Establish a platform to screen chemo-radiosensitizers for urothelial carcinoma
Date Issued
2005
Date
2005
Author(s)
DOI
zh-TW
Abstract
Background. Bladder urothelial carcinoma is chemo-sensitive and radio-sensitive. The standard treatment for muscle-invasive and non-metastatic bladder urothelial carcinoma is radical cystectomy with urinary diversion. It severely deteriorate the quality of life. Another choice for these patients is concurrent chemo-radiation therapy (CCRT). However, the long term survival of patients receiving CCRT is still worse than those having radical cystectomy. We intended to search for agents that can make tumor cells more sensitive to the effects of chemotherapy or radiation, i.e. chemo-radiosensitizer. Since numerous combinations will be challenged in this project, we are going to employ an industrial standard Taiguchi’s method in order to solve the best results. We hope the finding in this project can facilitate cancer therapy and also maintain the life quality of the patients.
Objectives. The goal of this study is to establish a platform to screen chemo-radiosensitizer for urothelial carcinoma. Because there are more than one agent will be examined in this study, we will introduce the Taiguchi method of analysis in order to check the best combination result. We will also evaluate the usefulness of the Taguchi method for future medical applications.
Methods. We used the urothelial carcinoma cell line NTUB1, which was derived from a patient with bladder cancer and established in our laboratory. Four chemotherapy agents (As2O3, cisplatin, paclitaxel, gemcitabin), three modulators as candidates for chemo-radiosensitizer (rofecoxib, curcumin, lycopene) and radiation were checked for their cyto-toxicity effects individually and in combination. And cyto-toxicity effect would be checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium（MTT）assay. The best combination was determined with the Taiguchi method and using the method could determine the value of the factors that result in the most consistent outcomes by signal-to-noise ratio. When concerning about the sequence may be another factor, we designed two combinations to check the order effect: experiment A (radiation -6hr-modulater-18hr-chemotherapy agent) and experiment B (radiation-6hr-chemotherapy agents-18hr-modulater). Flow cytometry would be used to check the mechanism of cyto-toxicity effect either by necrosis or apoptosis and it could show the cell cycles of these examined cells.。
Results. The most powerful combination of variables in experiment A was curcumin, lycopene, paclitaxel and radiation. And the most powerful combination of variables in experiment B was curcumin, lycopene, As2O3 and radiation. Low-dose curcumin, high-dose lycopene and low-dose radiation all played its role in either experiment A or experimental B. Flow cytometry showed no complete correlation between the results of cyto-toxicity and apoptosis. The more important factors in experiment A causing apoptosis were curcumin, arsenic, cisplatin, gemcitabine and radiation. And the more important factors in experiment B causing apoptosis were rofecoxib, lycopene, arsenic, paclitaxel and gemcitabine.
Conclusions. In our study, we have established a platform to screen chemo-radiosensitizers for urothelial carcinoma. We demonstrated the possibility to introduce the Taguchi method of analysis to perform the multiple variables in bio-medical study to accelerate the experiment. Low-dose curcumin has the most import place in two experiment design and it has the strong potential as chemo-radiosensitizer worth further study.
Subjects
田口氏L18表
化學及放射治療敏感劑
MTT assay
Taguchi method
chemo-radiosensitizer
SDGs
Type
text
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