• Journal of Gastric Cancer
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• v.10 no.4
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• pp.155-161
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• 2010

Purpose: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. Materials and Methods: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. Results: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. Conclusions: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3057-3062
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• 2013

Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.261-263
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• 1996

SK-302B, an antibiotic purified from soil Streptomyces sp. 302, was structurally identified as echinomycin (C/sub 50/H/sub 66/N/sub 11/S/sub 2/). In the present experiment, the possibility of SK-302B as an anticolon cancer agent was investigated by using chemosensitivity system (MTT assay, clonogenic assay). Treatment of SK-302B on various colon cancer cell lines resulted in a significant cytotoxicity and tumor colony formation inhibition. These studies showed that SK-302B had a potent inhibition on colon cancer cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.15 no.1
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• pp.35-48
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• 1993

The in vitro predictive tests in cancer chemotherapy of cancer cell lines to anticancer drugs were determined using novel dye exclusion assay [NDEA], [3H] thymidine incorporation, and clonogenic assay [CA>. Antitumor effect of Bleomycin, Cis-platin, Vinblastine, Methotrexate to HEp-2, B16 cell lines using rapid assays was compared with [CA> in this study. In dye exclusion assay of B l6 cell line, cancer cells were sensitive to Bleomycin at all concentrations, to Vinblastine at the level of peak plasma concentration [PPC], ${\times}1/10$ [PPC](P<0.05). And Bleomycin revealed relatively good cytotoxicity than that of CDDP and vinblastine at ${\times}10$[PPC], (P<0.05). HEp-2 cells were resistive to methotrexate at the level of ${\times}100$[PPC] (P<0.05) In [3H] thymidine incorporation assay, B 16 cells were sensitive to Bleomycin, CDDP, Vinblastine at the level of [PPC], ${\times}10$ [PPC](P<0.01). Dose-dependent drugs of bleomycin, CDDP were more sensitive than Vinblastine at high concentration (P<0.05). In clonogenic assay, HEp-2 cell line was sensitive to three drugs of all concentrations except ${\times}10$ [PPC] of CDDP. B 16 cell line was sensitive to all drugs(P<0,01). In comparison of chemosensitivity tests among three assays, the results were correlated(${\gamma}=0.99$, P<0.05).

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.160-166
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• 2007

Purpose: Recently, chemosensitivity tests have become widely used for the selection of effective drugs in gastric cancer patients. In this study, a chemosensitivity test was performed to select agents to increase the effectiveness of adjuvant chemotherapy. Materials and Methods: Chemosensitivity testing was performed in 81 gastric cancer patients that received a gastrectomy at the Yeungnam University Hospital. An ATP (adenosine triphosphate) based chemotherapy response assay was used. Clinicopatholgical factors such as sex, age, expression of tumor markers (CEA and CA19-9 levels), location of the tumor, morphology of advanced cancer, histological type, cell differentiation, depth of invasion, Lauren classification, Ming classification, lymphatic invasion, vascular invasion, neural invasion, lymph node metastasis and TNM stage were used to correlate the chemosensitivity and clinicopathological factors. Results: The most effective antitumor agents in gastric cancer patients were (in order of effectiveness) 5-FU, Epirubicin, lrinotecan and Oxaliplatin in our series. The chemosensitivity test showed a significant difference in susceptibility according to clinicopathological factors. Conclusion: Further studies on multidrug therapy are needed to evaluate synergistic effects of drugs. Therefore, for effective chemotherapy, it is more efficacious to select a chemosensitive drug than continue to use the same drug regimen.

• Journal of Korean Neurosurgical Society
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• v.50 no.5
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• pp.426-433
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• 2011

Objective : The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. Methods : Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. Results : Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months ($p$=0.07). Conclusion : HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.15 no.1
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• pp.37-50
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• 1989

The in Vitro chemosensitivity of fibroblast cell strains was determined using a semiautomated tetrazolium-based colorimetric assay(MTT assay) to 16 cosmetic materials. This assay is useful method to evaluate toxic effects of the chemicals. From assay results, we determined that the preservatives are more toxic than moisteurizers. The chemicals in the same group have a different toxicity. That is, in preservatives, Germall -115 is more toxic than Danisol -M, -p, and in surfactant sodium laurel sulfate than Myrj 52, and in moisteurizers, 1, 3-butylene glycol is more safe than the others. When the results from this assay for preservatives were compared with patch test results, good correlation was observed. Forthemore, this assay method can be used together with Patch test for the evaluation of the chemical toxicity, particularly in cosmetic field.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.216-220
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• 1999

A chemosensitivity assay with small replicate Mm5mt/cl C3H mammary tumor cell cultures was developed to determine whether changes in viral antigen expression and release into culture fluids could be utilized as an in vitro measure of modulating drug effect. The 52,000 MW viral envelope glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) was measured in culture fluids of control and drug-treated cultures while cell density was simultaneously determined by cell staining and OD 664 nm determination. While extra-cellular gp52 levels and cell density progressively increased over 72 hours for control cultures, declines in both parameters provided dual measures of effect for combination [N(phophonacetyl-L-aspartic acid)+5-fluorouracil], combination 〔N(phophonacetyl-L-aspartic acid )+5-fluoro-5'-deoxyuridine〕and single component treatment of this combination. At each treated time point, thesecombinations begin to produce a greater decline in both cell density and gp52 levels as compared to single drug treatments. These results indicate that N(phopho-nacetyl-L-aspartic acid) in combination can enhance the effectiveness of single drug.

• Journal of Microbiology and Biotechnology
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• v.14 no.2
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• pp.350-355
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• 2004

Sulforhodamine B (SRB) assay is a rapid, sensitive, and inexpensive method for measuring cell proliferation and chemosensitivity. However, the lactate dehydrogenase (LDH) release assay is generally used to measure cytototoxicity of infectious microorganisms against host cells. In this study, we investigated the possibility of applying the SRB assay to determine cytotoxicity for infectious microorganisms, and compared the results with those obtained by the LDH release assay. We used Vibrio vulnificus as a model of infectious microorganisms. The SRB assay showed that V vulnificus strongly induced cytotoxic activity against human intestinal cells, Caco-2 and INT-407 cells. The degree of cytotoxicity closely correlated with infection time and number ratios of V. vulnificus to intestinal cells (MOI, multiplicity of infection). Furthermore, cytotoxicity values obtained by SRB assay correlated well with results obtained by the LDH release assay, and both assays gave a linear response with respect to MOI Heat-inactivation of V. vulnificus for 35 min at $60^{\circ}C$ did not induce cytotoxic activity, indicating that viability of V. vulnificus is crucial for cytotoxic activity against intestinal cells. Although both assays are suitable as cytotoxicity endpoints, the SRB assay is recommended for measuring cytotoxicity of infectious microorganisms against host cells because of its significantly lower cost and more stable endpoint than the LDH release assay.