Tomohiro Chiba

Japanese Foundation for Cancer Research · Department of Cytology

Elevation of intracranial soluble amyloid-beta (Abeta) levels has been implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular events in neurons, which lead to memory loss in AD, however, remain elusive. Humanin (HN) is a short neuroprotective peptide abolishing Abeta neurotoxicity. Recently, we found that HN derivatives activate...

Amyloid beta (Abeta) has long been implicated in the pathogenesis of Alzheimer's disease (AD). Little is known, however, about the intracellular events in neurons which lead to memory loss related to AD. Focusing on the fact that an AD-specific neuroprotective peptide named humanin (HN) inhibits AD-related neurotoxicity by activating the JAK2/STAT3...

Cellular transformation is initiated by the activation of oncogenes and a closely associated developmental reprogramming of the epigenetic landscape. Transcription factors, regulators of chromatin states and microRNAs influence cell fates in development and stabilize the phenotypes of normal, differentiated cells and of cancer cells. The miR-302/36...

The p53 tumor suppressor plays a critical role in cancer, more than 50% of human tumors contain mutations or deletions of the TP53 gene. p53 can transactivate or repress target genes in response to diverse stress signals, such as transient growth arrest, DNA repair, cellular differentiation, senescence and apoptosis. Through an unbiased genome-wide...

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Point mutations in the telomerase reverse transcriptase (TERT) promoter, C228T and C250T and oncogene BRAFV600E have been investigated as risk factors for PTC. However, little research has been done on the single nucleotide polymorphism rs2853669 in the TERT promoter in PTC. T...

Objectives Clear cell carcinoma of the uterine corpus (CCCUC) and the ovary (CCCOV) is a rare disease and difficult to control once recurrence occurs. In this study, we compared the clinical course of CCCUC and CCCOV, based on the daily practice in our institution. Methods We reviewed the records of all patients diagnosed with clear cell carcinoma...

Background Triple-negative breast cancer (TNBC) is a biologically diverse disease, with characteristics such as homologous recombination deficiency (HRD), gene mutation, and immune reactions. Japan Breast Cancer Research Group 22 is a multicenter trial examining TNBC’s response to neoadjuvant chemotherapy (NAC) according to the HRD status. This tra...

The incidence of papillary thyroid carcinoma (PTC) is increasing worldwide. The biomarkers to identify aggressive types of PTC are limited, illustrating the need to establish reliable novel biomarkers. Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that modulates the folding of newly synthesized glycoproteins and stress-responsive pr...

The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December 2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japa...

Background Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sen...

Pilocytic astrocytomas rarely present with oligodendroglioma-like morphological features, which gives rise to a diagnostic challenge. In this report we present a case of pilocytic astrocytoma harboring the FGFR1 mutation, accompanied with a predominant oligodendroglioma-like component, thus initially diagnosed as oligodendroglioma. A 14-year-old fe...

Objective: Carcinosarcoma (CS) of the uterus or ovary is a rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features than its carcinoma counterpart. Four molecular subtypes of CS were recently established based on genomic aberration profiles (POLE, MSI, CNH, and CNL) and shown to be associat...

Background/aim: The telomerase reverse transcriptase (TERT) promoter has a regulatory single nucleotide polymorphism (rSNP), rs2853669, and occasionally shows point mutations C228T and C250T. Although C228T and C250T have been well examined to increase TERT promoter activity and are known as risk factors for thyroid carcinoma, the significance of...

Background: Uterine adenosarcoma, a rare uterine tumor subtype, is a biphasic tumor consisting of epithelial and mesenchymal elements. To date, there is no research comparing the histopathological features and immunohistochemistry of primary and recurrent tumors; furthermore, the relationship between pathology and the clinical course remains uncle...

Background: With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remai...

p> Background: Triple-negative breast cancer (TNBC) includes heterogenous molecular subtypes, e.g., basal-like, immunomodulatory, mesenchymal, mesenchymal stem cell and luminal androgen receptor subtypes. Chemotherapy is the standard care for patients with early TNBC, but advanced or metastatic disease has unfavorable prognosis. PARP inhibitors and...

Background: Uterine adenosarcoma, a rare subtype of uterine tumor, is a biphasic tumor consisting of epithelial and mesenchymal elements. There is no research comparing histopathological features of primary and recurrent tumors, including immunohistochemistry; furthermore, the relationship between pathology and the clinical course is unclear. We re...

Germline pathogenic ETV6 variants have been discovered in families with inherited thrombocytopenia and predisposition to hematological and solid malignancies. We present a patient with short stature who was initially diagnosed with chronic immune thrombocytopenia. Subsequently, the patient developed acute lymphoblastic leukemia, followed by mammary...

Follicular thyroid neoplasm is a common tumor, and consists of follicular thyroid adenoma (FTA) and carcinoma (FTC). The mechanisms of tumor development of FTA and FTC are not well‐understood. Single‐nucleotide polymorphisms (SNPs) and point mutations in the telomerase reverse transcriptase (TERT) promoter have been associated with tumor developmen...

We report a case of giant breast angiosarcoma. A 20-year-old woman noticed enlargement of her right breast and consulted her family doctor. The symptom had been stable for 4 months. Granulomatous mastitis was suspected. However, she complained that the enlargement had become rapid, and she was referred to our hospital. Her right breast was found to...

Background A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH), suggesting that PAH can be added as a new member of RNF213-associated vascular diseases including Moyamoya disease and peripheral pulmona...

Objectives There exist central nervous system tumor‐like lesions, resembling glioma on magnetic resonance imaging, although pathology shows active perivascular inflammation on biopsied brain tissues. As pathological diagnostic criteria have not been established, the nature of inflammatory cells was analyzed. Methods Biopsied brain tissues from tum...

Background: A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenos...

Some cancer cells lengthen their telomeres by alternative lengthening of telomeres (ALT); these are referred to as ALT cancer cells and do not express telomerase. The ALT mechanism involves the elongation of telomeric DNA repeats by homologous recombination. In interphase nuclei of ALT cancer cells, giant telomeres can be specifically observed by f...

Pulmonary arterial hypertension (PAH) pathogenesis shares similarities with carcinogenesis. One CD44 variant (CD44v) isoform, CD44v8-10, binds to and stabilizes the cystine transporter subunit (xCT), producing reduced glutathione and thereby enhancing the antioxidant defense of cancer stem cells. Pharmacological inhibition of xCT by sulfasalazine s...

BACKGROUND Glioblastoma (GBM) is poor-prognosis cancer and tumor recurrence is inevitable despite intensive chemoradiotherapy. Thus, insights into the mechanism of tumor recurrence are critical for improved patient treatment. Here, we describe our integrated genomic analyses using next-generation sequencing of the paired samples from initial and re...

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were a...

Background Glioblastoma (GBM) is poor-prognosis cancer and tumor recurrence is inevitable despite intensive chemoradiotherapy. Thus, insights into the mechanism of tumor recurrence are critical for improved patient treatment. Here, we describe our integrated genomic analyses using next-generation sequencing of the paired samples from initial and re...

Background:Epoprostenol infusion is the strongest and most convincing therapeutic strategy for severe pulmonary arterial hypertension (PAH). This study investigated the gastrointestinal side effects of epoprostenol. Methods and Results:The study group of 12 patients treated with epoprostenol (epoprostenol group) and 4 patients without epoprostenol...

Background: Brain involvement of hepatosplenic T-cell lymphoma (HSTL) has not been reported so far. Case description: We experienced an extremely rare case of HSTL, which is a rare and aggressive variant of peripheral T-cell lymphoma, generally showing predominant infiltration to the liver, spleen and bone marrow, involving the brain. A 41-year-...

INTRODUCTION Temozolomide (TMZ) induces inactivation of the DNA mismatch repair (MMR) genes in glioma especially with methylated MGMT promoter and hence causes hypermutator phenotype at recurrence. Here we show molecular changes that occur during TMZ treatment in glioma patients and those impacts on prognosis. METHODS We collected 67 glioma sample...

Ulcerative colitis (UC) associated colorectal cancer (CRC) is an important issue in long-term management of patients with UC. Lesions with chronic inflammatory mucosa as background may often be difficult to identify even by endoscopic observation. Traditionally, a random biopsy strategy was recommended, but problems with patient compliance, increas...

Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, inclu...

We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia wa...

Well-differentiated thyroid carcinomas have driver mutations involving growth factor receptor-tyrosine kinases (RTKs) or their intracellular signaling pathway, that is, the mitogen-activated protein kinase (MAPK) pathway. Sorafenib is a multikinase inhibitor of RTKs and the MAPK pathway and has recently been used for the treatment of unresectable w...

Giant-cell tumors of the tendon sheath (GCTTS) are among the most frequent soft tissue tumors of the hand. These tumors are usually localized and solitary. Here, we report a rare case of multiple GCTTS occurring at four different sites around the distal interphalangeal joint on the right index finger. We first performed excisional biopsy for one le...

The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the recept...

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Background: We previously reported about immune suppression in breast cancer patients at this meeting. In brief, tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were analyzed in 50 early or advanced breast cancer (BC) patients. To compare between 3...

Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here, we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases o...

STAT3 regulates various cellular functions, which is diverted to malignant phenotypes of cancer cells. Aberrant activation of STAT3 in cancer cells has motivated researchers to develop STAT3 inhibitors as a novel line of anticancer drugs. The attempt has not been successful so far. There are some hurdles to be overcome. Basic concepts of STAT3 inhi...

Supporting Information

Supporting Information

Supporting Information

Supporting Information Figure 10

Supporting Information

Supporting Information Figure 11

Supporting Information Figure 13

Supporting Information Table S1

Supporting Information Table S5

Supporting Information Table S6

Supporting Information Figure 14

Supporting Information Table S2

Supporting Information Figure 12

Supporting Information Table S3

Supporting Information Table S4

Supporting Information Table S7

Deregulation of signal transducer and activator of transcription 3 (Stat3) is attracting attentions in neurological disorders of elderly populations, e.g., Stat3 is inactivated in hippocampal neurons of Alzheimer’s disease (AD) brains, whereas it is often constitutively activated in glioblastoma multiforme (GBM), correlating with poor prognosis. St...

Distinct gene expression patterns, accompanied by particular epigenetic states, provide the basis for different stages of cellular differentiation. The programming of cells usually proceeds from stem cells to progenitor cells to differentiated progeny. The process, however, is not irreversible, and pluripotency can be reestablished in terminally di...

Interleukin-18 (IL-18) is a potent proinflammatory cytokine that augments both innate and acquired immune responses. It is also a crucial regulator of lymphocyte production of interferon-γ (IFN-γ), which can promote acute cellular rejection of transplanted solid organs. To evaluate the role of IL-18 in liver transplantation, we constructed an adeno...

Humanin (HN), a peptide of 24 amino acid residues, suppresses the neuronal cell death that is induced by the gene products of Alzheimer's disease. HN contains two Ser residues at positions 7 and 14. Because the proportion of D-Ser isomerized from L-Ser in proteins appears to increase as cellular organs age, we explored the structural effects of the...

Cholinergic dysfunction is implicated in the pathogenesis of memory impairment related to Alzheimer's disease (AD). Accordingly, regulation of M1 muscarinic acetylcholine receptor (M1 mAChR) has been one of the major targets in the development of novel drugs for AD. Utilizing an in vitro system for evaluation of the M1 mAChR, we have recently ident...

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol expo...

We report a method for specifically labelling the surface of cells with two kinds of chemical probes (near-infrared (NIR) fluorescent probes and magnetic resonance (MR) imaging probes) via two genetically expressed tags, and demonstrate the application for in vitro and in vivo dual imaging.

Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the...

Excitotoxicity has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). More recently, glial involvement has been shown to be essential for ALS-related motoneuronal death. Here, we identified an N-methyl-D-aspartate (NMDA) receptor co-agonist, D-serine (D-Ser), as a glia-derived enhancer of glutamate (Glu) toxicity to ALS mot...

Neuronal death is directly implicated in the pathogenesis of neurodegenerative diseases (NDDs). NDDs cannot be cured because the mechanisms underlying neuronal death are too complicated to be therapeutically suppressed. Neuroprotective factors, such as neurotrophins, certain growth factors, neurotrophic cytokines, and short neuroprotective peptides...

Neuronal death is directly implicated in the pathogenesis of neurodegenerative diseases (NDDs). NDDs cannot be cured because the mechanisms underlying neuronal death are too complicated to be therapeutically suppressed. Neuroprotective factors, such as neurotrophins, certain growth factors, neurotrophic cytokines, and short neuroprotective peptides...