Establishment of patient-like SCID mouse model by orthotopically implanting primary cultured cells from surgically-resected lung cancer tissues

Fujino, Haruhiko; Kondo, Kazuya; Miyoshi, Takanori; Ishikura, Hisashi; Takahashi, Yûji; Sawada, Naruhiko; Hirose, Yukiko; Takizawa, Hiromitsu; Nagao, Taeko; Shoji, Shuichi; Monden, Yasumasa

doi:10.3892/or.10.6.1709

Cited by 7 publications

(8 citation statements)

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“…The success rate of implantation was 50-75% in the 4 cell lines used in the present study. The implantation rate in this study was slightly lower than that in previous studies using the lung cancer cell lines Ma44-3, A549, Ma-11, FT and FM (70-90%) (10)(11)(12). We performed implantation using the cell lines Lu130, LC6 and Lu99 for the first time in this study.…”

Section: Discussionmentioning

confidence: 70%

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array

Matsuoka

Kondo

Takizawa

et al. 2014

International Journal of Oncology

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S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.

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Section: Discussionmentioning

confidence: 70%

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array

Matsuoka

Kondo

Takizawa

et al. 2014

International Journal of Oncology

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“…We used three types of NSCLC cell lines in the present study: A549 (human adenocarcinoma lung cancer cells), FT821 (human large cell lung cancer cells) and PC-9 (human adenocarcinoma cells). We established the FT821 cell line using a primary culture of surgically resected tissue provided by Dr Haruhiko Fujino (Tokushima University, Tokushima, Japan) (13). A549 (JCRB0076) cells were purchased from the Health Science Research Resources Bank (Osaka, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Considerable efforts have focused on developing clinically relevant models using orthotopic tumor implantation. We established an orthotopically implanted lung cancer model in SCID mice without thoracotomy (10)(11)(12)(13)(14)(15). We previously reported an animal model that consisted of the orthotopic implantation of lung cancer cell lines and showed a high frequency of lymphatic metastasis.…”

Section: Introductionmentioning

confidence: 99%

Non‑invasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDG‑PET/CT and CT

et al. 2018

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We established patient-like models of lung cancer metastasis by orthotopically implanting human non-small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small-animal computed tomography (CT) and positron-emission tomography-computed tomography (PET/CT) in these models to non-invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non-small cell lung cancer cell lines, A549, FT821 and PC-9, into SCID mice. These mice were then divided into three groups: Control, cis-diamminedichloroplatinum (II) (CDDP) (7-mg/kg CDDP, single administration intraperitoneally), and erlotinib (25 mg/kg erlotinib/day, oral administration 5 days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC-9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18 FDG-PET/CT and CT imaging non-invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.

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“…Even orthotopic models may differ in important tumor-stromal interactions and pharmacokinetic characteristics, depending on whether the tumors propagate in the lumen or on the airway epithelial surface of the lung. Most orthotopic NSCLC models use pleural injection (30,(37)(38)(39)(40)(41)(42)(43), which may be most relevant to locally invasive or metastatic disease in the lung. Other investigators, however, have used techniques similar to ours to implant tumors in the lung via tracheotomy (29,31,44,45).…”

Section: Discussionmentioning

confidence: 99%

Antitumor Activity of Hydrophilic Paclitaxel Copolymer Prodrug Using Locoregional Delivery in Human Orthotopic Non–Small Cell Lung Cancer Xenograft Models

Zou

Ghosh

et al. 2004

Clinical Cancer Research

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Paclitaxel (Taxol) has demonstrated clinical activity in non-small-cell lung cancer (NSCLC), but its use has not led to marked improvements in survival. This ineffectiveness can in part be attributed to inadequate delivery of effective drug levels to the lung via systemic administration and to drug resistance mechanisms. Locoregional drug administration and the use of drug copolymers are possible approaches to address these issues. In this study, we evaluated the activity of a poly(L-glutamic acid)-paclitaxel (PGA-TXL) formulation administered by intratracheal injection to mice bearing orthotopic human NSCLC tumors (H460, H358). H460 cells were found to be sensitive to paclitaxel and PGA-TXL in vitro, in a time-and concentration-dependent manner. In preliminary acute toxicity studies, PGA-TXL administered by intratracheal injection was found to be much less toxic than paclitaxel, as anticipated. Mice into which H460 cells had been implanted by intratracheal injection were given single-dose intratracheal treatments with paclitaxel (1.2 or 2.4 mg/kg) or with PGA-TXL (15 mg/kg, paclitaxel equivalents) 1 week later. When the mice were sacrificed at up to 65 days after tumor implantation, they were evaluated grossly for tumor at bronchial, neck, and lung sites. Control mice had tumors in 60% of all three sites, and all of the control mice had tumors in at least one site. The low-and high-dose Taxol groups had fewer incidences at these three sites (27-33%) and 60 -80% of these mice had tumors in at least one site. The PGA-TXL mice displayed a low (13%) incidence at these sites, and only 40% had detectable tumors. In a subsequent survival study with the intratracheal H358 model, control mice had a mean life span of 95 days, whereas both the intratracheal Taxol (2.5 mg/kg, every 7th day for three doses) and the intratracheal PGA-TXL (20 mg/kg, paclitaxel equivalents, every 7th day for three doses) groups had improved survival (mean life spans: 133.5 and 136.5 days, respectively). In pilot studies intended to compare the feasibility of the development of paclitaxel aerosols suitable for clinical application, based either on Cremophor solutions or on PGA backbones, only the latter gave acceptable particle size distributions and flow rates. These results encourage the development and application of Cremophor-free copolymer formulations of paclitaxel for locoregional treatment (e.g., as aerosol) of endobronchial malignant diseases.

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Establishment of patient-like SCID mouse model by orthotopically implanting primary cultured cells from surgically-resected lung cancer tissues

Cited by 7 publications

References 0 publications

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array

Non‑invasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDG‑PET/CT and CT

Antitumor Activity of Hydrophilic Paclitaxel Copolymer Prodrug Using Locoregional Delivery in Human Orthotopic Non–Small Cell Lung Cancer Xenograft Models

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