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Y Adachi

Publications and source records attributed to Y Adachi.

At least 19 recordsLinked to original sources
PubMed2001

The role of Kupffer cell oxidant production in early ethanol-induced liver disease.

Considerable evidence for a role of Kupffer cells in alcoholic liver disease has accumulated and they have recently been shown to be a predominant source of free radicals. Several approaches including pharmacological agents, knockout mice, and viral gene transfer have been used to fill critical gaps in understanding key mechanisms by which Kupffer cell activation, oxidant formation, and cytokine production lead to liver damage and subsequent pathogenesis. This review highlights new data in support of the hypothesis that Kupffer cells play a pivotal role in hepatotoxicity due to ethanol by producing oxidants via NADPH oxidase.

Adenoviridae↗
PubMed2001

A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging.

The treatment of advanced neuroblastoma (NB) or Ewing's sarcoma (ES) is one of the major challenges in pediatric oncology. Both malignancies are refractory to conventional therapies and have an extremely poor prognosis. High-dose myeloablative radiochemotherapy with autologous bone marrow or peripheral blood stem cell rescue is one of the most aggressive treatments attempted for these diseases but is often undermined by residual tumor cells contaminating the graft. Thus, in this approach, purging of tumor cells from the graft is key to the prevention of relapse after transplantation. We investigated a novel approach to eliminate tumor cells from the bone marrow or peripheral blood stem cell graft without causing stem cell damage through the use of a conditionally replicative adenovirus (Ad). ES and NB are sensitive to Ad infection, and advanced NBs express a high level of the growth/differentiation factor midkine (MK). We confirmed in this study that ES cell lines (SK-ES-1 and RD-ES) are also sensitive to Ad infection and express high levels of MK. In contrast, CD34+ stem cells are refractory to Ad infection and express very little MK. A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing. On the other hand, this virus caused no damage to CD34+ cells even after 3 h of infection at a dose of 1000 multiplicity of infection. We concluded that application of this replication-competent Ad to hematopoietic grafts could be a simple but effective procedure to achieve complete tumor cell purging.

Adenoviridae↗
PubMed2001

Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes.

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.

Adenoviridae↗
PubMed2001

Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers.

Matrix metalloproteinases (MMPs) have been implicated in tumor progression. Matrilysin, one of the matrix metalloproteinases, is frequently overexpressed in gastrointestinal cancers. The aim of our study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47 (42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor (T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.

Biomarkers, Tumor↗
PubMed2001

Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells.

Mammalian myeloid and epithelial cells express several kinds of antibacterial peptides (alpha-/beta-defensins and cathelicidins) that contribute to the innate host defense by killing invading micro-organisms. In this study we evaluated the LPS-neutralizing activities of cathelicidin peptides human CAP18 (cationic antibacterial proteins of 18 kDa) and guinea pig CAP11 using the CD14(+) murine macrophage cell line RAW264.7 and the murine endotoxin shock model. Flow cytometric analysis revealed that CAP18 and CAP11 inhibited the binding of FITC-conjugated LPS to RAW264.7 cells. Likewise, Northern and Western blot analyses indicated that CAP18 and CAP11 suppressed LPS-induced TNF-alpha mRNA and protein expression by RAW264.7 cells. Interestingly, CAP18 and CAP11 possessed LPS-binding activities, and they strongly suppressed the interaction of LPS with LPS binding protein that mediates the transport of LPS to CD14 to facilitate the activation of CD14(+) cells by LPS. Moreover, when CAP18 and CAP11 were preincubated with RAW264.7 cells, they bound to the cell surface CD14 and inhibited the binding of FITC-LPS to the cells. Furthermore, in the murine endotoxin shock model, CAP18 or CAP11 administration inhibited the binding of LPS to CD14(+) cells (peritoneal macrophages) and suppressed LPS-induced TNF-alpha expression by these cells. Together these observations indicate that cathelicidin peptides CAP18 and CAP11 probably exert protective actions against endotoxin shock by blocking the binding of LPS to CD14(+) cells, thereby suppressing the production of cytokines by these cells via their potent binding activities for LPS and CD14.

Acute-Phase Proteins↗
PubMed2001

Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria.

LPS-binding protein (LBP) and CD14 potentiate cell activation by LPS, contributing to lethal endotoxemia. We analyzed the contribution of LBP/CD14 in models of bacterial infection. Mice pretreated with mAbs neutralizing CD14 or LBP showed a delay in TNF-alpha production and died of overwhelming infection within 24 h, after a challenge with 250 CFU of virulent Klebsiella pneumoniae. Blockade of TNF-alpha also increased lethality, whereas pretreatment with TNF-alpha protected mice, even in the presence of LBP and CD14 blockade. Anti-LBP or anti-CD14 mAbs did not improve or decrease lethality with a higher inoculum (10(5) K. pneumoniae) and did not affect outcome following injections of low or high inocula of Escherichia coli O111. These results point to the essential role of LBP/CD14 in innate immunity against virulent bacteria.

Acute-Phase Proteins↗
PubMed2001

Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines.

We searched iron-deficient inducible cDNA, using subtraction cloning and mRNA from desferrioxamine-treated mouse macrophage Raw264.7 cells. We identified a pleomorphic adenoma gene like 2 (PLAGL2), one of PLAG superfamily proteins exhibiting antiproliferative properties on tumor cells. Mouse PLAGL2 consists of 496 amino acids with seven C2H2 zinc-fingers. PLAGL2 mRNA was induced in RAW264.7 cells, mouse erythroleukemia cells and Balb/c 3T3 cells when they were treated with desferrioxamine. Hypoxia also increased PLAGL2 mRNA. Expression of PLAGL2 in COS-7 cells led to nuclear localization. PLAGL2 had potential binding ability to GC-rich oligonucleotide and activated transcription of a gene with the binding sequence in transient reporter assay, a finding consistent with a case seen in a PLAGL2 homolog, ZAC-1. Transient co-transfection of PLAGL2 or ZAC1 cDNA and a reporter containing a lactate dehydrogenase A (LDHA) promoter carrying the hypoxia inducible factor-1 responsive element led to an increase in the basal transcription in Balb/c 3T3 and HepG2 cells. Activation in transcription from the LDHA promoter increased by desferrioxamine treatment or hypoxia was further enhanced when PLAGL2 was expressed. We propose that PLAGL2 is involved in the cell cycle arrest and apoptosis of tumor cells by regulating iron depletion- or hypoxia-inducible gene expression.

Amino Acid Sequence↗
PubMed2001

Expression of angiomodulin (tumor-derived adhesion factor/mac25) in invading tumor cells correlates with poor prognosis in human colorectal cancer.

Angiomodulin (tumor-derived adhesion factor/mac25/insulin-like growth factor binding protein-7), a cell-adhesive glycoprotein, is secreted by cancer cells and vascular endothelial cells. It may be involved in angiogenesis and modulation of the vascular functions necessary for tumor development. Although angiomodulin is expressed in colon cancer, there is limited information on it concerning cancer progression. In the present immunohistochemical study, we examined expression of angiomodulin in human colorectal cancer and its relationship with prognosis. A group of 89 surgically resected colorectal cancers was investigated immunohistochemically. In 37 cases (41.6%), angiomodulin was expressed in invading cancer cells. Early recurrence within 12 months after surgery was higher in patients with angiomodulin-expressing cancer than in those without (p < 0.05). The Kaplan-Meier life table revealed that patients with angiomodulin-positive tumor cells had a shorter survival time than those with negative cells (p < 0.01). The prognosis of patients with Dukes' C and angiomodulin-positive cells was apparently worse than that of patients with Dukes' D and angiomodulin-negative cells. Multivariate analysis with logistic regression indicated that only angiomodulin expression in cancer cells, lymph node metastasis and age remained significant prognostic variables for survival (p < 0.05). Angiomodulin showed correlations with poor prognosis, indicating that it may be a useful prognostic marker in patients with colorectal cancer.

Adult↗
PubMed2001

Evaluation of the cost for laparoscopic-assisted Billroth I gastrectomy.

BACKGROUND: Despite the rapid spread of laparoscopic gastric surgery in Japan, no one has yet evaluated the costs for this new technique. The aim of this study was to analyze and compare the hospital charges for laparoscopic-assisted gastrectomy with those for conventional open gastrectomy. METHODS: The study included 48 consecutive patients who underwent laparoscopic-assisted Billroth I gastrectomy and 43 who had a conventional open Billroth I gastrectomy for cure of early gastric cancer between May 1994 and April 2000. Hospital charges covered all costs incurred during the hospital stay; they were divided into charges for consultation, prescription, injection, nursing care, operating theater, laboratory, radiology, ward and meal, and others. RESULTS: The patients who underwent laparoscopic gastrectomy were similar to those who had open gastrectomy in terms of symptoms, concurrent illness, operation time, proximal resection margin, number of harvested lymph nodes, and stage of the disease. Hospital stay after laparoscopic gastrectomy was shorter than that after open gastrectomy (16.1 vs 20.5 days, p < 0.01). Charges for nursing care, charges for ward and meal, and total hospital charges were less in the laparoscopic group than in the open group ( yen5800 vs yen8010, p < 0.01; yen461 x 10(3) vs yen512 x 10(3), p < 0.05; yen1336 x 10(3) vs yen1411 x 10(3), p = 0.072). When we compared laparoscopic gastrectomies performed during 1994-96 with those done during 1997-2000, we found a decrease in charges for ward and meal and total hospital charges ( yen498 x 10(3) vs yen421 x 10(3), p < 0.01; yen1390 x 10(3) vs yen1277 x 103, p < 0.01). CONCLUSION: Laparoscopic-assisted Billroth I gastrectomy is less expensive than conventional open Billroth I gastrectomy because both the postoperative recovery period and the hospital stay are shorter. In patients who undergo gastrectomy, the additional costs of the disposable instruments can be fully offset by the lower charges for ward and meal and nursing care associated with laparoscopic gastrectomy.

Aged↗
PubMed2001

Morphology of the murine peritoneum after pneumoperitoneum vs laparotomy.

BACKGROUND: Although there have been studies of the effects of pneumoperitoneum on the peritoneal cavity, we still do not know whether the morphologic changes to the peritoneum are different for pneumoperitoneum vs laparotomy. Using scanning electron microscopy, we examined the murine peritoneum after pneumoperitoneum vs laparotomy and compared the changes. METHODS: Forty-five mice were anesthetized with diethyl ether and divided into seven groups. Pneumoperitoneum was established at 5 mmHg for 30 min with carbon dioxide (CO(2)) (n = 9), helium (n = 9), and air (n = 9). One group underwent laparotomy for 30 min (n = 9), and a control group underwent anesthesia only (n = 3). CO(2) pneumoperitoneum was further established at 10 mmHg for 30 min (n = 3) and at 5 mmHg for 60 min (n = 3). After the procedures, the peritoneum was resected from the mesenterium of the small intestine in each animal and examined by scanning electron microscope for morphologic changes of the mesothelial cells. RESULTS: Bulging up of the mesothelial cells was evident immediately after pneumoperitoneum, whereas detachment of the mesothelial cells was present immediately after laparotomy. Bulging up of the mesothelial cells was reduced at 24 h after CO(2) pneumoperitoneum and fully resolved at 72 h in all pneumoperitoneum groups, whereas the mesothelial cells remained detached at 72 h in the laparotomy group. Intercellular clefts were found immediately after helium pneumoperitoneum and were present at 24 h and 72 h after helium pneumoperitoneum, but they were not seen after air pneumoperitoneum and were only evident after CO(2) pneumoperitoneum at 10 mmHg. Depression of the mesothelial cell surface was observed when pneumoperitoneum lasted 60 min. CONCLUSION: Morphologic peritoneal alterations after pneumoperitoneum differed from those after laparotomy and were influenced by the type of gas, amount of pressure, and duration of insufflation. These peritoneal changes after pneumoperitoneum may be associated with a specific intraperitoneal tumor spread after laparoscopic cancer surgery.

Air↗
PubMed2001

Tolerance induction across Mls and minor histocompatibility complex by inhibiting activation of T helper type 1 in early period.

We have previously succeeded in inducing persistent donor-specific tolerance across Mls plus multiple minor histocompatibility barriers by portal venous (p.v.) injection of donor spleen or bone marrow cells plus cyclophosphamide (CY) treatment. Microchimerism was established in the lymph-hemopoietic organs of the tolerant recipients. However, the mechanisms, particularly the roles of CY in the tolerance induction, have not been clarified. We examined the tolerance induction using other anti-mitotic agents and evaluated the in vitro proliferative responses and cytokine expression of T cells from the recipients after stimulation with donor alloantigens. The administration of not only CY but also mitomycin C (MMC) and cytosin arabinoside (Ara C) elicited a prolongation of skin graft survival. CY induced tolerance when it was administered 2 days after the p.v. injection, but not immediately or 4 days after the p.v. injection. T cells collected from the tolerant recipients showed no proliferative responses as a result of stimulation with donor alloantigens whereas the responses of T cells from non-tolerant recipients were significantly enhanced. Interferon-gamma (IFNgamma) was extensively expressed in the non-tolerant T cells from 24 to 48 h after the stimulation with donor alloantigens. In contrast, the expression of IFNgamma was observed in the tolerant T cells from 72 h after the stimulation. Also, the tolerant T cells showed the expression of interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-beta1) from 72 h after the stimulation whereas the non-tolerant T cells did not. These data suggest that CY, when administered 2 days after the p.v. injection, induces persistent tolerance by inhibiting T helper type 1 (Th1) activity in the early period but not the Th1 activity in the later periods.

Animals↗
PubMed2001

Spinocerebellar ataxia type 6: founder effect in Western Japan.

An accumulation of SCA6 cases has been observed in the Chugoku area of Western Japan. In the Tottori prefecture, located in the northeastern part of the Chugoku district, we observed a cluster of SCA6 families within the eastern area, suggesting that there may be a founder in the Japanese SCA6 population. Genotyping with DNA microsatellite markers linked to the CACNL1A4 gene on chromosome 19p13 demonstrated shared allelic characteristics and revealed a common haplotype in the majority of Japanese families. The common haplotype of the shared (CAG)(22) repeat found in this study may indicate the meiotic stability of CAG repeats in SCA6 patients.

Chromosomes, Human, Pair 19↗
PubMed2001

Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells.

Vascular endothelial growth factor (VEGF) inhibits of the activation of transcription factor nuclear factor-kappaB (NF-kappaB) in hematopoietic progenitor cells (HPCs), and this is associated with alterations in the development of multiple lineages of hematopoietic cells and defective immune induction in tumor-bearing animals. Antibodies to VEGF have been shown to abrogate this effect. The mechanism by which VEGF antagonizes the induction of NF-kappaB was investigated in this study. Using supershift electrophoretic mobility shift analysis, we found that although tumor necrosis factor alpha (TNF-alpha) induced the nuclear translocation and DNA binding of p65-containing complexes, VEGF alone induced nuclear translocation and DNA binding of the complexes containing RelB. These results were confirmed by immunofluorescence confocal microscopy. VEGF effectively blocked TNF-alpha-induced NF-kappaB activation in HPCs from RelB-/- mice, however, similar to the effect observed in HPCs obtained from RelB+/- and RelB+/+ mice. This suggests that RelB is not required for VEGF to inhibit NF-kappaB activation. However, although TNF-alpha induced rapid activation of IkappaB kinase (IKK) as expected, this activity was substantially reduced in the presence of VEGF. This decreased IKK activation correlated with the inhibition of IkappaB alpha phosphorylation and degradation of IkappaB alpha and IkappaB epsilon in HPCs. VEGF alone, however, did not have any effect on phosphorylation of IkappaB alpha or degradation of IkappaB alpha and other inhibitory molecules IkappaB beta, IkappaB epsilon, or Bcl-3. SU5416, a potent inhibitor of the VEGF receptor I (VEGFR1) and VEGFR2 receptor tyrosine kinases, did not abolish the inhibitory effect of VEGF, indicating that the VEGF effect is mediated by a mechanism unrelated to VEGFR1 or VEGFR2 tyrosine kinase activity. Thus, VEGF appears to inhibit TNF-alpha-induced NF-kappaB activation by VEGFR kinase-independent inhibition of IKK. Therapeutic strategies aimed at overcoming VEGF-mediated defects in immune induction in tumor-bearing hosts will need to target this kinase-independent pathway.

Animals↗
PubMed2001

Induction of virus-specific cytotoxic T lymphocytes by in vivo electric administration of peptides.

Generally, major histocompatibility complex (MHC) class I presentation of peptide antigens only occur for proteins' which are actively synthesized and processed intracellularly, so that immunization with a cytotoxic T lymphocyte (CTL) target peptide does not usually elicit effective CTL responses. In the present study, we explored the use of epitope peptides by in vivo electroporation to introduce directly into the cytoplasm for the vaccine elicitation of virus-specific CTLs in a mouse system. BALB/c mice were immunized with human immunodeficiency virus (HIV) env (P18, residues 311-320) or hepatitis C virus (HCV) NS5 (P17, residues 2423-2434) with or without electric pulses. Effector cells against peptide-labeled target cells were elicited in mice immunized with peptides with electric administration but not without electric administration. Moreover, cytolytic activities of CTL against peptide-labeled target cells were enhanced by the addition of plasmid having the immunostimulatory sequence (ISS) or cDNA of the B7-1 molecule in electric administration of peptides. The results of the present study suggest that a peptide vaccine against a virus using electric administration is effective in eliciting virus specific CTLs.

Amino Acid Sequence↗
PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression.

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients' survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.

Adenocarcinoma↗
PubMed2001

Clinicopathologic study of early-stage mucinous gastric carcinoma.

BACKGROUND: Mucinous gastric carcinoma (MGC) is rare, and whether MGC behaves more aggressively than nonmucinous gastric carcinoma (NGC) is controversial. To the authors' knowledge, there is no study of early-stage MGC, and the pathology and prognosis of patients who have early MGC is unknown. The aim of this study was to clarify the clinicopathologic characteristics of early MGC. METHODS: Pathologic and prognostic data of 30 patients who had early MGC were compared retrospectively against data of 165 patients who had early NGC and 58 patients who had advanced MGC. We defined MGC as a tumor in which more than half of the tumor area contained extracellular mucin pools. We defined early gastric carcinoma as a tumor restricted to the mucosa or to the mucosa and submucosa (T1, International Union Against Cancer [UICC], 1997) regardless of lymph node metastasis. RESULTS: Early MGC tumors, compared with early NGC tumors, were characterized by macroscopic elevation (57% vs. 23%, P < 0.01) and invasion to the submucosa (83% vs. 44%, P < 0.01). Tumor size, frequency of lymph node metastasis, and patient outcome did not differ between the two types, and no patient with early MGC died of recurrence during a median follow-up period of 67 months. When early MGC was compared with advanced MGC, tumor size (2.9 cm vs. 9.4 cm, P < 0.01), frequency of lymph node metastasis (10% vs. 88%,P < 0.01), total gastrectomy (0% vs. 52%, P < 0.01), noncurative surgery (0% vs. 38%, P < 0.01), and recurrent death (0% vs. 57%, P < 0.01) differed significantly. CONCLUSIONS: Our results indicated that although the macroscopic features of early MGC differed from those of early NGC, patient prognosis and the frequency of lymph node metastasis did not differ. Neither did mucinous histology seem to influence outcome adversely after gastrectomy.

Adenocarcinoma, Mucinous↗
PubMed2001

Enhancement of port site metastasis by hyaluronic acid under CO2 pneumoperitoneum in a murine model.

BACKGROUND: The mechanism underlying the development and progression of port site metastasis after laparoscopic surgery for cancer is still not understood. Hyaluronic acid secreted from mesothelial cells is thought to be a key factor that causes adhesion between cancer cells and mesothelial cells. Using a murine model of carbon dioxide (CO2) pneumoperitoneum, we evaluated the effect of exogenous hyaluronic acid on port site metastasis. METHODS: BALB/c mice were injected with 5 A- 106 human gastric carcinoma (MKN45) cells and divided into four groups treated with or without hyaluronic acid and with or without pneumoperitoneum. Three weeks later, the frequency and weight of port site metastases were determined. The effects of hyaluronic acid on tumorigenicity and tumor growth were examined in mice subcutaneously injected with MKN45 cells. RESULTS: Port site metastasis occurred significantly less frequently in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group (75% vs 100%, p < 0.05). The port site metastatic tumor weighed significantly less in the control group (anesthesia only) than in the hyaluronic acid group (89 +/- 17 vs 288 +/- 35 mg, p < 0.05); it also weighed less in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group(87 +/- 24 vs 298 +/- 51 mg, p < 0.05). The frequency and weight of tumors in the subcutaneous tissue were not significantly different between groups with or without hyaluronic acid injection (95% vs 90%, 331 +/- 128 vs 322 +/- 115 mg). CONCLUSIONS: Under CO2 pneumoperitoneum, exogenous hyaluronic acid increased the frequency and weight of port site metastasis in a murine model. Hyaluronic acid secreted from mesothelial cells may be associated with the formation of port site metastasis after laparoscopic surgery for cancer under pneumoperitoneum.

Adjuvants, Immunologic↗