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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 181 records · Page 10Linked to original sources
PubMed1997

Allelotype and replication error phenotype of small cell lung carcinoma.

Allelotype and replication error (RER) phenotype analyses were performed to clarify the pathogenetic significance of inactivation of tumor suppressor genes and genomic instability in the genesis and progression of small cell lung carcinoma (SCLC). We examined 37 cases of SCLC for loss of heterozygosity (LOH) and microsatellite instability at 49 loci on all 39 nonacrocentric chromosomal arms. LOH was frequently (>70%) detected on chromosomes 3p (29/32, 90.6%), 5q (15/21, 71.4%), 13q (25/26, 96.2%), 17p (22/25, 88.0%), and 22q (24/33, 72.7%). Frequent LOH (>70%) on these loci was observed even among seven cases of stage I tumors. The incidence of LOH on all 39 nonacrocentric chromosomal arms was not significantly different between primary tumors and metastases. These results suggest that inactivation of multiple tumor suppressor genes accumulates relatively early during progression of SCLC and it may be responsible for clinically and biologically aggressive phenotype of SCLC. RER was observed in 6/37 (16.2%) of SCLC, however, RER at multiple loci was observed only in two cases. Therefore, it was indicated that genomic instability is uncommon, but might play a role in the genesis of a small subset of SCLC.

Alleles↗
PubMed1997

Factors affecting the radiologic appearance of peripheral bronchogenic carcinomas.

The use of high-resolution computed tomography and magnetic resonance imaging have allowed the detailed description of morphologic findings associated with lung cancer. In particular, the desmoplastic response of lung tissue to tumor growth has not been adequately described. This article reviews roentgenologic and pathologic correlations of primary lung carcinomas. An irregular or indistinct tumor margin may be caused by tumor infiltration, an irregular desmoplastic response to the tumor growth, or irregular contraction in the central portion of the tumor. Solid tumor growth, on the other hand, may be associated with a well-defined tumor margin, with or without displacement of adjacent anatomical structures.

Adenocarcinoma↗
PubMed1997

Combination therapy with antibody and interleukin-2 gene transfer against multidrug-resistant cancer cells.

In the present study, we examined the effect of interleukin-2 (IL-2) gene transfer into multidrug resistance (MDR) cancer cells on the therapeutic efficacy of MRK16. Human MDR ovarian cancer cells, AD10, were transduced with a bicistronic IL-2 retrovirus, Ha-IL2-IRES-Neo. The G418-resistant population, IL2-AD10, secreted IL-2 into the culture supernatant and did not form a tumor mass in nude mice. The IL2-AD10 cells were more susceptible to the cytotoxicity of murine spleen cells than AD10 cells in vitro. For examination of the effect of IL-2 gene transfer on the antitumor activity of MRK16 against P-glycoprotein-positive tumors, IL2-AD10 cells were co-transplanted s.c. with AD10 cells into nude mice in a ratio of 1:3, and the mice were treated with MRK16 on days 2 and 7. MRK16 markedly inhibited the growth of AD10 cells mixed with IL2-AD10 cells under conditions (0.3-1 microgram/body) where it showed only marginal effects on the growth of AD10 tumors. These findings suggest that IL-2 gene transfer potentiates the antitumor activity of MRK16 against MDR tumors.

Animals↗
PubMed1997

Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy.

PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

L-Myc overexpression and detection of auto-antibodies against L-Myc in both the serum and pleural effusion from a patient with non-small cell lung cancer.

Non-small cell lung cancer patient was found to have auto-antibodies against L-Myc in both the serum and pleural effusion. The titer of anti-L-Myc antibodies was higher in the pleural effusion than in the serum. Overexpression of L-Myc without DNA amplification was observed in the tumor cells. L-Myc antigen was not detected in either the serum or the pleural effusion. Anti-nuclear antibodies were also detected in both the serum and pleural effusion, although this patient did not have collagen-vascular disease.

Aged↗
PubMed1997

[Novel metastasis model of human lung cancer cells representing different histological types in SCID mice depleted of NK cells].

Metastasis is the major obstacle in cancer therapy. Lung cancer is divided into 4 histological groups, such as small cell carcinoma, squamous cell carcinoma, adenocarcinoma and large cell carcinoma, representing different clinical behaviors. Novel metastasis models of human lung cancer cells to the liver, kidneys and lymph nodes were established in SCID mice depleted of NK cells. In the model under study, small-cell carcinoma cells mainly formed lymph-node metastases, while squamous cell carcinoma cells mainly metastasized to the liver and kidneys. Moreover, adenocarcinoma cells formed lung metastases and malignant pleural effusion. These findings suggest that our model reflects clinical behavior of metastatic lung cancer and is useful for evaluation of antimetastatic modalities.

Adenocarcinoma↗
PubMed1997

[Overcoming of multidrug resistance by anti-P-glycoprotein monoclonal antibody].

P-glycoprotein is one of the key molecules in multidrug resistance. Monoclonal antibodies against P-glycoprotein could be useful tools for killing MDR tumor cells. To overcome multidrug resistance, many anti-P-glycoprotein monoclonal antibodies have been made such as MRK16 and MRK17. Conjugated moAb, such as bispecific antibody, immunotoxin and radioisotope conjugates have also been constructed to enhance the anti-tumor activity of moAb. Cytokine-gene transduction for accumulation and activation of monocytes may be hopeful to augment the therapeutic efficiency of anti-P-glycoprotein antibody. For clinical use, construction of human moAb, overcoming tumor heterogeneity, and protection of normal tissue by specifically targeting the tumor cells should be essential.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Distribution and contrast enhanced CT appearance of abdominal tuberculous lymphadenopathy].

PURPOSE: To clarify the contrast enhanced CT features and anatomic distribution of the disseminated vs non-disseminated tuberculosis (TB) involving abdominal lymph nodes. MATERIALS AND METHODS: The contrast enhanced CT findings of abdominal lymphadenopathy in 25 patients, including disseminated TB associated with miliary TB of the lung (n = 5) and non-disseminated TB (n = 20), were retrospectively evaluated in a blind review to assess our criteria of morphology, density and location of the involved lymphadenopathy. RESULTS: The enhancement patterns of disseminated TB were not different from those of non-disseminated TB. Ninety-six percent of the patients had peripheral rim enhancement, and 60% showed a multilocular appearance. The enlarged lymph nodes of TB were less than 4 cm in diameter. Lymphadenopathy caused by hematogenous dissemination often accompanied splenic involvement showing multiple low-density foci in the spleen. The predominant sites of lymphadenopathy of disseminated TB were hepatoduodenal ligamentous, hepatogastric ligamentous, mesenteric, and both upper and lower portions of the retroperitoneal lymph nodes, whereas non-disseminated TB mainly involved hepatoduodenal ligamentous, hepatogastric ligamentous, mesenteric and upper retroperitoneal lymph nodes, excluding the lower retroperitoneal lymph nodes. By combining contrast enhancement patterns and the anatomic distribution of lymphadenopathy shown on the contrast enhanced CT images, reviewers made a correct diagnoses of tuberculosis in 94%, of cases, with a specificity of 95% and sensitivity of 92%. CONCLUSION: Contrast enhanced CT patterns correlate well with the pathologic features of tuberculous lymphadenopathy. A different anatomic distribution between disseminated and non-disseminated TB involving the lower retropentoneal lymph nodes was recognized in this study.

Abdomen↗
PubMed1997

[Chronic eosinophilic pneumonia successfully treated with suplatast tosilate].

The patient was a 45-year-old woman in whom a chest X-ray film obtained on admission showed bilateral infiltrative shadows. A chest CT scan revealed areas of consolidation and ground-glass opacities. Examination of bronchoalveolar lavage fluid revealed many eosinophils, and specimens obtained by transbronchial lung biopsy showed thickened alveolar septa with infiltration of eosinophils. The numbers of eosinophils and the level of IgE in blood were low. The radiographic appearance improved after administration of suplatast tosilate. The level of interleukin 5 was high both in plasma and in bronchoalveolar lavage fluid before treatment, but the level of IL-5 in plasma was low after suplatast tosilate was given. Suplatast tosilate, which suppresses the production of cytokines, may be useful in patients with chronic eosinophilic pneumonia.

Anti-Allergic Agents↗
PubMed1997

Tumor suppressor genes in human lung cancer.

Lung cancer is the most common cause of cancer death in Japanese males, the incidence having increased markedly in recent years. Carcinogen exposure such as to tobacco-smoke and air pollution are associated with the probability of developing lung cancer. Aquired somatic mutations play an important role in the pathogenesis of environmentally induced lung cancers. Cytogenetic and molecular analysis of lung tumors has made it possible to examine this hypothesis and to search for candidate genes that may be targeted by chronic exposure to these carcinogens. Early studies implicate several distinct chromosomal loci (3p, 9p, 13q, 17p, and others) and suggest sequential genetic events occur during the initiation and progression of lung carcinogenesis. Several suppressor genes including Rb (13q), P53 (17p), and P16 (9p) have been identified and cloned at these chromosomal loci. The identification of putative tumor suppressor gene at chromosome 3p is still under work. Understanding the interaction of P53, RB, cyclins, and protein kinase inhibitors including P16 will be essential to the development of the next generation of diagnostic and therapeutic studies for lung cancer.

Chromosomes, Human↗
PubMed1997

Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis.

This study was designed to clarify the contribution of IL-8 as a specific neutrophil chemotactic factor in the human respiratory tract in various pulmonary diseases. The neutrophil chemotactic activity (NCA), neutrophil counts and IL-8 concentration in the bronchoalveolar lavage fluid (BALF) obtained from normal volunteers (NV), control patients (CP), patients with diffuse panbronchiolitis (DPB) and patients with idiopathic pulmonary fibrosis (IPF) were examined. Neutrophil counts, NCA and IL-8 concentration in BALF obtained from patients with DPB or IPF was significantly higher than that from NV or CP. The IL-8 concentration correlated with neutrophil count and also correlated with NCA in BALF from patients with IPF, whereas there was no correlation between these factors in BALF from DPB. These results suggest that the contribution of IL-8 to neutrophil accumulation of the lower respiratory tract is different between IPF and DPB.

Blood Cell Count↗
PubMed1997

Thrombin stimulates platelet-derived growth factor release by alveolar macrophages in rats--significance in bleomycin-induced pulmonary fibrosis.

Thrombin is a multifunctional enzyme generated at sites of vascular injury, and is known to be increased in the lungs in some types of fibrotic lung disease. In this study, to determine whether thrombin is associated with fibroblast growth and pulmonary fibrosis in these disorders, we examined whether a growth factor for fibroblasts (platelet-derived growth factor, PDGF) was released by thrombin-stimulated alveolar macrophages (AM). The culture supernatants of rat AM stimulated with 1 or 10 U/ml of thrombin showed a significant increase in fibroblast growth-stimulating activity (FGA). Pretreatment of the AM supernatant with anti-PDGF-AA antibody significantly decreased the FGA, but pretreatment with anti-PDGF-BB antibody did not. The supernatants of AM stimulated with thrombin also increased the growth of fibroblasts from the lungs of rats with bleomycin-induced lung injury. These results indicate that thrombin stimulates AM to release PDGF-AA, which is responsible, at least in part, for fibroblast growth and the development of pulmonary fibrosis in some types of fibrotic lung disease.

Animals↗
PubMed1997

Age-related increase of autoantibodies to interleukin 1 alpha in healthy Japanese blood donors.

Although autoantibodies to interleukin-1 alpha (IL-1 alpha autoantibodies) are known to be present in sera of apparently healthy humans, their frequency of occurrence and significance are unclear. To determine the prevalence of detectable IL-1 alpha autoantibodies in normal human blood, we screened the plasma of blood donors (6290 subjects: 3977 men and 2313 women, ages 16 to 64 yr) by a radioimmununoassay which we developed using a method that could detect over 5 ng/ml. Moreover, we investigated immunoglobulin class of IL-1 alpha autoantibodies and also their function. IL-1 alpha autoantibodies were detected in 14.6% of the 6290 donors. Their frequency was higher in males than females (16.6% vs. 11.2%, p < 0.01) and increased with age in both sexes. The proportion of subjects with a high IL-1 alpha autoantibodies titers also increased with age. We showed that IL-1 alpha autoantibodies were of the IgG class and that they had neutralizing function to IL-1 alpha by receptor assay. Neutralizing activity was only shown in plasma with concentration of IL-1 alpha autoantibodies, the level of which was over 1000 ng/ml. The affinity of the IL-1 alpha autoantibodies in plasma was between 2.1 x 10(-10) and 1.2 x 10(-9) M (mean 6.4 x 10(-10)M). Our results provide a basis for comparison with IL-1 alpha autoantibodies prevalence between healthy states and disease states, and suggest that IL-1 alpha autoantibodies may play a significant role in modulating the effects of excessive IL-1 alpha at local site or in systemic regions.

Adolescent↗
PubMed1997

[A case of rheumatoid lung exacerbated by acetaminophen-induced pneumonitis].

A 57-year-old man was admitted with a high fever, dry cough, severe dyspnea and an interstitial shadow bilaterally on chest roentogenogram. Although his illness was not diagnosed, he was treated with a high dose of methylprednisolone (1 g/day for 3 days) for acute interstitial lung disease. As the 3-day treatment was not effective, high-dose methylprednisolone therapy was repeated. Subsequently, he was treated with prednisolone (60 mg/day), after which his condition improved. After 8 months, the patient caught cold for which he was treated. Subsequently his previous lung disease appeared again. His illness, improved after steroid therapy. The patient had been treated with Shin-Ruru-A tablets during his first admission. A lymphocyte stimulation test for Shin-Ruru-A-Tablet, PL granule, and acetaminophen (which is the common constituent of the former two drugs), was positive. Polyarthralgia, bone lesions joint swelling, and a positive rheumatoid factor test were present on first admission. Therefore, his illness was diagnosed as rheumatoid arthritis (RA). As the interstitial shadow remained after treatment of the lung disease, a thoracoscopic lung biopsy was performed. The specimen revealed an intensive lymphocytic infiltration, perivasculatitis, and thickening of the alveolar septa. These findings corresponded with those of lung disease associated with RA. The results suggest that lung disease associated with collagen vascular diseases may be exacerbated by drug-induced pneumonitis.

Acetaminophen↗
PubMed1997

Model of malignant pleural effusion of human lung adenocarcinoma in SCID mice.

Malignant pleural effusion (PE) is a frequent problem in lung cancer. In this study, we established a model of malignant PE of human adenocarcinoma cells, PC-14, in SCID mice. Intravenously injected PC-14 cells formed colonies in the lungs as early as week 4 after tumor inoculation, and produced bloody PE in all recipient SCID mice by week 8. Pretreatment of SCID mice with anti-mouse IL-2 receptor beta chain antibody (TM-beta 1) to deplete natural killer (NK) cells markedly promoted the production of bloody PE and metastases to multiple organs, such as the lungs, liver, kidneys, and lymph nodes 4 weeks after tumor inoculation. Histological studies indicated that PC-14 cells formed colonies in the lungs, and then invaded the pleura and spread to the pleural cavity. To establish cell lines with a high potential to produce PE, we harvested PE, expanded the tumor cells in vitro, and injected them into SCID mice again. By four in vivo selection cycles in this way we obtained PC-14-PM4 cells, which produce lung metastases and PE earlier than PC-14 cells. The survival of SCID mice inoculated with PC-14-PM4 cells was significantly shorter than that of mice inoculated with PC-14 cells. The expressions of adhesion molecules, such as CD44, CD49d, ICAM-1, and MHC class I, on PC-14-PM4 cells tended to increase compared with PC-14 cells. These changes of adhesion molecules seem to be one of possible mechanisms involved in higher metastatic potential of PC-14-PM4 cells. PE models with PC-14 and PC-14-PM4 cells should be useful for biological and preclinical studies on malignant PE produced by human lung cancer.

Adenocarcinoma↗
PubMed1996

T helper 2 cytokines differently regulate monocyte chemoattractant protein-1 production by human peripheral blood monocytes and alveolar macrophages.

Th2 cytokines, such as IL-4, IL-10, and IL-13, suppress proinflammatory cytokine production by monocytes/macrophages. Since monocyte chemoattractant protein-1 (MCP-1) is presumed to play an important role in monocyte recruitment and activation during inflammatory and immune responses, we examined here the effects of these Th2 cytokines on MCP-1 production by human blood monocytes and alveolar macrophages. Unstimulated, highly purified blood monocytes did not produce MCP-1 spontaneously, while LPS treatment induced the production of MCP-1 and its mRNA expression. All Th2 cytokines tested suppressed LPS-induced MCP-1 production and its mRNA expression, although the suppressive effect of IL-13 was weaker than that of IL-4 or IL-10. In contrast, IL-10, but neither IL-4 nor IL-13, induced unstimulated peripheral blood monocytes to produce biologically active MCP-1 protein within 4 h, reaching a maximal level at 12 h. IL-10-induced MCP-1 production was reduced by pretreatment of IL-10 with anti-IL-10 Ab, negating the involvement of contaminated endotoxin. Moreover, IL-10 induced MCP-1 mRNA expression in unstimulated monocytes, independent of de novo protein synthesis. Furthermore, human alveolar macrophages produced MCP-1 spontaneously, and the production was inhibited by IL-4 or IL-13, but was augmented by IL-10. These findings suggest that IL-10 regulates MCP-1 production by monocytes/macrophages in a different way from other Th2 cytokines, such as IL-4 and IL-13, and contributes to host defense responses.

Cells, Cultured↗
PubMed1996

Detection of auto-antibodies against L-myc oncogene products in sera from lung cancer patients.

Auto-antibodies against L-myc oncogene products (L-Myc) in sera from lung cancer patients were examined using bacterially synthesized glutathione S-transferase (GST) L-Myc fusion proteins and Western blot analysis. The detection rate of anti-L-Myc antibodies in sera from lung cancer patients was 10%, while that in sera obtained from normal volunteers was 0%. Five patients with non-small-cell lung cancers (2 adenocarcinomas, 2 squamous-cell carcinomas and I large-cell carcinoma) were included in the group with anti-L-Myc antibodies. These auto-antibodies belonged to the IgG class and recognized the carboxy terminus of L-Myc. Circulating L-Myc was not detected in sera from patients with anti-L-Myc antibodies. Differences in age, sex, performance status, histology, stage, smoking history and prior treatment were not significantly different between anti-L-Myc antibody-positive and antibody-negative patients. Anti-nuclear antibodies were detected in 40% of lung cancer patients and 57% of those with anti-L-Myc antibodies. Our data suggest that detection of anti-L-Myc antibodies may be helpful in the diagnosis and evaluation of the host-immune response to L-Myc in a subset of lung cancer patients.

Aged↗