scholarly journals Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6115
Author(s):  
Prerna Singh ◽  
John Eley ◽  
Nayab Mahmood ◽  
Binny Bhandary ◽  
Tijana Dukic ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Radiation Therapy ◽  
Cell Lines ◽  
Bragg Peak ◽  
Proton Radiation ◽  
Linear Quadratic ◽  
Beam Radiation ◽  
Biological Effectiveness ◽  
Spread Out Bragg Peak

Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.

scholarly journals Effectiveness of Monoenergetic and Spread-Out Bragg Peak Carbon-Ions for Inactivation of Various Normal and Tumour Human Cell Lines

2008 ◽  
Vol 49 (6) ◽  
pp. 597-607 ◽  
Author(s):  
Mauro BELLI ◽  
Daniela BETTEGA ◽  
Paola CALZOLARI ◽  
Roberto CHERUBINI ◽  
Giacomo CUTTONE ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Bragg Peak ◽  
Human Cell Lines ◽  
Carbon Ions ◽  
Spread Out Bragg Peak

scholarly journals OC-0517: Investigation of the RBE variation of protons in the rat spinal cord within a spread-out Bragg peak

2017 ◽  
Vol 123 ◽  
pp. S273-S274 ◽  
Author(s):  
M. Saager ◽  
P. Peschke ◽  
S. Brons ◽  
M. Scholz ◽  
P.E. Huber ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bragg Peak ◽  
Rat Spinal Cord ◽  
Spread Out Bragg Peak

scholarly journals Induction chemotherapy with docetaxel and doxorubicin followed by proton beam radiation therapy for platinum-resistant unresectable sinonasal undifferentiated carcinoma

2021 ◽  
Vol 11 (3) ◽  
pp. 109-114
Author(s):  
A. A. Kachmazov ◽  
L. V. Bolotina ◽  
A. L. Kornietskaya ◽  
V. A. Tolstov ◽  
A. A. Fedenko
Keyword(s):  
Radiation Therapy ◽  
Induction Chemotherapy ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Undifferentiated Carcinoma ◽  
Proton Radiation ◽  
Beam Radiation ◽  
Sinonasal Undifferentiated Carcinoma ◽  
Neck Tumors ◽  
Platinum Resistant

Sinonasal undifferentiated carcinoma is a rare and aggressive tumor with an extremely poor prognosis. In the vast majority of cases, this tumor can not be resected due to its rapid local growth. Correct morphological diagnosis is impossible without a thorough differential diagnosis between sinonasal undifferentiated carcinoma and a number of lowgrade tumors of the nasal cavity and paranasal sinuses. Very few case reports and retrospective studies on sinonasal undifferentiated carcinoma have been published so far. No unified widely accepted guidelines on sinonasal undifferentiated carcinoma treatment are currently available due to the lack of statistically significant data from randomized clinical trials. The optimal treatment strategy should be based on an aggressive multimodal approach involving radical surgery, precision radiation therapy, and intensive chemotherapy. The benefits of systemic targeted therapy for patients with sinonasal undifferentiated carcinoma are still unclear. The best results can be achieved by employing tailored treatment approaches preferably in multidisciplinary cancer centers, where healthcare professionals experienced in managing patients with head and neck tumors can be involved. In this article, we report a case of complete radiological response after induction chemotherapy with docetaxel and doxorubicin and proton radiation therapy for the primary tumor area in a 53‑year-old female patient with non-resectable platinum-resistant sinonasal undifferentiated carcinoma.

BIOLOGICAL EFFICIENCY OF THE PROTON SCANNING BEAM OF THE THERAPEUTIC COMPLEX "PROMETHEUS" OF THE A.F. TSYB MEDICAL RADIOLOGICAL RESEARCH CENTER IN STUDIES ON CELL CULTURE OF MURINE MELANOMA B-16

2018 ◽  
Vol 64 (5) ◽  
pp. 678-682
Author(s):  
Yevgeniy Beketov ◽  
Olga Lepilina ◽  
Vyacheslav Saburov ◽  
Aleksandr Chernukha ◽  
Liliya Ulyanenko ◽  
...  
Keyword(s):  
Cell Culture ◽  
Proton Beam ◽  
Bragg Peak ◽  
Quadratic Model ◽  
Biological Efficiency ◽  
Proton Radiation ◽  
Linear Quadratic ◽  
Linear Quadratic Model ◽  
Number Of Factors ◽  
60Co Gamma

The basis for the use of protons for radiation therapy tasks is a fixed conventional value of their relative biological efficiency equal to 1,1. Numerous studies have showed that RBE of proton radiation is not a constant value and depends on a number of factors. The purpose of this study was to determine RBE of a thin scanning proton beam at the center of the distributed Bragg peak in experiments on the culture of murine B-16 melanoma cells. The cell suspension was irradiated in an aqueous phantom by a horizontal proton beam from three directions (0,90 and 180°) in doses from 2 to 8 Gy. Modulation of the energy of proton radiation was 47,5÷92,0 MeV. RBE protons were determined from the clonogenic activity of the cells compared with 60Co gamma quanta. A linear-quadratic model was used to construct the dose dependencies. Obtained RBE values of proton radiation (LET 3÷8 keV/μm) differed in the big party from the generally accepted value and was at the level of 10% survival rate of 1.5. The results obtained generally coincided with data of foreign authors performed on different facilities.

Know when to say when: Serial assessment of apoptosis and lymphocyte infiltrates with combined intraprostatic autologous dendritic cell immunotherapy/radiation therapy in high-risk prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 149-149
Author(s):  
S. E. Finkelstein ◽  
D. Gabrilovich ◽  
F. A. Rodriguez ◽  
T. Chuang ◽  
L. Kang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Radiation Therapy ◽  
Dendritic Cell ◽  
High Risk ◽  
Tumor Immunity ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
High Risk Prostate Cancer

149 Background: Previous work suggested combining local radiotherapy (XRT) with intratumoral syngeneic dendritic cell (DC) injection could result in apoptosis/cell death mediated induction of cytotoxic T lymphocytes (CTL) based anti-tumor immunity. However, the presence, timing, and effectiveness of effector CTL prior, during, and following combined XRT/intratumoral autologous DC injection in humans is unknown. Methods: Herein, we report on timing concerns of intraprostatic DC injection in vivo, in human; five HLA-A2+, high risk localized prostate cancer patients were treated on protocol using androgen suppression therapy (AS), external beam radiation therapy (EBRT, 45 Gy) followed by brachytherapy permanent interstitial implant with addition of autologous intraprostatic DC injections during EBRT, after fractions 5, 15, and 25 of 25. Multiple serial prostate biopsies were collected before initiation of treatment, during EBRT and at 3, 12, 24 and 36 months after completion of treatment. Biopsies were stained for CD3, CD4, CD8, and cleaved caspase 3, and evaluated in a blinded manner. Specific anti-tumor immunity was assessed via ELISpot IFN-gamma production by CTL stimulated by HLA-A2 peptides derived from sequences of proteins associated with prostate cancer. Results: Apheresis, DC injections, and biopsies were well tolerated. The pattern of distribution of CD8+ cells was consistent with prostate cancer antigen targeting, rather than non-specific organ infiltration. There was not immediate obvious intraprostratic infiltrate by CTL after DC injection in vivo, in humans. Measurable, induced increases in ELISpot titers in peripheral blood CTL were observed for some subjects and for some antigens, but non-specific immunity fluctuated. Conclusions: This initial translational experience demonstrates safety and timing of DC injection coordinated with combined AS and XRT. Design of future trials employing combination XRT and DC will consider timing concerns to match therapy-induced apoptosis/cell death. No significant financial relationships to disclose.

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