Binary Proton Therapy of Ehrlich Carcinoma Using Targeted Gold Nanoparticles.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.

Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

Biological Response of Chinese Hamster B14-150 Cells to Sequential Combined Exposure to Protons and 12C Ions.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.

Effects of Combined Exposure to Carbon Ions and Protons on the Pool of MCF-7 Breast Cancer Stem Cells In Vitro.

We studied the effects of single and combined action of protons and carbon ions 12C6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e. a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control (p<0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

Effects of Combined Action of Neutron and Proton Radiation on the Pool of Breast Cancer Stem Cells and Expression of Stemness Genes In Vitro.

Radiation response of cancer stem cells was studied in two breast cancer cell lines: luminal A (MCF-7) and triple negative (MDA-MB-231) subtypes. The relative number of CD44+CD24-/low cancer stem cells of the MCF-7 line increased by 1.7 times under the influence of γ-irradiation at a dose of 4 Gy (p=0.047 in comparison with the control). However, no significant changes were found in the relative number of cancer stem cells and the expression level of OCT4, NANOG, and SOX2 genes after neutron, proton beam irradiation or their combined action at a total equieffective dose of 4 Gy in comparison with the control in both cell lines. The absolute number of cancer stem cells decreased under the influence of neutron or proton radiation in comparison with the control (p<0.05 for both cell lines). At the same time, the effects of sequential exposures to neutron and proton radiation on the size of the cancer stem cell pool depended on the molecular subtype of cancer cells. Additive interaction was observed for MCF-7 line and antagonistic one for MDA-MB-231 line (coefficients of synergism were 0.96 and 0.45, respectively).

Post-Irradiation Recovery of B14-150 Fibrosarcoma Cells after Combined Irradiation with Low and High Linear Energy Transfer.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/µm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/µm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET.

Calculation of the Biological Efficiency of the Proton Component from 14.8 MeV Neutron Irradiation in Computational Biology with Help of Video Cards.

Fast neutron therapy, which previously has demonstrated effective results, but along with a large number of complications, can again be considered a promising treatment method in the treatment of cancer. One of the ways of analyzing the relative biological efficiency and accurate biological dose of fast neutrons in body tissues is to improve the algorithms of computational biology and mathematical modeling. A high-performance computing code was written which allows to estimate in real-time mode the biological dose of the proton component from the action of neutron radiation with an energy of 14.8 MeV. A comparative analysis of the computing performance on various video cards was also performed.

[Influence of platelets growth factors on spermatogenesis after electronic irradiation]. / Vliyanie faktorov rosta trombotsitov na spermatogenez posle oblucheniya elektronami.

BACKGROUND: The number of cases of male infertility is steadily growing every year, and therefore it is necessary to develop new methods for the diagnosis and treatment of this disease. It is known that plasma enriched with platelets, the α-granules of which contain growth factors, possesses high regenerative activity; therefore, we can expect positive results from its use for the restoration of spermatogenic epithelium. OBJECTIVE: Morphological assessment of spermatogenesis after local ß-irradiation with a dose of 8 Gy and the introduction of growth factors. MATERIAL AND METHODS: Wistar rats (n=135) were divided into groups: I - Control, II - 8IR, III - 8IR+LP-PRP+IGF, IV - 8IR+LP-PRP, and V - LP-PRP. Spermatogenesis in animals of groups II, III, and IV was inhibited by a single local irradiation with 8 Gy electrons. Then, for 11 weeks, LP-PRP was injected intraperitoneally to rats III and IV, and in group III - additionally IGF-1. The testes were examined by light microscopy, computer morphometry, micro-CT, and Western blotting. RESULTS: After irradiation, a decrease in spermatogenic epithelium and the number of germ cells was observed up to sub- and total germinal aplasia, fibrosis and an increase in the expression of caspase-3. Against the background of LP-PRP+IGF administration, the decrease in the proportion of germ cells (hypospermatogenesis) was less pronounced. CONCLUSION: The introduction of growth factors and other biologically active substances released from the α-granules of LP-PRP platelets leads to a delayed decrease in the quantitative and qualitative indicators of spermatogenesis, and the additional administration of IGF-1 enhances the regenerative processes that counteract the development of the effects of electron irradiation with a dose of 8 Gy.

Dose Field Shaping and Biological Effectiveness of the Effect of Pulsed Electron Accelerator Novac-11 on Mammalian Cells.

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable.

Evaluation of Antitumor Efficiency of High Intensity Radiation 169Yb Source on Experimental Sarcoma M-1.

Rats with sarcoma M-1 were exposed to high dose rate irradiation with 169Yb source. In 25 days after introduction of a trocar with sealed capsule with 169Yb source into the tumor, complete tumor regression was observed in 70% animals. The results suggest feasibility of using 169Yb source for high-dose rate brachytherapy and development of the personalized medicine approaches.

A comparative study of the biological effectiveness of 14-MeV neutron pulse and continuous radiation using mouse melanoma B-16 cells.

The study was carried out using compact neutron generators with a sealed tube operating in pulsed (neutron generator ING-031) and continuous (NG-14) modes. Neutron radiation was formed due to reaction T(d,n)(4)He. The average flow of 14-MeV neutrons was 6.6×10(9) ns(-1) for ING-031 and 1.2-1.6×10(10) n s(-1) for NG-14. Duration of an impulse was ∼1 ms and pulse frequency of 50 Hz. The gamma rays of (60)Со source with an average energy of 1.25 MeV were standard radiation. Biological efficacy was estimated using the clonogenic activity of mice melanoma B-16 cells. Comparison of biological effects of neutron irradiation in pulse and continuous modes showed no significant difference between them. RBE values of pulse (ING-031) and continuous (NG-14) neutron radiation were equal-in the range of 2.4-2.6. According to the clonogenic activity of melanoma B-16 cells no dose rate effect was observed within the studied range of neutrons doses and dose rates.