Data acquisition for the histoculture drug response assay in lung cancer

Yoshimasu, Tatsuya; Oura, Shoji; Hirai, Ikuko; Tamaki, Takeshi; Kokawa, Yozo; Hata, Kazuhito; Ohta, Fuminori; Nakamura, Rie; Kawago, Mitsumasa; Tanino, Hirokazu; Okamura, Yoshitaka; Furukawa, Tomoko

doi:10.1016/j.jtcvs.2006.06.030

Cited by 41 publications

(42 citation statements)

References 16 publications

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“…In most of these previous systems, viability of tumors has been demonstrated for up to 7 days (13)(14)(15)(16)(17)(18)(19). Here, we identified a mild effect of cultivation after 24 hours of culture (Fig.…”

Section: Discussionsupporting

confidence: 50%

“…A number of organotypic culture systems have been previously developed for human tumors (13)(14)(15)(16)(17)(18). In most of these previous systems, viability of tumors has been demonstrated for up to 7 days (13)(14)(15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…Methods for ex vivo culture of human tumors have been available for many years, and evidence shows that they can reliably reflect tumor growth in vivo (13)(14)(15)(16)(17)(18)(19). Here, we have developed and perfected an ex vivo culture method for NSCLC tumor samples that is both simple and reproducible.…”

Section: Introductionmentioning

confidence: 99%

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Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

et al. 2017

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To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that approximately 70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours. Variations in cisplatin sensitivity were noted with approximately 50% of cases responding ex vivo. Notably, explant responses to cisplatin correlated significantly with patient survival (P ¼ 0.006) irrespective of tumor stage. In explant tissue, cisplatin-resistant tumors excluded platinum ions from tumor areas in contrast to cisplatin-sensitive tumors. Intact TP53 did not predict cisplatin sensitivity, but a positive correlation was observed between cisplatin sensitivity and TP53 mutation status (P ¼ 0.003). Treatment of NSCLC explants with the targeted agent TRAIL revealed differential sensitivity with the majority of tumors resistant to single-agent or cisplatin combination therapy. Overall, our results validated a rapid, reproducible, and low-cost platform for assessing drug responses in patient tumors ex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

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Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

et al. 2017

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“…The result was equal or better than other studies on use of in vitro chemosensitivity assays in various cancers (Higashiyama et al, 2001;O'Toole et al, 2001;O'Toole et al, 2003;Yoshimasu et al, 2007). This result indicates that MTS is a preferable and convenient assay method for in vitro chemosensitivity test with malignant pleural effusion specimens from unresectable NSCLC patients.…”

Section: Discussionmentioning

confidence: 62%

Prediction of Chemotherapeutic Response in Unresectable Non-small-cell Lung Cancer (NSCLC) Patients by 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) Assay

Chen

Cheng²,

Chen³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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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)-2H-tetrazolium, 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.

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“…In addition, 8 parallel culture wells were designed to test the chemosensitivity of different parts of tumor specimen to avoid the issue of tumor heterogeneity. The efficacy rate for an individual agent using HDRA in vitro has a considerable good correlation with clinical response rate to each agent (30,31). Previous studies have reported that TS and DPD expression are correlated with fluorouracil sensitivity (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer

et al. 2017

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Abstract. Personalized chemotherapy with the use of biomarkers helps to maximize clinical efficiency. Therefore, the present study aimed to identify a potential method for identifying biomarkers in esophageal cancer. A total of 49 freshly resected tumor tissues and 72 paraffin-embedded specimens from patients with esophageal cancer were obtained. mRNA expression levels of ERCC1, BRCA1, TUBB3, FBW7, RRM1, MDM2, TS and TOP1 were measured quantitative reverse transcription polymerase chain reaction (RT-qPCR). In vitro chemosensitivity to cisplatin, docetaxel, gemcitabine, etoposide, fluorouracil and irinotecan were tested using histoculture drug response assay (HDRA). BRCA1 mRNA levels were positively correlated with resistance to cisplatin (P= 0.027) and sensitivity to docetaxel (P=0.002). TS mRNA levels were inversely correlated with fluorouracil sensitivity (P= 0.044), and TOP1 mRNA expression was positively correlated with irinotecan sensitivity (P= 0.008). In addition, high BRCA1 mRNA levels correlated with decreased median overall survival (mOS; P<0.001) and response rate (RR; P= 0.002) in cisplatin-fluorouracil chemotherapy group and also correlated with increased mOS (P<0.001) and RR (P= 0.023) in docetaxel-fluorouracil chemotherapy group. Overall, these results suggested that HDRA combined with RT-qPCR may serve as an effective method for screening biomarkers in personalized chemotherapy for esophageal cancer.

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Data acquisition for the histoculture drug response assay in lung cancer

Abstract: The histoculture drug response assay appears to be applicable to non-small cell lung cancer for the prediction of responses to chemotherapy.

Cited by 41 publications

References 16 publications

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

Prediction of Chemotherapeutic Response in Unresectable Non-small-cell Lung Cancer (NSCLC) Patients by 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) Assay

Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer

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