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

Ochiai,

doi:10.3892/mmr_00000113

Cited by 3 publications

(3 citation statements)

References 12 publications

(14 reference statements)

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“…Plates were incubated at 37 °C for approximately 4 days in a Bioscreen (LabSystems Oy), with 600 nm absorbance readings recorded every hour, and values plotted against time to obtain the growth curves for each individual condition. The area under curve (AUC) was calculated as an integrative parameter of total growth as described elsewhere 70 – 72 . Values obtained in the presence of the WGA-Fc were individually compared to a control curve in the absence of the fusion protein.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers

Liedke

Miranda

Gomes

et al. 2017

Sci Rep

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The majority of therapeutic strategies for mycosis require the protracted administration of antifungals, which can result in significant toxicities and have unacceptable failure rates. Hence, there is an urgent need for the development of improved therapeutic approaches, and monoclonal antibody-based drugs are potentially a powerful alternative to standard antifungals. To develop a broad antibody-like reagent against mycosis, wheat germ agglutinin (WGA) was linked to the effector Fc region of murine IgG2a. The resultant WGA-Fc displayed high affinity to purified chitin and bound efficiently to fungal cell walls, co-localizing with chitin, in patterns ranging from circular (Histoplasma capsulatum) to punctate (Cryptococcus neoformans) to labeling at the bud sites (Candida albicans and Saccharomyces cerevisiae). WGA-Fc directly inhibited fungal growth in standard cultures. WGA-Fc opsonization increased fungal phagocytosis, as well augmented the antifungal functions by macrophages. Prophylactic administration of WGA-Fc fully protected mice against H. capsulatum, correlating with a reduction in lung, spleen and liver fungal burdens. Administration of WGA-Fc also dramatically diminished pulmonary inflammation. Hence, the opsonic activity of WGA-Fc effectively modulates fungal cell recognition and promotes the elimination of fungal pathogens. Therefore, we propose WGA-Fc as a potential “pan-fungal” therapeutic that should be further developed for use against invasive mycoses.

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Section: Methodsmentioning

confidence: 99%

Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers

Liedke

Miranda

Gomes

et al. 2017

Sci Rep

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“…based on these results, we proposed that the in vitro antitumor effect of 5-FU was dependent on the AUC in colorectal cancer, and that the AUC-IR curve was reliable (15). Moreover, we calculated the individualized AUC IR50 , the AUC value which gives 50% growth inhibition, using the AUC-IR curve (18).…”

Section: Discussionmentioning

confidence: 99%

Identification of responders/non-responders to 5-fluorouracil based on individual 50% inhibitory area under the concentration curve of 5-fluorouracil obtained with collagen gel droplet-embedded culture-drug sensitivity test in colorectal cancer

Ochiai¹,

Nishimura²,

Watanabe³

et al. 2011

Oncology Letters

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Abstract. We previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells obtained from colorectal cancer (CRC) patients using the collagen gel droplet-embedded culturedrug sensitivity test (CD-DST). Multiple drug concentrations and contact durations, and 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. Moreover, the individualized AUC IR50 , the AUC value which gives 50% growth inhibition, was calculated using the AUC-IR curve. This study aimed to identify responders/non-responders to 5-FU based on the individual AUC IR50 obtained with CD-DST in order to establish individualized chemotherapy for CRC patients. The individual AUC IR50 was calculated from each AUC-inhibition rate regression curve in all patients using the CD-DST. The cumulative distribution of the individual AUC IR50 in CRC patients was evaluated. The cumulative distribution of the individual AUC IR50 was regressed over the sigmoid curve (logarithmic scale). The approximate expression was almost exactly y=ab^exp(-cx) (a=0.9739, b=1.7096E-21, c=0.8990, the sum of square residuals, 0.0279). In the 80 cases examined, no notable change was observed in the regression curve when the number of patients increased. A standard curve was obtained describing responders to 5-FU among all CRC patients. From this standard curve, we ascertained that non-responders accounted for approximately 5% of all patients. Moreover, we were able to classify responders into good or intermediate responders to 5-FU. The standard curve describing response to 5-FU in CRC patients offers a useful tool in the establishment of individualized chemotherapy.

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“…The activity of these enzymes has been reported to be extremely useful in individualization of 5-FU chemotherapy in CRC (23). Moreover, the individual 50% inhibitory area under the concentration curve of 5-FU using the CD-DST has been reported to be useful in determining individualized chemotherapy in CRC patients (24,25). Previous studies have investigated the correlation between the efficacy of irinotecan and topoisomerase-1, or that between the toxicity of irinotecan and uridine diphosphate glucuronosyltransferases 1A1 (21,22,(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test

Ochiai¹,

Nishimura²,

Watanabe³

et al. 2012

Oncology Letters

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Abstract. The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly-targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second-line chemotherapy must be abandoned in certain cases. Where possible, the most effective regimen should be selected as the first line of treatment. The aim of this study was to determine whether first-line chemotherapy may be individualized using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Specimens of primary tumors were obtained from 43 CRC patients who had received no preoperative chemotherapy. Informed consent to measure drug sensitivity was obtained from all patients. The CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally cultured tumor cells in a small collagen gel droplet. The CD-DST was performed and the growth inhibition rate (IR) was obtained under incubation conditions (5-FU with l-OHP at 6.0 and 3.0 µg/ml, or 5-FU with SN-38 at 6.0 and 0.2 µg/ml, respectively, for 24 h). The cumulative distributions of the growth IRs under each condition were evaluated based on the evidence that the clinical response rates to FOLFOX and FOLFIRI were almost the same. Individualization of first-line treatment was possible in all patients, with FOLFOX and FOLFIRI showing higher efficacy in 26 and 15 patients, respectively, and equal efficacy in 2 cases. This method has the potential to facilitate the establishment of individualized first-line chemotherapy for CRC and improve the prognosis in such patients.

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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

Cited by 3 publications

References 12 publications

Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers

Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers

Identification of responders/non-responders to 5-fluorouracil based on individual 50% inhibitory area under the concentration curve of 5-fluorouracil obtained with collagen gel droplet-embedded culture-drug sensitivity test in colorectal cancer

Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test

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