Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma‐bearing mice

Abstract

BACKGROUND:The objective of this study was to examine the combined effect of diffusing alpha‐emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development.METHODS:BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 (224Ra‐)–loaded stainless steel wires, releasing short‐lived, alpha‐emitting atoms from their surface. A concomitant regimen of cisplatin doses (5 mg/kg per dose) was given intravenously for the evaluation of the combined effect. Animals were monitored for tumor growth and survival.RESULTS:First, the authors observed that alpha particles and cisplatin inhibited SQ2 cell proliferation in vitro and promoted apoptosis. Treatment of tumor‐bearing mice indicated that, when a regimen of 2 separate doses of cisplatin was given concomitantly with a single intratumoral 224Ra‐loaded wire, there was moderate tumor growth inhibition relative to what was observed from each treatment alone. When tumors were treated with 2 radioactive wires positioned near the tumor base and a similar drug administration, the growth arrest effect intensified, and there also was a significant increase in survival rates. The combined treatment reduced both local tumor growth and metastatic spread to the lungs.CONCLUSIONS:Antitumor activity and overall survival of metastatic tumor‐bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation‐based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment. Cancer 2009. © 2009 American Cancer Society.

Ablation of experimental colon cancer by intratumoral224Radium-loaded wires is mediated by alpha particles released from atoms which spread in the tumor and can be augmented by chemotherapy

“…Treatment with two 224 Ra-loaded wires and 5-FU had a pronounced retardation eff ect that further led to complete cure of 4 out of 5 mice. DaRT treatment could also be eff ectively combined with chemotherapy to treat squamous cell (Cooks et al 2009b) and pancreatic carcinoma (Horev-Drori et al 2012). Yet, exposure of tumor cells in vitro to chemotherapeutic drugs did not increase their sensitivity to alpha particles (unpublished results), so we assume that the increase in survival of the animals treated by the combination is due to eradication of lung metastases by the chemotherapy.…”

Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression

“…Thus, oncomiR‐370 is successful in triggering cell migration by disturbing the TGFβ signaling pathway . The tumor suppressor miR‐218 promotes invasion and metastasis via targeting Robo1, and thereby activating the Slit/Robo1 signaling pathway . Tang et al discovered that GSK3β suppressed the expression of miR‐183‐96‐182 clusters (miRNA‐96, miRNA‐182, and miRNA‐183) through the β‐Catenin/Tcf/Lef‐1 pathway .…”

“…126 The tumor suppressor miR-218 promotes invasion and metastasis via targeting Robo1, and thereby activating the Slit/Robo1 signaling pathway. [127][128][129][130][131] Tang et al discovered that GSK3β suppressed the expression of miR-183-96-182 clusters (miRNA-96, miRNA-182, and miRNA-183) through the β-Catenin/Tcf/Lef-1 pathway. 132 It was found that miRNA-29s should have an effect on the Ras/Raf/MEK/ERK pathway, which acts on cell cycle progression by inducing of cell cycle regulatory proteins such as CDKs and cyclins.…”

Local Control of Lung Derived Tumors by Diffusing Alpha-Emitting Atoms Released From Intratumoral Wires Loaded With Radium-224

“…A second setup for in vitro irradiation by alpha particles relied on short exposures of cells, seeded on a 7.5-mm thick Kapton (polyamide) foil (Dupont, Luxembourg), to alpha particles emitted by a sealed 228 Th source (14). Cells were seeded on the Kapton foil at a density of 3 Â 10 5 cells/well and exposed to the alpha particle flux 24 h later.…”

“…In previous articles (12)(13)(14), we described a new form of brachytherapy, which allows the treatment of solid tumors by alpha particles. The method, named diffusing alphaemitters radiation therapy (DART), relies on the utilization of implantable radioactive sources that carry small activities of radium-224 ( 224 Ra, 3.7 days half-life), incorporated into their surface.…”