Development of a New In Vitro Chemosensitivity Test Using Collagen Gel Droplet Embedded Culture and Image Analysis for Clinical Usefulness

Kobayashi, Hisayuki

doi:10.1007/978-3-642-19022-3_5

Cited by 66 publications

(88 citation statements)

References 25 publications

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“…On the other hand, the CD-DST that we performed in this study had a potential for a high success rate on initial culture, needed a small number of cells, and used serum-free culture medium and image colorimetry to eliminate the influence of fibroblasts. 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).…”

Section: Discussionmentioning

confidence: 99%

“…CD-DST was performed on 31 primary lesions and 2 metastatic lymph nodes; 5-7-mm 2 tissues (about 0.25-0.5 mg) were collected mainly from the area surrounding the hardened part of the tumor. CD-DST was carried out according to the method invented and reported by Kobayashi et al (5,6), who used a human tumor cell primary culture system kit (Primaster ® ; Kurabo Industries Ltd., Osaka, Japan). Briefly, each sample was washed five times with 50 ml saline containing 1.0 mg/ml penicillin, 0.5 mg/ml kanamycin, and 2.5 µg/ml amphotericin B; this was followed by treatment with Dispersion Enzyme Cocktail EZ (Primaster ® reagent).…”

Section: Methodsmentioning

confidence: 99%

“…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)(8)(9).…”

Section: Introductionmentioning

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%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…In vitro chemosensitivity was examined using the collagen gel-droplet embedded culture drug sensitivity test (cD-Dst), as previously described by kobayashi et al, with minor modifications (10)(11)(12)(13). Briefly, surgically resected specimens were finely minced using a scalpel and digested in a cell dispersion enzyme solution ez (nitta gelatin inc.).…”

Section: Methodsmentioning

confidence: 99%

ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer

Inoue

Matsumoto²,

Yamada³

et al. 2010

Oncology Letters

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Abstract. copper-transporting P-type adenosine triphosphatase (AtP7B) is reportedly associated with platinum drug resistance in various solid tumors. However, the impact of AtP7B on platinum drug resistance in non-small cell lung cancer (nsclc) remains unclear. We investigated in vitro cisplatin (cDDP) sensitivity using the collagen gel-droplet embedded culture drug sensitivity test. the AtP7B mrnA expression level in each specimen was also examined using real-time polymerase chain reaction. the relationship between AtP7B expression and in vitro cDDP sensitivity was then evaluated. the AtP7B mrnA expression levels in cDDPresistant tumors were significantly higher than those in the cDDP-sensitive group (p=0.015; Mann-Whitney U test). our results suggested that AtP7B expression is a promising chemoresistance marker for cisplatin. Introductionthe anticancer drug cisplatin (cDDP), which contains platinum, is widely used for the treatment of solid tumors such as testicular, ovarian, cervical, bladder, head and neck, as well as non-small cell lung cancer (nsclc) (1). cDDP has been a key drug in chemotherapy against nsclc for more than 20 years.However, the overall response rate to cisplatin as a single agent against nsclc is no more than 20% (2). Furthermore, the development of resistance to cDDP is common during treatment of nsclc patients, and is an important concern for clinical oncologists. thus, exploring chemoresistance markers is significant. Mechanisms of CDDP resistance include a decrease in drug accumulation and enhanced detoxification, but an increase in DNA repair efficiency. However, studies are mainly limited to in vitro or in vivo experiments and none of the examined markers have been validated as common contributors to clinical cDDP resistance or the prognosis of patients with nsclc (3).copper-transporting P-type adenosine triphosphatase (AtP7B) plays a key role in copper distribution inside cells. AtP7B is expressed in liver and kidney and, to a lesser extent, in the brain in normal individuals (4,5). AtP7B is responsible for the export of copper from the liver; thus, mutations that disable the function of AtP7B may lead to excessive hepatic copper accumulation, as suggested by the impairment of biliary copper excretion in patients with Wilson disease (6). Previous studies suggested that the copper export system functions as efflux transporters for platinum drugs. Moreover, the immunohistochemical expression of AtP7B has been shown to be associated with resistance to platinum drugs in certain solid tumors (3,(7)(8)(9). However, the expression of AtP7B and its impact on cDDP resistance in nsclc have yet to be thoroughly investigated.this study aimed to investigate the predictive value of AtP7B gene expression on in vitro chemosensitivity to cDDP, using surgically resected specimens from patients with nsclc. Materials and methodsStudy population. eligible patients included those with a histological diagnosis of nsclc. these patients had not received chemotherapy nor radiotherapy and had undergone surgic...

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“…Chemosensitivity to 5-FU was analyzed using the CD-DST method according to the manufacturer's instructions (25,26). Briefly, each sample was treated with Dispersion Enzyme Cocktail EZ (Nitta Gelatin Inc., Osaka, Japan).…”

Section: Collagen Gel Droplet-embedded Culture Drug Sensitivity Testmentioning

confidence: 99%

Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastasis of colorectal cancer

Okumura

Shiomi²,

Mekata³

et al. 2006

Oncol Rep

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Abstract. The attainment of chemoresistance during tumor metastasis is often experienced. In this study, we evaluated the correlation between sensitivity to 5-fluorouracil (5-FU) and the mRNA expression level of several 5-FU-related metabolic enzymes [thymidylate synthase, dihydropyrimidine dehydrogenase (DPD), thymidylate phosphorylase (TP), orotate phosphoribosyl transferase, and uridine phosphorylase] in primary colorectal cancer and synchronous liver metastases from ten patients to investigate how colorectal cancer acquires 5-FU resistance during liver metastases. A liver metastasis model of xenotransplanted human colon cancer cell line (HCT116) in nude mice and several cell lines from metastatic liver tumors were also established and analyzed. Chemosensitivity and mRNA expression levels were measured by using collagen gel droplet-embedded culture drug sensitivity tests and real-time quantitative reverse transcriptionpolymerase chain reaction. Metastatic liver tumors were significantly more resistant to 5-FU than primary colorectal cancer (T/C, 88.7% versus 69.7%, p<0.05). DPD and TP mRNA levels were significantly higher in metastatic liver tumors (DPD: 10.36±1.81 versus 3.95±0.99, p<0.01; and TP: 18.80±4.96 versus 7.28±1.23, p<0.05) and inversely correlated with 5-FU sensitivity (DPD: R=0.570, p<0.05; TP: R=0.600, p<0.05). In the mouse model, metastatic liver tumors were significantly more resistant to 5-FU than HCT116 (T/C, 92.7%, 96.2% versus 68%, p<0.001). The DPD and TP mRNA levels increased with repeated liver metastases. DPD and TP may affect the acquisition of resistance to 5-FU during liver metastasis of colorectal cancer. This mouse model may be useful for analyzing the mechanisms of how colorectal cancer acquires resistance to 5-FU during liver metastases.

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Development of a New In Vitro Chemosensitivity Test Using Collagen Gel Droplet Embedded Culture and Image Analysis for Clinical Usefulness

Cited by 66 publications

References 25 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

ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer

Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastasis of colorectal cancer

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