Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors.

Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors.

Estimating the lifetime risk of cancer associated with multiple CT scans.

Multiple CT scans are often done on the same patient resulting in an increased risk of cancer. Prior publications have estimated risks on a population basis and often using an effective dose. Simply adding up the risks from single scans does not correctly account for the survival function.

Stimulatory effect of volatile urinary components from intact mice on the proliferative activity of splenic lymphoid tissue in irradiated animals.

Immunohistochemical and morphometric analyses have demonstrated long-distance stimulatory effects of the natural volatile components of the urine of intact mice on the proliferation of splenic lymphocytes in mice exposed to a single total γ-irradiation in a dose of 1 Gy. These results are in line with the data on stimulation of the humoral immune response to thymus-dependent antigen in irradiated mice exposed to urine specimens of intact animals.

Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector.

Autophagy plays an important role in neoplastic transformation of cells and in resistance of cancer cells to radio- and chemotherapy. p62 (SQSTM1) is a key component of autophagic machinery which is also involved in signal transduction. Although recent empirical observations demonstrated that p62 is overexpressed in variety of human tumors, a mechanism of p62 overexpression is not known.

[Thyroid cancer: lessons of chernobyl and prognosis for Fukushima].

Results of epidemiological studies of thyroid cancer incidence in Russia following the Chernobyl accident are presented in the article. Child population in territories contaminated with radionuclides who got thyroid dose from incorporated (131)I above 100-150 mGy, should be referred to a group at radiation risk. Prognostic estimates of increase in thyroid cancer incidence among the population living in close vicinity of the Fukushima Daiichi NPP were made with account for the Chernobyl data and recommendations of the International Commission on Radiological Protection.

Estimation of risk from medical radiation exposure based on effective and organ dose: how much difference is there?

The authors compare radiation risks of potential cancer following diagnostic radiation exposure evaluated with the use of organ and effective doses. Lifetime attributable risk values of CT scanning are estimated with the use of ICRP (Publication 103) risk models and Russian national medical statistics data. For populations under the age of 50, the risk evaluated using organ doses usually differs from that using effective doses by <30 %.

Methodology for estimating cancer risks of diagnostic medical exposure: with an example of the risks associated with computed tomography.

Because of fast growing medical radiation use, estimating possible late health effects of radiation, including potential cancer risk, is an issue of substantial interest. Since physicians make the decision to order or perform a radiological procedure, it is very important to provide them with objective information about possible radiation-associated risks. Methodology for estimating cancer risks based on recommendations of ICRP Publication 103 is presented in the paper.

[Therapy of patients with isolated metastasis in regional lymph nodes after primary treatment for skin melanoma].

The total of 186 metastatic skin melanoma patients with regional lymph nodes involvement (locoregional stage) received neoadjuvant chemotherapy and irradiation followed by extended lymphodissection. This therapy allowed obtaining favorable overall survival in most patients. Social aspect of the problem should also be noted - the tenacity in treatment of unfavorable prognosis patients using all treatment modalities available allows giving back the hope and extending the lifespan of many patients.

Radiation-epidemiological studies of thyroid cancer incidence in Russia after the Chernobyl accident (estimation of radiation risks, 1991-2008 follow-up period).

This study presents an analysis of the thyroid cancer incidence in the population of the most contaminated territories of Bryansk, Kaluga, Oryol and Tula oblasts affected by the Chernobyl accident. The follow-up period is 1991-2008, and the cohort size is 309 130 people. For that period 978 thyroid cancer cases were detected.

Leukemia incidence in the Russian cohort of Chernobyl emergency workers.

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose-response relationship.

[Where intestinal epithelial stem cells are localized? About molecular markers].

Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008-2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny.

[Methods of individual retrospective physical dosimetry in the problem of estimation of consequences of accidental irradiation].

The overview of the results of development, verification and application of the methods of individual retrospective physical dosimetry among population of settlements contaminated with radionuclides, which suffered from irradiation as a result of the accident in Chernobyl NPP, and among the population located in the vicinity of the Semipalatinsk nuclear test site is presented in the paper. The estimations of sensitivity of the methods of physical retrospective dosimetry are shown. The data on individual doses among population, which was irradiated as a result of accidental irradiation are presented as well.

[Mortality among the liquidators of the Chernobyl accident: dose dependences and groups of the potential risk].

Dynamics of the mortality and the mortality radiation risks among male emergency workers of 1986-1987 years of entrance to the Chernobyl zone is analyzed. The average dose of external gamma-exposure for this cohort equals 128 mGy. The size of the cohort at the beginning of the follow-up in 1992 was 47820 persons.

[Pharmacokinetic and dosimetric characteristics of new radiopharmaceutical based on complexes of 103Pd and albumin microspheres].

Results of the study of absorbed dose formed in organs and tissues of mice after administration of new therapeutic radiopharmaceutical on the base of 103Pd and albumin microspheres (MSA) are presented. Pharmacokinetic parameters of preparation distribution in the body of animals were experimentally determined and then absorbed doses were calculated using MCNP code for the developed mathematical model of mouse. It was shown that absorption of 103Pd-MSA in tumor, physical properties of 103Pd and daughter radionuclide 103mRh provide a targeted irradiation of tumor as compared with the adjusting tissues and critical organs.

The Chernobyl accident and its consequences.

The accident at the Chernobyl nuclear power plant was the worst industrial accident of the last century that involved radiation. The unprecedented release of multiple different radioisotopes led to radioactive contamination of large areas surrounding the accident site. The exposure of the residents of these areas was varied and therefore the consequences for health and radioecology could not be reliably estimated quickly.

Radiation exposure does not significantly contribute to the risk of recurrence of Chernobyl thyroid cancer.

Context: Papillary thyroid carcinoma (PTC) in patients exposed to environmental radioiodine after the Chernobyl accident is thought to have a relatively aggressive clinical course. Long-term results of treatment are not well known, especially in comparison with sporadic PTC.

Objective: The determination of risk factors for PTC recurrence in a controlled for baseline factors group of patients with radiation-related and sporadic PTC.

The neutron dose conversion coefficients calculation in human tooth enamel in an anthropomorphic phantom.

In the present study, MCNP4B simulation code is used to simulate neutron and photon transport. It gives the conversion coefficients that relate neutron fluence to the dose in tooth enamel (molars and pre-molars only) for 20 energy groups of monoenergetic neutrons with energies from 10-9 to 20 MeV for five different irradiation geometries. The data presented are intended to provide the basis for connection between EPR dose values and standard protection quantities defined in ICRP Publication 74.

Dental enamel EPR dosimetry: comparative testing of the spectra processing methods for determination of radiation-induced signal amplitude.

The aim of this investigation is to find out the optimal algorithm for mathematical processing of the EPR spectra of irradiated tooth enamel for estimating the amplitude of the radiation-induced signal, which is used for determination of the absorbed dose in enamel for retrospective individual dosimetry. A recently developed analytical model, which takes into account the line shape variation of the enamel EPR spectral components registered at different microwave power, was applied to spectra processing in various operation modes to simulate spectra processing techniques differing by the number of fitted parameters. The precision of dose determination at spectra processing was assessed by the root mean square deviation between experimental and nominal doses for sets of spectra of enamel samples irradiated in different doses and measured at different microwave power.

Estimation of individualized radiation risk from chronic occupational exposure in Russia.

Internationally, the upper limit of acceptable individualized risk from occupational exposure for nuclear industry workers is determined by the death probability 10(-3) y(-1). The same risk value of 10(-3) y(-1) is established by the radiation safety standards currently in force in Russia. The United Nations Scientific Committee on the Effects of Atomic Radiation has proposed the formulas for estimating individualized risk of developing cancer with allowance for radiation dose, age at exposure, attained age, and sex.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells.

Role of cyclooxygenases in the stimulatory effect of carcinogen 1,2-dimethylhydrazine on stem cell survival in the intestinal epithelium and bone marrow.

In vivo experimental studies showed that 1,2-dimethylhydrazine and product of its metabolism in the body azoximethane improve postradiation survival of two types of stem cells in the adult organism: hemopoietic stem cells and intestinal epithelial stem cells. This effect similar to the well-known radioprotective effect of E. coli lipopolysaccharide was observed, when the carcinogen was administered 1 day before gamma-irradiation.

Possible involvement of NO in the stimulating effect of pifithrins on survival of hemopoietic clonogenic cells.

Pifithrin alpha (PFTalpha), one of the first known low molecular weight modulators of activity of tumor suppressor p53, increases survival of hemopoietic clonogenic cells (evaluated by the criterion of formation of endogenous spleen CFU-C8 colonies in irradiated animals). This effect appeared when PFTalpha was administered either before or after irradiation. Increase in CFU-C8 was also observed after administration of two PFTalpha analogs, derivatives of 2-amino-4,5,6,7-tetrahydrobenzothiazole.

In vitro inhibitory effect of mesenchymal stem cells on zymosan-induced production of reactive oxygen species.

In vitro chemiluminescent test showed that human bone marrow mesenchymal stem cells and conditioned media dose-dependently inhibit production of reactive oxygen species by macrophages: 50% inhibition of chemiluminescence (compared to biocontrol) was observed at 1:1 mesenchymal stem cell/macrophage ratio or after addition of 20-25% conditioned media to the incubation medium. The observed mechanism of inhibition of production of reactive oxygen forms can play an essential role in the formation of local immunosuppressive microenvironment in the organism after allogenic transplantation of mesenchymal stem cells.