Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity

Le, Uyen; Kaurin, D.G.; Sloat, Brian R.; Yanasarn, Nijaporn; Cui, Zhengrong

doi:10.1016/j.radonc.2008.10.016

Cited by 15 publications

(8 citation statements)

References 34 publications

(60 reference statements)

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“…If the volume of the cells that survive irradiation in the absence of DEA is taken as V s , then the volume of the cells surviving irradiation in the presence of DEA injected into the tumor will be 0.9 V s . If the doubling time is the same in both cases and equals 5 days [17,26] and the tumor grows exponentially, then the growth delay time will not exceed 0.76 days in the tumor exposed to CERT.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of absorbed dose distribution in melanoma B16F10 during contrast enhanced radiotherapy with intratumoral administration of dose-enhancing agent

Lipengolts

Vorobyeva

Черепанов³

et al. 2018

BRSMU

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В фотон-захватной терапии (ФЗТ) величина поглощенной дозы определяется не только параметрами облучения, но и концентрацией дозоповышающего агента (ДПА) в облучаемом объекте. В данной работе было проведено расчетноэкспериментальное исследование распределения поглощенной дозы на опухолевой модели мышиной меланомы B16F10, после однократной интратуморальной инъекции висмута в качестве ДПА в форме водного раствора комплекса Bi-ДТПА. Оценку поглощенной дозы проводили для однофракционного рентгеновского облучения длительностью 28,5 мин. Количественное определение ДПА in vivo осуществляли при помощи микро-КТ, используя значения рентгеноплотности опухолевых тканей на полученных КТ-томограммах. В результате исследования установлено, что за счет присутствия ДПА в 6% объема опухоли поглощенная доза увеличивалась более чем в 2 раза и в 29% объема опухоли наблюдалось увеличение поглощенной дозы, отличное от 1. Время задержки роста опухоли, рассчитанное для полученного дозо-объемного распределения с учетом только непосредственного радиационного поражения опухолевых клеток, составило 0,76 суток, тогда как в ранее проведенных экспериментальных исследованиях данная величина равнялась 10 суткам. Полученное несоответствие может указывать на то, что торможение роста опухоли при ФЗТ с интратуморальным введением ДПА достигается за счет не только непосредственного радиационного поражения опухоли, но и иных противоопухолевых механизмов.

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Section: Discussionmentioning

confidence: 99%

Evaluation of absorbed dose distribution in melanoma B16F10 during contrast enhanced radiotherapy with intratumoral administration of dose-enhancing agent

Lipengolts

Vorobyeva

Черепанов³

et al. 2018

BRSMU

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“…The authors concluded that radiation improved the lytic sensitivity of the tumor cells to cytotoxic T cells by increasing apoptosis-inducing STAT1 activation, and suggested that localized irradiation should be combined with emerging immunotherapy in the future 87. Similarly, another recent preclinical study demonstrated that radiation is a powerful agent in improving synthetic dsRNA therapy for an in vivo mouse melanoma model 88. Lastly, a recent study by Khan et al demonstrated that riluzole, an inhibitor of glutamate release by human GRM1-expressing melanoma cells, enhanced radiosensitivity in melanoma cells in vitro and in vivo 89.…”

Section: Areas For Future Research and Growthmentioning

confidence: 99%

“… 87 Similarly, another recent preclinical study demonstrated that radiation is a powerful agent in improving synthetic dsRNA therapy for an in vivo mouse melanoma model. 88 Lastly, a recent study by Khan et al demonstrated that riluzole, an inhibitor of glutamate release by human GRM1-expressing melanoma cells, enhanced radiosensitivity in melanoma cells in vitro and in vivo. 89 Khan et al currently have a Phase I protocol underway for patients with melanoma brain metastases to test the role of combining riluzole with whole brain radiation.…”

Section: Areas For Future Research and Growthmentioning

confidence: 99%

Future of radiation therapy for malignant melanoma in an era of newer, more effective biological agents

Khan¹,

Almasan²

2011

OTT

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The incidence of melanoma is rising. The primary initial treatment for melanoma continues to be wide local excision of the primary tumor and affected lymph nodes. Exceptions to wide local excision include cases where surgical excision may be cosmetically disfiguring or associated with increased morbidity and mortality. The role of definitive or adjuvant radiotherapy has largely been relegated to palliative measures because melanoma has been viewed as a prototypical radiotherapy-resistant cancer. However, the emerging clinical and radiobiological data summarized here suggests that many types of effective radiation therapy, such as radiosurgery for melanoma brain metastases, plaque brachytherapy for uveal melanoma, intensity modulated radiotherapy for melanoma of the head and neck, and adjuvant radiotherapy for selected high-risk, node-positive patients can improve outcomes. Similarly, although certain chemotherapeutic agents and biologics have shown limited responses, long-term control for unresectable tumors or disseminated metastatic disease has been rather disappointing. Recently, several powerful new biologics and treatment combinations have yielded new hope for this patient group. The recent identification of several clinically linked melanoma gene mutations involved in mitogen-activated protein kinase (MAPK) pathway such as BRAF, NRAS, and cKIT has breathed new life into the drive to develop more effective therapies. Some of these new therapeutic approaches relate to DNA damage repair inhibitors, cellular immune system activation, and pharmacological cell cycle checkpoint manipulation. Others relate to the investigation of more effective targeting and dosing schedules for underutilized therapeutics, such as radiotherapy. This paper summarizes some of these new findings and attempts to give some context to the renaissance in melanoma therapeutics and the potential role for multimodality regimens, which include certain types of radiotherapy as aids to locoregional control in sensitive tissues.

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“…Over the past several decades, there had been numerous attempts to utilize synthetic dsRNA such as polyriboinosinic-polyribocytidylic acid, poly (I:C), to control tumors in animal models and clinical trials [ 3 , 12 - 14 ]. In general, it was found that synthetic dsRNA only slightly delayed tumor growth [ 15 - 17 ]. Increasing the dose of the synthetic dsRNA to improve its anti-tumor activity is not feasible because of the dose-dependent severe adverse effects [ 15 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…In general, it was found that synthetic dsRNA only slightly delayed tumor growth [ 15 - 17 ]. Increasing the dose of the synthetic dsRNA to improve its anti-tumor activity is not feasible because of the dose-dependent severe adverse effects [ 15 , 18 ]. Recently, there is a reviving interest in exploiting the anti-tumor activity of synthetic dsRNA by improving the delivery of dsRNA into tumor cells [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Replicase-based plasmid DNA shows anti-tumor activity

Rodriguez

Chung

et al. 2011

BMC Cancer

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BackgroundDouble stranded RNA (dsRNA) has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth.MethodsThe anti-tumor activity of a plasmid (pSIN-β) that encodes the sindbis RNA replicase genes (nsp1-4) was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells) and compared to a traditional pCMV-β plasmid.ResultsIn cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors.ConclusionRNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.

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Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity

Cited by 15 publications

References 34 publications

Evaluation of absorbed dose distribution in melanoma B16F10 during contrast enhanced radiotherapy with intratumoral administration of dose-enhancing agent

Evaluation of absorbed dose distribution in melanoma B16F10 during contrast enhanced radiotherapy with intratumoral administration of dose-enhancing agent

Future of radiation therapy for malignant melanoma in an era of newer, more effective biological agents

Replicase-based plasmid DNA shows anti-tumor activity

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