Prediction of chemotherapeutic response by collagen gel droplet embedded culture‐drug sensitivity test in human breast cancers

Takamura, Yuuki; Kobayashi, Hisayuki; Taguchi, Tetsuya; Motomura, Kazuyoshi; Inaji, Hideo; Noguchi, Shinzaburo

doi:10.1002/ijc.10208

Cited by 82 publications

(75 citation statements)

References 26 publications

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“…The CD-DST has the advantage of using an anticancer drug contact concentration that is comparable to the clinical therapeutic dose (5,6,10,25). In fact, the primary measurement success rate of the CD-DST was reported to be 87.5% in colorectal cancer, 79.2% in lung cancer, and 84.3% in breast cancer (11,26,27). For OSCC, the primary culture rate was 83.8% (26 of 31 cases) for primary tumors, 50% (1 of 2 cases) for metastatic lymph nodes, and 81.8% (27 of 33 cases) overall.…”

Section: Discussionmentioning

confidence: 99%

“…One hour later, a DF medium containing 10% fetal bovine serum was overlaid in each well; the plates were placed in a CO 2 incubator overnight at 37˚C. The anticancer drugs were added with the following final concentrations and incubated for 24 h: 0.5 µg/ml cisplatin (CDDP) (10), 0.7 µg/ml fluorouracil (5-FU) (10), and 0.1 µg/ml docetaxel (DOC) (11). For cases that needed multidrug combination chemotherapy, the respective concentrations were placed together in the same well.…”

Section: Methodsmentioning

confidence: 99%

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Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

et al. 2017

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Abstract. Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases. A total of 33 OSCC patients from whom 33 samples were obtained from January 2010 to September 2015 were included. CD-DST was performed, individually and in combination, on the three drugs [i.e., cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC)] and on super selective intra-arterial infusion chemoradiotherapy (IACRT). The overall evaluable rate of the CD-DST in OSCC was 81.8% (27 of 33 cases) and the sensitivity to each anticancer drug was evaluated. The in vitro efficacy rates of IACRT, cisplatin + 5-fluorouracil, and docetaxel + cisplatin + 5-fluorouracil (TPF) confirmed the estimated clinical response rates. In 14 of 33 patients, the results of CD-DST were compared with clinical efficacy, which was judged based on measurable lesions on imaging. For TPF therapy, the sensitivity test of the IACRT had a positive predictive value of 90.9% (10 of 11 cases) and a negative predictive value of 100% (3 of 3 cases); the accuracy of the susceptibility test for the anticancer agents was 92.8% (13 of 14 cases). The CD-DST may be useful in selecting multidrug combination chemotherapy and IACRT for OSCC, however, accumulation of further clinical data is required in the future. IntroductionThe treatment of advanced or unresectable oral squamous cell carcinoma (OSCC) is multidisciplinary and entails the use of both multidrug combination chemotherapy and radiotherapy (1-3). The usefulness of super selective intraarterial infusion chemoradiotherapy (IACRT) to deliver high concentrations of anticancer drugs to tumors has been reported (4). The selection of such anticancer drugs for IACRT had been based on statistical information and clinical reports on a number of cases (1-3); however, the expected therapeutic effects of these anticancer drugs have not been consistent and adverse events were common. Therefore, drug sensitivity testing prior to administration of an anticancer agent is ideal to avoid the serious side effects of less effective anticancer drugs. Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) uses an image colorimetric method to assess the combination of an anticancer drug and microcollagen gel embedded in a three-dimensional serum-free culture medium (3 to 10x10 3 cells/30 µg/drop) (5,6). It is a susceptibility test that is currently widely applied in various clinical fields, including gastrointestinal cancer (7-9). However, reports on the use of CD-DST in OSCC were few a...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

et al. 2017

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“…29 Moreover, drug resistance tests using collagen gel culture have proved to be accurate and highly predictive. 30,31 All cell lines used in this study express α2β1 integrin, 32 responsible for adhesion to collagen I. The other 3D model we investigated was spheroid culture, because in some cases cells in spheroids are more resistant to cytotoxic agents than in monolayer culture.…”

Section: Introductionmentioning

confidence: 99%

Indole-3-carbinol-induced death in cancer cells involves EGFR downregulation and is exacerbated in a 3D environment

et al. 2006

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(211 words)Indole-3-carbinol (I3C) is a promising anticancer dietary compound, which inhibits breast cancer in animal models. The objective of the current study was to characterize I3C-induced cells using an EGFR inhibitor resulted in apoptosis. EGFR modulation using EGF or an EGFR inhibitor markedly influenced viability and response to I3C in MDA-MB-468 cells in 3D conditions. EGFR expression was modulated by 3D conditions. Therefore, I3C-induced EGFR reduction in these cells is likely to be responsible for I3C-induced apoptosis.

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“…Iwahashi et al reported that overall survival was significantly better in a chemosensitivity-guided chemotherapy group than in a standard chemotherapy or non-chemotherapy group in advanced gastric cancer (10). There have been several studies employing the chemosensitivity assay in ovarian cancer, breast cancer and leukemia (11)(12)(13)(14), while the number of studies using CD-DST in particular are increasing (15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the individual 50% inhibitory area under the concentration curve of 5-fluorouracil based on the collagen gel droplet embedded culture drug sensitivity test in colorectal cancer

Ochiai¹

2009

Mol Med Rep

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Abstract.We have previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve. In the present study, we used the AUC-IR curve to calculate the individualized AUC IR50 , the AUC value that imparts 50% growth inhibition. Individual AUC IR50 was calculated in CRC patients, and its distribution was evaluated. The cumulative distribution of individual AUC IR50 was regressed over two lines (logarithmic scale). Among the 45 resectable CRC patients, those who achieved more than the individual AUC IR50 during post-operative 5-FUbased chemotherapy demonstrated a trend towards better disease-free survival compared to those who did not achieve AUC IR50 . Of the Dukes' D patients (n=10), those who achieved more than twice the individual AUC IR50 during post-operative 5-FU-based chemotherapy demonstrated significantly better survival rates (p=0.05) than those who did not. In this study, the distribution of the individual AUC IR50 suggested that approximately 6% of patients demonstrated very low 5-FU sensitivity. Therefore, the individual AUC IR50 was useful in classifying good, intermediate and poor 5-FU response. Achievement of the individual AUC IR50 may be a prerequisite for individualized 5-FU-based adjuvant chemotherapy. As well, the early achievement of twice the individual AUC IR50 may indicate an improved prognosis in Dukes' D patients. The individual AUC IR50 using CD-DST is useful in determining the individualized chemotherapy of CRC patients, thus CD-DST has the potential to facilitate the establishment of individualized chemotherapy for CRC. IntroductionIndividualized chemotherapy is a therapeutic strategy based on the features of a respective tumor, and has been proposed to improve patient clinical outcome while maintaining quality of life. In the field of gastrointestinal cancer, 5-fluorouracil (5-FU) is the drug most often used to assess antitumor effect. The drug sensitivity of tumor cells is one of the key factors that must be assessed in individualized chemotherapy for cancer patients. We have reported the 5-FU sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve (1). We have also reported that the growth inhibition rate, calculated from the AUC-IR curve, and the actual growth inhibition rate, at an AUC of 48 μg x h/ml, are identical. Based on these results, we proposed that the in vitro antitumor effect of 5-FU depends o...

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Prediction of chemotherapeutic response by collagen gel droplet embedded culture‐drug sensitivity test in human breast cancers

Cited by 82 publications

References 26 publications

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

Indole-3-carbinol-induced death in cancer cells involves EGFR downregulation and is exacerbated in a 3D environment

Evaluation of the individual 50% inhibitory area under the concentration curve of 5-fluorouracil based on the collagen gel droplet embedded culture drug sensitivity test in colorectal cancer

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