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Biomedical subjects

Setsuko Yamauchi

Publications and source records attributed to Setsuko Yamauchi.

7 recordsLinked to original sources

A phase I/II study comparing regimen schedules of gemcitabine and docetaxel in Japanese patients with stage IIIB/IV non-small cell lung cancer.

OBJECTIVE: Gemcitabine and docetaxel are non-platinum agents with activity in non-small cell lung cancer (NSCLC). This study was conducted to determine and evaluate the recommended regimen of gemcitabine-docetaxel and evaluated its efficacy and safety in chemonaive Japanese NSCLC patients. METHODS: In phase I, patients with stage IIIB/IV NSCLC were randomized and received either gemcitabine on days 1 and 8 plus docetaxel on day 1 or gemcitabine on days 1 and 8 plus docetaxel on day 8. The recommended regimen was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Efficacy and toxicity were evaluated in all patients. RESULTS: Twenty-five patients were enrolled in phase I and six patients were given the recommended regimen; gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8. An additional 34 patients were enrolled into phase II and administered with the recommended regimen. The response rate was 32.2% [95% confidence interval (CI) 20.6-45.6%] overall and 30.0% (95% CI 16.6-46.5%) in patients with the recommended regimen (40 patients). Although grade 3 interstitial pneumonia was observed in two patients (5.0%) who received the recommended regimen, both recovered shortly after steroid treatment. No unexpected events were observed throughout this study. CONCLUSIONS: Gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8 has comparable efficacy and more tolerable toxicities than previously reported platinum-based regimens. These results should be verified by a phase III study.

Adult↗

Oblique approach of computed tomography guided needle biopsy using multiplanar reconstruction image by multidetector-row CT in lung cancer.

The purpose of this study was to establish the technique of multiplanar reconstruction (MPR) with multidetector-row (MDR) computed tomography (CT) guided needle biopsy for the diagnosis to access very difficult lesions. The CT guided percutaneous biopsy are well-established methods to obtain cytological and histological material such as the peripheral tumors in lung cancer. Occasionally, the conventional CT cannot permit planning a trajectory to avoid passage through bones, avoidance of bullae, fissures or vessels. In addition, some lesions are situated in less favorable locations such as those in the costophrenic recess or close to the mediastinum. Rarely can we diagnose them. MPR with MDR-CT has recently become widely available with applications for thoracic lesions. MPR images have been used to evaluate the location of small peripheral lung nodules to the relation of bullaes, vessels, and costophrenic recess. To diagnose these lesions, the usefulness of MPR were evaluated for an planning of an oblique approach of CT guided needle biopsy. MPR images were reconstructed as a line from the needle entry point to the target lesion. The first oblique image applied as the direction of posterior-anterior and cranio-caudal axis, and the second oblique image applied as the direction of posterior-anterior and left-right. Eleven out of 151 patients were required MPR technique to allow possible access to target, because of avoidance of bone and fissures in the needle pass or located in the costophrenic recess, between April 2001 and December 2002. The 5/11 patients were at the upper site (segment 1, 2 and 6) behind the scapula and ribs, 3/11 patients were at the lower lobe (segment 10) in the costophrenic recess, and 3/11 were middle lobe or segment 3 covered by the ribs and fissures. All the lesions except one were histologically diagnosed. Five patients were adenocarcinoma, and the other five patients were benign tumors. Pneumothorax occurred in one patient before we obtained the specimens. MPR guided needle biopsy with oblique approach was thought to be useful for diagnosis of very difficult thoracic lesions and would obviate an unnecessary surgical thoracoscopy.

Aged↗

Expression of epidermal growth factor receptor (EGFR) and downstream-activated peptides in surgically excised non-small-cell lung cancer (NSCLC).

Extracellular signal-regulated kinases (ERKs), Akt, and signal transducer and activator of transcription 3 (STAT3) are on signal transduction pathways triggered by epidermal growth factor receptor (EGFR). The purpose of this study was to evaluate the expressions of these peptides and to correlate the level of EGFR expression with downstream-activated peptide expression in non-small-cell lung cancer (NSCLC). A total of 60 specimens were studied by immunohistochemistry. EGFR overexpression was detected in 78% of specimens, but no significant relationship was found between it and any clinicopathological factors investigated. Phosphorylated (p)-ERK, p-Akt, and p-STAT3 expressions were observed in 28, 53, and 58% of specimens, respectively, and p-Akt and p-STAT3 expressions were correlated with well-differentiated tumor (P=0.045 and 0.014, respectively). Half of the 60 specimens expressed two or three downstream-activated peptides. The level of EGFR expression was associated with expressions of p-ERK and p-Akt (P=0.045 and 0.020, respectively). In a preliminary analysis, no peptides examined had an impact on relapse-free survival. In summary, various signal transduction pathways appeared frequently to participate in NSCLC, and the level of EGFR expression appeared to correlate with those of activated ERK and Akt, suggesting some role of receptor overexpression in more potent downstream activation.

Adenocarcinoma↗

Additive effects of amrubicin with cisplatin on human lung cancer cell lines.

Amrubicin (AMR) is a novel, completely synthetic 9-aminoanthracycline derivative. Amrubicinol, the C-13 alcohol metabolite of AMR, inhibits purified human topoisomerase II (topo II). We examined the effect of the combination of cisplatin (CDDP) and amrubicinol in vitro using a small cell lung cancer cell line (SBC-3) and an adenocarcinoma cell line (Ma-1), by WST-1 assay and isobologram analysis. When the two drugs were used together either simultaneously or sequentially, their combined effects were additive. A high concentration of CDDP (300 microM) enhanced the topo II inhibitory activity of amrubicinol as determined by kinetoplast-DNA decatenation assay. On the other hand, amrubicinol increased formation of DNA interstrand cross-links (ICL) in the cells, as determined using ethidium bromide fluorescence binding assay (EBFA), for simultaneous exposure to CDDP (0-300 microM) and amrubicinol (2 microM) compared with CDDP alone. These biological interactions might result in additive interaction between amrubicinol and CDDP.

Anthracyclines↗

The association of adenocarcinoma and hemosputum in pulmonary malignancies.

BACKGROUND: Hemosputum was considered one of the popular symptoms of patients with centrally located carcinoma of the lung, especially squamous cell or small cell type. Recent studies reported a relative increase in adenocarcinoma compared with squamous cell carcinoma, especially in developed countries. OBJECTIVES: The main purpose of this study was to determine the trend of histological type associated with the occurrence of hemosputum in patients with pulmonary malignancy. METHODS: Retrospectively, the data from 1,050 patients with pulmonary malignancy who underwent bronchoendoscopic examination at our institution between May 1993 and May 2000 were analyzed. RESULTS: One hundred and forty-nine out of 1,050 patients had hemosputum. There were 66 patients with adenocarcinoma, 55 with squamous cell carcinoma, 15 with small cell carcinoma, 5 with large cell carcinoma, 3 with other cell type carcinoma and 5 with metastatic carcinoma. On bronchoendoscopic examination, abnormal findings in the segmental or more proximal bronchi were found in 82 patients, including 36 with squamous cell carcinoma, 31 with adenocarcinoma, 12 with small cell carcinoma, 2 with large cell carcinoma and 1 with metastatic carcinoma. On the other hand, 67 patients were diagnosed with pulmonary malignancy in the subsegmental or more distal area, including 35 with adenocarcinoma, 19 with squamous cell carcinoma, 3 with small cell carcinoma, 3 with large cell carcinoma, 3 with other cell type carcinoma and 4 with metastatic carcinoma. CONCLUSIONS: The most frequent histological type of malignancy with hemosputum was adenocarcinoma. The number of abnormalities in the peripheral region with hemosputum showed a progressive increase. The number of adenocarcinoma with hemosputum was increased in both central and peripheral regions.

Adult↗

Activated Akt expression has significant correlation with EGFR and TGF-alpha expressions in stage I NSCLC.

BACKGROUND: In vitro studies have indicated that epidermal growth factor receptor (EGFR) may intensify signaling output by the receptor's overexpression, heterodimerization with HER-2, or autocrine expression of ligands. The purpose of the present study was to evaluate the correlation between EGFR and its related proteins and to explore the prognostic value of the proteins. MATERIALS AND METHODS: Immunohistochemical staining of transforming growth factor alpha (TGF-alpha), EGFR, HER-2, and phosphorylated (p-)Akt was performed in specimens surgically excised from 91 consecutive patients with p-stage I non-small cell lung cancer (NSCLC). Expression or coexpression of TGF-alpha and the receptors were related to expression of p-Akt. The prognostic impact of these peptides was also tested. RESULTS: TGF-alpha, EGFR and HER-2 overexpressions were detected in 32%, 79% and 13% of tumors, respectively. Coexpressions of TGF-alpha & EGFR and EGFR & HER-2 were observed in 29% and 11% of tumors, respectively. P-Akt expression was found in 73% of tumors. Significant correlations between EGFR TGF-alpha or coexpression of TGF-alpha & EGFR and p-Akt expression were found (p=0.006, 0.008 and 0.010, respectively). No proteins examined had an impact on relapse-free survival. CONCLUSION: The Akt pathway is frequently involved in NSCLC and overexpression of EGFR and autocrine expression of TGF-alpha may increase the potency of Akt activation.

Carcinoma, Non-Small-Cell Lung↗