Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields
| Autor: | Daniel Mordechovich, Uri Weinberg, Yoram Palti, Aviran Itzhaki, Shay Cahal, Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Eilon D. Kirson, Mijal Munster |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Oncology medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Population Mitosis Deoxycytidine Electricity In vivo Cell Line Tumor Cricetinae Pancreatic cancer Internal medicine medicine Animals Humans Clonogenic assay education Tumor Stem Cell Assay Cell Size Chemotherapy education.field_of_study Mesocricetus Hepatology business.industry Gastroenterology medicine.disease Combined Modality Therapy Gemcitabine Pancreatic Neoplasms Treatment Outcome medicine.anatomical_structure Cancer cell business |
| Zdroj: | Pancreatology. 14:54-63 |
| ISSN: | 1424-3903 |
| Popis: | Objectives Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer. Methods The effect of TTFields in vitro was assessed using cell counts, clonogenic assays, cell cycle analysis and analysis of mitotic figures. The effect in vivo effect was studied in the PC1-0 hamster pancreatic cancer model. Results Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy. Conclusions These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer. |
| Databáze: | OpenAIRE |
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