scholarly journals Radiation-Induced Fibrotic Tumor Microenvironment Regulates Anti-Tumor Immune Response

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5232
Author(s):  
Jae-Kyung Nam ◽  
Ji-Hee Kim ◽  
Min-Sik Park ◽  
Eun Ho Kim ◽  
Joon Kim ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiation Therapy ◽  
Cytotoxic T Cells ◽  
Neutron Radiation ◽  
X Rays ◽  
Mesenchymal Transition ◽  
X Ray ◽  
High Let ◽  
Tumor Environment ◽  
Endothelial To Mesenchymal Transition

High linear energy transfer (LET) radiation, such as neutron radiation, is considered more effective for the treatment of cancer than low LET radiation, such as X-rays. We previously reported that X-ray irradiation induced endothelial-to-mesenchymal transition (EndMT) and profibrotic changes, which contributed to the radioresistance of tumors. However, this effect was attenuated in tumors of endothelial-specific Trp53-knockout mice. Herein, we report that compared to X-ray irradiation, neutron radiation therapy reduced collagen deposition and suppressed EndMT in tumors. In addition to the fewer fibrotic changes, more cluster of differentiation (CD8)-positive cytotoxic T cells were observed in neutron-irradiated regrowing tumors than in X-ray-irradiated tumors. Furthermore, lower programmed death-ligand 1 (PD-L1) expression was noted in the former. Endothelial-specific Trp53 deletion suppressed fibrotic changes within the tumor environment following both X-ray and neutron radiation therapy. In particular, the upregulation in PD-L1 expression after X-ray radiation therapy was significantly dampened. Our findings suggest that compared to low LET radiation therapy, high LET radiation therapy can efficiently suppress profibrotic changes and enhance the anti-tumor immune response, resulting in delayed tumor regrowth.

Study on the Size Dependence of AuNPs in Enhancement Radiation Effect for Superficial Kilovoltage X-Rays

2019 ◽  
Vol 290 ◽  
pp. 81-86
Author(s):  
Nur Shafawati binti Rosli ◽  
Azhar Abdul Rahman ◽  
Azlan Abdul Aziz ◽  
Shaharum Shamsuddin ◽  
Suhana Arshad
Keyword(s):  
Radiation Therapy ◽  
Free Radicals ◽  
Radiation Effects ◽  
Radiation Effect ◽  
Photoelectric Effect ◽  
Enhancement Effect ◽  
X Rays ◽  
Dose Enhancement ◽  
X Ray ◽  
Mcf 7

Radiation therapy and chemotherapy remain the most widely used treatment options in treating cancer. Recent developments in cancer research show that therapy combined with high-atomic number materials such as gold nanoparticles (AuNPs) is a new way to treat cancer, in which AuNPs are injected through intravenous administration and bound to tumor sites has enhanced tumor cell killing. Radiation therapy aims to deliver a high therapeutic dose of ionizing radiation to the tumor without exceeding normal tissue tolerance. In this work AuNPs have been used for the enhancement of radiation effects on breast cancer cells (MCF-7) for superficial kilovoltage X-ray radiation therapy. The use of AuNPs in superficial kilovoltage X-ray beams radiation therapy will provide a high probability for photon interaction by photoelectric effect. These provide advantages in terms of radiation dose enhancement. In this work, MCF-7 cells were seeded in the 96-well plate and treated with 13 nm, 50 nm and 70 nm AuNPs before they were irradiated with 80 kVp X-rays beam at various radiation doses. Photoelectric effect is the dominant process of interaction of 80 kVp X-rays with AuNPs. When the AuNPs are internalized into the MCF-7 cells, the dose enhancement effect is observed. The presence of AuNPs in the MCF-7 cells will produce a higher number of photoelectrons, and resulting more “free radicals” that will lead to increase in cell death. Then, these free radicals will lead to DNA damage to the MCF-7 cells. To validate the enhanced killing effect, both with and without AuNPs MCF-7 cells is irradiated simultaneously. By comparison, the results show that AuNPs significantly enhance cancer killing and the enhancement radiation effect was dependent on the size of AuNPs.

scholarly journals Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1087
Author(s):  
Bindeshwar Sah ◽  
Jing Wu ◽  
Adam Vanasse ◽  
Nil Kanatha Pandey ◽  
Lalit Chudal ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Reactive Oxygen Species Production ◽  
Radiation Energy ◽  
Nanoparticle Size ◽  
Oxygen Species ◽  
X Rays ◽  
Therapy Outcomes ◽  
X Ray ◽  
Average Size ◽  
Species Production

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles.

High linear energy transfer (LET) radiation therapy in recurrent, metastatic, or unresectable rectal adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 612-612
Author(s):  
P. Paximadis ◽  
D. Elliott ◽  
A. F. Shields ◽  
P. A. Philip ◽  
D. W. Weaver ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Local Control ◽  
Normal Tissue ◽  
Rectal Adenocarcinoma ◽  
Late Toxicity ◽  
Neutron Radiation ◽  
Neutron Dose ◽  
Mixed Beam ◽  
Photon Dose ◽  
High Let

612 Background: The purpose of this study was to retrospectively analyze the outcomes of patients with recurrent, metastatic, or unresectable rectal adenocarcinoma treated with mixed beam photon and high LET radiotherapy. Methods: Between 1995 and 2005, the high LET database was queried to identify patients with rectal adenocarcinoma. Local control and overall survival (OS) were calculated using the Kaplan-Meier method. Acute and chronic toxicities were graded using the common terminology criteria for adverse events (CTCAE) v4.0 grading system. Biological equivalent dose (BED) was calculated for tumor and normal tissue of both the photon dose and neutron dose for 10 patients. Results: 11 patients with recurrent, metastatic, or unresectable rectal adenocarcinoma were identified as being treated with mixed photon-neutron radiation. The median age of patients in the study was 58 (range: 38-79). There were 8 male patients and 3 female patients. Median follow-up was 6 months (range: 4-76 months). Patients received a median photon dose of 40Gy (range: 26-50.4Gy) and a median neutron dose of 8nGy (range: 6-10nGy). Seven patients received radiation given concurrently with 5-FU. The median OS was 16 months (range: 4-76 months), with 1 and 2-year OS of 56% and 22%, respectively. Local control was achieved in 9 of 11 (82%) patients. Local progression occurring in two patients occurred at 5 months after completion of RT. The median tumor BED in patients achieving local control was 72.5 Gy (range: 57.1-83.5 Gy). There was a nonsignificant difference in median normal tissue BED of patients with grade 3-4 late toxicity of 104.8 Gy (range: 81.1-115.1 Gy), compared with 95.3Gy (range: 89.0-104.6 Gy) for those patients with grade 1-2 late toxicity. Conclusions: Our experience demonstrates that treatment of unresectable rectal tumors with mixed photon-neutron achieved excellent local control. With the added capabilities of intensity modulated neutron radiation therapy (IMNRT), the incidence of treatment-related morbidity may be improved while taking advantage of the superior tumor control that high-LET radiation can impart. No significant financial relationships to disclose.

Potential for Therapeutic Gain - 29 MeV Neutrons versus 6 MeV Neutrons

2015 ◽  
Vol 1084 ◽  
pp. 559-566
Author(s):  
Jacobus Slabbert ◽  
Anne Vral
Keyword(s):  
Radiation Therapy ◽  
Tumor Cell ◽  
Cell Types ◽  
Cancer Type ◽  
X Rays ◽  
High Let Radiation ◽  
Therapeutic Gain ◽  
High Let

When a cancer type proves to be radioresistant to treatment with X-rays, the use of neutrons may constitute therapeutic gain provided the cells are relatively sensitive to high-LET radiation. In this work studies with different tumor cell types are reported following exposure to either photons or different neutron energies used in clinical radiation therapy. Potential for therapeutic gain is clearly noted for neutrons with a mean energy of 6 MeV whilst that for 29 MeV neutrons is dependent on the cell types used in the study.

scholarly journals Involvement of Extracellular Vesicles in Vascular-Related Functions in Cancer Progression and Metastasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2584 ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Yusuke Yoshioka ◽  
Marta Prieto-Vila ◽  
Takahiro Ochiya
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Cell Communication ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Tumor Environment ◽  
Endothelial To Mesenchymal Transition

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

scholarly journals Treating Cancer With X-ray Radiation Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Kristopher A. Lyons ◽  
Theodore H. Arsenault ◽  
Zi Ouyang
Keyword(s):  
United States ◽  
Radiation Therapy ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
The United States ◽  
X Rays ◽  
Receive Radiation Therapy ◽  
X Ray

Radiation therapy is an important cancer treatment. At least half of the cancer patients in the United States receive radiation therapy every year. X-rays are often used in radiation therapy. How are X-rays produced? How do we use X-rays to treat cancer? This article answers these questions and explains the physics behind radiation therapy.

scholarly journals Sponges are highly resistant to radiation exposure and cancer

2021 ◽  
Author(s):  
Angelo Fortunato ◽  
Jake Taylor ◽  
Jonathan Scirone ◽  
Athena Aktipis ◽  
Carlo Maley
Keyword(s):  
Somatic Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Lethal Dose ◽  
High Dose ◽  
X Rays ◽  
Cell Turnover ◽  
Cancer Resistance ◽  
Mesenchymal Transition ◽  
X Ray ◽  
Adaptive Immune Cells

There are no reports of cancer in sponges, despite them having somatic cell turnover, long lifespans and no specialized adaptive immune cells. In order to investigate whether sponges are cancer resistant, we exposed a species of sponge, Tethya wilhelma, to X-rays. We found that T. wilhelma can withstand 600 Gy of X-ray radiation. That is approximately 100 times the lethal dose for humans. A single high dose of X-rays did not induce cancer in sponges, providing the first experimental evidence of cancer resistance in the phylum, Porifera. Following X-ray exposure, we found an overexpression of genes involved in DNA repair, signaling transduction pathways and epithelial to mesenchymal transition. Sponges have the highest level of radiation resistance that has yet been observed in animals that have sustained somatic cell turnover. This may make them an excellent model system for studying cancer resistance and developing new approaches for cancer prevention and treatment.

scholarly journals A rebirth of radiation therapy with kV X-rays?

2019 ◽  
Vol 23 ◽  
pp. 85
Author(s):  
J. Kalef-Ezra
Keyword(s):  
Radiation Therapy ◽  
Experimental Models ◽  
X Rays ◽  
Dose Enhancement ◽  
X Ray ◽  
Normal Tissues ◽  
And Migration ◽  
Tissue Sparing ◽  
Dose Measurements ◽  
Therapy Studies

Novel clinical approaches using kV X-ray beams are currently under study, such as selective dose enhancement in malignant tissues due to the enhanced presence of atoms with high atomic number, Z, in tumors relative to normal tissues or the use of heavily spatially fractionated kV X-ray irradiation.Local dose enhancement by high Z atoms: A substantial dose gradient between normal and malignant tissues can be achieved by biologic targeting the cells to be “destroyed” with high Z atoms and its irradiation with photons in the energy region of tens of keV, such as synchrotron produced X-rays of energy above the K-edge. The selective accumulation of high Z atoms can be achieved by various techniques, such as by intravenous administration of a) contrast enhancement agents, b) some chemotherapeutic drugs c) nanoparticles and d) DNA precursors loaded with Z-atoms. Taking into account the limited availability and the high cost of GeV synchrotrons, brachytherapy sources could be used.Microbeam radiation therapy: Studies carried out in experimental models using spatially micro- fractionated beams have shown drastically elevated tissue radiation tolerance, with higher tissue sparing in healthy tissues than in malignant ones. This phenomenon is attributed by some investigators to the proliferation and migration of cells from the “low” dosed regions (~10 Gy) to the adjacent “heavily” dosed regions (many hundreds of grays). Multi-slit collimators allow for the production of X-ray microbeam arrays at 3rd generation synchrotron units. Monte Carlo simulations were tested versus direct dose measurements. Promising preclinical studies carried out so far, trigger studies on the development of alternative less expensive technologies.

scholarly journals Convergence of the Study on Monochromatic X-rays and the Research on Nanoparticles Opens Up a Possibility to Develop a New Type of Radiation Therapy

2020 ◽  
Author(s):  
Fuyuhiko Tamanoi ◽  
Kotaro Matsumoto ◽  
Tan Le Hoang Doan ◽  
Ayumi Shiro ◽  
Hiroyuki Saitoh
Keyword(s):  
Radiation Therapy ◽  
Cancer Cells ◽  
Mesoporous Silica Nanoparticles ◽  
Energy Levels ◽  
Cancer Therapies ◽  
X Rays ◽  
X Ray ◽  
Conventional Radiation ◽  
Combined Use ◽  
New Type

Conventional radiation therapy uses white X-rays that consist of a mixture of X-ray waves with various energy levels. In contrast, a monochromatic X-ray (monoenergetic X-ray) has a single energy level. Irradiation of high Z elements with a synchrotron generated monochromatic X-ray with the energy at or higher than the K-edge energy of the element results in the production of the Auger electrons that cause DNA damage leading to cell killing. Delivery of high Z elements into cancer cells and tumor mass can be facilitated by the use of nanoparticles. Mesoporous silica nanoparticles (MSNs) have been shown to be effective in delivering high Z elements to cancer cells. A proof of principle experiment was reported that demonstrated the feasibility of this approach. This opens up a possibility to pursue the Auger cancer therapy by the combined use of MSNs loaded with high Z elements and monochromatic X-rays. Similar cancer therapies using other types of quantum beams such as neutron, proton and carbon ion beams can be envisioned.

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