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Biomedical subjects

I Saiki

Publications and source records attributed to I Saiki.

At least 145 records · Page 8Linked to original sources
PubMed1991

Recombinant fusion polypeptide with cell- and heparin-binding domains of fibronectin inhibits liver metastasis of L5178Y-ML25 lymphoma cells.

We have investigated the effect of recombinant polypeptides with cell-binding domain (C-274) or with heparin-binding domain (H-271) and their fusion polypeptide (CH-271) on liver metastasis of murine lymphoid tumor. The polypeptides containing heparin-binding domain, H-271 and CH-271, were able to inhibit liver metastasis when co-injected i.v. with L5178Y-ML25 T-lymphoma cells, while C-274 with cell-binding domain showed much weaker antimetastatic activity. Treatment with H-271 or CH-271 substantially prolonged the survival time of mice injected i.v. with L5178Y-ML25 cells. CH-271, containing cell- and heparin-binding domains, was more antimetastatic than H-271. The reason why CH-271 was more effective in inhibiting liver metastasis than H-271 can not be explained in terms of a difference in the stability in the circulation or in the molecular size of the polypeptide. The polypeptides used in this study did not affect the tumor cell growth or viability in vitro. CH-271 was found to be still active in inhibiting liver metastasis even when natural killer cells or macrophages were removed from this system. Furthermore, multiple administrations of CH-271 after tumor implantation effectively inhibited liver metastasis and enhanced the survival rate as compared with H-271, C-274 and untreated control. Thus, the fusion of H-271 with C-274 (i.e. CH-271) augments the antimetastatic property of H-271, possibly through the interaction between tumor cells and the heparin-binding domain of fibronectin.

2-Chloroadenosine↗
PubMed1991

Inhibitory effect of antimetastatic fusion polypeptide of human fibronectin on tumor cell adhesion to extracellular matrices.

We investigated the inhibitory mechanism of liver metastasis by using recombinant fragments with cell- and/or heparin-binding domains (C-274, H-271 or the fusion fragment CH-271). Intravenous co-injection of L5178Y-ML25 cells with CH-271 was more effective for the inhibition of liver metastasis than C-274, H-271 or C-274 + H-271. Reduction of the arrest and retention of the radiolabeled tumor cells in the liver of mice was found when CH-271 was co-injected with tumor cells. L5178Y-ML25 cells adhered both concentration- and time-dependently to the substrates precoated with fibronectin, laminin and reconstituted basement membrane, Matrigel. The tumor cell adhesions to the substrates were inhibited in the presence of CH-271. The tumor cell interaction with CH-271-substrate was inhibited by heparin, and monoclonal antibodies (IST-1 or IST-2) against the heparin-binding domain of fibronectin. However, monoclonal antibodies against the cell-binding domain failed to block the interaction. Similarly, CH-271-mediated antimetastatic activity was also inhibited by the treatment of CH-271 with IST-1 before the co-injection with tumor cells, whereas monoclonal antibody against the cell-binding domain had no effect. Thus, the antimetastatic effect of CH-271 fusion fragment on liver metastasis of L5178Y-ML25 cells may be partly due to interference with the adhesive interaction of tumor cells with extracellular matrix or basement membrane components by a heparin-binding domain-dependent mechanism.

Animals↗
PubMed1991

Molecular properties of poly(RGD) and its binding capacities to metastatic melanoma cells.

We examined the binding capacity of anti-metastatic polypeptide containing repetitive Arg-Gly-Asp(RGD) sequence derived from cell binding site of fibronectin, poly(RGD), to the surface of tumor cells. Poly(RGD) competitively inhibited the binding of radiolabeled fibronectin to the cell surface more potently than oligo(RGD) or RGD tripeptide on a molar basis. Compared on a weight basis to oligo(RGD) or RGD peptide, poly(RGD) was more active than the oligo- and monomeric peptide at inhibiting tumor cell adhesion to immobilized fibronectin. The secondary structure of poly(RGD) was predicted to be a beta-turn from the data of CD spectra and its amino acid sequence. These findings suggest that poly(RGD)-mediated inhibition of cell adhesion is due to its potent binding capacity to fibronectin receptors on cell surface probably through its conformational properties.

Animals↗
PubMed1991

[A study on auditory disturbances after microvascular decompression for hemifacial spasm].

After establishing an operation of microvascular decompression by Jannetta in 1975, an improvement rate of hemifacial spasm have increased. However, postoperative hearing deficits, equilibrium disturbances and facial paresis have been described in some publications. Fifty-seven of 119 patients with hemifacial spasm operated from 1982 to 1989, were examined by audiometry before and after operation. In patients with tinnitus at the time of facial spasm and closing eyelids, tinnitus improved almost in many cases. Of 57 patients, 8 (5 with sensorineural hearing loss, 3 with conductive hearing loss) had postoperative hearing impairments in operated ears, and 7 (7 with sensorineural hearing loss) had in the other ears, too. Of 7 patients having sensorineural hearing loss observed for several months, 4 having slight sensorineural hearing loss recovered at the same hearing level before operation. In 2 patients having profound sensorineural hearing loss, however, hearing improvement did not observed in each case.

Adult↗
PubMed1990

Modulation of haptotactic migration of metastatic melanoma cells by the interaction between heparin and heparin-binding domain of fibronectin.

We utilized recombinant fibronectin polypeptides with cell-binding domain and heparin-binding domains (referred to as C-274 and H-271, respectively) and their fusion polypeptide (CH-271) to examine the role of sulfated polysaccharide heparin and/or the functional domains of fibronectin in modulating tumor cell behavior. Both C-274 and CH-271 polypeptides with cell-binding domains promoted the adhesion and migration of B16-BL6 melanoma cells, whereas H-271 did not. Heparin bound to the immobilized polypeptides with heparin-binding domain (H-271, CH-271, and a mixture of C-274 and H-271 or fibronectin) but did not affect the tumor cell adhesion to the substrates. At the same time, heparin or two monoclonal antibodies against the heparin-binding domain were able to inhibit the haptotactic migration to CH-271 or fibronectin, though not to C-274 or a mixture of C-274 and H-271. This suggests that although heparin did not affect tumor cell adhesion to the cell-binding domain near the heparin-binding domain in CH-271 or fibronectin, it did lead to a modulation of cell motility. It seems likely that the regulatory mechanism may depend on interaction between heparin-like molecules on the cell surface and the heparin-binding domain in fibronectin, rather than on simple steric hindrance or on the masking of the cell-binding domain caused by the binding of heparin to heparin-binding domain.

Animals↗
PubMed1990

Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells.

We have investigated the effects of sulfated chitin derivatives and heparin on the invasion of B16-BL6 melanoma cells through reconstituted basement membrane Matrigel which contains laminin, type IV collagen, heparin sulfate proteoglycan, and entactin. 6-O-sulfated chitin (S-chitin) and 6-O-sulfated and carboxymethyl chitin (SCM-chitin) significantly inhibited the penetration of tumor cells through Matrigel in parallel with the increased degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin derivative (SCM-chitosan) and CM-chitin had no effect. SCM-chitin with a high degree of sulfation (SCM-chitin III), which exhibited fairly low levels of anticoagulant activity, was more effective than intact heparin. SCM-chitin III and heparin were also shown to block the attachment and migration of tumor cells to laminin-coated substrates, which are considered to be involved in tumor invasion. The inhibition of cell attachment and migration by SCM-chitin III and heparin is likely to depend upon their specific binding to laminin molecules (possibly the heparin-binding domain). Degradation of heparan sulfate by heparanase was inhibited by SCM-chitin III and heparin in a dose-dependent manner. Surprisingly, SCM-chitin III could inhibit type IV collagenolytic activity of tumor cells more potently than heparin. Thus, nontoxic SCM-chitin III of low anticoagulant properties may provide a promising basis for the prevention of cancer metastasis.

Binding, Competitive↗
PubMed1990

Production of interleukin 1 from human monocytes stimulated by synthetic lipid A subunit analogues.

We have investigated that synthetic lipid A subunit analogues (GLA compounds) as well as E. coli type lipopolysaccharide (LPS) and synthetic lipid A (compound 506) are able to stimulate human monocytes to release IL-1 in vitro. Of monosaccharide-type GLA compounds, GLA-60 was found to be more active for the induction of IL-1 production than GLA-59 and GLA-27, and similar to that of LPS or compound 506. GLA-60 could induce not only the secretion of IL-1 into culture supernatant but also the expression of membrane-associated form of IL-1 in human monocytes. Furthermore, no detectable IL-2 activity was observed in the culture supernatant. These results show that synthetic lipid A analogues of low toxicity, in particular GLA-60, are active in inducing IL-1 production in human monocytes.

Cell Division↗
PubMed1990

Activation by synthetic lipid A subunit analogues (GLA compounds) of tumoricidal properties in human blood monocytes.

The authors have determined that synthetic lipid A subunit analogues (GLA compounds), as well as E. coli type lipopolysaccharide (LPS) and synthetic lipid A (compound 506), are able to stimulate human monocytes to become cytotoxic against tumour target cells in vitro. GLA-60, a synthetic lipid A subunit analogue of low toxicity, was found to be more active for the induction of tumoricidal monocytes than GLA-59, and similar to that of LPS. GLA-60 could induce not only the secretion of cytotoxic factor into the culture supernatant but also expression of the membrane-associated form of cytotoxic factor in human monocytes. Supernatant-mediated cytotoxicity was completely inhibited by the addition of monoclonal anti-human TNF antibody. These results indicate that a synthetic lipid A subunit analogue, GLA-60, would be a useful activator of tumoricidal monocytes in spite of its low toxicity.

Adjuvants, Immunologic↗
PubMed1990

Inhibition of tumor cell arrest in lungs by antimetastatic chitin heparinoid.

We have investigated the effect of sulfated chitin derivatives on the intravascular events in the metastatic cascade. 6-O-Sulfated carboxymethyl chitin (SCM-chitin III), as well as heparin, significantly inhibited the arrest of B16-BL6 cells in lungs after co-injection with radiolabeled tumor cells, but carboxymethylated chitin (CM-chitin) had no effect. Heparin showed a potent inhibitory effect on tumor cell-elicited platelet aggregation and on blood coagulation, which can subsequently enhance the survival, arrest and invasiveness of tumor cells, whereas SCM-chitin III showed much weaker properties. In contrast, SCM-chitin III was found to inhibit the adhesion of tumor cells to subendothelial matrix, while heparin did not. SCM-chitin III was still active in inhibiting experimental lung metastasis even in mice which had been pretreated with anti-asialo GM1 serum or carrageenan to eliminate NK cells or macrophages. Thus, these results suggest that SCM-chitin-mediated inhibition of tumor metastases is distinct from that by heparin and may be due to interference with tumor cell arrest in the capillaries and consequently to the inhibition of tumor cell adhesion to subendothelial matrix.

Animals↗
PubMed1990

Inhibition of lung metastasis by synthetic and recombinant fragments of human fibronectin with functional domains.

We have investigated the antimetastatic effect of synthetic or recombinant peptides containing the functional domains of fibronectin on experimental and spontaneous lung metastases of murine tumor cells. CS1 peptide which is present within type III homology connecting segment (IIICS) as well as C-274 (cell-binding domain) were able to inhibit experimental lung metastasis when co-injected intravenously (iv) with B16-BL6 melanoma cells, while H-271 (heparin-binding domain) could not. In the spontaneous metastasis model, multiple iv administrations of CS1 or C-274 after surgical excision of primary tumors caused a significant reduction of metastatic colonies in the lung. Both CS1 and C-274 significantly inhibited cell adhesion and migration to fibronectin-coated substrates when added freely in solution. CS1 peptide also inhibited the cell adhesion and migration to laminin-coated substrates, but C-274 did not. H-271 did not have any inhibitory effect on cell adhesion or migration to either of the substrates. Similarly, CS1 inhibited tumor invasion to both Matrigel/fibronectin- and Matrigel/laminin-coated filters, whereas C-274 inhibited the invasion to only Matrigel/fibronectin-coated filter. These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models. The use of such a peptide might offer a promising therapeutic approach for combatting or preventing cancer metastasis.

Amino Acid Sequence↗
PubMed1990

6-O-carboxymethyl-chitin (CM-chitin) as a drug carrier.

Gel was prepared from 6-O-carboxymethyl-chitin (CM-chitin) by the addition of iron(III) chloride under mild conditions without any organic solvent. The optimal conditions for the gel formation were 15 to 30 mM iron(III) chloride and 0.5 to 0.8 degree of substitution in CM-chitin. The amounts of bovine serum albumin (BSA) and the anticancer drug doxorubicin (DOX) incorporated into CM-chitin gels were more than 80% and 30%, respectively under the conditions described above. The release of BSA or DOX from the gels was observed to be increased by lysozyme digestion in a time-dependent manner. This result indicates that CM-chitin might prove useful as a carrier gel for the sustained release of drugs and cytokines, including vaccines.

Animals↗
PubMed1990

[Meningioma of pineal region].

A 58-year-old man was admitted to our hospital upon his request for an operation on a hemifacial spasm that had developed twelve years ago. The hemifacial spasm on the left side was the only positive neurological findings at the time of admission. However, a pre-operative neuroradiological examination revealed a meningioma originating in the falco-tentorial junction. Left neurovascular decompression was initially performed and was followed by the excision of the tumor through a right parietooccipital approach. The pathological diagnosis was meningothelial meningioma. The patient was discharged with no neurological deficit. There have been only a few reports on pineal meningioma and even now this type of tumor is considered to be rare. Some similar cases reported in the literature are reviewed. The clinical aspects, clinical features and the pathological entity are discussed.

Brain Neoplasms↗
PubMed1990

[A case of traumatic syringomyelia which disappeared after anterior decompression: a suggestion for surgical treatment of syringomyelia].

A 37-year-old man had received cervical spinal-cord injury 20 years previously. Recently, he complained of progressive spastic gait and was shown to have fracture dislocation of the C5 vertebral body which compressed the spinal cord posteriorly. He also had a syrinx from the C5 to C2 vertebral level. Postoperatively, this syrinx disappeared after anterior decompression of the C4 and C5 vertebral bodies. Such a case as this has never been reported, and this case may give a suggestion for surgical treatment of syringomyelia, because it is very natural that the most reasonable treatment of any disease is removal of the cause.

Adult↗
PubMed1989

Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.

We investigated that the antimetastatic and antiadhesive activities of peptides based on Arg-Gly-Asp adhesive signal in fibronectin could be augmented by their polymerization. Poly(Arg-Gly-Asp), which consists of a repetitive sequence of Arg-Gly-Asp, inhibited lung metastases in C57BL/6 mice more effectively than Arg-Gly-Asp tripeptide was able to do, when coinjected or separately injected with B16-BL6 cells. The adhesion of tumor cells to fibronectin was specifically inhibited by adding poly(Arg-Gly-Asp) but not unrelated peptides. In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells. The inhibitory effect of polymeric peptides containing the Arg-Gly-Asp sequence on lung metastases decreased according to the decreasing repeat units of the Arg-Gly-Asp core sequence. Polymeric peptides with Arg-Gly-Asp entrapped within the liposome membranes also caused a remarkable reduction of metastatic colonies. In a spontaneous metastasis model, multiple i.v. administrations of poly(Arg-Gly-Asp) after tumor inoculation caused the significant reduction of metastatic colonies in the lung but did not affect the growth (size) of primary tumor. We found that the polymerization (multivalency) of the Arg-Gly-Asp core sequence was able to augment the inhibition of tumor lung metastases in experimental and spontaneous metastasis models as well as the cell-adhesive property more effectively than a monovalent unit of Arg-Gly-Asp peptide.

Amino Acid Sequence↗
PubMed1989

Induction of an endogenous tumor necrosis factor in mice by murine recombinant interferon-gamma combined with a lipid A subunit analog (GLA-60) of low toxicity.

We have investigated the endogenous production of a serum cytotoxic factor when recombinant interferon-gamma (rIFN-gamma) is combined with synthetic lipid A subunit analogs of low toxicity (GLA compounds). The cytotoxic activity of the serum was measured by the crystal violet staining method with L929 cells as a target. Intravenous administration of rIFN-gamma followed by intravenous administration of lipopolysaccharide induced the endogenous production of a cytotoxic factor in the serum. The priming effect of rIFN-gamma appeared immediately and persisted for approximately 20 h after the injection. Administration of lipopolysaccharide as a trigger enhanced the production of the cytotoxic factor in the serum maximally 2 h after the injection. The cytotoxic activity in the serum was completely inhibited by anti-(mouse tumor necrosis factor) (TNF) antibody. A synthetic lipid A subunit analog (GLA-60), which is much less toxic in its endotoxin activities than lipopolysaccharide or synthetic lipid A (compound 506), induced the endogenous production of serum TNF in rIFN-gamma-primed mice. GLA-60 entrapped within liposomes induced the production of serum TNF in rIFN-gamma-primed mice more effectively than GLA-60 solubilized in phosphate-buffered saline. Intravenous or intranasal administrations of rIFN-gamma followed by intranasal administration of GLA-60 produced TNF in the lung washing fluid but not in the serum, indicating that TNF production can be induced locally rather than systemically by the alteration of the administration route of the primer and trigger. These results indicate that GLA-60, a lipid A subunit analog of low toxicity, is a beneficial triggering agent in the production of endogenous TNF, as well as having other immunopharmacological properties, and may provide a basis for cancer (metastases) treatment as a result of its ability to induce endogenous TNF.

Animals↗
PubMed1989

Antimetastatic effect of endogenous tumor necrosis factor induced by the treatment of recombinant interferon gamma followed by an analogue (GLA-60) to synthetic lipid A subunit.

We have investigated the effect of endogenous production of tumor necrosis factor (TNF) induced by the combination of recombinant interferon gamma (rIFN gamma) as a primer followed by GLA-60 as a trigger (rIFN gamma/GLA-60) on murine lung metastases caused by B16-BL6 melanoma. In order to examine the therapeutic effect of endogenous TNF on tumor metastasis, the ability of multiple administrations of rIFN gamma/GLA-60 to induce TNF production was also tested. The multiple administrations of rIFN gamma/GLA-60 at intervals of 2 days were effective for the induction of endogenous TNF in mice but continuous multiple administrations of them for 2-4 days were not. In tumor-bearing mice, the production of endogenous TNF by rIFN gamma/GLA-60 was less than that of normal mice, but treatment 3 days after the surgical excision of primary tumors showed the endogenous TNF production to be similar to that in normal mice. In the experimental lung metastasis model, intravenous administration of rIFN gamma followed by intravenous or intranasal administration of GLA-60 showed potent inhibition of lung metastases of B16-BL6 melanoma, whereas the reverse sequence of administration (GLA-60/rIFN gamma) or administration of a mixture of rIFN gamma and GLA-60, which cannot induce the production of TNF, caused no inhibition of lung metastases. These results indicated that the regression of tumor metastases by rIFN gamma/GLA-60 was mediated by the production of endogenous TNF in addition to the direct effects of both immunostimulants. Furthermore, the administration of rIFN gamma and GLA-60 significantly inhibited the tumor metastases in spontaneous lung metastasis model. These results may provide a promising approach for the treatment of cancer metastasis as a result of its ability to induce endogenous TNF.

Adjuvants, Immunologic↗
PubMed1989

Biological activities of synthetic polypeptides containing a repetitive core sequence (Arg-Gly-Asp) of cell adhesion molecules.

A unique polypeptide containing the repeated structure of core sequence from cell adhesion molecules, poly(Arg-Gly-Asp), was successfully prepared by the polymerization procedure with diphenylphosphoryl azide. This polypeptide dramatically inhibited the aggregation of platelets induced by adenosine diphosphate (ADP) or malignant melanoma cells.

Adenosine Diphosphate↗