Biomedical subjects

Masataka Onizuka

Publications and source records attributed to Masataka Onizuka.

16 recordsLinked to original sources

PubMed2006

Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma.

BACKGROUND: The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS: The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS: The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index > or = 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS: TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.

Aged↗

PubMed2006

Effectiveness of steroid treatment for hoarseness caused by idiopathic fibrosing mediastinitis: report of a case.

A 65-year-old woman was referred to our department for investigation and treatment of hoarseness. A chest computed tomography (CT) scan showed a mediastinal mass spreading into the aortopulmonary window. This finding and that of flexible laryngoscopy suggested that the hoarseness was being caused by left recurrent nerve involvement resulting in left vocal cord paralysis. Thus, we performed a mediastinoscopic biopsy via a parasternal incision. Pathological examination revealed dense fibrous tissue infiltrated with varied inflammatory cells. Because no etiological pathogen or neoplastic lesion was identified, we diagnosed idiopathic fibrosing mediastinitis and began treating the patient with prednisolone. After a course of treatment, the mediastinal lesion showed a remarkable response. The hoarseness resolved as the lesion became smaller. Laryngoscopy confirmed recuperation of vocal cord function. This report shows that steroid therapy is a treatment option for hoarseness caused by recurrent laryngeal nerve involvement of fibrosing mediastinitis, if administered under close observation.

Aged↗

PubMed2006

Excision after chemoradiotherapy of invasive thymoma extending into the right atrium: report of a case.

We report a case of invasive thymoma with intracardiac extension, resulting from the progression of intracaval growth, in a 56-year-old woman. Initially, the patient received two courses of chemotherapy, but the tumor showed only a modest response; however, subsequent radiotherapy reduced the tumor size further and the intracardiac lesion disappeared, making it possible to excise the tumor without cardiopulmonary bypass. Thus, when a thymoma does not respond well, we recommend radiotherapy as another treatment option, because its effects may allow for less invasive and more complete tumor excision.

Combined Modality Therapy↗

PubMed2006

Carcinomatous meningitis from non-small-cell lung cancer responding to gefitinib.

The prognosis for carcinomatous meningitis remains poor, and focal neurological dysfunctions usually do not improve despite the available treatment options. We report a case of carcinomatous meningitis from non-small-cell lung cancer treated with gefitinib, which brought about a sustained clinical response. A 40-year-old Japanese man was diagnosed with adenocarcinoma in the right lower lobe of the lung, and with multiple pulmonary and brain metastases. Six courses of carboplatin and paclitaxel chemotherapy and gamma-knife radiosurgery induced a near complete response in all lesions. However, 2 months later, cauda equina syndrome and left oculomotor paralysis from carcinomatous meningitis developed rapidly. Magnetic resonance imaging of the brain and spinal cord revealed the enhancement of leptomeningeal disseminations. The patient was treated with 250 mg/day gefitinib. All his neurological symptomatology disappeared within 2 weeks. The shrinkage of the leptomeningeal disseminations was confirmed by follow-up magnetic resonance imaging. The patient is currently doing well and is able to work. Cancer relapse was not observed at 4 months after the initiation of gefitinib. Although the survival benefit is controversial, gefitinib may have a role in the treatment of carcinomatous meningitis from non-small-cell lung cancer to improve neurological dysfunctions.

Adult↗

PubMed2005

Promoter methylation of DAL-1/4.1B predicts poor prognosis in non-small cell lung cancer.

PURPOSE: DAL-1/4.1B is an actin-binding protein originally identified as a molecule whose expression is down-regulated in lung adenocarcinoma. We have previously shown that a lung tumor suppressor, TSLC1, associates with DAL-1, suggesting that both proteins act in the same cascade. The purpose of this study is to understand the molecular mechanisms and clinical significance of DAL-1 inactivation in lung cancer. EXPERIMENTAL DESIGN: We studied aberration of the DAL-1 in 103 primary non-small cell lung cancers (NSCLC) and 18 lung cancer cells. Expression and allelic and methylation status of DAL-1 was examined by reverse transcription-PCR, microsatellite analysis, and bisulfite sequencing or bisulfite single-strand conformational polymorphism, respectively. RESULTS: Loss of DAL-1 expression was strongly correlated with promoter methylation in lung cancer cells, whereas DAL-1 expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine. The DAL-1 promoter was methylated in 59 (57%) primary NSCLC tumors, 37% of which were associated with loss of heterozygosity around the DAL-1 on chromosomal region 18p11.3. In squamous cell carcinomas, DAL-1 methylation was observed in 9 of 10 tumors at stage I, whereas the incidence of methylation gradually increased in adenocarcinomas as they progressed [13 of 36 (36%), 4 of 12 (33%), 14 of 17 (82%), and 3 of 3 (100%) tumors at stages I, II, III, and IV, respectively; P = 0.0026]. Furthermore, in adenocarcinomas, disease-free survival and overall survival were significantly shorter in patients with tumors harboring the methylated DAL-1 (P = 0.0011 and P = 0.045, respectively). CONCLUSIONS: DAL-1 methylation is involved in the development and progression of NSCLC and provides an indicator for poor prognosis.

Aged↗

PubMed2005

Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis.

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.

Adenocarcinoma↗

PubMed2005

Primary chondrosarcoma of the lung recognized as a long-standing solitary nodule prior to resection.

As the use of computed tomography (CT) increases, incidental lung nodules have become a clinical issue that is being addressed more than before. We detected a solitary lung nodule which was smooth-margined, round-shaped, 11 mm in size. Follow-up for 18 months after initial detection by chest CT did not show any interval change. To make a definitive diagnosis, video-assisted thoracic surgery was performed and the lesion was diagnosed as myxoid chondrosarcoma. In the 6-year postoperative follow-up, annual chest CT and bone scintigram did not reveal any abnormality, which excludes the possibility of a latent primary site other than the lung. Therefore, we considered the present case being of pulmonary origin. Accordingly, even though the lesion appeared unremarkable, surgical resection of solitary lung nodule should not be discouraged.

Adult↗

PubMed2005

A direct measurement of serum amylase levels produced by lung cancer.

The production of amylase by lung cancer has been previously diagnosed pathologically or immunohistochemically, or it has been confirmed by a decrease in serum levels after resection. It is possible to directly probe the continuous production of amylase by collecting samples from the inflow and outflow vessels of lung cancer. We herein describe an intraoperative measurement in which the amylase level in the pulmonary lobar vein was 3 times greater than that in the superior vena cava which was 6 times greater than the normal range. The venous level of amylase returned to a normal range after resection.

Amylases↗

PubMed2005

Diffuse pulmonary hamartoma: a case report.

Pulmonary hamartoma usually occurs as a benign, well-circumscribed single nodule in the lung parenchyma. We report on a unique case of hamartoma that extended along the bronchial tree, formed endobronchial polypoid lesions, and expanded into the lung parenchyma. The patient, a 48-year-old man, was admitted with dyspnea and chest pain. A transbronchial biopsy was performed on a tumorous lesion that was diagnosed histologically as a hamartoma. As this lesion was found to be growing diffusely along the bronchial tree, a left pneumonectomy was performed. Gross examination showed that yellowish soft tissue had surrounded the bronchial tree and extended into the lung parenchyma. Histologically, the lesion contained mainly mature adipose tissue, cartilage, and muscle tissue with a minor component of short spindle cells in a myxomatous matrix. The patient was diagnosed as having diffuse pulmonary hamartoma.

Cell Nucleus↗

PubMed2004

Effect of relocating to areas of reduced atmospheric particulate matter levels on the human circulating leukocyte count.

A high level of atmospheric particulate matter induces an increase in circulating polymorphonuclear leukocyte (PMN) counts and an increase in serum inflammatory cytokine levels. The particulate level in Antarctica is extremely low compared with that in industrial countries. We hypothesized that this low level would reduce circulating leukocyte counts and serum inflammatory cytokine levels in people visiting Antarctica from industrial countries. The number density of particulates with aerodynamic diameters of <10.0 microm was measured in Japan and in Antarctica during the 41st Japanese Antarctic Research Expedition. Circulating leukocyte counts, granulocyte colony-stimulating factor and interleukin-6 levels, and pulmonary function were determined at regular intervals in 39 expedition members. The particulate number density was <1% of that measured in Japan. Total leukocytes, segmented and band-formed PMN, monocyte counts, and serum interleukin-6 levels decreased in Antarctica compared with the initial values measured in Japan. Pulmonary function parameters did not change except for maximal voluntary ventilation. Particulate matter levels had more significant effects on segmented PMN, band-formed PMN, and monocyte counts than cigarette smoking and the type of work. Exposure to reduced atmospheric particulates is considered to be a major factor for decreasing circulating leukocyte counts and serum cytokine levels.

Adult↗

PubMed2004

MMP-2 activation and stepwise progression of pulmonary adenocarcinoma: analysis of MMP-2 and MMP-9 with gelatin zymography.

Small pulmonary adenocarcinomas can be classified on the basis of their histological characteristics and prognosis, and when classified as such, the prognosis of replacing-type adenocarcinoma with active fibroblast proliferation is significantly worse than adenocarcinoma without fibroblast proliferation. In order to clarify the biological mechanisms of the key to the morphological changes associated with active fibroblast proliferation, we examined the activities of matrix metalloproteinase (MMP)-2 and MMP-9, which are important enzymes in the stromal invasion by cancers. The active MMP-2 and MMP-9 content of 40 pulmonary adenocarcinomas that were less than 20 mm in diameter was measured by the gelatin zymography method. The quantity of active MMP-2 in the pulmonary adenocarcinomas with active fibroblast proliferation was higher than in the pulmonary adenocarcinomas without proliferation (P < 0.001), but there were no correlations between the histological features and the activation of MMP-9. The presence of active fibroblast proliferation in small pulmonary adenocarcinomas suggests that the cancer cells have acquired the ability to invade through the action of active MMP-2, and this is thought to be one of the reasons for the worse prognosis of pulmonary adenocarcinoma with active fibroblast proliferation.

Adenocarcinoma↗

PubMed2003

Pulmonary adenocarcinoma with massive lymphocyte infiltration: report of three cases.

We report on three cases of pulmonary adenocarcinoma with lymphoid stroma. In these cases the lesions were small pulmonary adenocarcinomas, less than 2 cm in diameter, and histologically diagnosed as poorly or moderately differentiated adenocarcinomas. Histologically, the tumors were characterized by a small number of cancer cells and numerous infiltrating lymphoid cells, especially CD8 positive T-cell lymphocytes. No Epstein-Barr virus (EBV) genomes were demonstrated by in situ hybridization in the tumor cells of any of the tumors. Lobectomy and regional lymph node dissection were performed and intrapulmonary and mediastinal lymph node metastases were demonstrated in one of these cases (pT4N0M0, pT1N2M0 and pT1N0M0). Two patients are alive and the other died of pneumonia 26 months after the operation. None of the patients experienced recurrence of carcinoma. This unique type of adenocarcinoma characterized by massive lymphocyte infiltration could be referred to as "pulmonary adenocarcinoma with lymphoid stroma".

Adenocarcinoma↗

PubMed2003

Phosphodiesterase type 4 inhibition of activated polymorphonuclear leukocytes in a simulated extracorporeal circulation model.

OBJECTIVES: Cardiopulmonary bypass is associated with a systemic inflammatory response syndrome and the risk of multiorgan injuries mediated by activated polymorphonuclear leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in polymorphonuclear leukocytes and plays a key role in the regulation of polymorphonuclear leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the functional changes of polymorphonuclear leukocytes by using simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with and without 10 micro mol/L rolipram. F-actin content and L-selectin and CD11b expression of polymorphonuclear leukocytes were measured by means of flow cytometry. Polymorphonuclear leukocyte deformability was evaluated with a microchannel array flow analyzer that had a similar diameter as the capillaries. Polymorphonuclear leukocyte elastase was measured with an enzyme immunoassay. RESULTS: Rolipram reduced the increase of F-actin content of polymorphonuclear leukocytes and the increase of transit time of 100 micro L of blood sample through a microchannel. Rolipram reduced the increase of CD11b expression and the decrease of L-selectin expression of polymorphonuclear leukocytes. Rolipram reduced the release of elastase from polymorphonuclear leukocytes. CONCLUSION: Rolipram inhibited the deformability change mediated by F-actin assembly, the changes in adhesion molecules, and the release of elastase from activated polymorphonuclear leukocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be a feasible therapeutic strategy to prevent the exaggerated inflammatory response related to cardiopulmonary bypass.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Blood flow does not correlate with the size of metastasis in our new intravital observation model of Lewis lung cancer.

We previously reported a novel in situ observation model for microcirculation of lung metastasis from subcutaneously implanted Lewis lung cancer into mouse. Using this model, we studied the correlation of blood flow and the size of lung metastasis. It was revealed that metastatic growth and its angiogenesis are suppressed by circulating angiogenesis inhibitors, such as angiostatin or endostatin, released from primary tumor. When we removed the primary tumor, the metastasized lung cancer significantly grew faster and larger. But the blood flow per area did not increase either inside or outside of the metastatic tumor. This suggests that the growth of metastatic tumor is directly regulated not by blood flow increase but by the other effects of the circulating factors.

Animals↗

PubMed2002

Intrabronchial orthotopic propagation of human lung adenocarcinoma--characterizations of tumorigenicity, invasion and metastasis.

Using the intrabronchial orthotopic propagation method, we evaluated the biological characteristics of human adenocarcinoma cell lines in vivo and examined the expressions of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their related proteins. Nine human lung adenocarcinoma cell lines, including A549, NCI-H23, NCI-H322, NCI-H358, Calu-3, PC-14, LC-2/ad, RERF-LC-KJ and PL16T, were injected into the peripheral bronchi of mice using this method. The mice were sacrificed at 4 and 8 weeks after tumor cell propagation and the lungs and other organs were observed macroscopically and histologically. We classified the adenocarcinoma cell lines, according to their intrapulmonary tumorigenicity, into the following three groups: (A) those that showed a high incidence of intrapulmonary implantation (>50%) (A549 and NCI-H358). A549 showed mediastinal lymph node metastasis and pleural dissemination; (B) those that showed a low incidence of intrapulmonary implantation (PC-14, NCI-H322, NCI-H23, Calu-3, and LC-2/ad); (C) those that showed no tumorigenicity in the lung (RERF-LC-KJ and PL16T). In order to characterize the biological differences between each cell line, we investigated the expressions of MMP-2 and MMP-9 and their related molecules by northern blot analysis. The expressions of MMP-2 and MMP-9 and their activators (membrane-type 1-MMP and urokinase-type plasminogen activator) were thought to be associated with the growth, invasion and metastasis of the human lung adenocarcinoma cell lines examined.

Adenocarcinoma↗

PubMed2002

Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung.

Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN activation. The aim of this study was to examine the effect of a PDE type 4 inhibitor, rolipram, on the functional changes and the retention of PMN in the lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN deformability was evaluated using silicon microchannels. Rolipram reduced the increase of F-actin and CD11b but did not change the decrease of L-selectin. Rolipram inhibited the increase of the transit time of PMN through the microchannel. We evaluated the retention of PMN in the lung in vivo by infusing labeled blood into the vena cava and examining the recovery into aortic root samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of PMN in the lung by reducing deformability change and CD11b upregulation of PMN.

3',5'-Cyclic-AMP Phosphodiesterases↗