The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Takashi Yoshiki - One of the best experts on this subject based on the ideXlab platform.
-
Intra-pancreatic, extra-tumoral perineural invasion (nex). An indicator for the presence of retroperitoneal neural plexus invasion by Pancreas Carcinoma.
Pathology International, 2008Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Takashi YoshikiAbstract:: A histopathologic study of 65 resected malignant lesions of the Pancreas was done to search for a histologic predictor for the presence of extra-pancreatic neural plexus involvement by Carcinoma cells. Extra-pancreatic neural plexus invasion by Pancreas Carcinoma cells, plx(+), was detected in 28 of 65 cases (43%). plx(+) was not significantly associated with tumor location, tumor size, histologic type, or lymph vessel invasion (ly) by Carcinoma cells but was significantly associated with rpe. Plx(+) was also significantly associated with mixed moderate and severe degrees of intra-pancreatic neural invasion (ne2/ne3 group), but not with mixed no and slight degrees (ne0/ne1 group). However, fourteen plx(+) cases were excluded in the ne2/ne3 group; they were found in the ne1 group. Therefore, ne factors appear to have a certain but limited usefulness for the prediction of plx(+). When a perineural invasion by tumor cells was found within the Pancreas but outside of the major mass of cancer, it was designated "intra-pancreatic, extra-tumoral perineural invasion (nex)". The presence of nex(+) was found in 37 cases, in which 24 out of the 28 plx(+) cases (85.7%) were included. A statistically significant association was found between plx(+) and nex(+). In particular, 12 out of the 14 plx- positive ne1 cases were nex(+). In ne1 cases, 33.3% (14/42) were plx(+), whereas in ne1 and nex(+) cases, 60% (12/20) were plx(+). There was a statistical significance between these two figures (p less than 0.05). Thus, nex(+) appears to be a useful indicator for plx(+), particularly in ne1 cases.
-
Phenotypes correlating to metastatic properties of Pancreas adenoCarcinoma in vivo: The importance of surface sialyl Lewisa antigen
International Journal of Cancer, 1996Co-Authors: Takashi Kishimoto, Hiroshi Ishikura, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using Carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GM I -treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI- 10, - 19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis' (SLe'), VLA-4/6, LFA- I /3, CEA, E-selectin, VCAM- I, NCAM, Mac- I, HLA-ABC/ DR/DQ, ICAM- I /2, production of interleukin- I a, tumor necro- sis factor-a, and matrix metalloproteinase, as well as susceptibil- ity to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe' was significantly associated with metastasis; numbers of metastatic colonies of SLea-positive and -negative cell lines were 21.6 k 33.9 and 6.5 -C 14.3 (p < O.Ol), respectively. Moreover, the intensity of surface SLe" expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe" monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM- I expression and liver metastasis was noted, the species- restricted function of ICAM- I makes interpretation difficult. Collective evidence indicates that expression of SLea is an important positive mediator in the hematogenous metastasis of Pancreas Carcinoma. @I 1996 Wiley-Liss, Inc. Metastasis via blood-borne routes, a distinguishing charac- teristic of malignant neoplasms, follows multistep interactions with host cells. The importance of certain properties of neoplastic cells with an aggressive phenotype has been evalu- ated in a variety of in vitro systems. When attempting to achieve suppression of metastasis in vivo, the relative contribu- tions of these properties have to be carefully evaluated. Detection of one or several major properties essential for blood-borne metastasis in vivo may possibly lead to control of metastasis. We searched for correlations between important phenotypes of pancreatic adenoCarcinoma cell lines and liver metastasis, using a nude mouse system. Attachment between Carcinoma and endothelial cells is an important process in the dekelopment of blood-borne metasta- sis. This attachment in vitro was seen to be mediated by E-selectin in several species of Carcinoma cell lines (Takada et al., 1991; Iwai et al., 1993). We reported that SLea on Pancreas Carcinoma cells is an important ligand for E-selectin on activated endothelial cells (Iwai et al., 1993), and that Pancreas Carcinoma cells produce IL-la in both soluble and functional membrane-bound forms to activate endothelial cells (Kaji et a/., 1995). These results suggested that these properties exhibited by Pancreas Carcinoma cell lines would modulate events related to Carcinoma cell-to-endothelial-cell attachment, thereby contributing to hematogenous metastasis in vivo. Another objective was to evaluate the in vivo impact of these properties on blood-borne metastasis. In this context, we included SLea expression by Pancreas Carcinoma cells in the list of phenotypes to be studied.
-
Interleukin (IL)-6 as a Pancreas Carcinoma-Derived Vascular Permeability Regulator in vitro
Pathology Research and Practice, 1996Co-Authors: Hiroshi Ishikura, Akihiro Ishizu, Hiroyuki Kato, Tamotsu Takahashi, Takashi YoshikiAbstract:Summary The interaction between Pancreas adenoCarcinoma and vascular endothelial cells in vitro was investigated. Culture media of Pancreas Carcinoma cells PCI-I0, but not PCI-24, induced an augmented albumin permeability across the endothelial monolayer, an event which was blocked by the calmodulin antagonist, W-7. Only marginal inhibitory effects were obtained using protein kinase inhibitors, H-7 and HA-I004. When cytokine production by Pancreas Carcinoma cells was examined, production of IL-6 in large amounts by PCI-I0, but not by PCI-24 cells was evident. As recombinant IL-6 generated a dose-dependent permeability increase, and as this effect was inhibited by W-7, we considered that the enhancement ofvascular permeability was mediated by this cytokine. The activity of culture supernatants for enhanced permeability was almost completely absorbed by the addition of an antibody specific for IL6. Tumor-derived IL-6 as a soluble mediator regulates vascular permeability in vitro, and the production ofthis factor by Pancreas adenoCarcinoma cells presumably modulates biologic behavior.
-
E-selectin expression induced by Pancreas-Carcinoma-derived interleukin-1α results in enhanced adhesion of Pancreas-Carcinoma cells to endothelial cells
International Journal of Cancer, 1995Co-Authors: Mitsuhito Kaji, Hiroshi Ishikura, Takashi Kishimoto, Akihiro Ishizu, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:: Cellular adhesion of sialyl-Lewis-a(SLea)-positive Pancreas Carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of Pancreas-Carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive Pancreas-Carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested Pancreas-Carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased Pancreas-Carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 Pancreas-Carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by Pancreas-Carcinoma cells, in this case, IL-1 alpha, may contribute to Pancreas-Carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
-
Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro
Cancer Immunology Immunotherapy, 1993Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Kazuhiro Iwai, Chisa Takahashi, Takashi YoshikiAbstract:The permanent Pancreas Carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on Pancreas Carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFNγ or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to Pancreas Carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFNγ, IFNγ treatment of Pancreas Carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.
Hiroshi Ishikura - One of the best experts on this subject based on the ideXlab platform.
-
Intra-pancreatic, extra-tumoral perineural invasion (nex). An indicator for the presence of retroperitoneal neural plexus invasion by Pancreas Carcinoma.
Pathology International, 2008Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Takashi YoshikiAbstract:: A histopathologic study of 65 resected malignant lesions of the Pancreas was done to search for a histologic predictor for the presence of extra-pancreatic neural plexus involvement by Carcinoma cells. Extra-pancreatic neural plexus invasion by Pancreas Carcinoma cells, plx(+), was detected in 28 of 65 cases (43%). plx(+) was not significantly associated with tumor location, tumor size, histologic type, or lymph vessel invasion (ly) by Carcinoma cells but was significantly associated with rpe. Plx(+) was also significantly associated with mixed moderate and severe degrees of intra-pancreatic neural invasion (ne2/ne3 group), but not with mixed no and slight degrees (ne0/ne1 group). However, fourteen plx(+) cases were excluded in the ne2/ne3 group; they were found in the ne1 group. Therefore, ne factors appear to have a certain but limited usefulness for the prediction of plx(+). When a perineural invasion by tumor cells was found within the Pancreas but outside of the major mass of cancer, it was designated "intra-pancreatic, extra-tumoral perineural invasion (nex)". The presence of nex(+) was found in 37 cases, in which 24 out of the 28 plx(+) cases (85.7%) were included. A statistically significant association was found between plx(+) and nex(+). In particular, 12 out of the 14 plx- positive ne1 cases were nex(+). In ne1 cases, 33.3% (14/42) were plx(+), whereas in ne1 and nex(+) cases, 60% (12/20) were plx(+). There was a statistical significance between these two figures (p less than 0.05). Thus, nex(+) appears to be a useful indicator for plx(+), particularly in ne1 cases.
-
Phenotypes correlating to metastatic properties of Pancreas adenoCarcinoma in vivo: The importance of surface sialyl Lewisa antigen
International Journal of Cancer, 1996Co-Authors: Takashi Kishimoto, Hiroshi Ishikura, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using Carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GM I -treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI- 10, - 19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis' (SLe'), VLA-4/6, LFA- I /3, CEA, E-selectin, VCAM- I, NCAM, Mac- I, HLA-ABC/ DR/DQ, ICAM- I /2, production of interleukin- I a, tumor necro- sis factor-a, and matrix metalloproteinase, as well as susceptibil- ity to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe' was significantly associated with metastasis; numbers of metastatic colonies of SLea-positive and -negative cell lines were 21.6 k 33.9 and 6.5 -C 14.3 (p < O.Ol), respectively. Moreover, the intensity of surface SLe" expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe" monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM- I expression and liver metastasis was noted, the species- restricted function of ICAM- I makes interpretation difficult. Collective evidence indicates that expression of SLea is an important positive mediator in the hematogenous metastasis of Pancreas Carcinoma. @I 1996 Wiley-Liss, Inc. Metastasis via blood-borne routes, a distinguishing charac- teristic of malignant neoplasms, follows multistep interactions with host cells. The importance of certain properties of neoplastic cells with an aggressive phenotype has been evalu- ated in a variety of in vitro systems. When attempting to achieve suppression of metastasis in vivo, the relative contribu- tions of these properties have to be carefully evaluated. Detection of one or several major properties essential for blood-borne metastasis in vivo may possibly lead to control of metastasis. We searched for correlations between important phenotypes of pancreatic adenoCarcinoma cell lines and liver metastasis, using a nude mouse system. Attachment between Carcinoma and endothelial cells is an important process in the dekelopment of blood-borne metasta- sis. This attachment in vitro was seen to be mediated by E-selectin in several species of Carcinoma cell lines (Takada et al., 1991; Iwai et al., 1993). We reported that SLea on Pancreas Carcinoma cells is an important ligand for E-selectin on activated endothelial cells (Iwai et al., 1993), and that Pancreas Carcinoma cells produce IL-la in both soluble and functional membrane-bound forms to activate endothelial cells (Kaji et a/., 1995). These results suggested that these properties exhibited by Pancreas Carcinoma cell lines would modulate events related to Carcinoma cell-to-endothelial-cell attachment, thereby contributing to hematogenous metastasis in vivo. Another objective was to evaluate the in vivo impact of these properties on blood-borne metastasis. In this context, we included SLea expression by Pancreas Carcinoma cells in the list of phenotypes to be studied.
-
Interleukin (IL)-6 as a Pancreas Carcinoma-Derived Vascular Permeability Regulator in vitro
Pathology Research and Practice, 1996Co-Authors: Hiroshi Ishikura, Akihiro Ishizu, Hiroyuki Kato, Tamotsu Takahashi, Takashi YoshikiAbstract:Summary The interaction between Pancreas adenoCarcinoma and vascular endothelial cells in vitro was investigated. Culture media of Pancreas Carcinoma cells PCI-I0, but not PCI-24, induced an augmented albumin permeability across the endothelial monolayer, an event which was blocked by the calmodulin antagonist, W-7. Only marginal inhibitory effects were obtained using protein kinase inhibitors, H-7 and HA-I004. When cytokine production by Pancreas Carcinoma cells was examined, production of IL-6 in large amounts by PCI-I0, but not by PCI-24 cells was evident. As recombinant IL-6 generated a dose-dependent permeability increase, and as this effect was inhibited by W-7, we considered that the enhancement ofvascular permeability was mediated by this cytokine. The activity of culture supernatants for enhanced permeability was almost completely absorbed by the addition of an antibody specific for IL6. Tumor-derived IL-6 as a soluble mediator regulates vascular permeability in vitro, and the production ofthis factor by Pancreas adenoCarcinoma cells presumably modulates biologic behavior.
-
E-selectin expression induced by Pancreas-Carcinoma-derived interleukin-1α results in enhanced adhesion of Pancreas-Carcinoma cells to endothelial cells
International Journal of Cancer, 1995Co-Authors: Mitsuhito Kaji, Hiroshi Ishikura, Takashi Kishimoto, Akihiro Ishizu, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:: Cellular adhesion of sialyl-Lewis-a(SLea)-positive Pancreas Carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of Pancreas-Carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive Pancreas-Carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested Pancreas-Carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased Pancreas-Carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 Pancreas-Carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by Pancreas-Carcinoma cells, in this case, IL-1 alpha, may contribute to Pancreas-Carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
-
Importance of E‐selectin (ELAM‐1) and sialyl lewisa in the adhesion of pancreatic Carcinoma cells to acttvated endothelium
International Journal of Cancer, 1993Co-Authors: Kazuhiro Iwai, Mitsuhito Kaji, Hiroshi Ishikura, Akihiro Ishizu, Hiroyuki Kato, Tatsuzo Tanabe, Chisa Takahashi, Hiroshi Sugiura, Takashi YoshtkiAbstract:: Adhesion molecules involved in attachment between human pancreatic Carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic Carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between Pancreas Carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on Pancreas Carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic Carcinoma cells to inflamed sites.
Hiroyuki Kato - One of the best experts on this subject based on the ideXlab platform.
-
Intra-pancreatic, extra-tumoral perineural invasion (nex). An indicator for the presence of retroperitoneal neural plexus invasion by Pancreas Carcinoma.
Pathology International, 2008Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Takashi YoshikiAbstract:: A histopathologic study of 65 resected malignant lesions of the Pancreas was done to search for a histologic predictor for the presence of extra-pancreatic neural plexus involvement by Carcinoma cells. Extra-pancreatic neural plexus invasion by Pancreas Carcinoma cells, plx(+), was detected in 28 of 65 cases (43%). plx(+) was not significantly associated with tumor location, tumor size, histologic type, or lymph vessel invasion (ly) by Carcinoma cells but was significantly associated with rpe. Plx(+) was also significantly associated with mixed moderate and severe degrees of intra-pancreatic neural invasion (ne2/ne3 group), but not with mixed no and slight degrees (ne0/ne1 group). However, fourteen plx(+) cases were excluded in the ne2/ne3 group; they were found in the ne1 group. Therefore, ne factors appear to have a certain but limited usefulness for the prediction of plx(+). When a perineural invasion by tumor cells was found within the Pancreas but outside of the major mass of cancer, it was designated "intra-pancreatic, extra-tumoral perineural invasion (nex)". The presence of nex(+) was found in 37 cases, in which 24 out of the 28 plx(+) cases (85.7%) were included. A statistically significant association was found between plx(+) and nex(+). In particular, 12 out of the 14 plx- positive ne1 cases were nex(+). In ne1 cases, 33.3% (14/42) were plx(+), whereas in ne1 and nex(+) cases, 60% (12/20) were plx(+). There was a statistical significance between these two figures (p less than 0.05). Thus, nex(+) appears to be a useful indicator for plx(+), particularly in ne1 cases.
-
Phenotypes correlating to metastatic properties of Pancreas adenoCarcinoma in vivo: The importance of surface sialyl Lewisa antigen
International Journal of Cancer, 1996Co-Authors: Takashi Kishimoto, Hiroshi Ishikura, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using Carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GM I -treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI- 10, - 19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis' (SLe'), VLA-4/6, LFA- I /3, CEA, E-selectin, VCAM- I, NCAM, Mac- I, HLA-ABC/ DR/DQ, ICAM- I /2, production of interleukin- I a, tumor necro- sis factor-a, and matrix metalloproteinase, as well as susceptibil- ity to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe' was significantly associated with metastasis; numbers of metastatic colonies of SLea-positive and -negative cell lines were 21.6 k 33.9 and 6.5 -C 14.3 (p < O.Ol), respectively. Moreover, the intensity of surface SLe" expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe" monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM- I expression and liver metastasis was noted, the species- restricted function of ICAM- I makes interpretation difficult. Collective evidence indicates that expression of SLea is an important positive mediator in the hematogenous metastasis of Pancreas Carcinoma. @I 1996 Wiley-Liss, Inc. Metastasis via blood-borne routes, a distinguishing charac- teristic of malignant neoplasms, follows multistep interactions with host cells. The importance of certain properties of neoplastic cells with an aggressive phenotype has been evalu- ated in a variety of in vitro systems. When attempting to achieve suppression of metastasis in vivo, the relative contribu- tions of these properties have to be carefully evaluated. Detection of one or several major properties essential for blood-borne metastasis in vivo may possibly lead to control of metastasis. We searched for correlations between important phenotypes of pancreatic adenoCarcinoma cell lines and liver metastasis, using a nude mouse system. Attachment between Carcinoma and endothelial cells is an important process in the dekelopment of blood-borne metasta- sis. This attachment in vitro was seen to be mediated by E-selectin in several species of Carcinoma cell lines (Takada et al., 1991; Iwai et al., 1993). We reported that SLea on Pancreas Carcinoma cells is an important ligand for E-selectin on activated endothelial cells (Iwai et al., 1993), and that Pancreas Carcinoma cells produce IL-la in both soluble and functional membrane-bound forms to activate endothelial cells (Kaji et a/., 1995). These results suggested that these properties exhibited by Pancreas Carcinoma cell lines would modulate events related to Carcinoma cell-to-endothelial-cell attachment, thereby contributing to hematogenous metastasis in vivo. Another objective was to evaluate the in vivo impact of these properties on blood-borne metastasis. In this context, we included SLea expression by Pancreas Carcinoma cells in the list of phenotypes to be studied.
-
Interleukin (IL)-6 as a Pancreas Carcinoma-Derived Vascular Permeability Regulator in vitro
Pathology Research and Practice, 1996Co-Authors: Hiroshi Ishikura, Akihiro Ishizu, Hiroyuki Kato, Tamotsu Takahashi, Takashi YoshikiAbstract:Summary The interaction between Pancreas adenoCarcinoma and vascular endothelial cells in vitro was investigated. Culture media of Pancreas Carcinoma cells PCI-I0, but not PCI-24, induced an augmented albumin permeability across the endothelial monolayer, an event which was blocked by the calmodulin antagonist, W-7. Only marginal inhibitory effects were obtained using protein kinase inhibitors, H-7 and HA-I004. When cytokine production by Pancreas Carcinoma cells was examined, production of IL-6 in large amounts by PCI-I0, but not by PCI-24 cells was evident. As recombinant IL-6 generated a dose-dependent permeability increase, and as this effect was inhibited by W-7, we considered that the enhancement ofvascular permeability was mediated by this cytokine. The activity of culture supernatants for enhanced permeability was almost completely absorbed by the addition of an antibody specific for IL6. Tumor-derived IL-6 as a soluble mediator regulates vascular permeability in vitro, and the production ofthis factor by Pancreas adenoCarcinoma cells presumably modulates biologic behavior.
-
E-selectin expression induced by Pancreas-Carcinoma-derived interleukin-1α results in enhanced adhesion of Pancreas-Carcinoma cells to endothelial cells
International Journal of Cancer, 1995Co-Authors: Mitsuhito Kaji, Hiroshi Ishikura, Takashi Kishimoto, Akihiro Ishizu, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:: Cellular adhesion of sialyl-Lewis-a(SLea)-positive Pancreas Carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of Pancreas-Carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive Pancreas-Carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested Pancreas-Carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased Pancreas-Carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 Pancreas-Carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by Pancreas-Carcinoma cells, in this case, IL-1 alpha, may contribute to Pancreas-Carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
-
Importance of E‐selectin (ELAM‐1) and sialyl lewisa in the adhesion of pancreatic Carcinoma cells to acttvated endothelium
International Journal of Cancer, 1993Co-Authors: Kazuhiro Iwai, Mitsuhito Kaji, Hiroshi Ishikura, Akihiro Ishizu, Hiroyuki Kato, Tatsuzo Tanabe, Chisa Takahashi, Hiroshi Sugiura, Takashi YoshtkiAbstract:: Adhesion molecules involved in attachment between human pancreatic Carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic Carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between Pancreas Carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on Pancreas Carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic Carcinoma cells to inflamed sites.
Masaru Miyazaki - One of the best experts on this subject based on the ideXlab platform.
-
renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary pancreatic surgery
Journal of The American College of Surgeons, 2006Co-Authors: Takeshi Suzuki, Hiroyuki Yoshidome, Fumio Kimura, Hiroaki Shimizu, Masayuki Ohtsuka, Atsushi Kato, Hideyuki Yoshitomi, Satoshi Nozawa, Shigeaki Sawada, Masaru MiyazakiAbstract:Background Advanced hepatobiliary-pancreatic malignancy occasionally involves major vasculatures, such as the portal vein or the inferior vena cava, and complete removal of the tumor is required for longterm survival. We used a left renal vein graft to reconstruct resected vessels in some patients. In this study, we evaluated early and late renal complications of this procedure. Study design We identified 14 patients undergoing vascular reconstruction with use of a left renal vein graft in hepatobiliary-pancreatic surgery. Renal function and graft patency were assessed by observing serum creatinine levels and radiologic findings during perioperative and followup periods. Results Of these 14 patients, 7 were men and 7 were women. Diseases included hilar cholangioCarcinoma in two, gallbladder Carcinoma in two, intrahepatic cholangioCarcinoma in one, Pancreas Carcinoma in five, hepatic metastasis in three, and mass-forming pancreatitis in one. No significant postoperative renal dysfunction was recognized, and the mean value of the maximal serum creatinine was 1.0 mg/dL during the perioperative period. Renal scintigraphy was performed in six patients postoperatively, and there was no significant left renal dysfunction. Mean followup time was 18months after operation, and no severe renal dysfunction was found. Graft patency, which was assessed with enhanced abdominal CT, was well maintained after operation. Conclusions The left renal vein could be safely obtained and used for vascular reconstruction in resection of hepatobiliary-pancreatic malignancy without adverse effects on early and longterm renal function.
Toshiyuki Takahashi - One of the best experts on this subject based on the ideXlab platform.
-
Intra-pancreatic, extra-tumoral perineural invasion (nex). An indicator for the presence of retroperitoneal neural plexus invasion by Pancreas Carcinoma.
Pathology International, 2008Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Takashi YoshikiAbstract:: A histopathologic study of 65 resected malignant lesions of the Pancreas was done to search for a histologic predictor for the presence of extra-pancreatic neural plexus involvement by Carcinoma cells. Extra-pancreatic neural plexus invasion by Pancreas Carcinoma cells, plx(+), was detected in 28 of 65 cases (43%). plx(+) was not significantly associated with tumor location, tumor size, histologic type, or lymph vessel invasion (ly) by Carcinoma cells but was significantly associated with rpe. Plx(+) was also significantly associated with mixed moderate and severe degrees of intra-pancreatic neural invasion (ne2/ne3 group), but not with mixed no and slight degrees (ne0/ne1 group). However, fourteen plx(+) cases were excluded in the ne2/ne3 group; they were found in the ne1 group. Therefore, ne factors appear to have a certain but limited usefulness for the prediction of plx(+). When a perineural invasion by tumor cells was found within the Pancreas but outside of the major mass of cancer, it was designated "intra-pancreatic, extra-tumoral perineural invasion (nex)". The presence of nex(+) was found in 37 cases, in which 24 out of the 28 plx(+) cases (85.7%) were included. A statistically significant association was found between plx(+) and nex(+). In particular, 12 out of the 14 plx- positive ne1 cases were nex(+). In ne1 cases, 33.3% (14/42) were plx(+), whereas in ne1 and nex(+) cases, 60% (12/20) were plx(+). There was a statistical significance between these two figures (p less than 0.05). Thus, nex(+) appears to be a useful indicator for plx(+), particularly in ne1 cases.
-
Phenotypes correlating to metastatic properties of Pancreas adenoCarcinoma in vivo: The importance of surface sialyl Lewisa antigen
International Journal of Cancer, 1996Co-Authors: Takashi Kishimoto, Hiroshi Ishikura, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using Carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GM I -treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI- 10, - 19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis' (SLe'), VLA-4/6, LFA- I /3, CEA, E-selectin, VCAM- I, NCAM, Mac- I, HLA-ABC/ DR/DQ, ICAM- I /2, production of interleukin- I a, tumor necro- sis factor-a, and matrix metalloproteinase, as well as susceptibil- ity to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe' was significantly associated with metastasis; numbers of metastatic colonies of SLea-positive and -negative cell lines were 21.6 k 33.9 and 6.5 -C 14.3 (p < O.Ol), respectively. Moreover, the intensity of surface SLe" expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe" monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM- I expression and liver metastasis was noted, the species- restricted function of ICAM- I makes interpretation difficult. Collective evidence indicates that expression of SLea is an important positive mediator in the hematogenous metastasis of Pancreas Carcinoma. @I 1996 Wiley-Liss, Inc. Metastasis via blood-borne routes, a distinguishing charac- teristic of malignant neoplasms, follows multistep interactions with host cells. The importance of certain properties of neoplastic cells with an aggressive phenotype has been evalu- ated in a variety of in vitro systems. When attempting to achieve suppression of metastasis in vivo, the relative contribu- tions of these properties have to be carefully evaluated. Detection of one or several major properties essential for blood-borne metastasis in vivo may possibly lead to control of metastasis. We searched for correlations between important phenotypes of pancreatic adenoCarcinoma cell lines and liver metastasis, using a nude mouse system. Attachment between Carcinoma and endothelial cells is an important process in the dekelopment of blood-borne metasta- sis. This attachment in vitro was seen to be mediated by E-selectin in several species of Carcinoma cell lines (Takada et al., 1991; Iwai et al., 1993). We reported that SLea on Pancreas Carcinoma cells is an important ligand for E-selectin on activated endothelial cells (Iwai et al., 1993), and that Pancreas Carcinoma cells produce IL-la in both soluble and functional membrane-bound forms to activate endothelial cells (Kaji et a/., 1995). These results suggested that these properties exhibited by Pancreas Carcinoma cell lines would modulate events related to Carcinoma cell-to-endothelial-cell attachment, thereby contributing to hematogenous metastasis in vivo. Another objective was to evaluate the in vivo impact of these properties on blood-borne metastasis. In this context, we included SLea expression by Pancreas Carcinoma cells in the list of phenotypes to be studied.
-
E-selectin expression induced by Pancreas-Carcinoma-derived interleukin-1α results in enhanced adhesion of Pancreas-Carcinoma cells to endothelial cells
International Journal of Cancer, 1995Co-Authors: Mitsuhito Kaji, Hiroshi Ishikura, Takashi Kishimoto, Akihiro Ishizu, Chisa Kimura, Toshiyuki Takahashi, Hiroyuki Kato, Takashi YoshikiAbstract:: Cellular adhesion of sialyl-Lewis-a(SLea)-positive Pancreas Carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of Pancreas-Carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive Pancreas-Carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested Pancreas-Carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased Pancreas-Carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 Pancreas-Carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by Pancreas-Carcinoma cells, in this case, IL-1 alpha, may contribute to Pancreas-Carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
-
Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro
Cancer Immunology Immunotherapy, 1993Co-Authors: Toshiyuki Takahashi, Hiroshi Ishikura, Hiroyuki Kato, Tatsuzo Tanabe, Kazuhiro Iwai, Chisa Takahashi, Takashi YoshikiAbstract:The permanent Pancreas Carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on Pancreas Carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFNγ or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to Pancreas Carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFNγ, IFNγ treatment of Pancreas Carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.
