PubMed Health⌕ Search

Biomedical subjects

Masahiro Asaka

Publications and source records attributed to Masahiro Asaka.

At least 19 recordsLinked to original sources
PubMed2005

Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability.

Proteolytic modification of insulin-like growth factor binding proteins (IGFBPs) plays an important physiological role in regulating insulin-like growth factor (IGF) bioavailability. Recently, we demonstrated that matrix metalloproteinase-7 (MMP-7)/Matrilysin produced by various cancer cells catalyzes the proteolysis of IGFBP-3 in vitro and regulates IGF bioavailability, resulting in an anti-apoptotic effect against anchorage-independent culture. In the present study, we investigated whether MMP-7 contributes to proteolysis of the other five IGFBPs, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6, and whether this results in phosphorylation of the IGF type 1 receptor (IGF-1R). MMP-7 cleaved all six IGFBPs, resulting in IGF-mediated IGF-1R phosphorylation, which was inhibited by EDTA treatment. These results suggest that MMP-7 derived from cancer cells can regulate IGF bioavailability in the microenvironment surrounding the tumor, where various kinds of IGF/IGFBP complexes are found, thereby favoring cancer cell growth and survival during the processes of invasion and metastasis.

3T3 Cells↗
PubMed2005

Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection.

Reactivation of resolved hepatitis B virus (HBV) infection, which is known as reverse seroconversion (RS), has been reported as a rare complication of allogeneic hematopoietic stem cell transplantation. We retrospectively studied HBV serologic markers in 14 recipients with pretransplant anti-hepatitis B surface antigen antibody (anti-HBs). Progressive decreases in anti-HBs titer were observed in all cases. In 12 cases, anti-HBs titer had decreased to under the protective value. RS occurred in seven cases after disappearance of anti-HBs. Although reseroconversion occurred in five cases, two cases remained in an HBV-carrier status after resolution of hepatitis. In the other five cases, RS did not occur even after disappearance of anti-HBs. The actual risks of anti-HBs disappearance and RS were estimated to be 75.0% and 39.8% at 2 years and 100.0% and 70.0% at 5 years, respectively. In conclusion, RS is a late-onset complication with high frequency that can be predicted by careful monitoring of progressive decrease in anti-HBs titer.

Adult↗
PubMed2005

Intraperitoneal injection of adenovirus expressing antisense K-ras RNA suppresses peritoneal dissemination of hamster syngeneic pancreatic cancer without systemic toxicity.

We examined the antitumor effect and safety of the adenovirus-mediated expression of antisense K-ras RNA in two peritoneal dissemination models of pancreatic cancer. First, we found that the infection of an adenovirus vector expressing antisense human K-ras RNA (AxCA-AS) induced significant apoptosis in vitro in human pancreatic cancer cells with K-ras mutation. Second, the intraperitoneal (ip) injection of AxCA-AS effectively suppressed the growth of human pancreatic cancer cells in the peritoneal cavity of nude mice. Third, in the hamster syngeneic peritoneal dissemination model, the ip injection of an adenovirus expressing antisense hamster K-ras RNA significantly suppressed the peritoneal growth of hamster pancreatic cancer cells, and no significant systemic toxicity was observed in the treated hamsters. This study suggests a feasibility of the development of a therapeutic strategy against pancreatic cancer based on the adenovirus-mediated transduction of an antisense K-ras construct.

Adenoviridae↗
PubMed2005

Long-term follow-up of a patient with idiopathic myelofibrosis associated with chromosome 11 and 13 abnormalities.

A case of a leukemic transformation following a 27-year history of idiopathic myelofibrosis (IMF) is presented. The patient had two chromosomal abnormalities: a deletion of chromosome 13, del 13(q12q14), and a deletion of chromosome 11, del 11(q14q23). This patient's final diagnosis was acute micromegakaryocytic leukemia, and she died 1 month after leukemic transformation with an additional chromosomal abnormality, trisomy 8. IMF with myeloid metaplasia associated with deletion of the long arms of chromosomes 11 and 13 has not been previously reported. We speculate that the leukemic transformation in this patient was associated with chromosomal abnormalities del 11 and trisomy 8.

Bone Marrow↗
PubMed2005

Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders.

Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and tumoricidal activity. It has been reported that MIF is associated with the pathogenesis of a variety of diseases. MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis. In experimental inflammatory disease, blockade of MIF bioactivity inhibited the severity of disease activity. On the other hand, MIF expression is also increased in tumor lesions, and MIF plays a role as a cell growth factor. MIF has been reported to be constitutively expressed in gut, liver, and pancreas. In patients with gastritis, inflammatory bowel disease, hepatitis, and pancreatitis, MIF expression was remarkably increased in both the serum and the local lesions. Blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis, colitis, hepatitis, and pancreatitis. On the other hand, MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro. Blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro. MIF plays important roles in the pathogenesis of gastrointestinal, hepatic, and pancreatic disorders.

Colonic Neoplasms↗
PubMed2005

In vitro induction of resistance to metronidazole, and analysis of mutations in rdxA and frxA genes from Helicobacter pylori isolates.

In clinical Helicobacter pylori isolates, metronidazole resistance has been associated with mutations in the rdxA and frxA genes. The aim of this study was to examine the role of the rdxA and frxA genes after the in vitro induction of metronidazole resistance. A total of five suscep-tible H. pylori isolates were initially exposed to different subinhibitory metronidazole concentrations to induce in vitro resistance to metronidazole. Susceptible and resistant strains after the in vitro induction of resistance were examined to evaluate mutations of the rdxA and frxA genes by sequence analysis. After the in vitro induction of resistance, analysis revealed that two and four susceptible strains developed resistance when cultured with 0.3 microg/ml and 0.6 microg/ml of metronidazole, respectively. Before and after the induction of resistance, none of the susceptible strains that developed low and moderate levels of resistance presented any mutation in either of the evaluated genes, whereas strains with high-level metronidazole resistance contained a simple mutation of the frxA gene, but no specific changes in the rdxA gene. Strains with moderate-level resistance contained both single and multiple mutations of rdxA and frxA, respectively, and the low-level-metronidazole-resistant strain contained a single mutation in the frxA gene, without any significant change in the rdxA gene. In this study, the strains that developed resistance were mainly associated with mutations of the frxA gene, suggesting the possibility that inactivation of this gene could originate metronidazole resistance. The results after the in vitro induction of resistance to metronidazole suggested the presence of additional metronidazole resistance mechanisms, other than mutations of the rdxA and/or frxA genes.

Anti-Infective Agents↗
PubMed2005

Phase II study of oral S-1 plus irinotecan in patients with advanced colorectal cancer: Hokkaido Gastrointestinal Cancer Study Group HGCSG0302.

We have previously reported on phase I/II studies of irinotecan plus S-1 therapy for advanced gastric cancer. Based on the safety and efficacy data that were obtained, this phase II study was planned to assess the efficacy of irinotecan plus S-1 for patients with advanced colorectral cancer. A total of 40 patients are enrolled at 13 medical institutions. The objective of this study was to establish a useful chemotherapy regimen for an out-patient setting.

Adenocarcinoma↗
PubMed2005

Reactivation of hepatitis B virus with rituximab.

Rituximab has become a useful drug for the treatment of non-Hodgkin's lymphoma (NHL) and such autoimmune diseases as idiopathic thrombocytopenic purpura and rheumatoid arthritis. When combined with cytotoxic agents, rituximab showed synergistic effects for the treatment of NHL. In such treatment, hepatitis B virus (HBV) reactivation is a crucial complication when patients are treated with immunosuppressive or chemotherapeutic agents. Despite its treatment efficacy, several studies have pointed out unusual viral infections after its administration that resulted in fatal hepatitis due to HBV reactivation. In the cases at the authors' institute, the authors analysed the kinetics of HBV antibodies, HBV-reactivation timing, and the prophylactic efficacy of lamivudine. The authors reviewed their cases and the previous literature to clarify the characteristics of HBV-reactivated patients who were administered rituximab.

Antibodies, Monoclonal↗
PubMed2005

Potential role of natural killer cell receptor-expressing cells in immunotherapy for leukemia.

Natural killer cell receptor (NKR)-expressing cells have cytolytic activity against leukemic cells, and solid tumor cells escape from T-cell recognition because of the low expression levels of class I HLA molecules in both allogeneic and autologous settings. This characteristic feature of NK cell recognition of target cells in contrast with that of T-cells provides a strategy to overcome tolerance in the tumor-bearing host. Furthermore, inhibitory NKR-expressing cells may have cytolytic activity and immunoregulatory functions. Several methods can be used to expand NKR-expressing cells for adoptive immunotherapy for leukemia and other malignant diseases. We review recent developments in the biology and clinical application of NKR-expressing cells, such as NK cells, lymphokine-activated killer cells, cytokine-induced killer cells, NKT cells, and other NKR-expressing cells.

Humans↗
PubMed2005

Successful reduced-intensity stem cell transplantation (RIST) for a patient with malignant lymphoma and an ileostomy.

A 56-year-old man was admitted for treatment of non-Hodgkin's lymphoma (NHL). He had undergone a partial small bowel and colon resection and had ileostomy due to bowel perforation induced by chemotherapy. After the operation, his disease status was in partial remission (PR), and reduced-intensity allogeneic stem cell transplantation (RIST) was therefore performed for further improvement of disease status. The conditioning regimen consisted of fludarabine and busulfan. Graft-versus-host disease (GVHD) prophylaxis was performed using cyclosporin and short-term methotrexate. The occurrence of serious infection during the period of neutropenia was prevented by the administration of amphotericin B, fluconazole and acyclovir. This case report provides important information on the appropriate strategy for treating patients who have ileostomy.

Antineoplastic Agents↗
PubMed2004

Low levels of insulin-like growth factor type 1 receptor expression at cancer cell membrane predict liver metastasis in Dukes' C human colorectal cancers.

PURPOSE: The aim of this study was to evaluate the prognostic significance of insulin-like growth factor type 1 receptor (IGF-1R) expression in Dukes' C human colorectal cancers (CRCs). EXPERIMENTAL DESIGN: Immunohistochemical staining for IGF-1R was done on formalin-fixed, paraffin-embedded specimens from 161 patients with curatively resected Dukes' C CRC and at least 5-year follow-up periods. We investigated the association between the levels of IGF-1R expression and the clinicopathologic parameters. To evaluate the accurate prognostic value of IGF-1R expression, we investigated two patterns of recurrence-free survival (RFS) according to the mode of recurrence, the hepatic-RFS (H-RFS), and the nonhepatic-RFS (nH-RFS). The influence of the pattern of IGF-1R immunostaining (membranous or cytoplasmic) on RFS was also estimated. RESULTS: High (diffuse staining) and low (focal staining) levels of IGF-1R expression were found in 45 (28%) and 116 (72%) specimens, respectively. The recurrence rate was significantly higher in the latter group (49 of 116) than the former group (9 of 45; P = 0.01). H-RFS was significantly longer for the former group than the latter group (P = 0.021), whereas no difference was found in nH-RFS between the two groups (P = 0.121). In multivariate analysis, the level of IGF-1R expression was an independent factor for H-RFS (P = 0.015) as were the depth of invasion and lymph vessel invasion (P = 0.006 and 0.022, respectively). Using a combination of the level of IGF-1R expression and these two factors, the prognostic value was further increased. When IGF-1R staining patterns (membranous or cytoplasmic) were compared, membrane staining of IGF-1R possessed prognostic significance. CONCLUSIONS: In Dukes' C CRC, focal membrane expression of IGF-1R in the primary tumor can predict a high risk of recurrence, especially liver metastasis. Understanding the mechanisms involved could lead to new therapeutic approaches for advanced CRC.

Adenocarcinoma↗
PubMed2004

Successful treatment of lymphoma with fludarabine combined with rituximab after immune thrombocytopenia induced by fludarabine.

A 47-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) follicular B-cell type (stage IVB). Although partial remission was observed after the administration of several combination chemotherapeutic agents, no more improvement was observed. After we finished the FND (fludarabine, mitoxantrone, dexamethasone) regimen, the patient's status improved. After the administration of the FND regimen, thrombocytopenia developed, and the platelet count did not recover to previous levels. After rituximab was administered for the treatment of thrombocytopenia, the platelet count recovered. Then we combined fludarabine and rituximab for the treatment of NHL. Although fludarabine was administered, the platelet count did not decrease when combined with rituximab. In the discussion, we analyze the characteristics and the treatment outcome of the thrombocytopenia induced by fludarabine reviewed in the literature.

Antibodies, Monoclonal↗
PubMed2004

Usefulness of magnifying endoscopic evaluation of the terminal ileum for a patient with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

The gastrointestinal tract is one of the common targets of acute graft-versus-host disease (GVHD), but accurate diagnosis is difficult because of the nonspecific nature of complicated diseases and the lack of diagnostic findings by conventional endoscopy. Recently, a magnifying endoscope has been developed and used for examining microstructures of the mucosa. Herein, we report the first use of a magnifying endoscope for a patient with gastrointestinal (GI) GVHD. Magnified endoscopic findings of atrophic and coalescent villi of the terminal ileum reflect histological findings of GVHD. Magnifying endoscopy of the terminal ileum may be useful for early detection and follow-up of GI GVHD.

Adolescent↗