Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of "off-the-shelf" T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce "off-the-shelf" and synthetic allogeneic T-cells.
View Article and Find Full Text PDFLimited T cell availability and proliferative exhaustion present major barriers to successful T cell-based immunotherapies and may potentially be overcome through the use of "rejuvenated" induced pluripotent stem cells derived from antigen-specific T cells (T-iPSCs). However, strict antigen specificity is essential for safe and efficient T cell immunotherapy. Here, we report that CD8αβ T cells from human T-iPSCs lose their antigen specificity through additional rearrangement of the T cell receptor (TCR) α chain gene during the CD4/CD8 double positive stage of in vitro differentiation.
View Article and Find Full Text PDFStudies in circulating tumor cells (CTCs) have proceeded to be accepted as prognostic markers in several types of cancers. But they are still limited because many are mainly from enumeration of CTCs. Here, we tried to evaluate the tumorigenicity of CTCs from advanced gastric cancer patients (n = 42).
View Article and Find Full Text PDFThe human epidermal growth factor receptor (HER) family plays a major role in cancer cell proliferation. Overexpression of these receptors occurs in various cancers, including breast cancer, and correlates with shorter time to relapse and lower overall survival. We recently reported that TAK-285, an orally bioavailable small molecule inhibitor of HER kinases, is not a p-glycoprotein substrate and penetrates the blood-brain barrier, suggesting favorable activity for the treatment of brain metastases.
View Article and Find Full Text PDFWe experienced two cases of esophageal web accompanying severe stricture that were treated by endoscopic incisions with an insulated-tip knife (IT-knife). With attention paid to the mucosa at the stricture, the lesion was incised with an IT-knife without complications. Sato's curved laryngoscope was used even in cervical esophageal lesions and an excellent field was secured.
View Article and Find Full Text PDFBreast cancer therapy has improved following the development of drugs with specific molecular targets, exemplified by inhibitors of human epidermal growth factor receptor-2 (HER2) or epidermal growth factor receptor (EGFR) such as trastuzumab and lapatinib. However, these drugs have little effect on brain metastasis due to the combined effects of poor penetration of the blood-brain barrier and their removal from the central nervous system (CNS) by the p-glycoprotein (Pgp) drug efflux pump. We investigated the effects of TAK-285, a novel, investigational, dual EGFR/HER2 inhibitor that has been shown to penetrate the CNS and has comparable inhibitory efficacy to lapatinib which is a known Pgp substrate.
View Article and Find Full Text PDFJ Biol Chem
November 2012
The role of "sphingolipid rheostat" by ceramide and sphingosine 1-phosphate (S1P) in the regulation of autophagy remains unclear. In human leukemia HL-60 cells, amino acid deprivation (AA(-)) caused autophagy with an increase in acid sphingomyleinase (SMase) activity and ceramide, which serves as an autophagy inducing lipid. Knockdown of acid SMase significantly suppressed the autophagy induction.
View Article and Find Full Text PDFSphingomyelin synthase (SMS) catalyzes the formation of sphingomyelin, a major component of the plasma membrane and lipid rafts. To investigate the role of SMS in cell signaling and migration induced by binding of the chemokine CXCL12 to CXCR4, we used mouse embryonic fibroblasts deficient in SMS1 and/or SMS2 and examined the effects of SMS deficiency on cell migration. SMS deficiency promoted cell migration through a CXCL12/CXCR4-dependent signaling pathway involving extracellular signal-regulated kinase (ERK) activation.
View Article and Find Full Text PDFTransferrin (Tf) endocytosis and recycling are essential for iron uptake and the regulation of cell proliferation. Tf and Tf receptor (TfR) complexes are internalized via clathrin-coated pits composed of a variety of proteins and lipids and pass through early endosomes to recycling endosomes. We investigated the role of sphingomyelin (SM) synthases (SMS1 and SMS2) in clathrin-dependent trafficking of Tf and cell proliferation.
View Article and Find Full Text PDFIntroduction: Hypertrophic adipocytes in obese states express the elevated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF). An increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) promotes triglyceride hydrolysis and may improve dysregulation of adipocyte metabolism. Here, we investigate the effect of dibutyryl-cAMP (a phosphodiesterase-resistant analog of cAMP) on the gene expression of PAI-1 and TF in adipocytes.
View Article and Find Full Text PDFPurpose: We evaluated the long-term pulmonary function after lobectomy for congenital cystic lung disease, in both infants and children, using radionuclide imaging (RI).
Methods: We performed a retrospective review of 93 patients who underwent resection of cystic lung lesions between 1974 and 2001. The results of postoperative lung volume/perfusion scintigraphy at 1 (n = 64), 5 (n = 32), and 10 years (n = 18) after surgery (V1, 5, 10/Q1, 5, 10) and mean transit time (MTT-a marker for air-trapping) at 1, 5, and 10 years after surgery (MTT1, 5, 10) were compared with respect to age at operation, preoperative infection, underlying disease, and type of surgery.
Slide tracheoplasty has become a standard procedure to treat long-segment congenital tracheal stenosis because it is a reasonable and simple technique. Slide tracheoplasty does not affect the carina during long-segment congenital tracheal stenosis management, and thus lesions of the carina, such as stenosis and tracheobronchomalacia can become important causes of extubation failure after surgery. In this manusript, we describe the effectiveness of our modified slide tracheoplasty, which includes reconstruction of the carina.
View Article and Find Full Text PDFThe significance of lymphadenectomy in surgery for various kinds of cancer has been widely debated, particularly in the gynecological field. The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-CWS) has been used as an effective adjuvant for immunotherapy of a variety of cancer patients. Here we tested the immunological importance of lymph nodes in treatment of ovarian cancer patients with BCG-CWS.
View Article and Find Full Text PDFAntiphospholipid antibodies found in antiphospholipid syndrome are autoantibodies to phospholipid-binding proteins, such as beta2-glycoprotein I (beta2GPI). We have previously reported that among these antibodies, the so-called lupus anticoagulants (LAs) augment beta2GPI binding to the phospholipid membrane surface, which is associated with the pathological action of LAs. However, the molecular mechanisms underlying this augmentation are uncertain.
View Article and Find Full Text PDFIEEE Trans Pattern Anal Mach Intell
January 2008
We introduce novel dissimilarity into a probabilistic clustering task to properly measure dissimilarity among multiple clusters when each cluster is characterized by a subpopulation in the mixture model. This measure of dissimilarity is called redundancy-based dissimilarity among probability distributions. From aspects of both source coding and a statistical hypothesis test, we shed light on several of the theoretical reasons for the redundancy-based dissimilarity among probability distributions being a reasonable measure of dissimilarity among clusters.
View Article and Find Full Text PDFThe activation of antitumor cytotoxic T-lymphocytes (CTLs) depends on how efficiently the relevant tumor antigen peptides are delivered into the major histocompatibility complex (MHC) class I presentation pathway in antigen presenting cells (APCs). An elegant approach to promote the peptide-MHC class I association has been described for enhanced peptide transportation into the endoplasmic reticulum (ER) by adding an ER insertion signal sequence (Eriss). Nevertheless, this approach does not appear potent enough to induce in vivo tumor protective immunity.
View Article and Find Full Text PDFRecent advances in tumor immunology have facilitated the development of cancer immunotherapy targeting tumor-associated antigens (TAAs). However, because TAAs were identified in only a few types of human cancer, novel vaccine strategies that utilize tumor cell-lysate (TCL), including unidentified TAAs as an antigen source, are needed. Herein, we describe the utility of fusogenic liposomes (FLs) as TCL-delivery carriers for both ex vivo dendritic cell-based vaccination and in vivo direct immunization in the murine B16BL6 melanoma model.
View Article and Find Full Text PDFFor better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases).
View Article and Find Full Text PDFUnlabelled: In this study, we attempted to evaluate the regional dynamic function of hepatocytes by introducing unique parameters in (99m)Tc-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99m)Tc-GSA) scintigraphy. (99m)Tc-GSA scintigraphy provides valuable information for the receptor population density. However, the conventional indices are the results of the analyses of 2 fixed points and, as a result, it is not possible to accurately estimate the regional dynamic function.
View Article and Find Full Text PDFWe previously reported a patient with hereditary hypotransferrinemia who suffered from severe anemia and growth retardation and was diagnosed on the basis of an extremely low level of serum transferrin (TF). By an isoelectric focusing analysis, we found that the patient and his father shared a variant TF protein with an abnormal isoelectric point. The study suggested that the patient was a compound heterozygote with a variant allele, encoding the mutant TF, of paternal origin and a null allele of maternal origin.
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