scholarly journals In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy

2021 ◽  
Vol 22 (18) ◽  
pp. 9762
Author(s):  
Junko Takahashi ◽  
Shinsuke Nagasawa ◽  
Motomichi Doi ◽  
Masamichi Takahashi ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Aminolevulinic Acid ◽  
Combined Treatment ◽  
Reactive Oxygen Species Generation ◽  
Photodynamic Diagnosis ◽  
High Dose ◽  
Severe Toxicity ◽  
Fractionated Radiotherapy ◽  
Post Surgery

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

scholarly journals FSMP-17. GLOBAL METABOLOMIC PROFILING OF GLIOBLASTOMA MULTIFORME REVEALS METABOLIC VULNERABILITIES IN RESPONSE TO RADIATION THERAPY

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Aarooran Durairaj ◽  
Melanie McReynolds ◽  
Congcong Wang ◽  
Joy He ◽  
Joshua Rabinowitz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Ionizing Radiation ◽  
Aminolevulinic Acid ◽  
Primary Brain Tumor ◽  
Metabolic Reprogramming ◽  
Pharmacological Intervention ◽  
Tumor Microenvironments ◽  
Metabolomic Profiling

Abstract Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, originates in astrocytes and oligodendrocytes and yields a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat the poor prognosis of GBM. Recent studies have established that GBM cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived GBM cell lines. Surprisingly, acute high dosage of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), a non-proteinogenic amino acid. Fractionation of radiation therapy resulted in dose-dependent changes in the heme synthesis pathway within these cells. Using an orthotopic xenograft mouse model of GBM, we identify several enzymatic vulnerabilities in vivo and discuss a novel combinatorial therapeutic approach of radiation and targeted pharmacological intervention. Our findings reveal the fundamental biosynthetic changes that GBMs adopt when exposed to ionizing irradiation as well as the benefits of a combinatorial approach.

scholarly journals Enhanced Survival in Mice Exposed to Ionizing Radiation by Combination of Gamma-Tocotrienol and Simvastatin

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 644-651 ◽  
Author(s):  
Rupak Pathak ◽  
Vidya Prasanna Kumar ◽  
Martin Hauer-Jensen ◽  
Sanchita Purohit Ghosh
Keyword(s):  
Body Weight ◽  
Ionizing Radiation ◽  
Military Service ◽  
Protective Efficacy ◽  
Combined Treatment ◽  
Subcutaneous Administration ◽  
Cell Recovery ◽  
Gamma Tocotrienol

Abstract Ionizing radiation exposure is a major concern for active military service members, as well as civilian population. Considering that the exposure is not predictable, it is imperative that strategies to counteract radiation damage must be discovered. Recent in vitro studies performed in our laboratory demonstrated that the vitamin E analog gamma-tocotrienol (GT3) in combination with cholesterol-lowering drugs (Statins), synergistically induced endothelial thrombomodulin, an anticoagulant with radio-protective efficacy. It was hypothesized that the combination of treatment with both GT3 along with Statins would provide better radiation protection in vivo than each drug individually. CD2F1 mice were injected subcutaneously with either vehicle or single dose of GT3 (200 mg/kg body weight) 24 hours before irradiation followed by oral or subcutaneous administration of various doses of simvastatin (25, 50, and 100 mg/kg body weight) before exposure to lethal doses (11.5 and 12 Gy) of Cobalt-60 (60Co) gamma-irradiation. The combined treatment group exhibited enhanced radiation lethality protection substantially, accelerated white blood cell recovery, and augmented restoration of bone marrow cellularity when compared to the animals treated with either drug exclusively. This information clearly suggests that combined treatment could be used as a safeguard for military personnel from exposure to harmful ionizing radiation.

A High Dose of Ionizing Radiation Induces Tissue-Specific Activation of Nuclear Factor-κB In Vivo

1999 ◽  
Vol 151 (6) ◽  
pp. 703 ◽  
Author(s):  
Daohong Zhou ◽  
Stephen A. Brown ◽  
Tao Yu ◽  
Gang Chen ◽  
Shirish Barve ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Nuclear Factor Κb ◽  
High Dose ◽  
Nuclear Factor ◽  
Tissue Specific

scholarly journals In Vivo Irradiation of Mice Induces Activation of Dendritic Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2391 ◽  
Author(s):  
Eszter Persa ◽  
Tünde Szatmári ◽  
Géza Sáfrány ◽  
Katalin Lumniczky
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Ionizing Radiation ◽  
Fold Increase ◽  
High Dose ◽  
Antigen Uptake ◽  
Dose Irradiation

It is becoming clear that ionizing radiation positively influences certain immune parameters, which opens the possibility for combining radio- and immunotherapies in cancer treatment. The presence of functionally competent dendritic cells (DCs) is crucial in mounting a successful antitumor immune response. While it has been shown that DCs are relatively radioresistant, few and contradictory data are available on how ionizing radiation alters the functional integrity of these cells. Therefore, our objective was to investigate the effect of whole-body irradiation on the function of splenic DCs. C57Bl/6 mice were irradiated with 0.1, 0.25, and 2 Gy X-rays and changes in the phenotype of splenic DCs were compared to unirradiated controls. An increase was seen in DC surface markers influencing DC-T cell interactions. In vivo cytokine production was determined by direct intracellular cytokine staining. Irradiation with 2 Gy induced a 1.6-fold increase in IL-1α production, while the combination of irradiation and lipopolysaccharide (LPS) treatment induced a 3.9-fold increase, indicating a strong synergism between irradiation and LPS stimulation. Interaction of DCs with effector and regulatory T cells was investigated in a mixed lymphocyte reaction. While DCs from control animals induced stronger proliferation of regulatory T cells, DCs from animals irradiated with 2 Gy induced stronger proliferation of effector T cells. Antigen uptake and presentation was investigated by measuring the capacity of DCs to internalize and present ovalbumine (OVA)-derived peptides on their major histocompatibility complex (MHCI) molecules. Irradiation with 2 Gy did not influence antigen uptake or presentation, while low doses stimulated antigen uptake and reduced the level of antigen presentation. In conclusion, high-dose in vivo irradiation induced increased expression of T cell costimulatory markers, enhanced production of proinflammatory cytokines and a stronger stimulation of effector T cell proliferation than that of regulatory T cells. However, it did not influence DC antigen uptake or presentation. On the other hand, low-dose irradiation increased antigen uptake and lowered antigen presentation of DCs, indicating that low- and high-dose irradiation act on different pathways in DCs.

148 Complementary in vitro and in vivo study of the promising combined treatment modality of ionizing radiation and patupilone (EP0906, epothilone B)

2006 ◽  
Vol 78 ◽  
pp. S49-S50
Author(s):  
B. Hofstetter ◽  
Ch. Oehler ◽  
V. Vuong ◽  
A. Broggini-Tenzer ◽  
I.F. Ciernik ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Treatment Modality ◽  
Combined Treatment ◽  
In Vivo Study ◽  
Epothilone B

Photodynamic Diagnosis with 5–Aminolevulinic Acid in the Treatment of Secondary Urethral Tumors: First in vitro and in vivo Results

2001 ◽  
Vol 39 (2) ◽  
pp. 178-182 ◽  
Author(s):  
L. Höltl ◽  
I. E. Eder ◽  
H. Klocker ◽  
A. Hobisch ◽  
G. Bartsch ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Photodynamic Diagnosis

scholarly journals The use of in vivo dosimetry within the combined treatment of uterine body cancer

2020 ◽  
Vol 55 (1) ◽  
pp. 35-38
Author(s):  
O. M. Sukhina ◽  
V. S. Sukhin ◽  
Y. B. Radzishevska ◽  
A. S. Sіmbіrova
Keyword(s):  
Cancer Patients ◽  
Linear Accelerator ◽  
Uterine Cancer ◽  
Combined Treatment ◽  
Relative Difference ◽  
In Vivo Dosimetry ◽  
Genital Cancer ◽  
Post Surgery ◽  
The Impact

Relevance: Radiotherapy is the standard post-surgery treatment in patients with uterine cancer. However, radiotherapy affects 90.0–100.0% of the volume of risk organs. Information on the actual dose delivered to critical structures is needed to ensure the quality of radiotherapy. The purpose of this study was to determine the impact of the type of ionizing radiation on the dose load on the rectal mucosa using in vivo dosimetry. Results: At the first and tenth sessions of treatment using a cobalt apparatus, the in vivo dosimetry showed that the minimum value of the dose received during the tenth cycle was higher by 0.1 Gy. That is, the deviations from the planned dose were less at the same maximum values. Both the average value and the median during the tenth cycle were also moderately higher. The relative difference between the dose planned and received during the tenth cycle was higher than during the first cycle by an average of 1.12575%, with a median of 0.82214. When conducting radiotherapy using a linear accelerator, the average and median values were higher in the second measurement despite almost identical minimum and maximum values. The relative difference between the planned and received doses during the tenth cycle was higher than during the first cycle by an average of 0.55619%, with a median of 0.42948. Conclusion: The conducted study showed an intro- and interindividual variability of in vivo dosimetry results during radiotherapy of genital cancer patients. In vivo dosimetric control showed that the relative difference between the doses calculated and received by the rectal mucosa upon reaching of 20.0 Gy dose in comparison to the first irradiation cycle were twice higher on the ROCUS-AM cobalt apparatus vs. the Clinac 600 C linear accelerator. The data obtained during the investigation indicates the need to develop innovative approaches to topometric preparation of genital cancer patients and to continue their dosimetric monitoring to establish the causes of discrepancies in the results.

scholarly journals The use of in vivo dosimetry within the combined treatment of uterine corpus cancer

2020 ◽  
Vol 55 (1) ◽  
pp. 30-32
Author(s):  
O. M. SUKHINA ◽  
V. S. SUKHIN ◽  
Y. B. RADZISHEVSKA ◽  
A. S. SІMBІROVA
Keyword(s):  
Cancer Patients ◽  
Linear Accelerator ◽  
Combined Treatment ◽  
Relative Difference ◽  
In Vivo Dosimetry ◽  
Uterine Corpus ◽  
Genital Cancer ◽  
Post Surgery ◽  
The Impact

Relevance: Radiotherapy is the standard post-surgery treatment in patients with uterine corpus cancer. However, radiotherapy affects 90.0–100.0% of the volume of risk organs. Information on the actual dose delivered to critical structures is needed to ensure the quality of radiotherapy. The purpose of this study was to determine the impact of the type of ionizing radiation on the dose load on the rectal mucosa using in vivo dosimetry. Results: At the first and tenth sessions of treatment using a cobalt apparatus, the in vivo dosimetry showed that the minimum value of the dose received during the tenth cycle was higher by 0.1 Gy. That is, the deviations from the planned dose were less at the same maximum values. Both the average value and the median during the tenth cycle were also moderately higher. The relative difference between the dose planned and received during the tenth cycle was higher than during the first cycle by an average of 1.12575%, with a median of 0.82214. When conducting radiotherapy using a linear accelerator, the average and median values were higher in the second measurement despite almost identical minimum and maximum values. The relative difference between the planned and received doses during the tenth cycle was higher than during the first cycle by an average of 0.55619%, with a median of 0.42948. Conclusion: The conducted study showed an intro- and interindividual variability of in vivo dosimetry results during radiotherapy of genital cancer patients. In vivo dosimetric control showed that the relative difference between the doses calculated and received by the rectal mucosa upon reaching of 20.0 Gy dose in comparison to the first irradiation cycle was twice higher on the ROCUS-AM cobalt apparatus vs. the Clinac 600 C linear accelerator. The data obtained during the investigation indicates the need to develop innovative approaches to topometric preparation of genital cancer patients and to continue their dosimetric monitoring to establish the causes of discrepancies in the results.

Sign in / Sign up

Export Citation Format

Share Document