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Biomedical subjects

S Iida

Publications and source records attributed to S Iida.

At least 19 recordsLinked to original sources

The CCR4 as a novel-specific molecular target for immunotherapy in Hodgkin lymphoma.

Here, we report that tumor cells from some patients (23.8%) with Hodgkin lymphoma (HL) are positive for CC chemokine receptor 4 (CCR4). We therefore tested the chimeric anti-CCR4 monoclonal antibody (mAb), KM2760, the Fc region of which is defucosylated to enhance antibody-dependent cellular cytotoxicity (ADCC), as a novel immunotherapy for refractory HL. KM2760 demonstrated a promising antitumor activity in the CCR4-positive HL-bearing mouse model in the therapeutic setting. Although KM2760 did not induce any ADCC mediated by mouse natural killer (NK) cells, it significantly enhanced phagocytosis mediated by mouse monocytes/macrophages against the CCR4-positive HL cell line in vitro. Together with the findings that KM2760 did not exhibit any complement-dependent cytotoxicity or direct antiproliferation activity in vitro, these data indicated that KM2760 exerted its robust in vivo antitumor activity via monocytes/macrophages in mice. In the human system, KM2760 enhanced phagocytic activity mediated by monocytes/macrophages. Furthermore, it induced robust ADCC mediated by NK cells against the CCR4-positive HL cell line in vitro. Thus, it is conceivable that KM2760 would have much more potent antitumor activity in humans than in mice. Collectively, this study strongly indicates that anti-CCR4 mAb could be a novel treatment modality for patients with CCR4-positive HL.

Animals↗

Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase inhibitor.

NF-kappaB is constitutively activated in adult T-cell leukemia (ATL) and is considered responsible for cell growth and prevention of cell death. In this study, we demonstrate that NF-kappaB is constitutively activated in various HTLV-1-infected T-cell lines and ATL-derived cell lines irrespectively of Tax expression as evidenced by the phosphorylation of IkappaBalpha and p65 subunit of NF-kappaB, activation of NF-kappaB DNA binding, and upregulation of various target genes including bcl-xL, bcl-2, XIAP, c-IAP1, survivin, cyclinD1, ICAM-1 and VCAM-1. The effects of a novel IkappaB kinase (IKK) inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP), were examined on cell growth of these cell lines and fresh ATL leukemic cells. We found that ACHP could inhibit the phosphorylation of IkappaBalpha and p65, as well as NF-kappaB DNA-binding, associated with downregulation of the NF-kappaB target genes and induce cell growth arrest and apoptosis in these cells. When Tax-active and Tax-inactive cell lines were compared, ACHP could preferentially inhibit cell growth of Tax-active cells. Moreover, ACHP exhibited strong apoptosis-inducing activity in fresh ATL cells. These findings indicate that ACHP and its derivatives are effective in inducing ATL cell death and thus feasible candidates for the treatment of ATL.

Apoptosis↗

Spontaneous regression of gastric varices after iatrogenic injury to a gastrorenal shunt.

We present a patient with gastric varices complicating portal hypertension caused by liver cirrhosis related to hepatitis C virus. The patient underwent balloon-occluded retrograde transvenous obliteration. The gastric varices almost completely disappeared, without any sclerotic agent being used, after iatrogenic injury of the gastrorenal shunt at the time of the interventional procedure.

Balloon Occlusion↗

Percutaneous transluminal angioplasty for hepatic arterial occlusion following hepatic arterial infusion chemotherapy.

We report a case in which hepatic arterial occlusion developed during repeated hepatic arterial infusion chemotherapy through an implanted port-catheter system for advanced malignant hepatic neoplasia. After successful recanalization of the hepatic artery by using percutaneous transluminal angioplasty, another port-catheter system was placed percutaneously by interventional radiology techniques, allowing the continuation of hepatic arterial infusion chemotherapy.

Angiography↗

Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.

We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar base that required a differential diagnosis because of clinical features and MR images that resembled the nasolabial cyst. The morphologic analysis on MR images revealed the characteristic appearance of the nasolabial cyst, and the sagittal MR image may be most helpful for diagnosing this rare disease.

Adolescent↗

Molecular mapping of a fertility restorer gene for Owen cytoplasmic male sterility in sugar beet.

We report here the molecular mapping of a fertility restorer gene (named Rf1) for Owen cytoplasmic male sterility in sugar beet. Eight AFLP and two RAPD markers, tightly linked to the Rf1 locus, were identified using bulked segregant analysis. Three AFLP markers, mAFEM972, mAFEM976 and mAFEM985, were found to co-segregate with the Rf1 allele in our mapping populations. With the help of RFLP markers, previously mapped on the sugar beet genome, we showed that Rf1 is positioned in the terminal region of linkage group Kiel III/Koeln IV. This map location agrees well with that found for the restorer gene X, which suggests that the Rf1 locus corresponds to the X locus. The availability of the molecular markers will facilitate the selection of maintainer-pollinator lines in breeding program and provide the foundation for map-based cloning of the Rf1 gene.

Beta vulgaris↗

Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis.

In multiple myeloma (MM), the interaction between myeloma cells and bone marrow microenvironment has an important role in the pathogenesis of MM. We first examined the inducing effect of myeloma cells on migration of human umbilical vein vascular endothelial cells (HUVECs). Five myeloma cell lines produced varying amounts of VEGF, and migration of HUVECs was induced by coculture with myeloma cells. We next examined the inhibitory effect of a novel synthetic retinoid Am80 (Tamibarotene) on both myeloma cells and HUVECs. Am80 is specific for the retinoic-acid receptor-alpha/beta, and has therapeutic effects in all-trans retinoic acid resistant acute promyelocytic leukemia. Am80 slightly inhibited the growth of both myeloma cells and HUVECs, and remarkably inhibited the growth of HUVECs stimulated by VEGF. Am80 showed little growth inhibition of bone marrow stromal cells (BMSCs), but it markedly inhibited migration of HUVECs by cocultured myeloma cells. Am80 inhibited VEGF-induced phosphorylation of VEGF receptor. In addition, VEGF-induced formation of tube-like structures in vitro and neovascularization in mouse corneas were significantly inhibited by Am80. These findings clearly demonstrate that Am80 is a potential inhibitor of angiogenesis caused by the interaction between vascular endothelial cells and myeloma cells, and might be a useful therapeutic agent against MM.

Animals↗

Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell malignancy.

MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the monokine induced by interferon-gamma(MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/leukemia by regulating the expression of various genes including MIG. Leukemia (2005) 19, 1471-1478. doi:10.1038/sj.leu.2403833; published online 16 June 2005.

Animals↗

A large-scale Agrobacterium-mediated transformation procedure with a strong positive-negative selection for gene targeting in rice (Oryza sativa L.).

A large-scale transformation procedure handling an adequate number of stable transformants with highly efficient positive-negative selection is a necessary prerequisite to successful gene targeting by homologous recombination, as the integration of a transgene by somatic homologous recombination in higher plants has been reported to be 10(-3) to 10(-5) compared with random integration by non-homologous end joining. We established an efficient and large-scale Agrobacterium-mediated rice transformation protocol that generated around 10(3) stable transformants routinely from 150 seeds and a strong positive-negative selection procedure that resulted in survivors at 10(-2) using the gene for diphtheria toxin A fragment as a negative marker. The established transformation procedure provides a basis for efficient gene targeting in rice.

Diphtheria Toxin↗

Solitary osteochondroma of the mandibular symphysis.

Osteochondroma is a benign neoplasm that usually develops in long bones and very rarely occurs in craniofacial bones. Nearly all reported mandibular osteochondromas have arisen in the condyle and the coronoid process, and occurrence in other locations is extremely rare. We describe a case of osteochondroma arising from the inferior border of the mandibular symphysis.

Adolescent↗

Prototype of simulation of orthognathic surgery using a virtual reality haptic device.

A maxillofacial simulator can support education and training. In the present study, cutting, separation, and quantitative rearrangement of bone during orthognathic surgery were simulated by means of a haptic device with virtual tactile perception. Computed tomographic (CT) images of two patients with severe jaw deformity, one women and one man, were input into the device. In the woman, Le Fort I osteotomy of the maxilla and sagittal splitting ramus osteotomy of the mandible were initially simulated. During surgery with the haptic device, separation and rearrangement of the maxilla and the ramus of the mandible were initially processed. However, there was discrepancy and overlapping of the ramus with the mandible. Intraoral vertical osteotomy of the right ramus was then performed, with satisfactory results and less discrepancy and interference. The simulation was referred to at surgery, and satisfactory surgical assistance was postoperatively confirmed on CT images. The male patient had severe jaw deformity due to unequal growth between the ramuses, resulting in anterior crossbite. Sagittal splitting ramus osteotomy with rotation of the mandible was successfully simulated. Because of its versatility and functions, the present device was found to be useful for simulating various procedures for orthognathic surgery and thereby three-dimensionally determine surgical movements.

Adult↗

Intrahepatic portosystemic venous shunt passing through the left inferior phrenic vein and draining into the left renal vein.

We report a case of an intrahepatic portosystemic venous shunt (IPSVS) passing through the left inferior phrenic vein and draining into the left renal vein and then to the inferior vena cava. We incidentally detected the IPSVS while performing a transcatheter arterial embolisation for the treatment of hepatocellular carcinoma. IPSVS with the left inferior phrenic vein as the draining vein is very rare. The complete pathway of this IPSVS could be clearly demonstrated by multidetector row CT during arterial portography.

Aged↗

Ameloblastomatous calcifying odontogenic cyst in the mandible.

Ameloblastoma is one of the well-known odontogenic tumours that can be associated with calcifying odontogenic cysts (COCs), but only a few reports include detailed clinical and radiographic features. In this paper we demonstrate a case of large ameloblastomatous COC in the mandible. The radiographic examination revealed the presence of a multilocular cystic lesion in the right posterior part of the mandible containing the impacted lower second molar with remarkable expansion toward both lingual and buccal side. This feature was different from the general findings of COC and rather resembled that of ameloblastomas.

Adolescent↗

Soft palate movement during sucking behavior.

To clarify the aspects and role of oropharyngeal closure, soft palate movements during sucking were observed and then assessed by electromyographic and fluoroscopic analyses. Three patterns of sucking movements by the palatoglossus and levator veli palatini muscles were analyzed with electromyographic means in seven healthy adults. Furthermore, a forced sucking maneuver, which required special effort to produce a strong sucking pressure by opening the jaw, was analyzed using lateral fluoroscopy in three of the subjects. During all tested sucking movements, the palatoglossus muscle showed continuous activity. The levator veli palatini muscle did not show remarkable activity during regular air sucking or water sucking when water was held in the oral cavity. However, its participation increased when intraoral sucking pressure was increased by opening the jaw, and lateral fluoroscopic examinations revealed that the soft palate was pulled toward the oral cavity to form a tight contact between the rostral portion of the soft palate and the retrotongue, causing the soft palate to make an "L" shape. The palatoglossus muscle plays a major role in palatal movement during sucking. Furthermore, the levator veli palatini muscle, whose activity was observed only during high-pressure sucking with an open jaw, may act to maintain tension in the soft palate against strong negative pressure in the oral cavity.

Adult↗

Percutaneous and laparoscopic approaches of radiofrequency ablation treatment for liver cancer.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) and microwave coagulation therapy (MCT) have been gaining acceptance as a standard method in the management strategy of liver cancer, for reasons of minimally invasive techniques and effective results. We present our experience of RFA and MCT in patients with liver cancer, and analyze retrospectively the advantages and disadvantages of both of the percutaneous and laparoscopic approaches. METHODS: Thirty-two consecutive patients (23 men and 9 women) with 19 hepatocellular carcinomas (HCC), 12 metastatic liver cancers, and recurrent cholangiocellular carcinoma (CCC), were enrolled in this study. Out of these 32 patients, as a prior laparotomy, 19 underwent hepatectomy, colectomy, gastrectomy or cholecystectomy, and 15 were treated with the laparoscopic approach, 17 treated with the percutaneous approach, and 2 treated with the combined approach of those two. All of these procedures were carried out under general anesthesia with ultrasound guidance. Seven and 30 days after these procedures, an assessment helical computed tomography was done. RESULTS: No sign of the residual tissues was noted in all patients except only one case. CONCLUSIONS: The percutaneous approach was thought to be a more practical and less invasive method regardless previous laparotomy. For the laparoscopic approach, tumors located at the hepatic surface or margin were preferable candidates.

Adult↗

Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia.

The SH2 domain-containing inositol 5'-phosphatase (SHIP) is crucial in hematopoietic development. To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines. A somatic mutation at codon 684, replacing Val with Glu, was detected in one patient, lying within the signature motif 2, which is the phosphatase active site. The results of an in vitro inositol 5'-phosphatase assay revealed that the mutation reduced catalytic activity of SHIP. Leukemia cells with the mutation showed enhanced Akt phosphorylation following IL-3 stimulation. K562 cells transfected with the mutated SHIP-V684E cDNA showed a growth advantage even at lower serum concentrations and resistance to apoptosis induced by serum deprivation and exposure to etoposide. These results suggest a possible role of the mutated SHIP gene in the development of acute leukemia and chemotherapy resistance through the deregulation of the phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3)/Akt signaling pathway. This is the first report of a mutation in the SHIP gene in any given human cancer, and indicates the need for more attention to be paid to this gene with respect to cancer pathogenesis.

Acute Disease↗

Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma.

Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sgamma3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

Alleles↗

Retrievable vena cava filter placement during treatment for deep venous thrombosis.

The purpose of our study is to evaluate the safety of insertion and removal of the retrievable vena cava filter and the efficacy of this filter in preventing pulmonary embolism during treatment of stenosis or obstruction of the lower extremity due to deep venous thrombosis. We retrospectively evaluated placement of 10 filters in 6 patients with lower extremity deep venous thrombosis who had undergone various treatments, including those utilizing techniques of interventional radiology. Worsening of or the new formation of pulmonary embolism was prevented in all patients. All attempts at both implantation and retrieval of the filter were safely accomplished. No complication related to filter placement occurred. Filters were left in the vena cava for permanent use when deep venous thrombosis was refractory to treatment. These results demonstrate that both placement and removal of the retrievable vena cava filter can be accomplished safely and that this type of filter is useful to prevent pulmonary embolism during treatment of deep venous thrombosis of the lower extremity. Further, the use of a retrievable vena cava filter might be preferred over that of a temporary vena cava filter, especially if further implantation of a filter becomes necessary since replacement with a permanent filter would not be required when using a retrievable vena cava filter.

Adult↗