Publications by authors named "Kenichi Harigaya"

Undifferentiated carcinoma of the gallbladder is a rare cancer type with a poor prognosis. The present study described a case of undifferentiated gallbladder carcinoma of the spindle- and giant-cell type, according to the 2010 World Health Organization classification. Hematoxylin and eosin staining revealed that the tumor consisted of dense interlacing bundles of spindle-shaped cells.

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Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility.

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Background: Chronic subdural hematoma (CSDH) is known to have a substantial recurrence rate. Artificial cerebrospinal fluid (ACF) is an effective irrigation solution in general open craniotomy and endoneurosurgery, but no evidence of its use in burr-hole surgery exists.

Objective: To identify the potential of ACF irrigation to prevent CSDH recurrence.

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In general, intravascular thrombus formation in the pulmonary arteries is considered to be the most common cause of chronic thromboembolic pulmonary hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like cells in endarterectomized tissues has been demonstrated.

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Mastermind (Mam) is one of the elements of Notch signaling, a system that plays a pivotal role in metazoan development. Mam proteins form transcriptionally activating complexes with the intracellular domains of Notch, which are generated in response to the ligand-receptor interaction, and CSL DNA-binding proteins. In mammals, three structurally divergent Mam isoforms (MamL1, MamL2 and MamL3) have been identified.

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We previously reported that substantial amounts of IL-10, an immunomodulatory cytokine, are produced by cell suspensions of fresh human metastatic melanoma tissues. Production diminished with continuous culturing of cells, which suggests a pivotal interactive role between melanoma cells and the tumor microenvironment. In this study, we found that the culture media obtained from LPS-stimulated peripheral blood mononuclear cells induced IL-10 production by metastatic melanoma cells.

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Article Synopsis
  • * In HeLa-S3 cells, knocking down HAS2 led to decreased spontaneous chemokinesis, suggesting that HA production is linked to cell movement, but adding external high molecular weight HA didn't enhance this movement.
  • * The study found that reducing HYAL2 or CD44 also diminished chemokinesis, while low molecular weight HA was able to reverse these effects, indicating a self-regulating mechanism in which HMW-HA contributes to
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Rho family G proteins including Rac regulate a variety of cellular functions, such as morphology, motility, and gene expression. Here we developed a fluorescence resonance energy transfer-based analysis in which we could monitor the activity of Rac1. To detect fluorescence resonance energy transfer, yellow fluorescent protein fused Rac1 and cyan fluorescent protein fused Cdc42-Rac1-interaction-binding domain of Pak1 protein were used as intermolecular probes of FRET.

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Article Synopsis
  • The protein hMena, related to actin regulation, is linked to cell movement and has been found overexpressed in various human cancers, indicating its potential role in tumor progression.
  • In a study of 52 cases of infiltrating ductal carcinoma (IDC), higher levels of hMena were associated with larger tumor sizes and certain cancer markers, suggesting it can predict poor outcomes for patients.
  • The research also explored the influence of the p53 protein, finding that introducing wild-type p53 into cancer cells reduced hMena expression, implying that functioning p53 may help regulate hMena levels in cancers like IDC.
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Osteoclast-like giant cell tumors rarely arise in the pancreas. Here we report the case of a 78-year-old woman who was diagnosed with a well-defined 3 cm multilocular mass in the pancreatic body by the use of ultrasonography, computed tomography and magnetic resonance imaging. The rim and the septa of the tumor were well enhanced.

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It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs).

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NKT cells demonstrate antitumor activity when activated to produce Th1 cytokines by DCs loaded with alpha-galactosylceramide, the prototypic NKT cell-activating glycolipid antigen. However, most patients do not have sufficient numbers of NKT cells to induce an effective immune response in this context, indicating a need for a source of NKT cells that could be used to supplement the endogenous cell population. Induced pluripotent stem cells (iPSCs) hold tremendous potential for cell-replacement therapy, but whether it is possible to generate functionally competent NKT cells from iPSCs has not been rigorously assessed.

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The Notch signalling pathway has a crucial function in determining cell fates in multiple tissues within metazoan organisms. On binding to ligands, the Notch receptor is cleaved proteolytically and releases its intracellular domain (NotchICD). The NotchICD enters the nucleus and acts cooperatively with other factors to stimulate the transcription of target genes.

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Follicular lymphoma often progresses to diffuse type lymphoma. To elucidate the mechanisms of the diffuse evolution of follicular lymphoma, we investigated the expression pattern of CD44 in 28 cases of follicular lymphomas (FLs) using an immunohistochemical method and semi-quantitative PCR-Southern blot analysis. The FLs were divided into four groups: i) intrafollicular (IF); ii) infiltrative (INF); iii) partially follicular (PF); and iv) minimally follicular (MF), according to the histological classification by Lukes and Collins.

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Mammarian enabled (Mena), a member of the Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) family of proteins, has been implicated in cell motility through regulation of the actin cytoskeleton assembly, including lamellipodial protrusion. Rac1, a member of the Rho family GTPases, also plays a pivotal role in the formation of lamellipodia. Here we report that human Mena (hMena) colocalizes with Rac1 in lamellipodia, and using an unmixing assisted acceptor depletion fluorescence resonance energy transfer (u-adFRET) analysis that hMena associates with Rac1 in vivo in the glioblastoma cell line U251MG.

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We present a case of an 83-year-old female patient with a collision tumour of an advanced Borrmann type 4 gastric cancer and a large gastric gastrointestinal stromal tumour (GIST). According to the deformity of the gastric wall caused by the GIST, type 4 cancer was difficult to identify by oesophagogastroduodenoscopy (OGD). The patient died of progressive gastric cancer related disease.

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The human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoprotein (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. Increasing evidence suggests that hMena over-expression is involved in human breast cancers, whereas the significance of hMena expression in colorectal carcinomas remains to be elucidated. In this study, we assessed the relative mRNA level of hMena using real-time PCR, showing that there is a statistically significant increase of hMena transcripts in matched human colorectal carcinomas and adjacent non-neoplastic colorectal epithelium (n=6, P=0.

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Fibronectin (FN) is thought to play an important role in various aspects of hematopoiesis through binding to very late antigen (VLA)-4 and VLA-5. Little is known, however, about the effects of FN on the proliferation of B cell progenitors. In this study, we investigated the effects of immobilized FN on the proliferation of the pre-B cell line, Nalm-6, which expresses both VLA-4 and VLA-5.

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Medial-to-intimal migration of SMCs is critical to atherosclerotic plaque formation and remodeling of injured arteries. Considerable amounts of the shed soluble form of the LDL receptor relative LR11 (sLR11) produced by intimal SMCs enhance SMC migration in vitro via upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. Here, we show that circulating sLR11 is a novel marker of carotid intima-media thickness (IMT) and that targeted disruption of the LR11 gene greatly reduces intimal thickening of arteries through attenuation of Ang II-induced migration of SMCs.

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The cell adhesion molecule CD44, which is the major hyaluronan receptor, has been implicated in the binding, endocytosis, and metabolism of hyaluronan. Previous studies have revealed that CD44 plays crucial roles in a variety of inflammatory diseases. In recent years, TLRs, which are ancient microbial pattern recognition receptors, have been shown to initiate an innate immune response and have been linked to a variety of inflammatory diseases.

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Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest.

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Rho family GTPases play a pivotal role in the regulation of numerous cellular functions associated with malignant transformation and metastasis. To evaluate the role of these GTPases in colorectal cancer, the protein expression levels and activities of these proteins in matched sets of tumor and non-tumor tissues of surgical specimens were analyzed. The relationship between the protein levels and activities in tumor tissues to the clinicopathological features was also assessed.

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Mastermind (Mam) is one of the elements of Notch signaling, an ancient system that plays a pivotal role in metazoan development. Genetic analyses in Drosophila and Caenorhabditis elegans have shown Mam to be an essential positive regulator of this signaling pathway in these species. Mam proteins bind to and stabilize the DNA-binding complex of the intracellular domains of Notch and CBF-1, Su(H), Lag-1 (CSL) DNA-binding proteins in the nucleus.

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Article Synopsis
  • A 13-year-old girl was diagnosed with vasospastic angina post-mortem, after experiencing recurrent toothaches since she was 10.
  • Despite normal evaluations at a medical center, she suffered a severe toothache and later collapsed at school, leading to her death.
  • Autopsy revealed significant coronary artery issues and multiple heart tissue injuries, indicating that her toothache was a symptom of a serious underlying heart condition, highlighting that vasospastic angina can affect young individuals and lead to sudden cardiac events.
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Elevated expression of c-myc has been detected in a broad range of human cancers, indicating a key role for this oncogene in tumor development. Recently, an interaction between FUSE-binding protein-interacting repressor (FIR) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and might be important for suppressing tumor formation. In this study, we showed that enforced expression of FIR induced apoptosis.

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