Dataset Information

Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy.

ABSTRACT: Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and chemotherapeutic agents. Human colon cancer cell lines HT29 and HCT116 were subjected to temperatures of 42 degrees to 50 degrees C for 15 min, in combination with 5-fluorouracil, oxaliplatin, or irinotecan at different sequences. Cytotoxicity was determined by MTT assay. The cell cycle progression was analyzed by flow cytometry with propidium iodide staining. The expression of several genes associated with drug sensitivity was quantitated by real-time RT-PCR before and after heat treatment. Either heat treatment at 45 degrees C by simultaneous or pre-treatment with three different chemotherapeutic agents didn't affect the cytotoxicity of the combined treatment to HT29 and HCT116 cells, except for irinotecan treatment in HCT116 cells. However, when pre-exposure to 45 degrees C, HCT116 cells, but not HT29 cells, developed resistance to these three drugs. In an analysis of cell cycle profile after the drug followed heat treatment, a longer delay in cell cycle progression in HCT116 cells was observed in comparison to HT29 cells. Furthermore, HCT116 and HT29 cells exhibited different expression profiles of several drug-related genes in response to heat treatment at 45 degrees C. An observation of a differential response to the drug and heat treatment sequences between two human colon cancer cell lines suggests that tumor heterogeneity and selection of chemotherapeutic agents need to be under consideration in the clinical setting.

SUBMITTER: Makizumi R

PROVIDER: S-EPMC2596320 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy.

Makizumi Ryouji R Yang Weng-Lang WL Owen Randall P RP Sharma Rohit R RR Ravikumar T S TS

International journal of clinical and experimental medicine 20080228 2

Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and chemo ...[more]

PMID: 19079666

Similar Datasets

Project description:PurposeAs an alleviative treatment measured in patients with unresectable advanced pancreatic cancer, radiofrequency ablation (RFA) needed more clinical data to prove its advantages and to explore limitations in its utilization. This study was determined to observe the efficacy of RFA, and to explore its impact on perioperative periphery carcinoma as well as the normal pancreatic tissues.MethodsClinical data of 32 patients with pancreatic cancer accepted RFA surgery were collected. Followed up patients' pain degree and the changes in serum tumor markers CA19-9 and CA 242 before and after surgery. Ex vivo, gave human pancreatic cancer cell line PANC-1 heat treatment to simulate the heat exposure condition periphery carcinoma was experienced during RFA surgery, and to observe the proliferation rate and HSP70 expression change compared with control group.ResultsOf the 32 patients, 1 died of upper gastrointestinal hemorrhage, and 29 survived for more than 5 months, 2 of which for more than 16 months. The average CA19-9 and CA 242 levels of the patients were significantly decreased in 3 months after surgery (t = 9.873, 5.978, P < 0.001). During in vitro experiments, the proliferation rate of PANC-1 cells after heating was significantly increased, accompanied with the increased HSP70 expression. The addition of HSP70 inhibitor can inhibit the rise of proliferation after heat therapy.ConclusionUtilizing RFA treat patients with unresectable advanced pancreatic cancer, could effectively relieve the pain, decline jaundice, and deduce tumor marker levels significantly. However, it failed to extend the long-term survival rate of the patients significantly. This study found that a higher proliferative rate accompanied with a higher HSP70 expression level were observed on in vitro cultured pancreatic carcinoma cells after heat treatment, which could be altered by HSP70 inhibitor. And these findings indicated that the heat exposure might impact periphery carcinoma during RFA surgery and HSP70 might play an important role in patients' prognosis.

Dataset Information

Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy.

Publications

Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets