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KMID : 0350519920450041263
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Journal of Catholic Medical College
1992 Volume.45 No. 4 p.1263 ~ p.1280
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Chemosensitivity Analysis for the Carcinoma of Digestive organ using the MTT Assay
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Abstract
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Over the past 20 years, numerous in vitro and in vivo trials for predicting the chemosensitivity of individual tumors have been reported. It is widely believed that there is a critical need in cancer treatment for a practical technology to allow
testing
of standard and experimental treatment modality directly in fresh human cancer specimen, rather than in established cell lines or subhuman tumor systems.
The succinate dehydrogenase inhibition(SDI) test has been introduced for the clinical chemosensitivity test, based on the corelation of the succinate dehydrogenase(SD) activity using 3(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium
bromide(MTT) as
a hydrogen receptor, with cell viability.
The SDI test is simple, inexpensive, and rapid technique for screening antitumor drugs.
In vitro MTT assay was applied for examining chemosensitivity with 37 specimens obtained from 16 gastric and 9 colorectal cancers.
The chemosensitivity was determined as positive when SD activity of the drug exposed cells was decreased to below 50% of that of control cells after the 3rd day of exposure.
@ES The results were as follows:
@EN 1. To determine the relationship of cell number to absorbance values, a standard curve was generated for HeLa cell. There was a linear relationship between the number of HeLa cells and the opetical density of the formazan produced(r=0.92).
2. The sensitivity rate of tumors against cisplatin(DDP) 35%, 5-fluorouracil(5-FU), adriamycin (ADM), vinblastine(VLB) 30%, cytosine arabinoside(Ara-C), etoposide(VP-16) 26%, mitomycin (MMC), vincristine(VCR) 22% and over all chmosensitive rates
of 22%
were noted in 23 specimens.
3. A decrease in SD sctivity was more evident in gastric cancer tissues when compared to colorectal cancer tissues for all drugs tested except 5-FU, MMC and methortrexate(MTX).
4. A decrease in SD activity was remarkable in the poorly differentiated cancer tissues compared to the well differentiated cancer tissue for all drugs tested except. MTX. There were statistical differences in DDP and Ara-C (P<0.05).
5. A decrease in SD activity was more evident in metastatic lymph nodes when compared to cancer tissuses. There were statistical differences in 5-FU, ADM MMC, Ara-C, VLB (P<0.05) and decrease in SD activity was remarkable in cancer tissues
compared to
normal tissues except carmustine(BCNU).
Comparing the SD activity of cancer tissues, lymph nodes, and normal tissues against 11 antitumor drugs, there were statistical differences in 5-FU, ADM, MMC, DDP, VP-16, Ara-C and VLB(P<0.05).
6. We calculated correlation coefficients between two drugs, there was strong correlation in sensitivities between DDP and VP-16(r=0.94), 5-FU and VLB (r=0.87), MMC and VCR (r=0.84), ADM and MMC( r=0.84). In contrast, correlations between MTX
and
VP-16
or DDP (r=0.23, 0.06), between VCR and cyclophosphamide (CPA) (r=0.05) were weak.
In conclusion, the authors suggest the chemosensitivity varied in the tissues. The origins of an organ tumor, the histological differentiation, and the difference of primary or metastatic lesion are critical for determining chemosensitivity. This
test
also useful for selecting sensitive drugs to treat individual cancer patients.
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