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Biomedical subjects

Masashi Handa

Publications and source records attributed to Masashi Handa.

11 recordsLinked to original sources
PubMed2005

Estrogen inhibits cell proliferation through in situ production in human thymoma.

PURPOSE: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. EXPERIMENTAL DESIGN: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. RESULTS: E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. CONCLUSIONS: E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Progesterone receptor in non-small cell lung cancer--a potent prognostic factor and possible target for endocrine therapy.

A possible involvement of gender-dependent factors has been postulated in development of human non-small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptor-positive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumor-node-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptor-positive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptor-positive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dose-dependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptor-positive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor-positive NSCLC patients.

Adult↗
PubMed2005

Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism.

Heme oxygenase-1 (HO-1) acts in cytoprotection against oxidants and aromatic hydrocarbons in cigarette smoke. A (GT)(n) dinucleotide repeat in the 5'-flanking region of the human HO-1 gene (alias HMOX1) reduces HO-1 inducibility and shows length polymorphism, which is grouped into three classes: class S (<27 GT), class M (27-32 GT), and class L (>/=33 GT) alleles. To investigate the correlation between the HO-1 gene polymorphism and the development of lung adenocarcinoma, we screened 151 Japanese patients with lung adenocarcinoma and 153 control subjects. Patients and control subjects were frequency-matched by age, gender, smoking history and proportion of chronic pulmonary emphysema. The proportion of class L allele frequencies, as well as that of genotypic frequencies in L allele carriers (LL, LM, and LS), were significantly higher in patients with lung adenocarcinoma than those of control subjects. The adjusted odds ratio (OR) for lung adenocarcinoma with class L allele vs non-L allele (M+S) was 1.6 [95% confidence interval (CI) 1.0-2.5, P=0.03] and that with L allele carriers vs. non-L allele carriers was 1.8 (95% CI 1.1-3.0, P=0.02). Furthermore, the risk of lung adenocaricinoma for L allele carriers versus non-L allele carriers was much increased in the group of male smokers (OR=3.3, 95% CI 1.5-7.4, P=0.004). However, in the female non-smokers, the proportion of L allele carriers did not differ between patients and control subjects (OR=0.93, 95% CI 0.4-2.0, P=0.85). These findings suggest that the large size of a (GT)(n) repeat in the HO-1 gene promoter may be associated with the development of lung adenocarcinoma in Japanese male smokers.

5' Flanking Region↗
PubMed2003

A rare case of a pulmonary granular cell tumor presenting as a coin lesion.

A 38-year-old man was found to show a well-defined oval-shaped homogeneous dense mass (20 x 30 mm) in the left upper lung field on chest X-ray. Left upper divisionectomy was performed under video-assisted thoracic surgery. Histology showed that the tumor cells had abundant eosinophilic granular cytoplasm, and were immunopositive for neuron-specific enolase, CD56, S-100 protein, and chromogranin. The proportion of Ki-67 positive cells was < 1%. An electron-microscopic examination showed many membrane-bound whorls in the cytoplasm. Although this was a very rare case presenting as an asymptomatic coin lesion, the histological features were the same as those demonstrated for granular cell tumor at common sites.

Adult↗
PubMed2003

Primary intrapulmonary thymoma successfully resected with vascular reconstruction.

Primary intrapulmonary thymomas are defined as intrapulmonary tumors without an associated mediastinal component and are very rare. We report a resected case of primary intrapulmonary thymoma with dissection of mediastinal lymph nodes and vascular reconstruction. Because the tumor directly invaded the right brachiocephalic vein, the vein was reconstructed with a graft, and then adjuvant radiation was performed postoperatively. The tumor was diagnosed as a lymphocyte dominant thymoma and B2 type thymoma in the WHO classification. There has been no evidence of recurrence in 6 years. Complete resection of the tumor with vascular reconstruction and adjuvant radiation should be considered in invasive intrapulmonary thymoma.

Biopsy, Needle↗
PubMed2003

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

OBJECTIVE: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS: The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Sex steroid hormone receptors in human thymoma.

In this study we examined the immunohistochemical localization of sex steroid receptors for estrogen alpha (ER alpha) and ER beta, progesterone-A (PR-A) and PR-B, and androgen (AR) in human thymoma (n = 132) and correlated these findings with various clinicopathological parameters. We used RT-PCR and real-time PCR to further study the expression of these receptors in 20 thymoma cases. Immunoreactivity for all sex steroid receptors was detected in the nuclei of thymoma epithelial cells. The percentage of immunopositive cases and the H-score values for each receptor (mean +/- SD) were: ER alpha, 66% and 85.8 +/- 80.2; ER beta, 7% and 7.2 +/- 8.7; PR-A, 4% and 2.7 +/- 4.9; PR-B, 49% and 55.8 +/- 68.3; and AR, 15% and 14.1 +/- 11.7, respectively. The results of real-time PCR were consistent with those of immunohistochemistry, especially results for ER alpha, PR-B, and AR. A significant positive correlation was detected between immunoreactivity for ER alpha and PR-B. ER alpha immunoreactivity was inversely correlated with tumor size, clinical stage, WHO classification, and Ki-67 labeling index. In addition, the status of ER alpha immunoreactivity was significantly associated with a better clinical outcome in thymoma patients. Results from our study suggest that estrogens may inhibit thymoma growth via ER alpha, and that ER alpha immunoreactivity may act as a prognostic factor in human thymoma.

Adult↗
PubMed2002

A prospective trial of systematic nodal dissection for lung cancer by video-assisted thoracic surgery: can it be perfect?

BACKGROUND: There have been no reports evaluating the completeness of systematic nodal dissection with video-assisted thoracic surgery (VATS). In order to elucidate the completeness of the dissection, we have conducted a prospective trial with patients having primary lung cancer. METHODS: Patients with clinical stage I lung cancer were the candidates for this study. Thoracotomy was performed with a small skin incision of 7 cm to 8 cm in length. Through these small wounds and two trocars, pulmonary resection was performed and then hilar and mediastinal lymph nodes were dissected. After that, a standard thoracotomy was carried out by another surgeon to complete systematic nodal dissection. RESULTS: Video-assisted thoracic surgery lobectomy with lymph node dissection was accomplished in 17 right lung cancer patients and 12 left lung cancer patients. On the right side, the average numbers of resected lymph nodes by VATS and remnant lymph nodes were 40.3 and 1.2, respectively. The average weights of dissected tissues by VATS and remnant tissues were 10.0 g and 0.2 g, respectively. On the left side, there were 37.1 and 1.2 lymph nodes and 8.3 g and 0.2 g of weight of dissected tissues. No nodal involvement was observed in the remnant lymph nodes. CONCLUSIONS: The lymph node dissection with VATS was technically feasible and the remnant ("missed" by VATS) lymph nodes and tissues were 2% to 3%, which seems acceptable for clinical stage I lung cancer.

Adult↗
PubMed2002

Retinoid receptors in the developing human lung.

Nuclear receptors and their ligands are known to play very important roles in lung development. Among these receptors, retinoid receptors, members of the steroid/thyroid hormone receptor superfamily, are classified into retinoic acid receptor (RAR) isoforms alpha, beta, and gamma and retinoid X receptor (RXR) isoforms alpha, beta, and gamma. In addition, isoforms I and II of the orphan receptor chicken ovalbumin upstream promoter-transcription factor (COUP-TF) have been shown to negatively regulate the activation of retinoid receptors. Both of these receptors have been shown to regulate lung development in the mouse. In the present study we utilized immunohistochemistry and real-time quantitative PCR to examine the expression of RAR-alpha, -beta and -gamma, RXR-alpha, -beta and -gamma and COUP-TFII in the human fetal lung at 13-16 gestational weeks, a very critical stage of human pulmonary development, in order to study possible roles in pulmonary morphogenesis by comparing these findings with those of the adult lung. RXR-gamma immunoreactivity was detected at both proximal (epithelia and mesenchyme of the trachea and bronchi associated with cartilage) and distal (epithelia and mesenchyme of smaller distal bronchi) sites in the fetal lung, but was markedly weaker in the adult lung. RAR-beta immunoreactivity was detected in distal mesenchymal cells of the fetal lung, but was not discernible in distal mesenchymal cells in the adult lung (bronchioles, alveolar ducts and alveolus). Relatively intense RAR-gamma immunoreactivity was detected in the chondrocytes of bronchial cells. COUP-TFII immunoreactivity was detected with a similar pattern to that of RAR-beta. Real-time quantitative PCR analyses revealed that mRNA levels of RXR-gamma at proximal and distal sites (ratio of fetal lung/adult lung: 3.4+/-0.05-fold and 3.1+/-0.03-fold respectively; P <0.01), RAR-beta at distal sites (2.4+/-0.01-fold; P <0.05) and RAR-gamma at proximal sites (2.2+/-0.11-fold; P <0.05) were significantly higher in the fetus than in the adult.

Adult↗
PubMed2002

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma. METHODS: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%). Clinical factors and prognoses of the 2 groups were analyzed. RESULTS: There were 58 patients with the solid-type tumor image and 85 patients with the faint density-type tumor image. The number of patients with tumor size of less than 20 mm in the faint density-type tumor group (n = 30) was significantly higher than that in the solid-type tumor group (n = 8, P =.008). The 5-year survival of patients with faint density-type tumors was 74.1%, whereas that in patients with solid-type tumors was 54.2% (P =.013). Furthermore, the survival curve of patients with the solid-type computed tomographic image combined with ground-glass opacity was similar to that of patients with the faint density-type image. Multivariate analysis revealed the prognostic influence of the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image on survival (P =.029, relative risk = 0.48) and showed to be of second highest influence after the N factor. CONCLUSIONS: It is suggested that the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor in patients with small peripheral lung adenocarcinoma.

Adenocarcinoma↗