Stratified phase II trial to establish the usefulness of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer

Naitoh, Hiroyuki; Yamamoto, Hiroshi; Murata, Satoshi; Kobayashi, Hisayuki; Inoue, K; Tani, Tohru

doi:10.1007/s10120-013-0320-4

Cited by 22 publications

(23 citation statements)

References 19 publications

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“…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)(8)(9). However, reports on the use of CD-DST in OSCC were few and none have evaluated multidrug combination chemotherapy or IACRT.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…Briefly, 100 µl of culture medium was added in each well of E-Plate 96 (Acea Biosciences) to obtain equilibrium. 2x10 4 cells for cell line cells or 1x10 5 for human primary HCC cells in 100 µl of culture medium were seeded in E-Plate 96, which was coated by biocompatible microelectrode. After 18 h, cells were treated with 25, 12.5, 6.26, 3.13 and 1.56 µM, respectively.…”

Section: Cell Viability Assay Cell Viability Was Monitored By Xcel-mentioning

confidence: 99%

“…One part of the primary HCC cells was used for cell viability test monitored by xCEL-Ligence RTCA. The rest part of the cells was performed using collagen gel droplet-embedded CD-DST followed by the standard procedure (5). Briefly, HCC cells were cultured in the collagen droplet which provided a 3-D environment for HCC cells.…”

Section: Cell Viability Assay Cell Viability Was Monitored By Xcel-mentioning

confidence: 99%

Vacquinol‑1 induces apoptosis in hepatocellular carcinoma cell

Sun

et al. 2018

Mol Med Report

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Vacquinol‑1 (Vacq), a quinolone derivative, has recently been reported to display potent antitumor effects in glioblastomas by inducing cellular massive vacuolization and cell death. However, whether Vacq induces cytotoxicities in other types of cancers, and the potential underlying mechanism, remain to be investigated. In the present study, it was revealed that Vacq suppressed cell growth and colony formation in the hepatocellular carcinoma (HCC) cell lines BEL7402 and Huh7. In addition, treatment with Vacq increased the number of early and late apoptotic cells as assessed by ﬂow cytometry with fluorescein isothiocyanate‑conjugated Annexin V and propidium iodide double staining. Notably, the effect by Vacq in the tested cells could be inhibited by pretreatment with a broad specificity caspase inhibitor Z‑VAD‑FMK, suggesting that Vacq may induce apoptosis in HCC cells. Morphologically, exposure to Vacq resulted in nuclear fragmentation and the apoptotic body formation in HCC cells. Furthermore, Vacq treatment increased the cleavage of caspase‑3, caspase‑9 and poly(adenosine diphosphate‑ribose) polymerase‑1. Mechanistic analysis revealed that Vacq upregulated the expressions of pro‑apoptotic proteins [B‑cell lymphoma 2 (bcl‑2)‑associated X protein (Bax) and Bcl‑2‑like protein 11] and downregulated the pro‑survival protein, Bcl‑2, expression in HCC cells. Furthermore, Vacq induced Bax translocation. Of note, Vacq displayed inhibitory effects on patient‑derived HCC cells in two‑dimensional (2D) and three-dimensional (3D) cultures. Taken together, the data suggested that Vacq induced intrinsic apoptosis and may be utilized as an effective reagent for HCC treatment.

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“…No systematic research has demonstrated the exact thymic tumor responses to chemotherapy. Former studies have indicated that the collagen gel droplet embedded culture‐drug sensitivity test (CD‐DST) could approximate the clinical effect in different types of malignant tumors and have a high predictive accuracy for response to chemotherapy, reaching up to 84.1% . In this study, we report on the chemosensitivity of 100 patients with TETs by CD‐DST.…”

Section: Introductionmentioning

confidence: 96%

Evaluating the effectiveness of chemotherapy for thymic epithelial tumors using the CD‐DST method

Zhang

et al. 2020

Thoracic Cancer

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Background: Thymic epithelial tumors (TET) are frequently eligible for curative-intent surgical resection. For locally advanced TETs, chemotherapy has been used to both reduce the tumor burden and achieve prolonged disease control. However, effective therapy for this disease largely remains to be determined. Here, we report the chemosensitivity of 100 patients with TETs determined by the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). Methods: A total of 100 patients with TETs underwent surgical resection. The efficacy of antitumor agents on TET cells was tested by CD-DST. Results: Thymic epithelial tumors were pathologically confirmed after surgery: two cases were type A thymoma, 17 were type AB, 12 were type B1, 44 were type B2, 12 were type B3, and there were 13 cases with thymic carcinoma. A total of 36% patients with TETs were sensitive to different types of chemotherapeutic agents. There was no significant differences in age, histological type, clinical staging, or association with autoimmune diseases between sensitive and nonsensitive cases. Type B1 and B2 thymoma were relatively more sensitive to chemotherapeutic agents (6/12 and 18/44, respectively), while sensitivity of type B3 cases to chemotherapeutic agents was much lower (only 2/12). Cases with type A thymoma were not sensitive to any antitumor drugs. Among 11 chemotherapeutic agents tested in our study, the sensitivity of TETs to EPI was the highest (16%). No patients with thymoma were sensitive to Alimta (Pemetrexed). Conclusions: Our work illuminates the effectiveness of chemotherapy for TETs and provides important clues for choosing antitumor drugs with relatively high drug sensitivity to TETs in advance.

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Stratified phase II trial to establish the usefulness of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer

Cited by 22 publications

References 19 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

Vacquinol‑1 induces apoptosis in hepatocellular carcinoma cell

Evaluating the effectiveness of chemotherapy for thymic epithelial tumors using the CD‐DST method

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