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

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.

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

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.

Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [¹⁸F] FDG PET-CT.

Positron emission tomography-computed tomography (PET-CT) with [18F] fluorodeoxyglucose (FDG) has recently been applied for evaluating tumor response to anticancer therapy. The aim of the present study was to evaluate the utility of FDG PET-CT in monitoring non-invasively and repeatedly the inhibitory effect of cisplatin (CDDP) on an orthotopic lung cancer model. Validation of in vivo FDG uptake in human lung cancer Ma44-3 cell line in an orthotopic SCID mouse model was carried out.

Aberrant methylation of tumour-related genes in thymic epithelial tumours.

Background: Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma.

Methods: We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features.

Photodynamic therapy using a second generation photosensitizer, Talaporfin.

Background: Photodynamic therapy (PDT) using Talaporfin is an attractive treatment for central-type early lung cancer. It was noted that some patients had altered levels of arterial oxygen saturation as indicated by pulse oximeter (SpO2) and arterial oxygen saturation levels in blood gas analysis (SaO2) during PDT. The present experiments were designed to provide an explanation for these findings.

Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase expression in tumor tissue, regarding the efficacy of postoperatively administered UFT (tegafur+uracil) in patients with non-small cell lung cancer.

Background: UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined.

Patients And Methods: Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery.

Fluoroscopy-assisted thoracoscopic resection of pulmonary nodules after computed tomography--guided bronchoscopic metallic coil marking.

Objective: To localize small and deeply situated pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, we developed a marking procedure that uses a metallic coil.

Methods: Nine patients underwent video-assisted thoracoscopic surgery for the removal of 11 pulmonary lesions. Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic metallic coil marking was performed with an ultrathin bronchoscope, with simulation by means of virtual bronchoscopy.

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.

Objective: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat.

Methods: Fifteen male, bred, 12-week-old Jcl-Wister rats were used.

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer.

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line.

Thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung cancer: relationship between mRNA expression and activity.

Background: UFT (Tegafur + Uracil) has been reported to be effective for postoperative adjuvant chemotherapy of non-small cell lung cancer (NSCLC) in a randomized prospective study. Recently, many clinical studies have demonstrated that UFT is effective for cancer with a low activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In the present study, we investigated TS and DPD activity in resected tumors and corresponding normal lungs and the relationship between the activity and the mRNA expression of TS and DPD in NSCLC.

Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects.

To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans.

Green fluorescent protein expression and visualization of mediastinal lymph node metastasis of human lung cancer cell line using orthotopic implantation.

Background: Suppression of lymphatic metastasis improves survival in lung cancer patients. We have reported a patient-like model of lung cancer metastasis based on orthotopic implantation in severe combined immunodeficiency (SCID) mice and demonstrated the lymphogenous spread histologically using human NSCLC cell lines.

Materials And Methods: To visualize micrometastases, we transfected the Aequorea Victoria jellyfish green fluorescent protein (GFP) gene to the cancer cell line.

Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors.

Background: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma.

Methods: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital.

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

In our previous studies, we established a lymphogenous metastatic SCID mouse model using orthotopic implantation of human lung cancer cell lines. However, the lymphogenous metastatic potential of each cell line in our models does not reflect that of a primary tumor. In this study, we made orthotopic implanted models using primary cultured cells from surgically-resected lung cancer tissues.

Frequent microsatellite instability in lung cancer from chromate-exposed workers.

Although chromium has been the most extensively investigated metal with respect to mutagenicity and carcinogenicity, its genetic effects in humans are only partly understood. Our previous study demonstrated that lung cancer from chromate-exposed workers infrequently (20%) displayed p53 gene mutations as well as a particular mutation pattern. In the present study, we examined the replication error (RER) and loss of heterozygosity (LOH) in 38 lung cancers from 28 chromate-exposed workers (chromate lung cancer group) and in 26 lung cancer patients without chromate exposure (non-chromate lung cancer group), using six microsatellite markers containing CA repeats: D3S647 (3p23), D3S966 (3p21.