title: Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer xenograft with gemcitabine.
abstract: We sought to investigate whether concurrent exposure to pulsed high-intensity focused ultrasound (HIFU) and the chemotherapeutic drug gemcitabine would enhance apoptosis in pancreatic cancer. A pancreatic cancer xenograft model was established using BALB/c nude mice and human pancreatic cancer cells (PANC-1). In the first study, mice were randomly allocated into one of four groups: control (n = 4), HIFU alone (n = 4), gemcitabine (GEM) alone (n = 28) and concurrent treatment with HIFU and gemcitabine (HIGEM) (n = 28). The GEM and HIGEM groups were subdivided into four subgroups (16 mice) according to the drug dose injected (50-200 mg/kg) and another four subgroups (16 mice) according to the time interval between drug injection and HIFU treatment (each subgroup, n = 4). Apoptosis rates were evaluated using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and percentage of necrosis, as evaluated with Harris' hematoxylin solution and eosin Y stain, 3 d after treatment. The second study was performed to evaluate tumor growth rates of the four groups. Each group was treated weekly for 3 wk, and tumor size was periodically measured for up to 4 wk from the beginning of treatment. In the first study, overall rates of apoptosis were significantly higher in the HIGEM group than in the GEM group (p = 0.02). In a subgroup analysis, HIGEM was superior to GEM in enhancing apoptosis at gemcitabine dosages of 150-200 mg/kg gemcitabine and intervals between gemcitabine and HIFU less than 2 h (p = 0.01). In the second study, HIGEM treatment resulted in the slowest tumor growth. However, despite a visible distinction, none of the differences found between the HIGEM and GEM groups were statistically significant (p > 0.05). Treatment with both HIFU and gemcitabine might enhance cell apoptosis and reduce tumor growth in pancreatic carcinoma. For this concurrent treatment, a high dosage of gemcitabine and a short-term delay before HIFU are recommended to maximize the therapeutic effect.
authors: Department of Radiology, Seoul National University Hospital, Seoul, Korea.
authors: Eun Sun
authors: ES
authors: Lee
authors: Jae Young
authors: JY
authors: Lee
authors: Haeri
authors: H
authors: Kim
authors: YoonSeok
authors: Y
authors: Choi
authors: Jisuk
authors: J
authors: Park
authors: Joon Koo
authors: JK
authors: Han
authors: Byung Ihn
authors: BI
authors: Choi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Animal study; Gemcitabine; High-intensity focused ultrasound ablation; Pancreatic neoplasms