H Tsubouchi1, S Takao, T Aikou. 1. First Department of Surgery, Kagoshima University School of Medicine.
Abstract
BACKGROUND: Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test. METHODS: Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio). RESULTS: Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established. CONCLUSIONS: Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.
BACKGROUND: Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test. METHODS: Nine humanpancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio). RESULTS: Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established. CONCLUSIONS: Nine humanpancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.
Authors: Sarah E Mathis; Anthony Alberico; Rounak Nande; Walter Neto; Logan Lawrence; Danielle R McCallister; James Denvir; Gerrit A Kimmey; Mark Mogul; Gerard Oakley; Krista L Denning; Thomas Dougherty; Jagan V Valluri; Pier Paolo Claudio Journal: PLoS One Date: 2014-08-21 Impact factor: 3.240