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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 163 records · Page 9Linked to original sources
PubMed1997

Combined therapy of multidrug-resistant human lung cancer with anti-P-glycoprotein antibody and monocyte chemoattractant protein-1 gene transduction: the possibility of immunological overcoming of multidrug resistance.

We determined whether transduction of the monocyte chemoattractant protein-1 (MCP-1) gene into MDR human lung cancer cells affected their tumorigenicity and sensitivity to antibody-dependent cellular cytotoxicity (ADCC) reaction mediated by the anti-P-glycoprotein (P-gp) monoclonal antibody MRK16. The human MCP-1 gene inserted into an expression vector (BCMGSNeo) was transfected into MDR human small-cell lung cancer (H69/VP) cells. Monocyte chemotactic activity was found in culture supernatants collected from MCP-1-transfected H69/VP cells, but not in supernatants of parent and mock-transfected cells. In an in vitro experiment, recombinant MCP-1 did not affect monocyte-mediated ADCC against H69/VP cells when added to the monocyte culture in either the activation or the effector phase at sufficient concentrations to attract and activate monocytes. Tumorigenicity and growth rates of MCP-1-producing H69/VP cells in nude mice were similar to those of parental cells and mock-transfected cells. However, systemic treatment with MRK16 was more effective in inhibiting the formation of tumors by MCP-1-gene-transfected cells than by mock-transfected cells. Systemic treatment with MRK16 also inhibited the growth of a mixture (1:1) of MCP-1-producing cells and mock-transfected cells. These results suggest that combination therapy with MRK16 and MCP-1 gene transduction may be a useful immunological strategy to inhibit the growth of human MDR cancer cells expressing P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice.

We investigated whether local production of macrophage colony-stimulating factor (M-CSF), responsible for migration and activation of monocytes/macrophages at a tumor growth site, affected the metastatic pattern of lung cancer. For this, highly metastatic human squamous (RERF-LC-AI) or small (H69/VP) cell lung carcinoma cells were transduced with the human M-CSF gene inserted into pRc/CMV-MCSF to establish M-CSF-producing clones (MCSF-AI-9-18, MCSF-AI-9-24, and MCSF-VP-5). M-CSF gene transduction had no effect on the expression of surface antigen or on in vitro proliferation. After s.c. injection into SCID mice, the growth rates of M-CSF-producing cells were slower than those of parent or mock-transduced cells. In the metastatic model in SCID mice depleted of natural killer cells, RERF-LC-AI cells formed metastases mainly in the liver and kidneys, whereas H69/VP cells metastasized mainly to the liver and systemic lymph nodes. The numbers of metastatic colonies of MCSF-AI-9-18 and MCSF-AI-9-24 cells in the liver but not the kidneys were significantly reduced. The development of lymph node metastases of MCSF-VP-5 cells was also less than that of parent or mock-transduced cells. Treatment of SCID mice with anti-human M-CSF antibody resulted in a significant increase in liver metastases of their M-CSF gene transfectants. No significant differences were observed in the distributions in mice or in the in vitro invasive potentials of MCSF-AI-9-18 cells and Neo-AI-3 cells. These findings indicate that the antimetastatic effect of M-CSF may be specific to particular organs, suggesting the influence of heterogeneity of organ microenvironments on the metastasis of lung cancer.

Animals↗
PubMed1997

Treatment for non-Hodgkin's lymphoma (stage I, II) of the elderly: usefulness of local and regional irradiation and reduced dose chemotherapy.

PURPOSE: To examine the usefulness and safety of a new treatment regimen consisting of irradiation to the involved area and adjacent lymph node area, and reduced dose chemotherapy for elderly patients with non-Hodgkin's lymphoma. METHODS AND MATERIALS: The core of this study was 38 elderly patients older than 65 years old with intermediate or high grade non-Hodgkin's lymphoma, and concomitantly suffering from some other geriatric disease. They received involved area irradiation (40 Gy), adjacent lymph node irradiation (30 Gy), and reduced dose chemotherapy (two cycles of 50-70% ACOP: Doxorubicin, Cyclosphosphamide, Vincristine, Prednisone or 70% MACOP-B: Doxorubicin, Cyclophosphamide, Vincristine, Methotrexate, Bleomycin, Prednisone for 4 weeks). RESULTS: The completion rate of the treatment regimen was 100%. The 5-year local control rate was 98%. The 5-year disease-free survival rate and the 5-year cause-specific survival rate for all patients were 70 and 82%, respectively. No treatment deaths were observed, and the rate of serious complications arising from the treatment was 3%. CONCLUSIONS: The newly conducted treatment regimen proved to be safe and useful for elderly patients with non-Hodgkin's lymphoma concomitantly suffering from some other geriatric disease.

Aged↗
PubMed1997

Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene transfer.

A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20, induced cachexia, as evidenced by progressive weight loss and severe hypoglycemia. Several lines of evidence indicate that a pro-inflammatory cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the establishment of cachexia in this model. Because IL-10 can potentially inhibit the production of pro-inflammatory cytokines including IL-6, we evaluated the effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript was detected at tumor sites of mice inoculated with parental or control vector transfectant cells, and serum IL-6 levels were markedly increased in these mice. The injection of parental cells into IL-6-deficient mice induced cachexia with elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor cells are a major source of IL-6. The inoculation of IL-10-transfectant cells kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL-10 levels without affecting the growth rates of colon 26 cells both in vitro and in vivo. However, the implantation with IL-10-transfectant cells reduced the expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6 levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not exhibit progressive weight loss, a reduction in food intake, or severe hypoglycemia, which was observed in mice inoculated with parental or control vector-transfectant cells. Collectively, these results suggest that IL-10 gene transfer prevented the occurrence of cachexia with a concomitant inhibition of IL-6 production at the tumor sites.

Animals↗
PubMed1997

Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus.

Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor alpha (TNF-alpha), and interferon-gamma (IFN-gamma) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1beta, IL-6, and TNF-alpha. No IL-12 or IFN-gamma activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-alpha activity in about 10% of the serum samples tested. However, no IL-1beta, IL-12, or IFN-gamma activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1beta, TNF-alpha, and IL-6, and IFN-gamma mRNA in six of eight subjects, although no IFN-gamma was detected in any of the 20 samples of milk tested. RSV exposure resulted in a 2- to 100-fold increase in the expression of IL-1beta, IL-6, and TNF-alpha mRNA as well as cytokine protein. Although RSV infection enhanced the expression of IFN-gamma mRNA, no detectable IFN-gamma was produced by the milk macrophages. These observations suggest that the milk macrophages are actively engaged in the physiological production of IL-1beta, IL-6, TNF-alpha, and IFN-gamma in the mammary gland and continue to possess the capacity to increase production of these cytokines in response to RSV and possibly other viral infections.

Cytokines↗
PubMed1997

Interleukin-12-mediated killer activity in lung cancer patients.

The authors investigated the interleukin (IL)-12-inducible killer activity of blood mononuclear cells (MNC) from 30 untreated primary lung cancer patients and 24 control subjects. Cytotoxicity was assayed as 4-h 51Cr release from Daudi lymphoma cells or lung cancer cells (H-69, N-291 and PC-9). MNC from lung cancer patients exhibited similar killer activity to those from control subjects after in vitro incubation with IL-12 for 4 days. Effective killer induction by IL-12 was observed even in MNC from advanced lung cancer patients and patients with small cell lung cancer. IL-12 and a suboptimal dose of IL-2 had additive effects in inducing killer activity in MNC from both lung cancer patients and control subjects. On the other hand, with an optimal dose of IL-2, IL-12 suppressed killer induction. Addition of IL-12 alone or in combination with IL-2 resulted in interferon (IFN)-gamma production by MNC from lung cancer patients as well as control subjects. These observations suggest that IL-12 could be useful for immunotherapy of lung cancer in humans.

Adjuvants, Immunologic↗
PubMed1997

Stimulatory effect of reconstituted basement membrane components (matrigel) on the colony formation of a panel of human lung cancer cell lines in soft agar.

Lung cancers have been distinguished into small-cell lung cancer (SCLC) and non-small cell-lung cancer (NSCLC) types on the basis of their clinical behaviors and their responses to treatment. Moreover, growth of most SCLC cell lines in liquid culture medium is nonadherent, while that of most NSCLC cell lines is adherent. In this study, we examined the effect of matrigel (reconstituted basement membrane components), which is known to have growth-stimulatory activity on various human tumor cell lines in immunodeficient mice, on soft-agar colony formation of a panel of SCLC and NSCLC cell lines to clarify its mechanism of growth stimulation of cancer cells. Matrigel enhanced colony formation of all 9 NSCLC cell lines and 4 of 9 SCLC cell lines. There was a statistically significant difference (P < 0.01) between colony formations with and without matrigel of NSCLC cell lines, but not for SCLC cell lines. In liquid culture medium, all 9 NSCLC lines and 3 of 9 SCLC lines adhered to plastic dishes, whereas the other SCLC lines did not. Matrigel enhanced colony formation of all 3 adherent-type SCLC lines and 1 of 6 nonadherent-type NSCLC lines. Matrigel enhanced colony formation of both of 2 adherent-type non-lung cancer cell lines and 1 of 2 nonadherent-type leukemia cell lines. Neither transforming growth factor beta, collagen type IV, fibronectin, nor laminin, which are components of matrigel, enhanced colony formation of an NSCLC cell line in soft agar. The increase in the colony number of the NSCLC cell line by matrigel was abrogated by the protein kinase inhibitors staurosporine and UCN-01.

Adult↗
PubMed1997

Intraosseous neurilemmoma of the fibula.

We present a case of intraosseous neurilemmoma of the fibula in a 56-year-old woman. The case showed the typical radiographic appearance except for the presence of spotted calcifications that mimicked a cartilaginous tumor. Enhanced MR images revealed the heterogeneity of the tumor, which consisted of Antoni type A and B tissue.

Bone Neoplasms↗
PubMed1997

Ischiopubic insufficiency fractures: MRI appearances.

OBJECTIVE: To evaluate the MRI appearances in insufficiency fractures. DESIGN: A retrospective analysis of spin echo MR images with gadolinium-enhancement was undertaken with the emphasis on the signal change and the shape of the fracture gap and the adjacent bone marrow. PATIENTS: Five elderly women who had ischiopubic insufficiency fractures (pubis, 4; ischium 1) underwent MRI to exclude the possibility of pathologic fractures. RESULTS AND CONCLUSIONS: In no case was contrast enhancement noted at the fracture gap or the adjacent bone marrow, but a cleft-life, elongated bright signal area suggesting "fluid collection" was noted within the fracture gap. Absence of contrast enhancement and "fluid collection" at the fracture gap might suggest non-union of a fracture, which is additional information provided only by MRI.

Aged↗
PubMed1997

Intrapleural instillation of interferon gamma in patients with malignant pleurisy due to lung cancer.

The effect of intrapleural instillation of recombinant human interferon gamma (IFN gamma) at increasing doses of (1-12) x 10(6) U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable levels of IFN gamma remained in the pleural effusion as well as in patients' serum up to 7 days after instillation of 2 x 10(6) U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin(IL)-1 beta and IL-6, in the pleural effusion remained almost stable after IFN gamma instillation. On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFN gamma. IL-2- and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFN gamma to control pleural effusion in this treatment schedule, IFN gamma instilled by an intrapleural route had a potential local antitumor activity. Moreover, since IFN gamma persists in pleural effusions for a long time after a single instillation, such a therapy in combination with other fibrogenic biological response modifiers can be promising.

Aged↗
PubMed1997

Differential expressions of cyclin A and the retinoblastoma gene product in histological subtypes of lung cancer cell lines.

Cell-cycle-dependent phosphorylation of the tumor-suppressor protein product of the retinoblastoma gene (RB) is mediated by a family of cyclin-dependent kinases and cyclins. We examined the expressions of RB protein and cyclin A protein in 13 small-cell lung cancer (SCLC) lines and 14 non-small-cell lung cancer (NSCLC) lines by immunoblotting. RB protein was not present or was of a mutant type in 77% of the SCLC lines (10/13) but was present in all the NSCLC lines. Cyclin A was expressed in 38% of the SCLC lines (5/13) and in 86% of the NSCLC lines (12/14). A positive correlation (P = 0.0034) between expression of cyclin A and wild-type RB protein was found by Fisher's exact probability test. Densitometric analysis of the expression of RB protein in RB(+) lung cancer lines showed that the phosphorylated form was predominant in 2/3 of the SCLC and 8/14 of the NSCLC lines. The positive correlation between the expressions of RB protein and cyclin A suggests that RB protein in most RB(+) lung cancer cell lines is a target of cyclin-A-dependent kinase and that the tumor-suppressor function may be inactivated by phosphorylation.

Adenovirus E1A Proteins↗
PubMed1997

Systemic and local immune responses of four cases with lower respiratory tract illness due to reinfection with respiratory syncytial virus.

Four infants and children who had tracheobronchitis or bronchiolitis by respiratory syncytial virus (RSV) reinfection were presented. Their clinical features, systemic and local immune reactions to RSV were compared with those of eleven age-matched patients who had lower respiratory tract illness with primary RSV infection. Moderate antibody activities in their nasopharyngeal secretions and sera which were comparable to those of convalescent phase of primary infection were observed within several days after onset of illness; however, their clinical symptoms, such as fever or wheezing, lasted almost as long as in primary RSV infection. These observations suggest that the higher serum and secretory antibody activity to RSV during acute phase does not always bring about clinical amelioration in RSV reinfection. The contribution of immunopathological reaction between RSV and RSV-specific antibodies might also be considered as a cause of inflammation during the acute phase of RSV reinfection.

Antibody Formation↗
PubMed1997

Warthin's tumor of the parotid gland with extension into the parapharyngeal space.

A case of Warthin's tumor of the parotid gland which extensively extended into the parapharyngeal space is presented. The tumor border against the parotid gland was ill-defined but the border towards the parapharyngeal structures was clear. Solid portions of the tumor appeared hypointense relative to the gland on both unenhanced T1- and T2-weighted MR images without fat suppression, whereas cystic portions appeared hypointense on T2-weighted images and hyperintense on unenhanced T1-weighted images. Pathologic study showed that the ill-defined margin was caused by inflammation and cystic material consisted of highly proteinaceous material. We concluded that the atypical extension into the parapharyngeal space of the tumor was caused by its location in the deep lobe of the parotid gland and its bulky size.

Adenolymphoma↗
PubMed1997

Assessment of parotid masses: which MR pulse sequences are optimal?

The objective of this paper is to determine which MR pulse sequences are optimal for delineation of lesion and predicting pathologic nature of lesion with signal intensity. A prospective study was performed in 53 parotid masses (39 benign and 14 malignant lesions) in 53 patients. Signal intensity of lesion was visually assessed and lesion/parotid contrast-to-noise ratios were measured. On visual assessment, detection sensitivity was 100% for nonenhanced nonfat-suppressed T1-weighted images, 91% for nonfat-suppressed fast spin-echo (FSE) T2-weighted images, 83% for gadolinium-enhanced fat-suppressed T1-weighted images, and 75% for fat-suppressed FSE T2-weighted images. The highest contrast-to-noise ratios were obtained with nonenhanced T1-weighted images. Hypointensity of lesion relative to the parotid gland on nonfat-suppressed FSE T2-weighted images was seen in 11 of 14 malignancies, 12 of 15 Warthin tumors, and two of 18 pleomorphic adenomas. Cystic portion of hyperintensity on nonenhanced T1-weighted images was solely seen in benign tumors (n = 11). Thus, the highest accuracy (81%) (79% sensitivity and 82% specificity) for predicting malignancy was obtained with a criterion of hypointensity on nonfat-suppressed FSE T2-weighted images plus absence of cystic portion of hyperintensity on nonenhanced T1-weighted images. Nonenhanced T1-weighted images combined with nonfat-suppressed FSE T2-weighted images is optimal for delineation of lesion and prediction of pathologic nature of parotid masses.

Adolescent↗
PubMed1997

Functional analysis of vif genes derived from various primate immunodeficiency viruses.

Replication property in cells of human and simian immunodeficiency viruses (HIVs and SIVs) lacking intact vif gene was evaluated. Of 10 vif mutants constructed in vitro of the major four HIV/SIV groups, only those derived from HIV-1 and HIV-2/SIVmac displayed replication defect. The cell lines non-permissive for the vif mutants of HIV-1 and SIVmac were found to be different. To determine whether Vif is exchangeable between HIV-1 and SIVmac, chimeric virus clones with respect to the vi gene were constructed and virus replication in the cells non-permissive for the vif mutant viruses was monitored. Productive infection in these cells of chimeric viruses clearly indicated that Vif is functionally exchangeable, and that Vifs of different virus origin act through a similar mechanism.

Animals↗
PubMed1997

Lung nodule conspicuity using unsharp mask filters with storage-phosphor-based computed radiography.

PURPOSE: To compare the performance of various types of unsharp mask filter applied in storage-phosphor-based computed radiography (SR), and to improve the detection of faint nodules of the lung cancer type. MATERIAL AND METHODS: A total of 120 SR radiographs were obtained by means of an anthropomorphous chest phantom and a combination of 3 types of small simulated nodule (5-mm sphere-shaped, and 5-mm and 10-mm hemisphere-shaped) placed on the phantom's surface. Eight combinations of nodule site were selected from 16 predetermined chosen sites, and 5 types of parameter were used for unsharp mask filtering. Eight observers evaluated the images, and the detectability of the lung nodules was evaluated from the images by a ROC analysis. RESULTS: The visibility of the 10-mm hemispherical nodules was nearly equivalent at each site when 5 types of unsharp mask filter were used. The detection of the 5-mm nodules with mid-frequency suppressing and very-low-frequency enhancing filters was better than with a conventional (department standard) mid-frequency enhancing filter. CONCLUSION: Mid-frequency suppressing versions of the filter helped to demonstrate faint nodular opacity, which is often shown by early bronchogenic carcinoma. This filter could replace conventional filters in the detection of lung nodules.

Carcinoma, Bronchogenic↗
PubMed1997

Hemodialysis-related arthropathy. A prospective MR study with SE and GRE sequences.

PURPOSE: A prospective examination of hemodialysis-related arthropathy by MR imaging with SE and GRE sequences was undertaken to verify whether the low signal intensity on T2-weighted SE images is caused by a paramagnetic susceptibility effect derived from amyloid or from hemosiderin. MATERIAL AND METHODS: Twenty-seven joints (19 hip joints, 6 discovertebral joints of 5 lumbosacral spines and 1 cervical spine, 2 shoulder joints) in 14 patients undergoing long-term hemodialysis (duration 10-22 years, mean 17) were examined with SE T1-weighted, T2-weighted and GRE T2*-weighted sequences. RESULTS: The signal intensity of the intraarticular and periarticular masses of the involved joints was basically isointense to the muscle in all 3 pulse sequences. No significantly low signal area was found on GRE T2*-weighted images. CONCLUSION: The low signal areas in the hemodialysis-related arthropathy on SE T2-weighted images are not caused by a paramagnetic susceptibility effect, but probably by the hypocellular and fibrous nature of amyloid-containing tissues. Therefore the GRE sequence can be helpful for differentiating hemodialysis-related amyloid arthropathy from chronic hemarthrosis or juxta-articular brown tumor.

Adult↗