreversible form of growth arrest, evidence in the literature has suggested that subpopulations of senescent tumor cells may retain proliferative capacity. To directly address this question, H460 non-small cell lung cancer cells induced into senescence by exposure to etoposide, and enriched...
Human DYRK1A gene encoding Dual-specificity tyrosine (Y)- Regulated Kinase 1A (DYRK1A) is a dosage-dependent gene whereby either trisomy or haploinsufficiency result in developmental abnormalities. However, the function and regulation of this important protein kinase are not fully understood. Here we report proteomic analysis of DYRK1A in human cel...
Objectives: Exosomes (Exos) are 30-150 nm wide nanovesicles originating from the endosomal network and are found in most body fluids. Production of Exos increases in cancer, making Exos potential biomarkers. Exos are a fundamental driver of intercellular communication by transferring proteins, lipids and miRNA. Analysis of Exos and their interactio...
High levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are hallmarks of solid tumors, promoting genomic instability as well as uncontrolled proliferation. In inflammatory diseases such as diabetes, hypertension, atherosclerosis and cancer, loss of nitric oxide (NO) production is a common feature. Recent experiments demonst...
Purpose/Objective(s):
Exosomes (Exos) are 30–150 nm wide nanovesicles originating from the endosomal network and are found in most body fluids. Production of Exos increases in cancer, making Exos potential biomarkers. Exos are a fundamental driver of intercellular communication by transferring proteins, lipids, and miRNA. They can potentiate diseas...
Cancer development and progression have been linked to oxidative stress, a condition characterized by unbalanced increase in ROS and RNS production. The main endogenous initiators of the redox imbalance in cancer cells are defective mitochondria, elevated NOX activity, and uncoupled NOS3. Traditionally, most attention has been paid to direct oxidat...
Inhibitors of poly(ADP-ribose) polymerase (PARP) are clinically used as single-agent therapy for tumors with BRCA1 or BRCA2 mutations. One approach to expanding the use of PARP inhibitors to a wider range of tumors is to combine them with cytotoxic chemotherapy or radiotherapy. Preclinical studies in experimental animals and tumor cells in culture...
Previously we demonstrated that nitric oxide (NO), generated in macrophages or released from the NO-donors, inhibits expression of the breast cancer type 1 susceptibility protein (BRCA1) in the different cell lines (Yakovlev, Cancer Res., 2013). BRCA1 protein contributes to cell viability in multiple ways, including homologous recombination repair...
Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied wi...
Regardless of etiology, inflammatory conditions are characterized by overexpression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide and reactive nitrogen species (NO/RNS) in epithelial and inflammatory cells at the site of carcinogenesis.
NO/RNS produced in inflamed tissues can contribute to the process of carcinogenesi...
Purpose
This study tests whether racial differences in genetic polymorphisms of four genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiotherapy and indicate potential therapeutic targets.
Methods and Materials
This prospective study examines genetic polymorphisms tha...
Epidemiological evidence accumulating over the years has provided a positive correlation between cancer incidence and chronic inflammation. Regardless of etiology, inflammatory conditions are characterized by overexpression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide/reactive nitrogen species (NO/RNS) in epithelial...
Loss or inhibition of Poly(ADP-ribose) polymerase 1 (PARP1) activity results in accumulation of DNA single-strand breaks, which are subsequently converted to DNA double-strand breaks (DSBs) by the cellular replication and/or transcription machinery. Breast cancer type 1 susceptibility protein (BRCA1) is essential for homologous recombination repair...
Here evidence suggests that nitric oxide synthases (NOS) of tumor cells, in contrast to normal tissues, synthesize predominantly superoxide and peroxynitrite. Based on HPLC analysis, the underlying mechanism for this uncoupling is a reduced tetrahydrobiopterin: dihydrobiopterin ratio (BH4:BH2)found in breast, colorectal, epidermoid and head and nec...
Molecular and epidemiological evidence has established important roles for reactive oxygen/reactive nitrogen species (ROS/RNS) in tumor cells, supporting stromal cells and infiltrating leukocytes in tumor initiation and progression. RNS-dependent posttranslational protein modifications (tyrosine nitration and S-nitrosylation) are well-accepted mark...
Signal transducer and activator of transcription 3 (Stat3) is a key mediator in the development of many cancers. For 20 years, it has been assumed that Stat3 mediates its biological activities as a nuclear localized transcription factor activated by many cytokines. However, recent studies from this laboratory and others indicate that Stat3 has an i...
Elevated levels of nitric oxide (NO) and reactive nitrogen species (RNS) may link inflammation to the initiation, promotion, and progression of cancer. Traditionally, this link has been thought to be mediated by the effects of NO/RNS in generating DNA damage. However, this damage also stimulates DNA repair responses with subsequent blocks to cell p...
The link between inflammation and cancer was proposed more than 150 years ago when Virchow suggested that malignancies tend to arise at sites of chronic inflammation. Recent studies have established that elevated levels of nitric oxide/reactive nitrogen species (NO/RNS) generated in the inflammatory microenvironment are associated with several cond...
The link between inflammation and cancer was proposed more than 150 years ago when Virchow suggested that malignancies tend to arise at sites of chronic inflammation. Recent studies have established that elevated levels of nitric oxide/reactive nitrogen species (NO/RNS) generated in the inflammatory microenvironment are associated with several cond...
Models for exploring tyrosine nitration in proteins have been created based on 3D structural features of 20 proteins for which high-resolution X-ray crystallographic or NMR data are available and for which nitration of 35 total tyrosines has been experimentally proven under oxidative stress. Factors suggested in previous work to enhance nitration w...
How specificity and reversibility in tyrosine nitration are defined biologically in cellular systems is poorly understood. As more investigations identify proteins involved in cell regulatory pathways in which only a small fraction of that protein pool is modified by nitration to affect cell function, the mechanisms of biological specificity and re...
To identify temporal changes in protein expression in the irradiated rat lung and generate putative mechanisms underlying the radioprotective effect of the manganese superoxide dismutase mimetic MnTE-2-PyP(5+).
Female Fischer 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy and killed from day 1 to 20 weeks after irradia...
Previous studies demonstrate that nitric oxide (NO) promotes p53 transcriptional activity by a classical DNA damage responsive mechanism involving activation of ATM/ATR and phosphorylation of p53. These studies intentionally used high doses of NO donors to achieve the maximum DNA damage. However, lower concentrations of NO donors also stimulate rap...
The NF-kappaB family of transcription factors is an important component of stress-activated cytoprotective signal transduction pathways. Previous studies demonstrated that some activation mechanisms require phosphorylation, ubiquitination, and degradation of the inhibitor protein, IkappaBalpha. Herein, it is demonstrated that ionizing radiation in...
Commentary to:Inhibition of the CaM-Kinases Augments Cell Death in Response to Oxygen Radicals and Oxygen Radical Inducing Cancer Therapies in MCF-7 Human Breast Cancer CellsOswaldo G. Rodriguez-Mora, Michelle M. LaHair, Mark J. Evans, Charles J. Kovacs, Ron R. Allison, Claudio H. Sibata, Kawana S. White, James A. McCubrey and Richard A. Franklin
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