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C Koike

Publications and source records attributed to C Koike.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of sialylglycoconjugate(s) in the initial phase of metastasis of liver-metastatic RAW117 lymphoma cells.

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.

Animals↗
PubMed1997

Tumor cells with organ-specific metastatic ability show distinctive trafficking in vivo: analyses by positron emission tomography and bioimaging.

To elucidate the behavior of various metastatic tumor cells with different characteristics in the blood flow, we have developed a system to investigate real-time trafficking using positron emission tomography. In this study, positron-labeled cells, i.e., lung-metastatic B16BL6 melanoma and two sublines of liver-metastatic RAW117 large cell lymphoma, were injected i.v., and the trafficking of these cells was noninvasively determined. All sublines tested accumulated in the lungs immediately after injection, presumably because the lungs were the first organ passed through after i.v. injection. The elimination of RAW117 cells from the lungs, however, was fast compared with that of B16BL6 cells. The latter showed a release rate from the lungs of less than 1%/min, whereas that of RAW117 cells was greater than 2%/min. Reflecting the elimination from lungs, RAW117 cells accumulated in the liver in a time-dependent manner. Biodistribution of metastatic cells was also analyzed by whole-body autoradiography after injection of 5-[125I]iodo-2'-deoxyuridine-labeled cells, using a bioimaging analyzer system. The method is invasive; however, it enables a precise determination of the biodistribution of metastatic cells. Bioimaging analyzer system analysis also showed the organ-specific accumulation of these metastatic cells. Furthermore, colonized distribution of B16BL6 cells in the lungs and that of RAW117 cells in the liver were observed. The present data suggest that the trafficking of metastatic tumor cells greatly influences the organ specificity of cancer metastasis.

Animals↗
PubMed1996

Functional role of sialyl Lewis X and fibronectin-derived RGDS peptide analogue on tumor-cell arrest in lungs followed by extravasation.

Our study demonstrates that synthetic sialyl Lewis X (SLex) as a ligand for selectins and fibronectin-derived RGDS peptide analogue [Ar(DRGDS)3] inhibits lung metastases produced by i.v. co-injection of B16-BL6 melanoma cells. To investigate the inhibitory mechanisms in a living animal, we performed positron-emission tomography (PET) analysis after i.v. injection of [2-18F]2-fluoro-2v-deoxy-D-glucose-labeled tumor cells with or without liposomal SLex or Ar(DRGDS)3. The real-time PET measurement for the first 120 min, started immediately after injection, showed that tumor-cell arrest, i.e., accumulation in the target organ (lung) was remarkably inhibited by liposomal SLex, but not inhibited by Ar(DRGDS)3 or liposomal Me-SLex, which is not recognized by selectins. In contrast, Ar(DRGDS)3 inhibited the invasion of B16-BL6 cells into reconstituted basement membrane (Matrigel) following tumor arrest, whereas SLex- or Me-SLex-entrapped liposomes did not affect tumor invasion. In the metastatic processes containing tumor-cell lodgement and arrest in the target organ followed by extravasation (invasion), SLex resulted in the inhibition of initial arrest of tumor cells, presumably tumor-endothelium interaction, while Ar(DRGDS)3 achieved inhibition of tumor invasion into basement membrane at later steps of the cascade, consequently leading to inhibition of metastasis. Thus, tumor-cell arrest in lungs in the metastatic processes must be precisely and properly controlled by different adhesion molecules at different stages, which are similar to those observed in leukocyte-endothelium interaction.

Amino Acid Sequence↗
PubMed1996

Establishment of a human DAF/HRF20 double transgenic mouse line is not sufficient to suppress hyperacute rejection.

To solve the chronic donor organ shortage, the pig is considered to be a possible donor candidate for human transplantation. However, hyperacute rejection occurs due to the activation of the complement cascade. Therefore, the introduction of human complement inhibitors into animal cells has been proposed as a means to prevent such exologous complement activation. To investigate the extent to which complement inhibitors are resistant to human sera in discordant animals, we established transgenic mice lines which expressed either human decay-accelerating factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The results showed that all the mice in groups a, b, and c died immediately after injection. Three of the mice in group d died, while seven survived but showed hyperpnea and low activity. The pathological findings of groups a, b, and c included severe coagulation; however, the survivors of group d showed less severe symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent complement activation to some extent; however, its effectiveness is not considered to be sufficient for clinical use in transplantation.

Animals↗
PubMed1996

Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs.

Analogs of a synthetic peptide having the L-arginine-L-glycine-L-aspartic acid (RGD) sequence have been found to decrease metastatic colonization. To enhance the metastasis-suppressing efficacy of these analogs, we sought to stabilize these analogs and to prolong their circulation time by incorporating them into a liposomal formulation. Various structures of RGD analogs grafted to hydrophobic groups were synthesized and then incorporated into liposomes. Liposomes composed of distearoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol and appropriate RGD analogs were injected intravenously along with B16BL6 murine melanoma cells into mice. Liposomal RGD (0.6 mumol of the analog equivalent to ca. 200 micrograms RGD peptides) inhibited lung colonization up to 76%. This dose is an order of magnitude lower than that for comparable inhibition reported for free RGD. Multi-dose administration of liposomal RGD (0.15 mumol of the analog) also inhibited the spontaneous lung metastasis of cells from a primary tumor site of B16BL6 cells subcutaneously implanted into the footpad of mice. Taken together, our data indicate that liposomal RGD may serve as a useful anti-metastatic agent.

Amino Acid Sequence↗
PubMed1996

The production of heparin cofactor II is not regulated by inflammatory cytokines in human hepatoma cells: comparison with plasminogen activator inhibitor type-1.

Using the Northern blot technique, we screened 6 human hepatoma cell lines to investigate the regulation mechanism of heparin cofactor II (HC II) biosynthesis. We found that HuH-7 and Hep G2 cells constitutively expressed the HC II gene. In conditioned medium, HuH-7 cells constantly produced HC II that was functionally active and formed a complex with thrombin in the presence of dermatan sulfate. HC II is thought be an acute phase reactant, and, therefore, we examined the effects of the major inflammatory cytokines, IL-6, IL-1 beta, and TNF-alpha, on the regulation of HC II production in HuH-7 and Hep G2 cells. In HuH-7 cells, the antigen and mRNA levels of plasminogen activator inhibitor type-1 (PAI-1), an acute phase protein produced by hepatocytes, were increased in response to stimulation with either IL-6 or IL-1 beta or both, but HC II antigen and mRNA levels were not changed by the same stimulation. Even when Hep G2 cells were treated with a combination of three cytokines, IL-6, IL-1 beta, and TNF-alpha, HC II antigen and mRNA levels were not changed; however, PAI-1 antigen and mRNA levels were clearly increased. These results suggest that the production of HC II in hepatoma cells is not regulated by the major inflammatory mediators, IL-6, IL-1 beta, and TNF-alpha.

Blotting, Northern↗
PubMed1995

Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties.

Although a number of studies have indicated that highly metastatic cells tend to adhere more to target endothelium in vitro than low or non-metastatic cells, direct evidence about the correlation between cellular adhesiveness and organ disposition of the cells has not been obtained. Using positron emission tomography (PET), we have developed a novel technique that enables the non-invasive detection of the real-time tumor cell trafficking. The present study shows the correlation between trafficking of murine large cell lymphoma RAW117 and the adhesion properties of the cells in vitro. Cells accumulated in the liver time-dependently, and accumulation of RAW117-H10, liver metastatic subline cells, was more intense than that of RAW117-P, the parental cells, indicating that the metastatic potential is correlated with the in vivo accumulation of the cells in the target tissue. To examine whether the adhesion properties of the cell membrane determine the cell trafficking, we performed PET analysis after altering the adhesion properties on the cell membrane by means of cellular protein kinase C modulation, since the modulation of this enzyme is known to alter the surface adhesion molecules, i.e., those of the integrin superfamily. The treatment of RAW117-P with 12-O-tetradecanoylphorbol 13-acetate, which caused augmentation of adhesion to hepatic sinusoidal microvessel endothelial cells (HSE) in vitro, enhanced the hepatic accumulation of the cells in vivo. On the contrary, treatment of RAW117-H10 with the protein kinase C inhibitor H-7, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, which reduced the adhesion activity of the cells to HSE, suppressed their accumulation in the liver, although the suppression was observed only during the first 30 min after administration of the cells. These data suggest that the adhesion properties of metastatic lymphoma cells are critical for the accumulation of these cells in the target tissue.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗