Biomedical subjects

Satoru Todo

Publications and source records attributed to Satoru Todo.

At least 73 records · Page 4Linked to original sources

PubMed2004

Amelioration of hyperglycemia in streptozotocin-induced diabetic mice with fetal pancreatic allografts: prevention of rejection by donor specific transfusion in conjunction with CTLA4Ig.

INTRODUCTION: Fetal pancreas has been considered as an alternative donor source for islet transplantation since it has potent capacity for beta cell differentiation and proliferation. However, prevention of fetal pancreatic allograft rejection can be hardly achieved compared with adult islet allografts. AIMS: The aim of the study is to determine whether donor specific transfusion (DST) in conjunction with CTLA4Ig has any favorable effect on prevention of fetal pancreatic allograft rejection in mice. METHODS: BALB/c splenocytes (SPC, 1 x 10) were injected iv into C57BL/6 mice in conjunction with CTLA4Ig (ip, 50 microgram, day 0, 2, and 4). Fourteen days later, the mice were made diabetic with streptozotocin (STZ, iv) and donor specific or third party pancreatic allografts were transplanted beneath the kidney capsule. RESULTS: Morphologically, it was found that rejection of fetal pancreatic allografts can be prevented at 30 days after transplantation only when donor specific allografts were grafted into the mice treated with DST in conjunction with CTLA4Ig. Functionally, 3 out of 9 diabetic mice became normoglycemic by 120 days after transplantation of fetal pancreatic allografts. CONCLUSION: DST in conjunction with CTLA4Ig can have a favorable effect on prevention of fetal pancreatic allograft rejection resulting in amelioration of STZ-induced diabetes in mice.

Abatacept↗

PubMed2004

Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.

OBJECTIVE: We sought to determine the outcome of living donor liver transplantation (LDLTx) in 316 adult patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: LDLTx has increasingly been performed worldwide, but the impact of the procedure on HCC has not been evaluated in a large series. METHODS: Between October 1989 and December 2003, 1389 adults underwent LDLTx at 49 centers in Japan. In 316 (22.8%) who received LDLTx for HCC (70 females, 22%, median age 57 years; and 246 males, 88%, median age, 54 years), we analyzed pretransplant clinical status, imaging diagnosis, transplant procedure, pathologic study of explanted liver, and outcome. In 232 patients (73.4%), various surgical and nonsurgical therapies had been employed prior to LDLTx. The median follow-up period was 16 months (range, 2.5-72.0) RESULTS: Currently, 236 (74.7%) of the patients are living. One- and 3-year patient survivals were 78.1% and 69.0%, respectively. Model end-stage liver disease score and preoperative serum alpha-fetoprotein level were independent risk factors for patient survival. Forty patients (12.7%) developed HCC recurrence. Alpha-fetoprotein level, tumor size, vascular invasion, and bilobar distribution were independent risk factors for HCC recurrence. Grade of histologic differentiation of HCC showed close correlation with tumor characteristics and recurrence. One- and 3-year recurrence-free survivals were 72.7% and 64.7%, respectively. When the Milan criteria were applied, patient survival and disease-free survival at 3 years were 78.7% and 79.1%, respectively, in patients who met the criteria, and 60.4% and 52.6%, respectively, in those who did not. CONCLUSION: LDLTx can achieve acceptable survival in HCC patients, even when liver function is markedly impaired, or HCC is uncontrollable by conventional antitumor treatments.

Adult↗

PubMed2004

Peripheral anatomic evaluation using 3D CT hepatic venography in donors: significance of peripheral venous visualization in living-donor liver transplantation.

OBJECTIVE: The purpose of this study was to determine clinical roles for 3D CT hepatic venography in the evaluation of peripheral hepatic venous anatomy during living-donor liver transplantation. MATERIALS AND METHODS: Subjects comprised 54 donors (age range, 20-60 years) who had undergone surgery to donate a liver for transplantation. Visualization of each hepatic venous branch and total visualization using 3D CT hepatic venography were evaluated. Maximum venous branch order visualized was graded as nil, first branch, second branch, or third branch or more. The distance between the hepatic surface and the tip of each hepatic venous branch was classified as 0-5 mm, 6-10 mm, 11-15 mm, 16-20 mm, or 21-25 mm. Quality of total 3D CT hepatic venography was evaluated subjectively as poor, good, fair, or excellent. Dominance of large hepatic veins in the right lobe, peripheral branching pattern of the middle hepatic vein, and branching pattern of the vein draining segment IVb were also assessed. RESULTS: Most hepatic venous branches (96.2% [275/286]) were visualized up to at least the second-order branches, and 93.7% (268/286) of branches were within 10 mm of the hepatic surface. As for total visualization, 98% (53/54) of cases were regarded as excellent. The dominant vein in the right lobe was the right hepatic vein in 27 cases, inferior hepatic vein in 25, and middle hepatic vein in one. The branching pattern of the middle hepatic vein was type 1 in 36 cases, type 2 in nine, and type 3 in eight. Segment IVb vein branched from the middle hepatic vein in 20 patients, and from the left hepatic vein in 34. CONCLUSION: Because 3D CT hepatic venography visualizes peripheral hepatic venous branches in detail, the technique is useful for determining operative indications in living-donor liver transplantation.

Adult↗

PubMed2004

[Neoadjuvant chemoradiotherapy for advanced squamous cell carcinoma of thoracic esophagus].

Advanced thoracic esophageal cancer has a poor prognosis despite advances in surgery, such as three-field lymph node dissection. Multimodal therapy is needed to improve local control, resectability and survival rate. Fifteen patients with advanced squamous cell carcinoma of the thoracic esophagus were treated with neoadjuvant chemoradiotherapy (NAC) combined with concurrent radiation (30 Gy/12 f) and 3 courses of 5-FU and CDDP (CDDP 5 mg/m2/day + 5-FU 250 mg/m2/day: day 1-5: div). In the absence of unresectable disease and surgical risk, 12 patients underwent esophagectomy (Group 1) and 3 patients underwent additional chemoradiotherapy because of high surgical risk (Group 2). Side effects consisted of nausea, vomiting and myelo-suppression in 8 patients, but all patients tolerated and completed a full course of NAC. The effective rate (CR + PR) of NAC was 58.3% in Group 1 and 66.7% in Group 2. No patients showed pathological CR. Two-year survival rate was 28.1% in Group 1 (PR: 33.3%, NC: 20.0%) and 33.5% in Group 2. This protocol had acceptable toxicities but did not show survival benefit. Further trials are necessary to improve survival rate.

Aged↗

PubMed2004

Immunological evaluation of vaccination with pre-designated peptides frequently selected as vaccine candidates in an individualized peptide vaccination regimen.

We previously conducted a trial of an 'individualized' regimen, in which cancer patients were vaccinated with peptides after the confirmation of pre-existing peptide-specific cytotoxic T lymphocyte (CTL) precursors. In this study, we performed a new trial of 'pre-designated' regimen, in which cancer patients were vaccinated with peptides that were frequently selected as vaccine candidates in the preceding individualized regimen. Eighteen cancer patients (10 with uterine cervical cancer and 8 with gastric cancer) were enrolled in the new regimen. The pre-designated regimen was well tolerated by all patients. Although peptide-specific CTL precursors and humoral responses increased in the majority of patients with the pre-designated regimen, neither of the responses correlated with clinical outcome. Three patients had long stable disease, and their pre-vaccination peripheral blood mononuclear cells contained peptide-specific CTL precursors reactive to more than 2 of 4 peptides. With the pre-designated regimen, the levels of pre-existing immunoglobulin G reactive to non-vaccinated peptides decreased in 5 of 15 patients with progressive disease, and their time to progression was very short, whereas such a decrease was rarely observed in the preceding individualized regimen. These results suggest that the pre-designated regimen can elicit a primary immune response, but may incidentally suppress pre-existing immune responses.

Adult↗

PubMed2004

Decreased expression of the candidate tumor suppressor gene ING1 is associated with poor prognosis in advanced neuroblastomas.

ING1 has been identified as a novel candidate tumor suppressor gene using a genetic suppressor element (GSE) strategy. Ectopic expression of ING1 in mammalian cultured cells causes cell cycle arrest and apoptosis through a p53-dependent and/or p53-independent pathway. However, there has been no report on the prognostic significance of the ING1 expression level in human cancers, though the expression of the wild-type ING1 gene is significantly decreased in breast, lymphoid and gastric cancers as compared with their corresponding normal tissues. In order to explore the possible involvement of ING1 in tumorigenesis of neuroblastoma, we examined the expression levels of ING1 mRNA in 32 primary neuroblastomas by using a quantitative real-time PCR. ING1 mRNA was expressed independently of the disease stages. however, low levels of ING1 mRNA were significantly associated with a poor prognosis (log-rank test, p=0.017). Multivariate analysis showed that the expression level of ING1 was closely related to survival (p=0.020), even after controlling with age (p=0.008) or stage (p=0.025), while it was only marginally significant after controlling with TrkA expression (p=0.063). Mutation analysis revealed that there was no mutation or deletion of the ING1 gene except 1 silent mutation at codon 188 in primary neuroblastomas examined. Taken together, our results suggest for the first time that a decreased level of ING1 expression is a novel indicator of poor prognosis in advanced stages of neuroblastoma, and that ING1 may play a crucial role in genesis and progression of neuroblastoma.

Blotting, Northern↗

PubMed2004

[Liver regeneration in living-donor liver transplantation].

Liver regeneration in living-donor liver transplantation is summarized from the authors' data. In donors, liver function tests recovered to within the normal range 2 weeks after surgery regardless of graft type. At 2 weeks, the volumetric recovery of the remnant liver was 65% and 80% of the original volume in right and left lobe donors, respectively. These results suggest that functional recovery occurs earlier than morphologic restoration in donors. In recipients, the factor that affected the regeneration rate in size 4 weeks after transplantation was only implanted graft size; the rate was greater in patients in whom smaller grafts were implanted. In recipients with a rate of two or more, however, high portal vein pressure and flow were observed. Further, persistent low platelet counts and hyperbilirubinemia were seen in those patients. These results indicate that size enlargement may be caused by engorgement, and functional recovery is not achieved concurrently with morphologic restoration, especially in patients with smaller grafts. In patients with fulminant hepatic failure who receive auxiliary partial orthotopic liver transplantation, sequential histopathologic observations of the diseased liver revealed that liver regeneration initiates from cytokeratin 17-positive ductules and at least 1 year is necessary for complete recovery.

Hepatocytes↗

PubMed2004

[In vitro chemosensitivity test for hepatocellular carcinoma using collagen-gel droplet embedded cultures].

This study evaluated an in vitro assay for chemosensitivity test using a collagen-gel droplet-embedded culture drug sensitivity test (CD-DST) for hepatocellular carcinoma (HCC). In 25 patients with HCC, in vitro chemosensitivity to 5-fluorouracil (5-FU), epirubicin (EPI), and cisplatin (CDDP) was examined by CD-DST, and 5-FU, EPI, and paclitaxel (PTX) were examined in 38 patients with breast cancer. Successful rates of chemosensitive evaluation by CD-DST were 64% for HCC and 79% for breast cancers. Although chemosensitivities of breast cancer were 5-FU 23.1%, EPI 83.3%, and PTX 67.7%, only one HCC sample was sensitive to EPI. Growth rates of HCC for 7 days of culture were significantly lower than those of breast cancers (1.04 vs 3.61). The culture methods for HCC in CD-DST should be improved to estimate accurate results.

Antineoplastic Agents↗

PubMed2003

Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies.

BACKGROUND: We have previously demonstrated that blockade of either CD80/86-CD28 or CD40-CD154 costimulatory pathways by using adenovirus vector coding CTLA4Ig (AdCTLA4Ig) or CD40Ig (AdCD40Ig) genes induced donor-specific tolerance in rat liver transplantation. In this study, we asked whether these gene-therapy-based costimulation blockade would induce tolerance in cardiac transplantation. METHODS: Heterotopic heart transplantation was performed in a full major histocompatibility complex (MHC) barrier combination of ACI (RT1avl) to Lewis (LEW, RT1l) rats. Vector (1 x 10(9) plaque forming unit [PFU]), AdLacZ, AdCTLA4Ig, or AdCD40Ig, was administered intravenously to recipient animals immediately after grafting, and graft survival, serum CTLA4Ig/CD40Ig levels, and graft histology were assessed. Tolerance was determined by secondary skin-graft challenging. RESULTS: Allografts of both untreated and AdLacZ controls were promptly rejected within 7 days, whereas a single treatment with AdCTLA4Ig or AdCD40Ig significantly prolonged median graft survival to 55.5 and 28.5 days, respectively. In contrast, the combined AdCTLA4Ig and AdCD40Ig gene therapy maintained high CTLA4Ig and CD40Ig levels through the posttransplant period and allowed long-term cardiac allograft survival for more than 270 days. However, both donor and third-party skin grafts were rejected in the animals who harbored cardiac grafts over 150 days. Also, typical features of chronic rejection were evident in the long-term surviving grafts. CONCLUSION: Simultaneous blockade of CD28 and CD154 pathways by AdCTLA4Ig plus AdCD40Ig induces a strong immunosuppression that allows long-term acceptance of full MHC mismatched cardiac graft in rats. This strategy, however, was not enough to induce tolerance to skin grafts and to avoid chronic rejection, as shown in the liver-transplantation model.

Abatacept↗

PubMed2003

Negative autoregulation of p73 and p53 by DeltaNp73 in regulating differentiation and survival of human neuroblastoma cells.

p73, mapped to 1p36.2-3, is a p53-related tumor suppressor but is also induced by the oncogene products such as E2F1, raising a question whether p73 is a tumor suppressor gene or oncogene. p73 has several splicing variants including DeltaNp73 which lacks the NH(2)-terminal transactivation domain. In developing neurons, DeltaNp73 is expressed abundantly and seems to inhibit the pro-apoptotic function of p53. However, the role of TAp73 and DeltaNp73 as well as their regulatory mechanism in cell growth and differentiation of neuroblastoma cells are poorly understood. We have found that TAp73 directly activates the transcription of endogenous DeltaNp73 by binding to the TAp73-specific target element located at position-76 to 57 within the DeltaNp73 promoter region. DeltaNp73 was physically associated with TAp73alpha, TAp73beta and p53, and inhibited their transactivation activities when used reporters of Mdm2, Bax or DeltaNp73 itself in SAOS-2 cells. Overexpression of DeltaNp73 in SH-SY5Y neuroblastoma cells promoted cell survival by competing with p53 and TAp73 itself. Thus, our results suggest that the negative feedback regulation of TAp73 by its target DeltaNp73 is a novel autoregulatory system for modulating cell survival and death, that is also functioning in neuroblastoma cells.

Cell Differentiation↗

PubMed2003

Alveolar echinococcosis: MR findings in the liver.

PURPOSE: To clarify the magnetic resonance (MR) imaging findings of alveolar echinococcosis in the liver. MATERIALS AND METHODS: Thirty-five patients with 50 lesions histologically proven to be alveolar echinococcosis were evaluated with MR imaging. Lesions were assessed with regard to the distribution pattern of solid and cystic components and pattern of contrast material enhancement. RESULTS: Cystic components exhibited two patterns at T2-weighted MR imaging: small round cysts and large and/or irregular cysts. Forty-eight lesions (96%) contained small round cysts. Twenty-six lesions (52%) had large and/or irregular cysts. Forty-five lesions (90%) were associated with a solid component. MR imaging characteristics were categorized into five types: multiple small round cysts without a solid component (two lesions [4%], type 1), multiple small round cysts with a solid component (20 lesions [40%], type 2), a solid component surrounding large and/or irregular cysts with multiple small rounds cysts (23 lesions [46%], type 3), a solid component without cysts (two lesions [4%], type 4), and a large cyst without a solid component (three lesions [6%], type 5). In most cases (97%), contrast enhancement was weak. CONCLUSION: The MR findings of alveolar echinococcosis in the liver are multiple small round cysts with a weakly enhanced solid component. The cystic component can be a large and/or irregular lesion, and such lesions are depicted clearly at T2-weighted MR imaging.

Adolescent↗

PubMed2003

Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator.

BACKGROUND: An inducible costimulator (ICOS) has been found to be a novel costimulator for T-cell activation, although its precise role in transplant immunobiology remains unclear. This study determined whether ICOS plays an essential role in rejection of intrahepatic islet allografts in streptozotocin-induced diabetic mice. METHODS: Mononuclear cells in the liver of mice were isolated and examined by flow cytometry with respect to expression of ICOS in association with rejection, and the effects of in vivo treatment with an anti-ICOS antibody on survival of intrahepatic islet allografts were determined. RESULTSFlow cytometric analysis of mononuclear cells in the liver of normal untreated mice revealed that ICOS is expressed on CD4+CD3int natural killer T cells. The expression of ICOS was up-regulated on CD4+CD3bright T cells and expanded CD8 T cells in the liver in association with rejection. Posttransplant short-term administration of anti-ICOS antibody alone produced a significant prolongation of islet allograft survival. Administration of the antibody in conjunction with a subtherapeutic regimen of FK506 prevented rejection, leading to the acceptance of islet allografts. CONCLUSION: ICOS has an essential role in rejection of intrahepatic islet allografts and the blockade of ICOS interaction might be a novel approach for preventing islet allograft rejection.

Animals↗

PubMed2003

She4p/Dim1p interacts with the motor domain of unconventional myosins in the budding yeast, Saccharomyces cerevisiae.

She4p/Dim1p, a member of the UNC-45/CRO1/She4p (UCS) domain-containing protein family, is required for endocytosis, polarization of actin cytoskeleton, and polarization of ASH1 mRNA in Saccharomyces cerevisiae. We show herein that She4p/Dim1p is involved in endocytosis and actin polarization through interactions with the type I myosins Myo3p and Myo5p. Two-hybrid and biochemical experiments showed that She4p/Dim1p interacts with the motor domain of Myo3/5p through its UCS domain. She4p/Dim1p was required for Myo5p localization to cortical patch-like structures. Using random mutagenesis of the motor region of MYO5, we identified four independent dominant point mutations that suppress the temperature-sensitive growth phenotype of the she4/dim1 null mutant. All of the amino acid substitutions caused by these mutations, V164I, N168I, N209S, and K377M, could suppress the defects of endocytosis and actin polarization of the she4/dim1 mutant as well. She4p/Dim1p also showed two-hybrid interactions with the motor domain of a type II myosin Myo1p and type V myosins Myo2p and Myo4p, and was required for proper localization of Myo4p, which regulates polarization of ASH1 mRNA. Our results suggest that She4p/Dim1p is required for structural integrity or regulation of the motor domain of unconventional myosins.

Cytoskeletal Proteins↗

PubMed2003

Chromosomes that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors: evidence suggesting the involvement of the same genes in the tumorigenesis of high- and low-risk neuroblastomas.

We performed two-color fluorescence in situ hybridization analysis to detect the numbers of chromosomes 1 and 17, 1p deletion, and 17q gain in 177 neuroblastomas, including 101 tumors that were found by a mass-screening program for infants. Sixty-eight tumors with disomy 1 or tetrasomy 1 were classified as the Dis1 group, and 109 tumors with trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1 were classified as the Tris1 group. 17q gain was the most frequent genetic event, followed by 1p deletion, and MYCN amplification in both Dis1 and Tris1 tumors. However, the incidence of all the genetic events was higher in Dis1 tumors than in Tris1 tumors. These findings suggest that Tris1 tumors are more resistant to acquiring the genetic events than are Dis1 tumors. In addition, there was an accumulation of genetic events in more advanced stages, with the exception of a high incidence of 17q gain in the stage IVS Tris1 tumors. Comparative genomic hybridization analysis, which was performed in 59 of the 177 tumors, showed that chromosomes partially lost or gained in Dis1 tumors coincided with chromosomes totally lost or gained in Tris1 tumors. Dis1 and Tris1 tumors were considered to have near-diploid/tetraploid and near-triploid/pentaploid chromosome numbers, respectively. These findings suggest that the same tumor-suppressor genes or oncogenes may be involved in the development and progression of both high- and low-risk neuroblastomas, and that the ploidy state of the tumor plays a fundamental role in the heterogeneous behavior.

Allelic Imbalance↗

PubMed2003

Ten-year results of a randomized trial on adjuvant chemo-endocrine therapy with tamoxifen for stage II breast cancer.

BACKGROUND: A prospective randomized multi-center study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of futraful (FT) and tamoxifen (TAM) for postoperative adjuvant therapy for stage II breast cancer after curative surgery. METHODS: Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX) 20 mg/body on the day of surgery and 10 mg/body the next day, followed by oral FT 600 mg/day for 2 years from the 14th day after surgery; treatment B, the same pattern of DOX administration followed by combined therapy with FT and TAM 20 mg/day for 2 years. The number of patients was 428 (treatment A 210 and treatment B 218), of whom 418 (97.7%) were followed for 10 years for analysis. RESULTS: Significantly higher 5- and 10-year overall survival (OS) rates were observed with treatment B compared with treatment A (p=0.0101 and 0.0219). Node-positive patients appeared to derive more benefit from TAM than node-negative patients. The difference in 10-year OS between treatment A and treatment B was more evident than that of the 5-year OS in patients with more than 4 positive nodes (p=0.0313 vs. 0.0479). No increase in adverse reactions was seen as a result of combining TAM with FT. CONCLUSION: The study results demonstrate that for stage II breast cancer concomitant administration of FT and TAM is superior to FT alone for postoperative adjuvant therapy, and administration of TAM for 2 years may contribute not only to 5-year survival rates but also to 10-year survival rates of node-positive patients.

Adenocarcinoma↗

PubMed2003

A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats.

BACKGROUND: A Rho-ROCK signal system induces vascular contraction and neutrophil migration, both of which are characteristic features found with ischemia and reperfusion injury of the liver. We tested our hypothesis that a novel ROCK I inhibitor, Y-27632, attenuates hepatic ischemia and reperfusion injury. METHODS: Rats underwent 70% partial hepatic ischemia for 120 minutes and subsequent reperfusion. Y-27632 of 10mg/kg was given orally 1 hour before ischemia, while distilled water was given to the control animals. One week animal survival, systemic hemodynamics, hepatic tissue blood flow, liver function tests, plasma endothelin-1, serum hyaluronic acid levels, myeloperoxidase activity and malondialdehyde level in liver tissue, membrane attack complex-1 and intracellular adhesion molecule-1 staining, and histological architecture were analyzed. RESULTS: Y-27632 prolonged 1-week animal survival from 25% of untreated animals to 75% accompanied with significant amelioration of hepatic tissue blood flow, liver function tests and histological architecture without any adverse effects on systemic hemodynamics. In addition, plasma endothelin-1 and serum hyaluronic acid levels decreased markedly compared to the control, concomitant with remarkable suppression of membrane attack complex-1 stain positive neutrophils infiltration, myeloperoxidase activity and malondialdehyde level. CONCLUSION: Present study suggests that activation of a Rho-ROCK signal system is associated with ischemia and reperfusion injury of the liver, and that Y-27632 may be an attractive agent for application in major liver resection using temporary inflow occlusion and hepatic preservation.

Alanine Transaminase↗

PubMed2003

Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide.

There is no standard treatment modality for advanced gastric cancer (GC) at the present time. To develop a new treatment modality, we investigated the immunological responses of advanced GC patients (n = 13, 9 non-scirrhous and 4 scirrhous types) vaccinated with peptides to a regimen under which pre-vaccination peripheral blood mononuclear cells (PBMCs) were screened for their reactivity in vitro to each of 14 peptides on HLA-A24 or 16 peptides on -A2 allele, then only the reactive peptides (maximum: 4) were administered in vivo. This regimen was generally well tolerated, although grade I levels of fever and local skin reactions were observed in several patients. Delayed-type hypersensitivity (DTH) to the vaccinated peptides was observed in 4 patients. Increased cellular and humoral immune responses to the vaccinated peptides were observed in post-vaccination PBMCs from 4 of 8 patients and in post-vaccination sera of 8 of 10 patients tested, respectively. Prolonged survival was observed in patients showing cellular and humoral immune responses to the vaccinated peptides in the post-vaccination samples, including all 4 patients with the scirrhous type. These results encourage further development of peptide-based immunotherapy for GC patients.

Adenocarcinoma↗

PubMed2003

Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis.

Macrophage migration inhibitory factor (MIF) functions as a pluripotent cytokine involved in broad-spectrum pathophysiological events in association with inflammation and immune responses. Several reports, including ours, have suggested that MIF is also involved in tumorigenesis; however, its precise role has not been fully investigated. We examined the effectiveness of anti-MIF antibodies on tumor growth and tumor-associated angiogenesis using murine colon cancer cell line, colon 26. We observed a significant inhibition of growth of tumors embedded on the back of BALB/c mice by treatment with anti-MIF antibodies. Next, we implanted a Millipore chamber filled with colon cancer cells in the subcutaneous fascia of the flanks of mice and then treated them with anti-MIF antibodies. We found that angiogenesis was markedly suppressed within the region of the subcutaneous fascia that was in contact with the chamber. To further assess the role of MIF in tumorigenesis, we established MIF transgenic mice, which demonstrated that tumor growth and the associated angiogenesis were significantly enhanced in comparison with control mice.

Animals↗