Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models
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Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models. / Frenzel, Thorsten; Siekmann, Jordana; Grohmann, Carsten; Valentiner, Ursula; Schmitz, Rüdiger; Riecken, Kristoffer; Fehse, Boris; Schumacher, Udo; Lange, Tobias; Krüll, Andreas.
In: INT J RADIAT ONCOL, Vol. 100, No. 4, 15.03.2018, p. 1044-1056.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models
AU - Frenzel, Thorsten
AU - Siekmann, Jordana
AU - Grohmann, Carsten
AU - Valentiner, Ursula
AU - Schmitz, Rüdiger
AU - Riecken, Kristoffer
AU - Fehse, Boris
AU - Schumacher, Udo
AU - Lange, Tobias
AU - Krüll, Andreas
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2018/3/15
Y1 - 2018/3/15
N2 - PURPOSE: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models.METHODS AND MATERIALS: A total of 1 × 106human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Chemotherapy was given as a single intraperitoneal injection of cisplatin. Radiation therapy was 5 × 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control group A) and at the end of the experiment (control group B). Proapoptotic, antiproliferative, antiangiogenic, and hypoxic effects were assessed by Feulgen, Ki67, S1P1 receptor, and hypoxia-inducible factor 1α staining, respectively. Quantitative Alu-polymerase chain reaction was used to determine circulating tumor cells in the blood, and disseminated tumor cells in the lungs, bone marrow, liver, and brain.RESULTS: In both xenograft models, RT and RChT abrogated local tumor growth, indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in the case of relapse-free surgery could similar effects be achieved by OP.CONCLUSIONS: Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regard to suppression of circulating tumor cells and disseminated tumor cells.
AB - PURPOSE: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models.METHODS AND MATERIALS: A total of 1 × 106human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Chemotherapy was given as a single intraperitoneal injection of cisplatin. Radiation therapy was 5 × 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control group A) and at the end of the experiment (control group B). Proapoptotic, antiproliferative, antiangiogenic, and hypoxic effects were assessed by Feulgen, Ki67, S1P1 receptor, and hypoxia-inducible factor 1α staining, respectively. Quantitative Alu-polymerase chain reaction was used to determine circulating tumor cells in the blood, and disseminated tumor cells in the lungs, bone marrow, liver, and brain.RESULTS: In both xenograft models, RT and RChT abrogated local tumor growth, indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in the case of relapse-free surgery could similar effects be achieved by OP.CONCLUSIONS: Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regard to suppression of circulating tumor cells and disseminated tumor cells.
KW - Journal Article
UR - https://www.sciencedirect.com/science/article/pii/S0360301617341706
U2 - 10.1016/j.ijrobp.2017.11.044
DO - 10.1016/j.ijrobp.2017.11.044
M3 - SCORING: Journal article
C2 - 29485046
VL - 100
SP - 1044
EP - 1056
JO - INT J RADIAT ONCOL
JF - INT J RADIAT ONCOL
SN - 0360-3016
IS - 4
ER -
