Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST)

Kawamura, Masafumi; Gika, Masatoshi; Abiko, Tomohiro; Inoue, Yoshimasa; Oyama, Takahiko; Izumi, Yuichi; Kobayashi, Hisayuki; Kobayashi, Koichi

doi:10.1007/s00280-006-0292-8

Cited by 43 publications

(33 citation statements)

References 6 publications

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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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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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“…In vitro chemosensitivity was examined using the collagen gel-droplet embedded culture drug sensitivity test (CD-DST) method, as described by kobayashi et al (12,13) and kawamura et al (14), with minor modifications. Briefly, surgically resected specimens were finely minced using a scalpel and digested in cell dispersion enzyme solution Ez (Nitta Gelatin Inc.).…”

Section: Methodsmentioning

confidence: 99%

Association of ATP7A expression and in vitro sensitivity to cisplatin in non-small cell lung cancer

Inoue¹,

Matsumoto²,

Yamada³

et al. 2010

Oncology Letters

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Abstract. Expression of copper-transporting P-type adenosine triphosphatase A (ATP7A) is reportedly associated with platinum drug resistance in various types of solid tumors. However, the impact of ATP7A expression on platinum drug resistance in non-small cell lung cancer (NSCLC) has yet to be adequately elucidated. In vitro cisplatin (CDDP) sensitivity was investigated using the collagen gel-droplet embedded culture drug sensitivity test, and the ATP7A mRNA expression levels were assessed by real-time polymerase chain reaction in surgically resected specimens of NSCLC. The relationship between the ATP7A expression levels and the in vitro CDDP sensitivity was then evaluated. The ATP7A mRNA expression levels in the CDDP-resistant tumors were significantly higher than those in the CDDP-sensitive tumors (p=0.0167, Mann-Whitney U test). In conclusion, the results suggest that evaluation of ATP7A expression is useful as a marker for cisplatin chemoresistance. IntroductionCisplatin (CDDP), an anticancer drug containing platinum, is widely used in the treatment of solid tumors, such as testicular, ovarian, cervical, bladder, head and neck, and non-small cell lung cancers (NSCLC) (1). CDDP has been used as a key drug for chemotherapy against NSCLC for more than 20 years.However, the overall response rate to cisplatin used as a single agent is reported to be no more than 20% in patients with NSCLC (2). Furthermore, development of resistance to CDDP is common during treatment of NSCLC and is therefore a significant factor to be considered by clinical oncologists. Subsequently, exploration of a chemoresistance marker is crucial. The mechanisms underlying the development of CDDP resistance include decreased drug accumulation, enhanced detoxification and increased DNA repair efficiency. However, previous studies have been limited mainly to the in vitro or in vivo level. Additionally, no study has shown factors that have been validated as common contributors to clinical CDDP resistance and prognosis in NSCLC patients (1).Copper-transporting P-type adenosine triphosphatase A (ATP7A) plays a significant role in copper distribution within cells. ATP7A is expressed in the intestinal epithelium as well as in most other tissues apart from the liver (3-7). Binding of Cu to ATP7A triggers highly regulated subcellular relocalization that involves movement from the basal position in the trans-Golgi network to the plasma membrane (3,8). Defective function of ATP7A causes Menkes disease, and the pathology of Menkes disease reflects the inadequate mobilization of Cu from a number of tissues. Previous studies suggested that the copper export system also functions as an efflux transporter for platinum drugs. These studies also showed an association between ATP7A expression and resistance to platinum drugs in malignancies (9-11). However, the ATP7A expression level and its impact on CDDP resistance in NSCLC has yet to be adequately elucidated.The present study aimed to investigate the predictive value of ATP7A gene expression for the in vitr...

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“…The sensitivity rates of the patients to chemotherapeutic agents varied from 8.8% to 88.2%, and from highest to lowest was: NDP, CDDP, GEM, VNR, 5-Fu, Pemetrexed, DOC and BLM. This result demonstrates that the response of each patient to chemotherapeutic agents was different due to its heterogeneity, which has been reported by Kawamura M et al (2007). Individualized chemotherapy based on chemosensitivity test is urgently advocated in clinical practice.…”

Section: Discussionmentioning

confidence: 54%

“…The whole plate was cultured for -mean OD blank controls )/(OD control groups -OD blank controls )] ×100. The inhibition rate of 50% or more was considered as being sensitive to the individual chemotherapeutic agent in vitro (Kawamura et al, 2007;Higashiyama et al, 2010;Higashiyama et al, 2012), and the sensitivity rate of each patient to chemotherapeutic agents was calculated as follows: Sensitivity rate (%) = (number of chemosensitive cases/number of evaluated cases) ×100.…”

Section: Cell Isolation and Mts Assaymentioning

confidence: 99%

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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Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST)

Abstract: The results show that CD-DST is capable of selecting the responders and the respective optimal regimens, and also delineating the patients less likely benefit from treatment.

Cited by 43 publications

References 6 publications

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

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

Association of ATP7A expression and in vitro sensitivity to cisplatin in non-small cell lung cancer

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

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