Interleukin-1beta gene polymorphisms associated with risk of lung cancer in Japanese.
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Aged↗
Biomedical subjects
Masami Sato
Publications and source records attributed to Masami Sato.
Microarray analysis of promoter methylation in lung cancers.
Aberrant DNA methylation is an important event in carcinogenesis. Of the various regions of a gene that can be methylated in cancers, the promoter is the most important for the regulation of gene expression. Here, we describe a microarray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip (PMAD). For each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved (unmethylated+methylated) DNA fragments were amplified and labeled with Cy3 and Cy5 respectively, then hybridized to a microarray containing the promoters of 288 cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were normalized to signals from Msp I-cleaved (unmethylated+methylated) DNA fragments (Cy5). Normalized signals from lung cancer cell lines were compared to signals from normal lung cells. About 10.9% of the cancer-related genes were hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study. Further analysis of primary tumors indicated that the frequency of hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD method is effective at finding epigenetic changes during cancer.
Adenocarcinoma↗
Antibiotic effects of WP-0405, a thermo-setting ofloxacin gel, on methicillin-resistant Staphylococcus aureus keratitis in rabbits.
PURPOSE: The chemotherapeutic effects and pharmacokinetics properties of WP-0405 (a thermo-setting in situ 0.3% ofloxacin-containing ophthalmic gel) and ofloxacin (a conventional 0.3% ofloxacin solution) on methicillin-resistant Staphylococcus aureus (MRSA) keratitis were compared in a rabbit model. METHOD: The single-instillation pharmacokinetics of WP-0405 and ofloxacin in the cornea, aqueous humor, conjunctiva, and iris-ciliary body were determined in normal rabbit eyes. To compare the duration of antimicrobial action, WP-0405 or ofloxacin was instilled oncedaily in an early-treatment model of keratitis, and corneas were either removed immediately or 4 or 8 h postinstillation. In another experiment, WP-0405 was instilled two or three times daily to compare its antibiotic efficacy with three-times daily instillation of ofloxacin in the same early-treatment model of keratitis; corneas were then removed after determining the extent of the abscess area. In another experiment, WP-0405 was instilled four or eight times daily to compare its effects with eight-times daily instillation of ofloxacin in a late-treatment model of keratitis, and corneas were removed. The number of viable bacteria in the corneas was determined in all experiments. RESULTS: Cmax and AUC0- in tissues treated with WP-0405 were 1.5-3.4-fold and 1.8-2.9-fold greater than those treated with ofloxacin, respectively. WP-0405 significantly reduced the number of viable bacteria for up to 8 h after a single instillation. WP-0405 not only significantly reduced the number of viable bacteria, but also the size of the abscess area at the same frequency of instillation. When compared to ofloxacin, WP-0405 exhibited an approximately equivalent antibiotic effect, with fewer administrations. CONCLUSIONS: As a result of its pharmacokinetics, WP-0405 had a more potent, longer-acting antibiotic effect than did ofloxacin. Furthermore, because of its lower required instillation frequency, which would improve patient compliance, WP-0405 has great potential therapeutic benefits.
Administration, Topical↗
Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.
To establish cytological features of pulmonary large cell neuroendocrine carcinoma (LCNEC), we evaluated the cytological characteristics of LCNEC. Samples from 25 histologically confirmed LCNECs (14 touch imprint (TI) and 11 curettage) were analyzed. The findings were compared with those for seven small cell lung carcinomas. Cytological findings of TIs were as follows: Tumor cells were medium- to large-sized, round or polygonal, and nuclear polymorphism was observed. Some of the tumor cells had clearly identified cytoplasms, but naked nuclei were frequently observed. Nuclei were round, oval, or polygonal, and possessed thin and smooth nuclear membranes. The nuclear chromatin pattern was finely or coarsely granular. One or two nucleoli were observed in the nuclei, but were inconspicuous in some cases. Tumor cells appeared in clusters, and rosette formation was observed, but single cells were frequently observed also. Necrotic background and nuclear streaking were frequently observed. In brush or curettage specimens, the number of cells observed on a glass was small, but the findings were almost the same as those for the TI samples. TI samples have characteristic features, such as a neuroendocrine morphologic pattern, large cell size, abundant cytoplasm, finely or coarsely granular chromatin of the nucleus, and prominent nucleoli, and the diagnosis of LCNEC is possible. In brush or curettage specimen, the LCNEC diagnosis may be possible if a sufficient number of tumor cells are obtained.
Carcinoma, Neuroendocrine↗
Successful closure of an empyema space associated with persistent bronchopleural fistula: Muscle transposition combined with endobronchial plug.
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Aged↗
Computed tomographic images reflect the biologic behavior of small lung adenocarcinoma: they correlate with cell proliferation, microvascularization, cell adhesion, degradation of extracellular matrix, and K-ras mutation.
BACKGROUND: We previously reported that the computed tomographic M/L ratio (area of the tumor in the mediastinal computed tomographic image/area of the tumor in the lung computed tomographic image) of small peripheral lung adenocarcinoma is correlated with patient prognosis. METHODS: Immunostaining for p53, bcl-2, Ki-67, vascular endothelial growth factor, CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 2, and mutation of K-ras was assessed in 131 surgically resected, primary peripheral lung adenocarcinomas of 30 mm or less in maximum diameter to clarify the relationship between computed tomographic findings and biologic activities. RESULTS: The numbers of patients with high labeling indexes of Ki-67 and high expression of vascular endothelial growth factor, CD34, matrix metalloproteinase 2, and matrix metalloproteinase 9 in the solid-type group (computed tomographic M/L ratio > or = 50%) were significantly higher than those in the faint density-type group (computed tomographic M/L ratio < 50%; P = .04 for Ki-67, P = .03 for vascular endothelial growth factor, P = .0009 for CD34, P = .001 for matrix metalloproteinase 2, and P = .00001 for matrix metalloproteinase 9). The number of patients with high levels of CD44v6 or tissue inhibitor of matrix metalloproteinase 2 staining in the faint density-type group was significantly higher than that in the solid-type group (P = .02 for CD44v6 and P = .01 for tissue inhibitor of matrix metalloproteinase 2). Independent variables capable of predicting computed tomographic M/L ratio included CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 2 (P = .0093, P = .0003, P = .0027, and P = .01, respectively; binary logistic regression analysis). CONCLUSIONS: Our results suggest that the computed tomographic image of small lung adenocarcinoma is correlated with biologic activities and thus provides possible prognostic information.
Adenocarcinoma↗
Are difficulties during transbronchial lung biopsy/brushing through a fiberoptic bronchoscope based on the bronchial anatomy?
Some of the difficulties encountered during transbronchial lung biopsy through a flexible bronchofiberscope are due to anatomical reasons, namely the branching angles of some subsegmental bronchi from their mother bronchi are large, and differences in branching angles during respiration may also be large. This makes insertion of forceps difficult. We have sometimes experienced difficulties reaching the target lesion during a transbronchial approach. Which subsegmental bronchi make transbronchial lung biopsy/brushing difficult, and are such difficulties due to anatomical reasons? To answer these questions, we firstly surveyed 10 bronchologists regarding which five subsegmental bronchi they considered to be the most difficult for transbronchial biopsy/brushing. We then measured the branching angles of subsegmental bronchi in 106 cadaver lungs. Finally, in six volunteers, we also measured differences in branching angles of the subsegmental bronchi between the point of forced inspiration and the point of forced expiration on CT images. According to the survey, left B(1+2)c was considered to be the most difficult for insertion by nine doctors, followed by bilateral B6a by seven, right B1a by five, left B3a by five and left B(1+2)a by four. The results of our dissections showed that a branching angle of over 60 masculine was present in more than 10% of specimens in B3a, B6a and B6c in the right lung and in B(1+2)c, B3a, B6a and B6c in the left lung. In addition, three-dimensional reconstructed images revealed that the angles of some subsegmental bronchi changed during respiration. Inter-individual variations were present in most subsegmental bronchi. The direction of movement of each subsegmental bronchus during respiration varied. In addition, maximum degrees of difference in angles between volunteers were sometimes as much as 80 degrees . In conclusion, branching angles of subsegmental bronchi from their mother bronchi are large in B3a, B6a and B6c in the right lung and in B(1+2)c, B3a, B6a and B6c in the left lung. Most of these correspond to those which many bronchologists felt to be difficult for insertion. In addition, changes in the angles of subsegmental bronchi during respiration are likely to partially account for difficulties encountered during transbronchial approaches.
Aged↗
Anti-allergic agent tranilast decreases development of obliterative airway disease in rat model of heterotopic tracheal transplantation.
BACKGROUND: Tranilast is an anti-allergic agent known to inhibit the release of histamine, interleukin-1beta, transforming growth factor beta1, and platelet-derived growth factor from various cells and currently is used to treat allergic diseases, keloids, and hypertrophic scars. We evaluated the ability of tranilast to inhibit the development of obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation. METHODS: We transplanted tracheal segments from donor rats (Brown Norway) into subcutaneous pouches in major histocompatibility complex-incompatible recipient rats (Lewis). At Days 21 and 28 after transplantation, we histologically assessed the harvested allografts scored the degree of OAD, on a scale from zero to 4 as previously described, caused by fibroproliferative tissue. RESULTS: Recipient animals treated orally with 400 mg/kg/day tranilast throughout the experiment showed significantly decreased OAD compared with control animals, with a histologic score of 1.1 +/- 0.4 vs 3.0 +/- 1.3, respectively (mean +/- SD, p=0.007), at Day 21 after transplantation and 2.0 +/- 1.4 vs 3.9 +/- 0.4, respectively (mean +/- SD, p=0.017), at Day 28 after transplantation. CONCLUSION: These results showed that treatment with tranilast significantly decreased fibroproliferative airway changes associated with allograft rejection in a rat model of tracheal transplantation, suggesting that tranilast may be useful in preventing bronchiolitis obliterans after lung transplantation.
Administration, Oral↗
A rare case of hemangioma arising from the azygos vein: Informative procedure with endobronchial ultrasonography.
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Azygos Vein↗
Beta-blocker prevented repeated pulmonary hypertension episodes after bilateral lung transplantation in a patient with primary pulmonary hypertension.
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Adrenergic beta-Antagonists↗
Comparative histology of lymph nodes from aged animals and humans with special reference to the proportional areas of the nodal cortex and sinus.
Lymph nodes are composed of a lymphocyte-rich area or cortex (subdivided into the superficial and deep cortex and the medullary cord) and another, macrophage-rich area (incorporating the subcapsular and medullary sinuses). We measured the proportional area of the cortex in lymph nodes from aged experimental mammals (rats, guinea pigs, dogs and rabbits) and elderly Japanese humans. The cervical, axillary and inguinal nodes were generally richer in cortex tissue than the pulmonary regional and mesenteric nodes. Histological heterogeneity and medullary sinus dominance were much more evident in the human nodes than in those from animals, except for the guinea pig thoracic node. Human pulmonary regional nodes were characterized by a large medullary sinus; in guinea pigs, these nodes had a similar histology but the T lymphocyte-containing areas were smaller and thinner than in humans. The paraaortic node was well developed in humans and dogs, but not in other animals tested. These species- and region-specific histological differences may influence the evaluation of experimental animal models of lymph node function, such as those recently identified for research into sentinel nodes.
Aged↗
Chromosome 12, frequently deleted in human pancreatic cancer, may encode a tumor-suppressor gene that suppresses angiogenesis.
Several lines of evidence have suggested that the long arm of chromosome 12 may carry a tumor-suppressor gene(s) that plays a role in pancreatic ductal carcinogenesis. We have previously found a significant association between loss of heterozygosity of the 12q arm and a poor prognosis in pancreatic cancer patients. In this study, we introduced a normal copy of chromosome 12 into some pancreatic ductal carcinoma cells. Both anchorage-dependent and -independent proliferations as well as invasiveness were similar throughout the hybrid clones when compared with their corresponding parental cells. In sharp contrast, significant suppression of tumorigenesis was observed after inoculation of the hybrid clones into nude mice. Measurements made up to 1 month later showed that there was a significant delay in the growth of tumors into which the introduced normal copy of chromosome 12 had been restored. More significantly, using our dorsal skin chamber and an intravital microscopy system experiment in SCID mice, we demonstrated and visualized directly that implantation of the hybrids failed to promote the angiogenic phenotype encountered in the parental cells. Gene expression profiling using the complementary DNA microarray system identified a set of 24 genes differentially expressed between the hybrids and parental cells. An additional set of 18 genes was also identified that were differentially expressed between the hybrid clone that lost its growth-suppression activity and one that retained such activity. Another set of 25 genes mapped on 12q was detected that showed high expression levels in the hybrid clones retaining growth-suppressive activity. In summary, this study provides the first functional evidence of the existence of an additional tumor-suppressor gene(s) on chromosome 12, whose absence is responsible for the pathogenesis in pancreatic ductal carcinogenesis.
Animals↗
The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias.
OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does not produce signs or symptoms before the patient dies from other causes. We sought to determine whether overdiagnosis bias is a factor when screening for squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi Population-Based Lung Cancer Screening Registry for high-risk patients who were seen between January 1, 1982 (when sputum cytology tests were added for men with long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture, Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test results that were positive for squamous cell carcinoma but had normal radiograph findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5 year). END POINTS: Five-year and 10-year survival rates from primary lung cancer in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients, 15 (34%) remained asymptomatic. The survival rate due to primary lung cancer death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years. Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer. CONCLUSION: Given that the two thirds of the untreated patients with squamous cell carcinoma of the bronchus died from lung cancer within 10 years, overdiagnosis bias does not appear to be a factor in screening for this disease. Thus, we recommend that patients with radiographically occult squamous cell carcinoma of the bronchus undergo tumor treatment after localization.
Aged↗
A new technique for endobronchial ultrasonography and comparison of two ultrasonic probes: analysis with a plot profile of the image analysis software NIH Image.
STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is currently the sole clinical method available for delineating the bronchial wall structure; however, the image resolution is inadequate. Thus, an improved image analysis system is needed for both a more accurate and more readily interpretable endobronchial ultrasonogram. MATERIALS AND METHODS: A total of 10 patients underwent pulmonary resection for lung cancer. EBUS was performed on the bronchi of the resected lungs, which had been immersed in physiologic saline solution. The same bronchial lesion in each specimen was imaged with two probes: 20 MHz and 30 MHz. The images were analyzed using the plot profile derived from freeware image analysis software: NIH Image (National Institutes of Health; Bethesda, MD). The measured echo intensity of the bronchial wall was statistically analyzed. RESULTS: A normal bronchial wall image consists of five layers, and the plot profile shows a W-shaped curve. The mean value of the echo intensity of each peak or trough of the W-shaped curve was calculated and compared for both probes. The differences in the mean echo intensity between both the third and fourth layer and the second and fourth layer were found to be significantly greater with the 30-MHz probe than with the 20-MHz probe. The echo intensity curve of a central-type lung cancer was not W shaped, indicating that the bronchial wall was not composed of the normal five layers. CONCLUSION: We employed image analysis software and drew a plot to obtain a W-shaped curve from the EBUS image data. This enabled us to make an objective assessment of the laminar structure of the bronchial wall. In order to clearly recognize the laminar structure of the bronchial wall, the 30-MHz probe was found to be more useful than the 20-MHz probe.
Bronchi↗
[Management of central-type early lung cancer: an evidence-based clinical guideline].
With the support of the Japan Ministry of Health, Labour and Welfare, clinical guidelines for the management of lung cancer have been completed according to evidence-based methods. In this article, we focus on the guidelines for central-type early lung cancer. Reviewing a total of 3,196 reports that include key words related to central-type early lung cancer, 41 were selected and applied to determine recommendations for diagnostic or therapeutic methods. Among diagnostic methods, sputum cytology for the high-risk group and bronchoscopy for patients with positive sputum cytology were evaluated as recommendable. Among therapeutic methods, surgery and photodynamic therapy were evaluated as recommendable. For some methods, including fluorescence bronchoscopy and endobronchial ultrasonography brachitherapy, there was insufficient evidence to conclude that they are efficacious. At present, efforts to clarify the efficacy of these methods should be continued.
Bronchoscopy↗
Reduction of recipient macrophages by gadolinium chloride prevents development of obliterative airway disease in a rat model of heterotopic tracheal transplantation.
BACKGROUND: Recent studies have shown the possible role of growth factors and the involvement of macrophages as a source of them in the pathogenesis of bronchiolitis obliterans (BO) after lung transplantation. OBJECTIVE: The authors intended to determine whether depletion of recipient macrophages by gadolinium chloride (GdCl3) resulted in decreased obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation. METHODS: A tracheal segment of donor rats (Brown Norway) was transplanted into a subcutaneous pouch of fully major histocompatibility complex-incompatible recipient rats (Lewis). Recipients were injected intravenously with 80 mg/kg of GdCl3.6H2O or saline on days 0, 7, and 14 posttransplant. Allografts were harvested on days 7, 14, 17, and 21 and the degree of OAD resulting from fibroproliferative tissue was pathologically scored on a scale of 0 to 4. A portion of allografts was submitted to reverse-transcriptase polymerase chain reaction analysis to examine mRNA expression for platelet-derived growth factor (PDGF), basic fibroblast growth factor, and transforming growth factor-beta1. RESULTS: Immunohistochemical studies confirmed reduction in the number of ED2+ macrophages in tracheal allografts by GdCl3 injection. GdCl3 treatment significantly decreased OAD of allografts, with the histologic score of 1.4+/-0.3 in the treated animals compared with 3.0+/-0.5 in the controls (mean+/-SE, P=0.02) at day 21 posttransplant, and this was accompanied by decreased PDGF-A and PDGF-B gene expression in the GdCl3 group at day 17 posttransplant. CONCLUSIONS: Macrophage reduction by GdCl3 resulted in significantly decreased OAD development and reduced PDGF mRNA expression in allografts. This suggests a potential effectiveness of therapies targeting recipient macrophages in preventing BO after lung transplantation.
Animals↗
Interferon gamma expression and clinical features in patients with acute retinal necrosis syndrome.
BACKGROUND: Interferon gamma (IFN-gamma) has been reported to play an important role during virus infections. The purpose of this study was to examine the relationship between IFN-gamma expression and the clinical course of patients with acute retinal necrosis syndrome (ARN) associated with the varicella-zoster virus (VZV). METHODS: Six patients with ARN were studied. The aqueous and/or vitreous were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay during the follow-up period. The presence of VZV genome was also determined by PCR. The results were correlated with the clinical data and features and compared with patients with other ocular diseases. RESULTS: A statistically significant higher level of IFN-gamma was detected in the aqueous and/or vitreous in eyes with ARN than in eyes with other ocular diseases. A statistically significant positive correlation was observed between the level of IFN-gamma in the vitreous and the final visual acuity. IFN-gamma was reduced to undetectable levels within 30 days after the initial eye symptoms. Three of five patients had severe inflammation initially, and the visual acuity gradually recovered with the disappearance of VZV and higher levels of IFN-gamma. Conversely, the other 2 patients showed mild inflammation, had a slow decrease of visual acuity with persistent VZV, and lower levels of IFN-gamma expression. CONCLUSION: Our results suggest that IFN-gamma may be one of the factors that plays an important role in the clinical course of VZV-associated ARN.
Acyclovir↗
Combination use of vitamin K(2) further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats.
Bisphosphonate is a potent inhibitor of bone resorption, which results in the increase of bone volume. However, bisphosphonate treatment may lead to extremely low bone turnover and abnormal bone microstructure. In this study, we examined whether the combination of bisphosphonate with vitamin K(2) treatment may have beneficial effects on bone turnover and trabecular microstructure as well as on bone volume loss by using tail-suspension model rats. In these model rats, bone mineral density (BMD) decreased with histological evidence of enhanced bone resorption and suppressed bone formation. By bisphosphonate treatment, BMD was increased compared with that of tail-suspended rats. Osteoclast surface per bone surface (Oc.S/BS) and number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and mineral apposition rate (MAR) decreased, suggesting extreme suppression of bone turnover. However, trabecular structure examined by microfocus CT was apparently abnormal. By contrast, combination of bisphosphonate with vitamin K(2) leads to further increase of bone volume. MAR and BFR as well as Oc.S/BS and N.Oc/B.Pm were increased compared with those of the bisphosphonate-treated group. However, abnormal structure of trabeculae in secondary spongiosa was not completely ameliorated. These data suggested that concomitant use of vitamin K(2) with bisphosphonate excessively ameliorates too much suppression of bone turnover while more efficiently preventing bone volume loss.
Absorptiometry, Photon↗