Petrov Institute of Oncology

Saint Petersburg, Russia

Petrov Institute of Oncology

Saint Petersburg, Russia

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Anisimov V.N.,Petrov Institute of Oncology | Egorov M.V.,Moscow State University | Krasilshchikova M.S.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry | Lyamzaev K.G.,Moscow State University | And 14 more authors.
Aging | Year: 2011

The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging. © Anisimov et al.


Skulachev M.V.,Moscow State University | Antonenko Y.N.,Moscow State University | Anisimov V.N.,Petrov Institute of Oncology | Chernyak B.V.,Moscow State University | And 18 more authors.
Current Drug Targets | Year: 2011

Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H2 from its oxidized form that appears as a result of the antioxidant activity of SkQ1H2. SkQ1H2 prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H2O2-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondriamediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis. © 2011 Bentham Science Publishers Ltd.


Malek A.,Petrov Institute of Oncology
Experimental Metastasis: Modeling and Analysis | Year: 2013

Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists. © Springer Science+Business Media Dordrecht 2013.


PubMed | Petrov Institute of Oncology
Type: Journal Article | Journal: Hereditary cancer in clinical practice | Year: 2011

Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR) of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose) polymerase (PARP). Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC). Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC) patients; studies involving non-selected (i.e., both sporadic and hereditary) CRC with high-level microsatellite instability (MSI-H) suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP). Hereditary medullary thyroid cancers (MTC) have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.


PubMed | Petrov Institute of Oncology
Type: Journal Article | Journal: Aging | Year: 2011

The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging.


Anisimov V.N.,Petrov Institute of Oncology | Zabezhinski M.A.,Petrov Institute of Oncology | Popovich I.G.,Petrov Institute of Oncology
Advances in Gerontology | Year: 2011

We reviewed current approaches to evaluating the efficacy and safety of potential lifespan-extending drugs (geroprotectors). We described and approved our own protocol for evaluation of geroprotectors in mice. Principles and criteria for assessing the gist of the argument of the geroprotective properties of pharmacological drugs in experiments with animals and humans are discussed. © Pleiades Publishing, Ltd., 2011.


PubMed | Petrov Institute of Oncology
Type: Journal Article | Journal: Acta naturae | Year: 2012

Hereditary breast-ovarian cancer syndrome contributes to as much as 5-7% of breast cancer (BC) and 10-15% of ovarian cancer (OC) incidence. Mutations in the canonical genesBRCA1andBRCA2occur in 20-30% of affected pedigrees. In addition toBRCA1andBRCA2 mutations, germ-line lesions in theCHEK2,NBS1, andPALB2genes also contribute to familial BC clustering. The epidemiology of hereditary breast-ovarian cancer in Russia has some specific features. The impact of the founder effect is surprisingly remarkable: a single mutation,BRCA15382insC, accounts for the vast majority ofBRCA1defects across the country. In addition, there are two other recurrentBRCA1alleles:BRCA14153delA andBRCA1185delAG. BesidesBRCA1, in Russia breast cancer is often caused by germ-line alterations in theCHEK2andNBS1genes. In contrast toBRCA1andBRCA2, theCHEK2andNBS1heterozygosity does not significantly increase the OC risk. Several Russian breast cancer clinics recently started to investigate the efficacy of cisplatin in the therapy ofBRCA1-related cancers; initial results show a unique sensitivity ofBRCA1-associated tumours to this compound.

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