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Biomedical subjects

Y Saijo

Publications and source records attributed to Y Saijo.

At least 37 records · Page 2Linked to original sources

Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene.

Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We constructed a recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the sensitivity to all six drugs regardless of the cellular p53 status, and a synergism was observed by the isobolic method in combination studies (D<1). We conclude that our strategy using adenoviral mediated p53 gene transfer to cancer cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an improvement of lung cancer chemotherapy.

Adenoviruses, Human↗

Expression of the 37-kDa laminin binding protein in murine lung tumor cell correlates with tumor angiogenesis.

Expression of the 37-kDa laminin binding protein (37LBP), a precursor protein of the 67-kDa laminin receptor, correlates well with the biological aggressiveness of cancer cells. Previously, we have established murine lung cancer cell lines T11 and T15, in which 37LBP expression was remarkably diminished, and reported that the mean survival time of the T11 and the T15-recipients was significantly prolonged compared with that of the control cell lines (P29 and T42). In the present study, immunohistochemical findings of the tumors demonstrated that the microvessel density in the T11 (28. 1+/-7.2/mm(2)) and in the T15 tumor (29.7+/-6.5/mm(2)) were significantly lower than that observed in P29 (46.3+/-8.7/mm(2)) or in T42 (50.5+/-4.4/mm(2)). Expression of vascular endothelial growth factor (VEGF) was repressed in T11 and T15 compared with its expression in P29 and T42. It was also shown that conditioned media of T11 and T15 cells exhibited significantly reduced proliferation and migration of the capillary endothelial cells. These results suggest that decreased expression of 37LBP in antisense-RNA transfectant may relate to its low tumorigenicity, and that this effect may be partly caused by the diminished tumor angiogenesis of murine lung cancer.

Animals↗

Effect of a novel vasoconstrictor endothelin-1 (1-31) on human umbilical artery.

To clarify the action of a novel endothelin-1 with 31 amino acids, ET-1 (1-31), on fetal circulation, its vasoconstrictive activity on human umbilical and uterine arteries was investigated in comparison with that of a conventional ET-1 (1-21). UFER micro-easy magnus was used for determination of vasoconstriction. The contraction of umbilical artery by KCl was significantly weaker than that of the uterine artery. In ETs, constriction by KCl was set as control, and the rate of constriction of uterine and umbilical arteries was used for comparison. The constriction of human uterine artery induced by ET-1 (1-31) was also significantly weaker than that by ET-1 (1-21). On the contrary, ET-1 (1-31) was a potent constrictor on the umbilical artery equally to ET-1 (1-21). The present study is the first to demonstrate that ET-1 (1-31) has a contractile activity on human vessels. Furthermore, the regulatory mechanism on constriction of umbilical artery is different from that observed in a systemic vessel, indicating a particularly important role of ET-1 (1-31) in fetal circulation.

Adult↗

Visualization of human umbilical vein endothelial cells by acoustic microscopy.

The morphology and acoustic properties of the human umbilical vein endothelial cells (HUVECs) were evaluated using a scanning acoustic microscope system. HUVECs were cultured for 4 days and exposed to the endotoxin for 4 h. The frequency of the scanning acoustic microscope was variable between 100 and 210 MHz. By changing the measuring frequency, ultrasonic amplitude and phase were measured and the quantitative value of attenuation was calculated. Before and after endotoxin stimuli, HUVECs were observed by scanning acoustic microscopy and the attenuation was measured. The acoustic images were successfully obtained to identify the outer shape of the HUVEC and the location of the nucleus in the cell. The attenuation of the nucleus is higher than that of the cytoplasm. The attenuation of the cytoplasm was increased and became inhomogeneous after endotoxin exposure. This finding would be related to the change of F-actin filaments, which is the main component of the cytoskeleton. Scanning acoustic microscopy is useful for assessing the cellular viscoelastic properties since it can detect both the morphological and acoustic changes without contacting the cellular surface.

Acoustics↗

Microscopy.

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Elasticity↗

Induction of antitumor immunity by combined immunogene therapy using IL-2 and IL-12 in low antigenic Lewis lung carcinoma.

Interleukin-2 (IL-2) and interleukin-12 (IL-12) are crucial cytokines that induce potent antitumor responses in a variety of animal cancer models. Although single gene transfer of either IL-2 or IL-12 exhibits limited antitumor effects, the combination of IL-2 and IL-12 has been shown to induce a stronger antitumor response and to cure tumor-bearing mice. To examine the conditions necessary for tumor rejection, we varied the local concentration of IL-2 and IL-12 by introducing these genes into Lewis lung carcinoma (LLC) cells via retroviral vectors and/or an adenoviral vector and evaluated the growth of inoculated LLC cells (5 x 10(5) cells). In contrast to the result when using a stepwise dose increase of IL-2 either without or with a fixed production of IL-12 (4-5 ng/5 x 10(5) cells/24 hours, insufficient for tumor rejection by itself), rejection of the tumor was achieved in 75% of the mice when the IL-12 secretion was combined with high and transient IL-2 production (42 ng/5 x 10(5) cells/24 hours) using additional adenoviral vector transduction (100 multiplicities of infection). An abundant infiltration of both CD4+ (47.4/mm2) and CD8+ (85.6/mm2) T cells was a characteristic finding in the dual gene-transfected LLC tumors. Importantly, consistent with the rejection of rechallenged parental cells, tumor-specific cytotoxic T lymphocytes were induced only from the splenocytes of mice inoculated with the dual gene-transduced LLC cells, suggesting the existence of protective antitumor memory. In addition, only vaccination of dual gene-transduced LLC cells inhibited the growth of pre-established LLC tumors. These results indicate that generation of a pivotal antitumor response likely depends on the synergistic combination and concentration of IL-2 and IL-12 in the local milieu by which tumor-specific immune memory is established.

Adenoviridae↗

Over-expression of a single Ca2+-dependent protein kinase confers both cold and salt/drought tolerance on rice plants.

A rice gene encoding a calcium-dependent protein kinase (CDPK), OsCDPK7, was induced by cold and salt stresses. To elucidate the physiological function of OsCDPK7, we generated transgenic rice plants with altered levels of the protein. The extent of tolerance to cold and salt/drought stresses of these plants correlated well with the level of OsCDPK7 expression. Therefore, OsCDPK7 was shown to be a positive regulator commonly involved in the tolerance to both stresses in rice. Over-expression of OsCDPK7 enhanced induction of some stress-responsive genes in response to salinity/drought, but not to cold. Thus, it was suggested that the downstream pathways leading to the cold and salt/drought tolerance are different from each other. It seems likely that at least two distinct pathways commonly use a single CDPK, maintaining the signalling specificity through unknown post-translational regulation mechanisms. These results demonstrate that simple manipulation of CDPK activity has great potential with regard to plant improvement.

Adaptation, Physiological↗

Evaluation of the inner-surface morphology of an artificial heart by acoustic microscopy.

The total artificial heart (TAH) is being developed for permanent replacement of the natural heart instead of heart transplantation. The need for detecting the material fatigue in the TAH is increasing in order to guarantee long-term use. In this study, the inner surface morphology of the TAH was evaluated by a specially developed scanning acoustic microscope (SAM) system operating in the frequency range of 100-200 MHz. The inner sac of our TAH consisted of polyvinylchloride coated with polyurethane, and the SAM investigations were performed before and after the implantations in goats. The amplitude images of the SAM demonstrated protein adhesion on the inner surface of the TAH after the animal experiment, and the phase images showed distortion of the wall with spatial resolution of 0.2 microm. These results suggest the feasibility of a high-frequency ultrasound for evaluating the material fatigue of TAH.

Animals↗

Bilateral pneumothoraces with multiple bullae in a patient with asymptomatic bronchiolitis obliterans 10 years after bone marrow transplantation.

A 16-year-old boy developed bronchiolitis obliterans (BO) 10 years after BMT for myelodysplastic syndrome. Although the patient complained of almost no dyspnea on exertion, he had mild hypercapnea with a markedly reduced forced expiratory volume of 0.32 l. Chest X-rays showed occasional bilateral minimal pneumothoraces, which is in accordance with the existence of multiple small bullae found on the pleural surface at video-assisted thoracic surgery. Histologic examination of the biopsied lung revealed BO. This case indicates that BO in adolescence following BMT and possible chronic GVHD may be masked because of lung immaturity at BMT, and BO after BMT may be associated with multiple pleural bullae.

Adolescent↗

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗

Autologous high-killing cytotoxic T lymphocytes against human lung cancer are induced using interleukin (IL)-1beta, IL-2, IL-4, and IL-6: possible involvement of dendritic cells.

Although CTLs bear main immune responses in human tumors, stable CTL clones against human lung cancer have rarely been generated. Our previous study demonstrated efficient autologous CTL induction in human gastric cancer and glioblastoma by cytokine combination of interleukin (IL)-1beta (167 IU/ml), IL-2 (67 IU/ml), IL-4 (67 IU/ml), and IL-6 (134 IU/ml). In this study, we demonstrated successful induction of autologous stable CTLs in five of six patients with lung adenocarcinoma from mixed-lymphocyte tumor culture using this cytokine combination. All CTLs revealed potent and specific killing activity against autologous target cells (over 75% in CD8+ CTLs and over 50% in CD4+ CTLs at an E:T ratio of 10 for 24 h). Using a series of antibodies, CD8+ CTLs showed to recognize tumor-specific antigens of lung cancer cells through HLA class I. In the separate experiments, failure of CTL induction from monocyte-depleted peripheral blood mononuclear cells and appearance of cells with characteristics of dendritic cells from adherent peripheral blood mononuclear cells in the culture of the same concentration of IL-1beta, IL-4, and IL-6 indicated that CTLs can be efficiently generated by this cytokine combination via possible dendritic cell induction. This is the first study of an efficient and reproducible in vitro CTL induction against human lung cancer.

Adenocarcinoma↗

Acoustic properties of atherosclerosis of human aorta obtained with high-frequency ultrasound.

The ultrasonic properties of the tissue elements in the aorta were measured using a scanning acoustic microscope (SAM). Twelve autopsied aortas were formalin-fixed, frozen and sectioned at 10 microm thickness and mounted on glass slides for SAM investigation. A specially developed SAM system operating in the frequency range of 100-200 MHz was employed, and color-coded images of the two-dimensional (2-D) distributions of attenuation and sound speed were displayed. The region-of-interest (ROI) for attenuation and sound speed measurements was determined by comparison of optical and acoustic images. The average value of the slope of attenuation was 0.61 dB/mm/MHz and the sound speed was 1568 m/s in the normal intima; 2.5 dB/mm/MHz, 1760 m/s in the calcificated lesion; 1.7 dB/mm/MHz and 1677 m/s in the fibrosis; and 0.34 dB/mm/MHz, 1526 m/s in the fatty material, respectively. Acoustic microscopy provides the basic data for understanding the IVUS imaging of atherosclerosis, as well as on the pathological features of atherosclerosis.

Aorta, Abdominal↗

Exogenous recombinant human IL-12 augments MHC class I antigen expression on human cancer cells in vitro.

We investigated whether expressions of MHC class I and class II antigens relevant to tumor antigen presentation were changed on human tumor cells cultured with or without recombinant human IL-12(rhIL-12). We showed that the expression of MHC class I antigen on UTC-8, 28-1Cl and SBC-3 cells was augmented when these cancer cells were cultured with rhIL-12. The expression of class II antigen was slightly raised on UTC-8 and 28-1Cl cells by rhIL-12, but not enhanced on SBC-3 cells. These results suggest that rhIL-12 may provide possible enhancement of immunologic tumor recognition, and cytotoxic activity of lymphocytes against tumors through the enhanced expression of MHC class I antigen.

Carcinoma, Squamous Cell↗

[A case of paraesophageal omental herniation].

A 48-year-old woman underwent routine chest roentgenography and a mass shadow was seen in the posterior mediastinum. CT, MRI and celiac arteriography were performed, and paraesophageal omental herniation was diagnosed. Paraesophageal omental herniation is uncommon, and there have been no reports cases with complications. Therefore, this case is being followed-up carefully.

Celiac Artery↗