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T Suda

Publications and source records attributed to T Suda.

At least 55 records · Page 3Linked to original sources
PubMed2001

An oxidized derivative of cholesterol increases the release of soluble vascular cell adhesion molecule-1 from human umbilical vein endothelial cells in culture.

Treatment of human umbilical vein endothelial cells (HUVECs) with 7-ketocholesterol resulted in an increased release of soluble vascular cell adhesion molecule-1 (VCAM-1) into culture medium. 7-Ketocholesterol did not enhance the expression of mRNA for VCAM-1. 7 beta-Hydroxy- or 25-hydroxycholesterol had no effect on soluble VCAM-1 levels. Western blot analysis revealed that soluble VCAM-1, in the conditioned medium of both 7-ketocholesterol-stimulated and control cells, had a molecular size of 100 kDa. Stimulation of the TNF-alpha-treated HUVECs with 7-ketocholesterol further increased the levels of soluble VCAM-1 in the culture medium. Again, 7-ketocholesterol did not affect the VCAM-1 mRNA level, which was enhanced by TNF-alpha. Pretreatment of the cells with tissue inhibitor of membrane metalloproteinase-2 (TIMP-2) completely inhibited the release of VCAM-1 in response to 7-ketocholesterol but TIMP-1 had no effect. Adherence of mononuclear cells to TNF-stimulated HUVEC monolayers was slightly inhibited by 7-ketocholesterol, but this oxysterol did not affect the basal adherence to non-stimulated HUVECs. Immunofluorescent staining of the cells confirmed diffuse perinuclear distribution of VCAM-1 in HUVECs treated with TNF-alpha, but 7-ketocholesterol did not affect the intensity or distribution of immunofluorescence. We conclude that 7-ketocholesterol releases VCAM-1 from the endothelium probably by a proteolytic process.

Blotting, Western↗
PubMed2001

A significant participation of orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat.

Orexins are novel hypothalamic peptides which stimulate food intake. In view of the well-known tight connection between the nutritional state and the reproductive function, in this study we examined a possible role of orexin-A in the generation of ovarian steroid-induced luteinizing hormone (LH) and prolactin (PRL) surges in ovariectomized rats. Experiments were performed on both normally-fed and 3-day-fasted rats. Although fasting led to abolition of both LH and PRL surges, intracerebroventricular administration of orexin-A (0.3 and 3.0 nmol) resulted in a dose-dependent recovery of the hormonal surges. In addition, anti-orexin-A antisera given to normally-fed rats completely abrogated the surges of both hormones. These results demonstrate for the first time a significant participation of orexin-A in the preovulatory LH and PRL surges in the rat.

Animals↗
PubMed2001

Agouti-related peptide prevents steroid-induced luteinizing hormone and prolactin surges in female rats.

We studied the effect of Agrp (agouti-related peptide) on LH (luteinizing hormone) and PRL (prolactin) surges in ovariectomized rats primed with estradiol and progesterone. The rats displayed characteristic LH and PRL surges that were completely abolished by starving. Injection of either 1 nmol or 3 nmol Agrp (83-132), a potent antagonist of the orexigenic MC3 and MC4 receptors, completely prevented both the LH and PRL surges. We also investigated the effects of either a single or double injection of anti-Agrp serum to fasted animals, which were without LH and PRL surges. A single injection of the antiserum was without effect, but the rats that received double injection of anti-Agrp serum partially reinstated both the LH and PRL surges. Although the onset of LH and PRL surges was significantly delayed in the double treated group, the highest levels of the surges for both hormones were statistically indistinguishable compared with the control group. These data give a clear indication that endogenous Agrp may be involved in LH and PRL surges during starvation, providing further evidence that the melanocortin system is important for these hormonal surges in female rats.

Agouti-Related Protein↗
PubMed2001

Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat.

We previously reported that the melanocortin 4 receptor may play a significant role in mediating the preovulatory surges of luteinizing hormone and prolactin in the rat. In order to confirm this previous finding, in the present study we examined and compared the effects of intracerebroventricular administrations of 1.0 nmol of MT II (a non-selective melanocortin 3 and 4 receptor agonist) and 10 nmol of gamma(1)-melanocyte-stimulating hormone (a selective melanocortin 3 receptor agonist) on luteinizing hormone and prolactin surges in starved, gonadal steroid-primed ovariectomized female rats, which is a model deprived of inherent surges of the two hormones. MT II significantly recovered the surge of prolactin, but not of luteinizing hormone (although a tendency to increase was seen), and gamma(1)-melanocyte-stimulating hormone was without effect on both hormones. This study corroborated our previous report through a different and direct approach that the melanocortin 4 receptor, but not the melanocortin 3 receptor, plays a significant role in mediating the preovulatory prolactin surge in the rat.

Animals↗
PubMed2001

Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis.

Neuropilin 1 (NP-1) is a receptor for vascular endothelial growth factor (VEGF) 165 (VEGF165) and acts as a coreceptor that enhances VEGF165 function through tyrosine kinase VEGF receptor 2 (VEGFR-2). Transgenic overexpression of np-1 results in an excess of capillaries and blood vessels and a malformed heart. Thus, NP-1 may have a key role in vascular development. However, how NP-1 regulates vascular development is not well understood. This study demonstrates how NP-1 can regulate vasculogenesis and angiogenesis in vitro and in vivo. In homozygous np-1 mutant (np-1(-/-)) murine embryos, vascular sprouting was impaired in the central nervous system and pericardium. Para-aortic splanchnopleural mesoderm (P-Sp) explants from np-1(-/-) mice also had vascular defects in vitro. A monomer of soluble NP-1 (NP-1 tagged with Flag epitope) inhibited vascular development in cultured wild-type P-Sp explants by sequestering VEGF165. In contrast, a dimer of soluble NP-1 (NP-1 fused with the Fc part of human IgG) enhanced vascular development in cultured wild-type P-Sp explants. Moreover, the NP-1-Fc rescued the defective vascular development in cultured np-1(-/-) P-Sp explants. A low dose of VEGF alone did not promote phosphorylation of VEGFR-2 on endothelial cells from np-1(-/-) embryos, but simultaneous addition of a low dose of VEGF and NP-1-Fc phosphorylated VEGFR-2 significantly. Moreover, NP-1-Fc rescued the defective vascularity of np-1(-/-) embryos in vivo. These results suggest that a dimer form of soluble NP-1 delivers VEGF165 to VEGFR-2-positive endothelial cells and promotes angiogenesis.

Animals↗
PubMed2001

The molecular basis of osteoclast differentiation and activation.

Osteoclasts develop from haemopoietic cells of the monocyte-macrophage lineage. Osteoblasts or stromal cells are essentially involved in osteoclastogenesis through cell-cell interaction with osteoclast progenitor cells. Recent findings indicate that osteoblasts/stromal cells express osteoclast differentiation factor (ODF, also called RANKL, TRANCE and OPGL) as a membrane-associated factor in response to several osteotropic factors to support osteoclast differentiation. ODF is a new member of the tumour necrosis factor (TNF) ligand family. Osteoclast precursors, which express RANK, a TNF receptor family member, recognize ODF through cell-cell interactions with osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF). Osteoclastogenesis inhibitory factor (OCIF, also called OPG), is a secreted TNF receptor, which acts as a decoy receptor for ODF. ODF is responsible for inducing not only differentiation, but also activation of osteoclasts. Interleukin 1 alpha (IL-1 alpha) can be substituted for ODF in inducing the activation of osteoclasts. Recently, it was shown that mouse TNF alpha stimulated the differentiation of M-CSF-dependent mouse bone marrow macrophages into osteoclasts in the presence of M-CSF without any help of osteoblasts/stromal cells. Osteoclast formation induced by TNF alpha was inhibited by antibodies against TNF type 1 receptor (TNFR1) or TNFR2, but not by OCIF. Osteoclasts induced by TNF alpha formed resorption pits on dentine slices only in the presence of IL-1 alpha. These results demonstrate that TNF alpha stimulates osteoclast differentiation through a mechanism independent of the ODF-RANK interaction. TNF alpha and IL-1 alpha may play an important role in pathological bone resorption due to inflammation.

Animals↗
PubMed2001

Expression of Fas ligand is an early event in colorectal carcinogenesis.

BACKGROUND AND OBJECTIVES: Fas ligand (FasL) is expressed in many cancers and plays an important role in establishing immunologically privileged environments that allow tumors to escape the host's immune surveillance. We investigate the expression of FasL in human colorectal cancer and colorectal adenoma and elucidate the relationship between FasL expression and the clinicopathological characteristics of colorectal cancers. METHODS: We examined 214 colorectal cancer specimens and 83 colorectal adenoma specimens. Expression of FasL was determined by immunohistochemical staining using a specific monoclonal antibody. We analyzed the relationship between the results of FasL expression and clinicopathological data statistically. RESULTS: FasL expression was detected in 173 (80.8%) of 214 colorectal carcinomas and 34 (40.9%) of 83 colorectal adenomas. The status of FasL expression in colorectal carcinoma was independent of clinicopathological features including tumor stage, histologic grade, lymphatic invasion, venous invasion, lymph node metastasis, liver metastasis, and Dukes stage. In colorectal adenoma, FasL expression was more frequently observed in high-grade atypia than in low-grade atypia (P = 0.05). CONCLUSIONS: FasL expression is commonly observed not only in cancer but also in highly dysplastic tissue. These observations suggest that FasL expression may be an important event in the transformation process leading to adenocarcinoma.

Adenocarcinoma↗
PubMed2001

The membrane-bound but not the soluble form of human Fas ligand is responsible for its inflammatory activity.

The ectopic expression of Fas ligand (FasL/CD95L) in tissues or tumors induces neutrophil infiltration and the destruction of the tissues or the rejection of tumors. It has been suggested that the infiltrated neutrophils are responsible for the latter phenomena. FasL is synthesized as a type II transmembrane protein, and soluble FasL is produced by a proteolytic mechanism from the membrane-bound form. We previously demonstrated that uncleavable membrane-bound FasL of mice induces IL-1 beta release from inflammatory cells, and suggested that the IL-1 beta enhances neutrophil infiltration. However, recent papers reported that human soluble FasL is directly chemoattractive to neutrophils in vitro and proposed that the soluble form of FasL is responsible for its inflammatory activity. Therefore, in this report, we investigated which form is responsible for the inflammatory activities of human FasL. We produced tumor cell lines expressing one or both forms of human FasL. Cells expressing both forms or only the membrane-bound form of FasL induced neutrophil infiltration when transplanted into the peritoneal cavity of syngeneic mice, while cells expressing only the soluble form did not. Purified soluble FasL failed to induce neutrophil infiltration in vivo. IL-1 beta release from inflammatory peritoneal exudate and acceleration of tumor rejection were also mediated by membrane-bound but not soluble FasL. These results indicate that the membrane-bound form of FasL is primarily responsible for its inflammatory activity.

Animals↗
PubMed2001

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗
PubMed2001

Expression and potential role of angiopoietins and Tie-2 in early development of the mouse metanephros.

Angiopoietins (Ang) are secreted factors which bind the Tie-2 receptor and modulate endothelial growth. This signalling system is known to be expressed in later stages of maturation of the mouse metanephros, the adult kidney precursor. In this study, by using reverse transcription polymerase chain reaction and Northern and Western blotting, we demonstrated that Ang-1, Ang-2, and Tie-2 were expressed during early metanephrogenesis when interstitial and glomerular capillaries begin to form. By using immunohistochemistry, embryonic kidney capillaries in the interstitium and glomeruli expressed Tie-2 at a later stage of differentiation compared with vascular endothelial growth factor receptor-2 and platelet-endothelial cell adhesion molecule. Addition of 200 ng/ml Ang-1 to explanted embryonic day (E) 12.5 metanephroi increased the proportion of vascular glomeruli that formed during 1 week in culture. These results are consistent with the hypotheses that Tie-2 has a role in vascular growth in the early stages of mammalian nephrogenesis and that Tie-2 activation may maintain the integrity of recently formed interstitial and glomerular vessels.

Angiopoietin-1↗
PubMed2001

Role of hematopoietic stem cells in angiogenesis.

Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here we show that hematopoietic stem cells (HSCs) are essential for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embryos, which lack definitive hematopoiesis. These embryos showed defective angiogenesis in the head, pericardium, and fetal liver. Para-aortic splanchnopleural (P-Sp) explant cultures on stromal cells (P-Sp cultures) did not generate definitive hematopoietic cells and showed defective angiogenesis in the AML1-null embryo. Disrupted angiogenesis in P-Sp cultures from AML1-null embryos was rescued by addition of HSCs. HSCsspecifically produce angiopoietin-1 (Ang1). Thus HSCs,which expressAng1, directly promoted migration of ECs. These findings suggest that HSCs alone prepare the hematopoietic microenvironment.

Angiopoietin-1↗
PubMed2001

Expression of mouse osteocalcin transcripts, OG1 and OG2, is differently regulated in bone tissues and osteoblast cultures.

Osteocalcin is a noncollagenous protein that is abundant in mineralized bone matrix. Mice have a gene cluster of osteocalcin that consists of OG1, OG2, and ORG. We established a new method to directly analyze the expression levels of OG1, OG2, and ORG mRNAs relative to total osteocalcin mRNA. They were amplified as 371-bp fragments by reverse transcription-polymerase chain reaction (RT-PCR) at the same time using common primers, digested with ApaLI, and separated in a polyacrylamide gel. ApaLI digestion did not affect the mobility of the OG1-derived 371-bp fragment, whereas both 371-bp fragments, derived from OG2 and ORG, were digested into 350 bp. Total RNA prepared from mouse bone was then subjected to RT-PCR followed by ApaLI digestion. OG1 and OG2 mRNAs were found to be expressed at ratios of 80%-86% and 14%-20%, respectively, to the total osteocalcin mRNA in mouse bone. The ratios were almost constant in various bones in vivo, independent of the animal's genetic background, age, or gender, or different parts of bone. RT-PCR using specific primers revealed that mouse bone tissues strongly expressed osteocalcin mRNA derived from OG1 and OG2, but not ORG. In contrast, cells cultured in vitro showed different expression ratios of osteocalcin mRNA: 53%-65% for OG1 and 35%-47% for OG2 to the total osteocalcin mRNA in the osteoblast cell line and primary osteoblasts in culture even though they formed many mineralized bone nodules. Similar results were obtained in both KS483 osteoblasts and C2C12 myoblasts, when they were cultured with bone morphogenetic protein-2 (BMP-2) to induce osteocalcin mRNA. Taken together, these findings indicate that OG1 is the predominant transcript among the three osteocalcin genes in mouse bone in vivo. It is also suggested that the expression of OG1 and OG2 is regulated differently in bone tissues and osteoblast cultures.

Animals↗
PubMed2001

Recipient intramuscular gene transfer of active transforming growth factor-beta1 attenuates acute lung rejection.

BACKGROUND: Gene transfer into the donor graft has been demonstrated to be feasible in reducing ischemia-reperfusion injury and rejection in lung transplantation. This study was undertaken to determine whether intramuscular gene transfer into the recipient can also reduce subsequent lung graft rejection. METHODS: Brown Norway rats served as donors and F344 rats as recipients. Recipient animals were injected with 10(10) plaque-forming units of adenovirus encoding active transforming growth factor beta1 (group I, n = 6), beta-galactosidase as adenoviral controls (group II, n = 6), or normal saline without adenovirus (group III, n = 6) into both gluteus muscles 2 days before transplantation. Gene expression was confirmed by enzyme-linked immunosorbent assay. Graft function was assessed on postoperative day 5. RESULTS: Successful gene transfection and expression were confirmed by the presence of active transforming growth factor beta1 protein in muscle and plasma. Oxygenation was significantly improved in group I (group I vs II and III, 353.6 +/- 63.0 mm Hg vs 165.7 +/- 39.9 and 119.1 +/- 41.5 mm Hg; p = 0.02 and 0.004). The muscle transfected with the transforming growth factor beta1 showed granulation tissue with fibroblast accumulation. CONCLUSIONS: Intramuscular adenovirus-mediated gene transfer of active transforming growth factor beta1 into the recipients attenuates acute lung rejection as manifested by significantly improved oxygenation in transplanted lung allografts. This intramuscular transfection approach as a cytokine therapy is feasible in transplantation and may be useful in reducing rejection as well as reperfusion injury.

Adenoviridae↗
PubMed2001

Efficient naked plasmid cotransfection of lung grafts by extended lung/plasmid exposure time.

BACKGROUND: Multiple gene cotransfection may be an effective strategy to modulate concurrent pathologic events after lung transplantation. We investigated in vivo naked plasmid lung cotransfection during cold preservation and the role of lung parenchyma/naked plasmid exposure time. METHODS: F344 rats underwent left main bronchus instillation of pCF1-CAT (chloramphenicol acetyl transferase) (130 microg) +/- pCF1-beta-Gal (beta-galactosidase) (130 microg) in saline. Part Ia: 4 degrees C preservation versus cotransfection. Lung isografts (4 groups, n = 8) were stored after transfection for 1 (2 groups: one received only pCF1-CAT), 6, and 18 hours. Recipient sacrifice was after 48 hours. Part Ib: 4 degrees C preservation versus transgene expression. Rats were sacrificed 48 hours after transfection in a nontransplant setting (2 groups, n = 8; one received only pCF1-CAT). In a third group (n = 8) lungs were harvested 24 hours after transfection, stored for 18 hours, and recipients were sacrificed after 24 hours. The CAT and beta-Gal enzymatic-linked immunosorbent assays were performed. Part II: Lung/plasmid exposure time. In three groups (n = 6) after pCF1-CAT transfection the left main bronchus was not clamped, clamped for 10 minutes, or clamped for 1 hour. Sacrifice was after 48 hours. RESULTS: Part Ia: Lung CAT protein was (in picograms per 100 microg of total protein): median, 42 (range, 25 to 95) after 1 hour (only CAT); 67 (19 to 296) after 1 hour, 32 (6 to 157) after 6 hours; and 9 (5 to 243) after 18 hours. Lung beta-Gal protein was (in picograms per 100 microg of total protein): median, 20 (range, 5 to 353) after 1 hour; 17 (6 to 157) after 6 hours; 4 (1 to 74) after 18 hours (1 hour versus 18 hours, p = 0.04 for both proteins). CAT and beta-Gal production were significantly correlated (p = 0.0001, r = 0.924). Part Ib: Lung CAT protein was (in picograms per 100 microg of total protein): median, 2 (range, 0.6 to 10) no transplant, only CAT; 7 (0.3 to 13) no transplant; 3 (0.9 to 14) transplant. Part II: Left lung CAT protein was (in picograms per 100 microg of total protein): median, 31 (range, 6 to 83) no clamp; 74 (25 to 430) 10 minutes of clamp; 111 (30 to 263) 1 hour of clamp. Right lung CAT protein was (in picograms per 100 microg of total protein): median, 0.06 (range, 0 to 0.9) no clamp; 1 (0 to 6) 10 minutes of clamp; 1 (0 to 18) 1 hour of clamp. CONCLUSIONS: Efficient lung isograft endobronchial cotransfection results from using naked plasmid. Cold preservation affects transfection efficiency but not transgene expression. Lung parenchyma/naked plasmid exposure time determines transfection efficiency.

Animals↗
PubMed2001

Protein kinase C-dependent and -independent inhibition of Ca(2+) influx by phorbol ester in rat pancreatic beta-cells.

Phorbol esters were used to investigate the action of protein kinase C (PKC) on insulin secretion from pancreatic beta-cells. Application of 80 nM phorbol 12-myristate 13-acetate (PMA), a PKC-activating phorbol ester, had little effect on glucose (15 mM)-induced insulin secretion from intact rat islets. In islets treated with bisindolylmaleimide (BIM), a PKC inhibitor, PMA significantly reduced the glucose-induced insulin secretion. PMA decreased the level of intracellular Ca(2+) concentration ([Ca(2+)](i)) elevated by the glucose stimulation when tested in isolated rat beta-cells. This inhibitory effect of PMA was not prevented by BIM. PMA inhibited glucose-induced action potentials, and this effect was not prevented by BIM. Further, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a non-PKC-activating phorbol ester, produced an effect similar to PMA. In the presence of nifedipine, the glucose stimulation produced only depolarization, and PMA applied on top of glucose repolarized the cell. When applied at the resting state, PMA hyperpolarized beta-cells with an increase in the membrane conductance. Recorded under the voltage-clamp condition, PMA reduced the magnitude of Ca(2+) currents through L-type Ca(2+) channels. BIM prevented the PMA inhibition of the Ca(2+) currents. These results suggest that activation of PKC maintains glucose-stimulated insulin secretion in pancreatic beta-cells, defeating its own inhibition of the Ca(2+) influx through L-type Ca(2+) channels. PKC-independent inhibition of electrical excitability by phorbol esters was also demonstrated.

Action Potentials↗
PubMed2001

Simultaneous detection of colorectal carcinoma liver and lung metastases does not warrant resection.

BACKGROUND: Recent evidence suggests that metastasectomy is efficacious for selected patients with hepatic and pulmonary metastases from a colorectal primary. The aim of this study was to identify a subgroup of patients who best benefit from hepatic and pulmonary metastasectomy among those with colorectal carcinoma metastases. STUDY DESIGN: We analyzed retrospectively a total of 136 patients who underwent resection of hepatic or pulmonary metastases of colorectal origin at Niigata University Medical Hospital between 1982 and 2000. The median follow-up period was 94 months. Eighty-four patients underwent hepatectomy alone, 25 underwent pulmonary resection alone, and 27 underwent both hepatic and pulmonary resection. The 27 patients undergoing hepatic and pulmonary resection were divided into two groups: 17 patients with sequentially detected hepatic and pulmonary metastases and 10 patients with simultaneously detected metastases. Survival time was determined from the date of initial metastasectomy. Differences in cumulative survival were evaluated using the log-rank test. Sixteen factors were assessed for their influence on the survival of the 27 patients undergoing resection of hepatic and pulmonary metastases; univariate and multivariate analyses were used in this evaluation. RESULTS: Patient survival after hepatic and pulmonary resection was comparable with that after hepatectomy alone (p = 0.536) and that after pulmonary resection alone (p = 0.294). Among the 27 patients undergoing hepatic and pulmonary resection, the outcomes after resection were significantly better in patients with sequentially detected metastases (cumulative 5-year survival of 44%) than in those with simultaneously detected ones (cumulative 5-year survival of 0%) (p < 0.001). On multivariate analysis sequential detection of hepatic and pulmonary metastases was the strongest independent favorable prognostic factor (p <0.001). CONCLUSIONS: Patients with sequentially detected hepatic and pulmonary metastases from a colorectal primary are good candidates for aggressive metastasectomy. Simultaneous detection of these metastases does not warrant resection.

Adult↗
PubMed2001

Immunohistochemical analysis of distribution of RON receptor tyrosine kinase in human digestive organs.

The immunohistochemical distribution of RON receptor tyrosine kinase in digestive organs of both human fetus and adult, including the esophagus, stomach, duodenum, small intestine, colon, rectum, liver, gallbladder, pancreas, and spleen, was investigated semiquantitively using an affinity-purified rabbit polyclonal antibody. RON was observed to be widely distributed throughout various digestive organs and cell types in humans. The immunoreactivity for RON was observed in the epithelium of the esophagus, small intestine, colon, hepatocytes, Kupffer cells, and splenic macrophages both in the adult and the fetus, suggesting that the MSP/RON signaling pathway possesses the proper biological properties to possibly be involved in morphogenesis or differentiation of cells in these organs and cell types. Several organs differed in immunoreactivity between adult and fetus. No immunoreactive cells were found in the pancreas of adults; however, immunoreactivity was observed in acinar cells and in some of the duct or ductular cells and endocrine cells of the islet of the fetus. Similarly, immunoreactivity was not observed in gastric mucosa except in the intestinal metaplastic cells in adults; however, immunoreactivity was found in the foveolar epithelium of the stomach of the fetus. Although the biological significance of RON in malignancy is unclear, the presence of RON immunoreactivity in the fetus and it lack in the adult may indicate that RON is a oncofetal substance in human pancreas and stomach.

Adult↗