Radiotherapy For Malignant Tumors Research Articles

Microglia in radiation-induced brain injury: Cellular and molecular mechanisms and therapeutic potential.

Radiation-induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation-induced brain injury. This article critically examines recent developments in understanding the role of microglia activation in radiation-induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition. Post-irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation-induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation-induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation-induced brain injury. The intricate microenvironment and molecular mechanisms associated with radiation-induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.

Study on the mechanism of ginsenoside Rg5 attenuating radiation myocarditis through GDF11-SIRT1 pathway.

e15098 Background: Radiation-induced Heart Disease (RIHD) refers to the damage caused by the radiation dose to the heart during radiotherapy for malignant tumors (especially chest tumors), generally including myocardial disease, pericardial disease, coronary artery disease, etc. It generally occurs during radiotherapy or within months to years after radiotherapy. It is reported that the incidence within 5-10 years after the end of radiotherapy is about 10%-30%. With the advancement of equipment and technology, radiotherapy has become increasingly involved in malignant tumors and has become one of the most important treatments for thoracic tumors. Radiation heart disease will significantly reduce the quality of life of patients with malignant tumors after radiotherapy. and survival rate. Although the incidence of RIHD can be reduced by optimizing radiotherapy technology, current technology cannot eliminate the risk of RIHD4. Therefore, it is of great clinical significance to explore how to reduce the incidence and severity of radiation heart disease. Methods: In vitro cultured cardiomyocyte model: used to analyze the impact of Rg5 on cardiomyocytes at the molecular level. Animal model: Construct an animal model of radiation heart disease to evaluate the protective effect of Rg5. Construction of iPCS organoid model to verify that Rg5 attenuates radiation heart disease mediated through Sirt1. Results: Immunohistochemistry, HE staining and Masson staining in early animal experiments showed that Rg5 can slow down radiation heart disease caused by radiotherapy. Immunohistochemistry results showed that SIRT1, HDAC3, PINK1, PARKIN, MFN2 and GDF11 showed obvious differences in expression, while SIRT6 and DRP1 did not. There were obvious differences. At the same time, immunofluorescence double staining of DRP1+SIRT1, MFN2+SIRT1, and HDAC3+SIRT1 was further performed to clarify their intracellular spatial relationship. After using iPSCs to induce cardiac endothelial cells, double immunofluorescence staining of mitochondrial markers and endothelial marker CD31 was performed. The results showed that radiotherapy can cause damage to vascular endothelial cells, reduce vascular integrity, reduce mitochondrial length, and impair function. Ginsenoside Rg5 can reduce this trend. From the common database of single-cell myocardial tissue, it was found that markers such as SIRT1, HDAC3, PINK1, MFN2, GDF11, and GPX4 have similar expression profiles in cardiomyocytes and are more likely to regulate each other. Conclusions: Ginsenoside Rg5 can regulate cardiac radiation injury through the HSP90α-HDAC3-GDF11-SIRT1 axis.It is expected to provide new therapeutic targets for the prevention and treatment of radiation heart disease, making ginsenoside Rg5 of great value in radiotherapy sensitization and radiation heart protection.

The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.

Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.

Targeted nuclear irradiation with a proton microbeam induces oxidative DNA base damage and triggers the recruitment of DNA glycosylases OGG1 and NTH1

DNA is the major target of radiation therapy of malignant tumors. Ionizing radiation (IR) induces a variety of DNA lesions, including chemically modified bases and strand breaks. The use of proton beam therapy for cancer treatment is ramping up, as it is expected to reduce normal tissue damage. Thus, it is important to understand the molecular mechanisms of recognition, signaling, and repair of DNA damage induced by protons in the perspective of assessing not only the risk associated with human exposure to IR but also the possibility to improve the efficacy of therapy. Here, we used targeted irradiation of nuclear regions of living cells with controlled number of protons at a high spatio-temporal resolution to detect the induced base lesions and characterize the recruitment kinetics of the specific DNA glycosylases to DNA damage sites. We show that localized irradiation with 4 MeV protons induces, in addition to DNA double strand breaks (DSBs), the oxidized bases 7,8-dihydro-8-oxoguanine (8-oxoG) and thymine glycol (TG) at the site of irradiation. Consistently, the DNA glycosylases OGG1 and NTH1, capable of excising 8-oxoG and TG, respectively, and initiating the base excision repair (BER) pathway, are recruited to the site of damage. To our knowledge, this is the first direct evidence indicating that proton microbeams induce oxidative base damage, and thus implicating BER in the repair of DNA lesions induced by protons.

Radiation Skin Injury Care in Radiotherapy for Oncology: Mechanisms, Drug Therapy and Novel Biomaterial Application Strategies

AbstractRadiation skin injury (RSI) is a frequent adverse effect of radiation therapy for malignant tumors. It often leads to problems such as decreased quality of life in patients and interferes with the normal course of radiation therapy (RT). With the rising incidence of tumors and the burgeoning number of patients undergoing RT, the care of RSI is of crucial importance in cancer patient treatment. Currently, drugs and biomaterials are widely used in the care of RSI. However, there is no international consensus on the current protocol for the therapeutic care of RSI. Many drugs and biomaterials cannot be applied to the appropriate type of radiation dermatitis, resulting in unfavorable results in the therapeutic care of RSI. The choice of appropriate drugs and biomaterials for the therapeutic care of the different types of RSI is essential to improving the quality of life of patients. This article first reviews the main mechanisms of acute and chronic RSI. Subsequently, the application of drugs and novel biomaterials in the preventive, acute, and chronic phases of the care of RSI is summarized. Finally, the suggestions and protocols for the application of novel biomaterials in the care of RSI are discussed, as are the current challenges and future prospects for the development of combined biomaterials and integrated care solutions.

Pathogenesis and therapy of radiation enteritis with gut microbiota.

Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause radiation enteritis complications. Gastrointestinal tract contains numerous microbes, most of which are mutualistic relationship with the host. Abdominal radiation results in gut microbiota dysbiosis. Microbial therapy can directly target gut microbiota to reverse microbiota dysbiosis, hence relieving intestinal inflammation. In this review, we mainly summarized pathogenesis and novel therapy of the radiation-induced intestinal injury with gut microbiota dysbiosis and envision the opportunities and challenges of radiation enteritis therapy.

The effects of Lactobacillus reuteri microcapsules on radiation-induced brain injury by regulating the gut microenvironment.

A radiation-induced brain injury (RIBI) is a major adverse event following radiotherapy of malignant tumors. RIBI would affect cognitive function, leading to a series of complications and even death. However, the pathogenesis of RIBI is still unclear, and it still lacks specific therapeutic drugs. The gut-brain bidirectional communication may be mediated by various microbiota and metabolites in the gastrointestinal tract. Probiotics are closely related to physiological health. The theory of the gut-brain axis provides us with a new idea to improve the gut microenvironment by supplementing probiotics against RIBI. Here, Lactobacillus reuteri microcapsules (LMCs) were prepared, which were predominantly irregular spheres with a rough surface under a scanning electron microscope and a narrow size distribution ranging from 20 to 700 μm. The transmission electron microscopy images showed that the structure of microcapsules containing Lactobacillus reuteri (L. reuteri) was a core and shell structure. The survival of L. reuteri in microcapsules was significantly more than that of free L. reuteri in the simulated stomach environment of pH 1.2. 16S rDNA sequencing showed that LMCs observably increased the relative abundance of Lactobacillus in RIBI mice. More importantly, compared with the RIBI model mice, the behavior of RIBI mice treated with LMCs was significantly improved. In addition, LMCs greatly alleviated the pathological damage of the hippocampus and intestines in the mice after irradiation and reduced the level of TNF-α and IL-6 in vivo. Generally, LMCs are a promising oral preparation, which provide new ideas and methods for the treatment of RIBI.

Is the linear no-threshold (LNT) model relevant for radiotherapy?

Initially considered as a kind of radiobiological law, the linear no-threshold (LNT) model, which by definition supports the absence of any threshold for cancer risk induction after irradiation, is nowadays more reasonably described as a pragmatic and prudent approach by the International Organizations. However, it remains today a dogma in radiological protection. Actually, this model had been essentially developed for the radiological protection of a general population against low, and sometimes very low, doses of irradiation. Radiation oncologists are dealing with a totally different situation since they deliver, on purpose, high doses of radiations in more or less limited volumes of the body of cancer patients, patients for whom no other alternatives do exist to get rid of their malignant tumors. Simultaneously, the radiation oncologists inevitably give low and even very low doses at distance from the so-called target volumes. In such a specific situation, what is the carcinogenicity of these low doses and the relevance of the LNT model in radiotherapy? Thus, this paper addresses three critical questions: 1) what is the risk acceptability of the radiation doses delivered by radiotherapy of malignant tumors? 2) what is the real carcinogenic risk of (very) low doses delivered at distance from the target volume? 3) are the clinical radiotherapy data, i.e., the number of second primary cancers, accumulated since more than a century, consistent with the LNT model? In conclusion, the LNT model appears to be poorly adapted to the high doses locally delivered to cancer patients and dramatically overestimates, in most cases, the risk of secondary radio-induced cancers. In fine, the real risk of the LNT model in radiotherapy would be to promote radiophobia in cancer patients and to see some of them turning away from a life-saving treatment.

Carbon Ion Beam Boost Irradiation in Malignant Tumors of the Nasal Vestibule and the Anterior Nasal Cavity as an Organ-Preserving Therapy.

BackgroundSurgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.MethodsBetween 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan–Meier estimation was used for statistical assessment.ResultsThe median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.ConclusionCIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.

Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin.

Radiation-induced bone injury (RIBI) is one of the complications after radiotherapy for malignant tumors. However, there are no effective measures for the treatment of RIBI in clinical practice, and the mechanism of RIBI is unclear. We use a single high-dose ionizing radiation (6Gy) to analyze the effect of radiotherapy on osteoblast function. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were cocultured with irradiated osteoblasts to examine their therapeutic effects and mechanisms on osteoblast injury. The hUCB-MSC transplantation mouse model is used to confirm the in vivo role of hUCB-MSC treatment in radiation bone injury. Western blot analysis, qRT-PCR, immunohistochemistry, and immunofluorescence staining were used to analyze gene expression and angiogenesis. The apoptosis and migration of osteoblasts were measured by Hoechst staining, scratch test, and transwell. The differentiation of osteoblasts was measured by ALP and Alizarin red staining and transmission electron microscopy. The bone-related parameters of mice were evaluated by micro-CT analysis. We found that radiation can damage the DNA of osteoblasts; induce apoptosis; reduce the differentiation, migration, and adhesion of osteoblasts, leading to lipogenesis of bone marrow mesenchymal stem cells (BMSCs) and reducing the source of osteoblasts; and increase the number of osteoclasts in bone tissue, while MSC treatment prevents these changes. Our results reveal the inhibitory effect of radiation on osteoblast function. hUCB-MSCs can be used as a therapeutic target for the development of new therapeutic strategies for radiotherapy of bone injury diseases.

Radiotherapy of Malignant Tumors: Photons or Protons? Part 1. Bragg Peak and the Brief Characteristics of a Proton Beam

The first paper of a series of three publications briefly presents the characteristics a proton beam, as well as the information of companies producing noncommercial techniques for photon and proton therapies. The following second and third parts will briefly consider the clinical and economic efficiency of proton versus photon radiotherapy in the treatment of cancer patients and prospects for its development in oncological practice.

Тhe effect of cancer patients’ positioning accuracy during radiation therapy sessions using medical linear electron accelerators on the parameters of their individual 3D dose distribution

Due to the rapid development and further improvement of radiation treatment technologies oncologists have an opportunity to precisely deliver individual dose distributions to the tumor, minimizing the doses obtained by critical organs and healthy structures. For the correct and successful application of these complex methods of radiation therapy, it was necessary to enforce the requirements for the technical and dosimetric parameters of the radiotherapy equipment. The purpose of the research is to determine the magnitude of the possible error for patients’ positioning during their radiotherapy treatments using medical linear accelerators by modeling the impact of the patient’s body on the treatment couch. To determine the values of a possible error, the authors have considered the design and characteristics of a typical treatment couch, developed a model of the “average” patient’s body (phantom), which allowed changing the load to the treatment couch with a step of 1 kg. The position parameters of treatment couches were determined for the main types of localization of radiation therapy for malignant tumors: head and neck tumors, breast tumors and pelvic tumors. Numerical values of the treatment coach deviations from prescribed horizontal position were experimentally established for a load from 40 to 180 kg for a treatment couch used at the N.N. Alexandrov National Cancer Centre of Belarus. Based on the obtained experimental data, the necessity to correct the patient's treatment conditions at the stage of treatment planning were confirmed in order to ensure the delivery accuracy of individual dose distributions as required by the radiation therapy protocols. Authors stated that an analysis of the dependence of the deviations in the dose delivered to the patients on the deviation of the radiotherapy table from its horizontal position should be carried out for each radiotherapy table used in clinical practice. The development and implementation of a mechanism that will allow considering this information when choosing the parameters of the patient’s treatment session and prescribing the dose for any localization of malignant neoplasms is needed.

Radioactive Enteritis and Gut Microecology

Radioactive enteritis(RE)is one of the most serious and common complications of intestinal tract caused by radiotherapy for malignant tumors in abdominal cavity,pelvic cavity,or retroperitoneum.Involved intestinal diseases are widespread,complex,and persistent,which make treatment difficult and ineffective.Short bowel syndrome can develop in some serious cases.Gut flora is the largest and most complex micro-ecosystem in human body and has a wide range of functions.Studies have shown that intestinal flora plays an important role in radiation-induced RE.This article summarizes recent research advances in the relationship between RE and gut flora.

Model-based calculation of thyroid gland normal tissue complication probability in head and neck cancer patients after radiation therapy.

Primary hypothyroidism is one of the late complications that can occur after radiation therapy for malignant tumors in the head and neck region. The aim of this retrospective study was to show the validity of the Lyman-Kutcher-Burman (LKB) normal tissue complication model for thyroid gland based on clinical results. Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine serum levels before radiation therapy, 3months after the beginning of radiation therapy, and afterwards at each follow-up visit. Cumulative incidence was calculated using the Kaplan-Meier method. Dose-volume histogram, total dose, fractionation schedule, total duration of the treatment, and other parameters were used for normal tissue complication probability calculation based on the LKB model. The model was evaluated after fitting with the three sets of parameters for grade 2 hypothyroidism: 1)"Emami," where n = 0.22; m = 0.26, and D50 = 80 Gy; 2)"mean dose," where n = 1; m = 0.27, and D50 = 60 Gy; and 3)"Lyman EUD," where n = 0.49; m = 0.24, and D50 = 60 Gy. Avalue 3.0 Gy was used for α/βratio RESULTS: Eighty-three patients treated with volumetric modulated arc therapy for head and neck cancers at the University Hospital Martin, Slovakia, from January 2014 to July 2017, were included in the retrospective study. Median follow-up was 1.2years. Cumulative incidence of hypothyroidism grade2 or higher after 12and 24months was 9.6 and 22.0%, respectively. Normal tissue complication probability values calculated with mean dose and Lyman EUD parameters showed the best correlation with our clinical findings. Empirically based modelling of normal tissue complication probability was valid for our cohort of patients. With carefully chosen parameters, the LKB model can be used for predicting the normal tissue complication probability value.

LATE RADIATION TOXICITY AFTER RADICAL RADIOTHERAPY FOR GENITAL CANCER.

Radiation therapy for malignant tumors of the female genital area, even with the use of modern radiotherapy equipment and dosimetric planning, causes the development of local radiation changes. An approach involving methodsof general and local exposure is used in their treatment. One of the most promising directions is the creation of optimal combinations of medicines (in the form of ointments, gels, aerosols, suppositories, etc.), which have a therapeutic effect on the inflammatory process. The article reflects the clinical course and stage of occurrence of late radiation reactions of the skin, vaginal/cervix mucosa, bladder, and intestines, as well as the features of their treatment.Literary data and own practical experience in the treatment of radiation complications are presented. Whenreviewing the topic under study, it could be concluded that the leading cause of the development of local radiationdamage is the errors in the planning and implementation of radiation therapy, when high absorbed doses thatexceed the tolerance of healthy tissues are used. Another reason for this is the poor accounting for dose distribution of ionizing radiation in tissues, the presence of concomitant diseases in patients, and the underestimation ofthe long-term effects of radiation.

Artificial Intelligence: opportunities and challenges in radiotherapy

Artificial Intelligence are emerging as poweful tools for many field including medicine. It has be applied to radiation therapy in different degree, such as automatic OAR or tumor volume segmentation, automatic radiotherapy planning, prediction of toxicity and prognostic, etc. In this article, the research progress on Artificial Intelligence in the radiotherapy for malignant tumor was reviewed. Key words: Artificial Intelligence; Neoplasms/radiotherapy

Опыт использования протонной лучевой терапии в объединенном институте ядерных исследований, г. Дубна

First experiments on using proton beams for radiotherapy of malignant tumours at the 680 MeV proton synchrocyclotron of the V.P. Dzhelepov Laboratory of Nuclear Problems of the Joint Institute for Nuclear Research (DLNP JINR) have been initiated by Prof. V.P. Dzhelepov and were started in 1967. 28 patients with different types of superficially located malignancies, such as skin melanomas, metastases of cancer to peripheral nodes, larynx cancers and so on, were treated during the period of 1967–1971. Then the method of scanning rotation irradiation of deep-seated tumours was developed and started to use at DLNP JINR. 50 patients with esophagus cancer, larynx cancer and metastases of malignant tumors were treated with that technique. During the period of 1974–1984 the synchrocyclotron was modified to the Phasotron with the increase of output current. At the same time, a multi-room Medico-technical complex for hadron radiotherapy of cancer patients was constructed. It allows tumour treatment with wide and narrow horizontal beams of protons (70–660 MeV), negative pions (30–80 MeV), high-energy neutrons (mean energy 350 MeV), and with their combinations. The complex includes also the standard gamma-therapy unite Rokus-M with 60Co source for external irradiation. The unique equipment has been developed and constructed, including full-scale PET, X-ray CT for topometry of patients in sitting position, and proton CT. A new round of the development started in December 1999 when a specialized radiological department of patient capacity of 25 beds was opened in Dubna. Since 2000 regular sessions have been conducted in research of proton therapy efficiency in irradiation of patients with neoplasms located in the head, neck and other parts of the body. 1283 patients have received courses of radiotherapy at the Phasotron beams by the end of 2018. The technique of 3D conformal proton radiotherapy in which the maximum of the formed dose distribution conforms most accurately to the shape of the irradiated target has been realized and put into operation. In this way, the maximum sparing effect is achieved in normal tissues and organs surrounding the tumor. The statistical analysis of the proton treatment results of two classes of neoplasms treated with the JINR proton beam (arteriovenous malformation) of the brain and the skull base chordomas and chondrosarcomas) are presented. A new project of the development and construction of a modern superconducting cyclotron SC202 dedicated for proton radiotherapy was prepared recently by the staff of the DLNP JINR and Institute of Plasma Physics Chinese Academy of Sciences (Hefei, China). It is supposed that the accelerator will become the base of a new Proton Therapy Centre in Dubna. It will consist of two treatment rooms: the first one will be equipped with static wide horizontal proton beam and a therapeutic chair, and the second one is planned to provide with gantry for a pencil proton beam dynamic scanning and a positioner for supine patient position during irradiation.

Diffuse optical spectroscopy assessment of rodent tumor model oxygen state after single-dose irradiation

Modern radiation therapy of malignant tumors requires careful selection of conditions that can improve the effectiveness of the treatment. The study of the dynamics and mechanisms of tumor reoxygenation after radiation therapy makes it possible to select the regimens for optimizing the ongoing treatment. Diffuse optical spectroscopy (DOS) is among the methods used for non-invasive assessment of tissue oxygenation. In this work DOS was used for in vivo registration of changes in oxygenation level of an experimental rat tumor after single-dose irradiation at a dose of 10 Gy and investigation of their possible mechanisms. It was demonstrated that in 24 h after treatment, tumor oxygenation increases, which is mainly due to an increase in the oxygen supply to the tissues. DOS is demonstrated to be efficient for study of changes in blood flow parameters when monitoring tumor response to therapy.

A Rat Model of Radiation Vasculitis for the Study of Mesenchymal Stem Cell-Based Therapy.

Radiation vasculitis is one of the most common detrimental effects of radiotherapy for malignant tumors. This is developed at the vasculature of adjacent organs. Animal experiments have showed that transplantation of mesenchymal stem cells (MSCs) restores vascular function after irradiation. But the population of MSCs being engrafted into irradiated vessels is too low in the conventional models to make assessment of therapeutic effect difficult. This is presumably because circulating MSCs are dispersed in adjacent tissues being irradiated simultaneously. Based on the assumption, a rat model, namely, RT (radiation) plus TX (transplantation), was established to promote MSC homing by sequestering irradiated vessels. In this model, a 1.5 cm long segment of rat abdominal aorta was irradiated by 160kV X-ray at a single dose of 35Gy before being procured and grafted to the healthy counterpart. F344 inbred rats served as both donors and recipients to exclude the possibility of immune rejection. A lead shield was used to confine X-ray delivery to a 3 cm×3 cm square-shaped field covering central abdominal region. The abdominal viscera especially small bowel and colon were protected from irradiation by being pushed off the central abdominal cavity. Typical radiation-induced vasculopathy was present on the 90th day after irradiation. The recruitment of intravenously injected MSCs to irradiated aorta was significantly improved by using the RT-plus-TX model as compared to the model with irradiation only. Generally, the RT-plus-Tx model promotes MSC recruitment to irradiated aorta by separating irradiated vascular segment from adjacent tissue. Thus, the model is preferred in the study of MSC-based therapy for radiation vasculitis when the evaluation of MSC homing is demanding.

IDENTIFYING OPTIMAL LOCATION AND NECESSARY QUANTITY OF WAREHOUSES IN LOGISTIC SYSTEM USING A RADIATION THERAPY METHOD

The paper suggests a method for determining the optimal location of service points (warehouses) based on the method for optimal planning of radiation therapy of malignant tumors. This method enabled us to identify the location of the most optimal number of warehouses taking into account their capacity for the required volume of freight transportation and distance from warehouses to consumers. The results of the study coincide with the results obtained by using the method of ant algorithm. The proposed method of finding the optimal location of warehouses enables to significantly minimize the cost of delivering goods from a producer to a consumer.