Language：English   Publishing type：Research paper (scientific journal)  

Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness.

DOI： 10.1111/pin.13442

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial-mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44+CD90+ and CD44-CD90- populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44+CD90+ cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes.

DOI： 10.3390/ijms24054996

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/cancers15020468

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model. METHODS: We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database. RESULTS: Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of αSMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis. CONCLUSIONS: We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients.

DOI： 10.1186/s13058-022-01557-5

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.

DOI： 10.1038/s41598-022-08791-z

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Introduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2-/-) developed more sever liver damage than wild-type (WT) mice with increased interferon-γ (IFNγ) production. Hepatic ERK phosphorylation was enhanced in Spred2-/- mice, and pretreatment of Spred2-/- mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFNγ production. Neutralization of IFNγ abolished the damage with decreased hepatic Stat1 activation in Spred2-/- mice. IFNγ was mainly produced from CD4+ and CD8+ T cells, and their depletion decreased liver damage and IFNγ production. Transplantation of CD4+ and/or CD8+ T cells from Spred2-/- mice into RAG1-/- mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2-/- mice as compared to WT mice. Conversely, liver damage, IFNγ production and the recruitment of CD4+ and CD8+ T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4+ and CD8+ T cells produced lower levels of IFNγ than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNγ production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage.

DOI： 10.1016/j.jare.2021.03.014

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) is shown to promote the progression of breast cancer. We previously identified cancer cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential regulator of MCP-1 production in the murine 4T1 breast cancer, but it played a minimum role in overall MCP-1 production. Here, we evaluated the crosstalk between 4T1 cells and fibroblasts. When fibroblasts were co-cultured with 4T1 cells or stimulated with the culture supernatants of 4T1 cells (4T1-sup), MCP-1 production by fibroblasts markedly increased. 4T1 cells expressed mRNA for platelet-derived growth factor (PDGF)-a, b and c, and the PDGF receptor inhibitor crenolanib almost completely inhibited 4T1-sup-induced MCP-1 production by fibroblasts. However, PDGF receptor antagonists failed to reduce MCP-1 production in tumor-bearing mice. Histologically, 4T1 tumors contained a small number of αSMA-positive fibroblasts, and Mcp-1 mRNA was mainly associated with macrophages, especially those surrounding necrotic lesions on day 14, by in situ hybridization. Thus, although cancer cells have the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk does not play a major role in MCP-1 production or cancer progression in this model. Unraveling complex crosstalk between cancer cells and stromal cells will help us identify new targets to help treat breast cancer patients.

DOI： 10.3390/cimb43030122

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUNDS: Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells. METHODS AND RESULTS: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10 μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the 'cadherin switching'. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C. CONCLUSION: PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase/Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.

DOI： 10.1007/s11033-021-06625-1

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND PURPOSE: To investigate prion protein (PrP) deposits in cutaneous tissues of patients of glycosylphosphatidylinositol (GPI)-anchorless prion diseases with neuropathy. METHODS: Cutaneous tissue samples from three patients with GPI-anchorless prion diseases were obtained, two cutaneous biopsy samples from the lower leg of Case 1 (Y162X) and Case 3 (D178fs25), and a cutaneous sample taken from the abdomen during an autopsy of Case 2 (D178fs25). We performed immunohistochemistry for PrP to look for abnormal PrP deposits. RESULTS: PrP deposits were observed in the dermal papilla, the sweat glands, the hair follicles, the arrector pili muscles, and peripheral nerves of all examined cases of GPI-anchorless prion disease with neuropathy. The abnormal PrP accumulation was frequently localized at the basement membrane, and colocalized with laminin. CONCLUSION: Immunohistochemical detection of PrP in cutaneous samples could be used to definitively diagnose GPI-anchorless PrP disease with neuropathy.

DOI： 10.1111/ene.14720

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC), and the expression was decreased in carcinoma in situ (CIS) and infiltrating urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and the expression of the cell proliferation marker Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 counters cancer progression in non-invasive papillary carcinoma possibly through inhibiting the Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in cancers with high malignancy. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma.

DOI： 10.1371/journal.pone.0254289

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2-/- mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2-/- lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2-/- and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2-/- fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2-/- mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.

DOI： 10.1038/s41598-020-73752-3

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Blood vessel invasion (BVI) is a prognostic indicator in various cancers. Elastic stain, which highlights blood vessel walls, is commonly used to detect BVI. In the breast, however, its diagnostic usefulness is limited because it also highlights some intraductal carcinoma components, which often mimic BVI. In this study, we aimed to improve BVI detection in breast cancer and developed a double staining: Victoria blue for elastin and immunohistochemistry for collagen IV. Collagen IV fibers were retained along the basement membranes of intraductal carcinoma components, whereas they were rearranged or lost in BVI. From these observations, we defined BVI as the presence of tumor cells inside an elastic ring with a rearrangement or loss of collagen IV fibers. Using these criteria, we found BVI in 148 cases (49%) among 304 cases of primary operable invasive breast carcinoma, and the presence of BVI correlated significantly with poor prognosis. By contrast, we detected BVI in 94 cases (31%) or 14 cases (5%) by elastic van Gieson or CD31 immunostaining among the same cases, respectively, with no statistically significant association with prognosis. Thus, elastin and collagen IV double staining facilitates the detection of BVI in breast cancer and is useful to predict prognosis.

DOI： 10.1111/pin.12971

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Transcription factor ERG (erythroblast transformation-specific (ETS)-related gene) is essential in endothelial differentiation and angiogenesis, in which microRNA (miR)-200b-3p targeting site is expected by miRNA target prediction database. miR-200b is known decreased in hepatocellular carcinoma (HCC), however, the functional relation between ERG and miR-200b-3p, originating from pre-miR-200b, in HCC angiogenesis remains unclear. We investigated whether hepatocyte-derived miR-200b-3p governs angiogenesis in HCC by targeting endothelial ERG. Levels of miR-200b-3p in HCC tissues were significantly lower than those in adjacent non-HCC tissues. Poorly differentiated HCC cell line expressed lower level of miR-200b-3p compared to well-differentiated HCC cell lines. The numbers of ERG-positive endothelial cells were higher in HCC tissues than in adjacent non-HCC tissues. There was a negative correlation between the number of ERG-positive cells and miR-200b-3p expression in HCC tissues. Culture supernatants of HCC cell lines with miR-200b-3p-overexpression reduced cell migration, proliferation and tube forming capacity in endothelial cells relative to the control, while those with miR-200b-3p-inhibition augmented the responses. Exosomes isolated from HCC culture supernatants with miR-200b-3p overexpression suppressed endothelial ERG expression. These results suggest that exosomal miR-200b-3p from hepatocytes suppresses endothelial ERG expression, and decreased miR-200b-3p in cancer cells promotes angiogenesis in HCC tissues by enhancing endothelial ERG expression.

DOI： 10.1038/s41598-020-67425-4

PubMed

researchmap

Web of Science

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Fibroblasts are a major component of cancer tissue and known to contribute to cancer progression. However, it remains unknown whether they are derived from local fibroblasts or of other origin. This study was designed to identify the contribution of local stromal cells to cancer stroma in human epithelial ovarian cancer. Seventy-six cases of surgically resected primary ovarian carcinoma (48 cases confined to the ovaries and 28 cases with distant metastases) and 17 cases of secondary ovarian tumor (e.g. colon cancer metastasized to the ovary) were enrolled in this study. The tissues were immunostained for forkhead box protein L2 (FOXL2), a transcription factor crucial for ovarian development and function, and markers for cancer-associated fibroblasts (CAFs) and inflammatory cells. Under normal condition, FOXL2 expression was restricted to ovarian stromal cells and some other types of cells in female genital tracts and never found in other sites of the body. FOXL2-positive cells were found in all primary and secondary tumors in the ovary, and were the dominant stromal cells in most cases. In contrast, only a few FOXL2-positive cells were found in peritoneal seeding sites of four serous carcinoma cases, and all the other tumors at extraovarian sites had no FOXL2-positive cells. FOXL2-positive cells in the ovarian lesion variably expressed CAFs markers, such as alpha-smooth muscle actin and fibroblast activating protein, as determined by double immunostaining. Background inflammation, but not histological subtype or origin of the neoplasm seemed to correlate with the proportion of FOXL2-positive cells. These results suggest that ovarian stromal cells are the main source of cancer stroma in the ovary but do not seem to move to distant sites via circulation together with tumor cells. Our results also support the hypothesis that cancer-associated fibroblasts may originate locally, which was previously demonstrated using animal models.

DOI： 10.1371/journal.pone.0205494

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

Immunohistochemistry using paraffin sections.
There are several options for some steps and all the options are listed on Steps section.
The suitable options for each antibody is noted on Guidelines&warnings section.

DOI： 10.17504/protocols.io.s8dehs6

researchmap

Publisher：{ZappyLab}, Inc.  

DOI： 10.17504/protocols.io.s8dehs6

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Acute liver injury (ALI) is characterized by hepatocyte damage and inflammation. In the present study, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences ALI induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Compared to wild-type mice, Spred2-/- mice developed exacerbated liver injury represented by enhanced hepatocyte damage and inflammation. Enhanced ERK activation was observed in Spred2-/--livers, and the MEK/ERK inhibitor U0126 ameliorated ALI. Hepatic tumour necrosis factor α (TNFα) and interleukin (IL)-1β levels were increased in Spred-2-/--livers, and the neutralization of TNFα dramatically ameliorated ALI, which was associated with decreased levels of endogenous TNFα and IL-1β. When mice were challenged with D-GalN and TNFα, much severer ALI was observed in Spred2-/- mice with significant increases in endogenous TNFα and IL-1β in the livers. Immunohistochemically, Kupffer cells were found to produce TNFα, and isolated Kupffer cells from Spred2-/- mice produced significantly higher levels of TNFα than those from wild-type mice after LPS stimulation, which was significantly decreased by U0126. These results suggest that Spred2 negatively regulates D-GalN/LPS-induced ALI under the control of TNFα in Kupffer cells. Spred2 may present a therapeutic target for the treatment of ALI.

DOI： 10.1038/s41598-017-18380-0

PubMed

researchmap

Language：English   Publisher：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

患者は50代女性。半年前から徐々に増悪する右鼻閉を訴えていた。画像検査にて頭蓋底に浸潤する右鼻腔・右篩骨洞腫瘤を指摘され、摘出術が施行された。組織学的に上皮下に紡錐形核を有する均一な細胞が束状に増殖しており、staghorn patternを示す血管がみられた。細胞異型や核分裂像に乏しく、壊死はみられなかった。免疫組織化学的に紡錐形細胞はS100蛋白(+)、α-smooth muscle actin(+)、Ki-67陽性率は1%以下であった。電子顕微鏡にて細胞質内にfocal dense plaqueを、RT-PCRにてPAX3-FOXO1融合遺伝子産物が認められた。以上より近年sinonasal tractに発生する新しい腫瘍の一つとして提唱された、biphenotypic sinonasal sarcomaと診断した。(著者抄録)

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.22034/APJCP.2017.18.6.1617

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown. METHODS: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed. RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1, M0). CONCLUSIONS: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.

DOI： 10.1186/s13027-017-0130-0

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown. METHODS: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed. RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1, M0). CONCLUSIONS: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.

DOI： 10.1186/s13027-017-0130-0

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本病理学会  

17歳、男性。てんかん発作を幼少期より繰り返していた。3歳時の頭部CTでは病変を指摘されなかったが、13歳時に左中前頭回の脳表に石灰化を伴う病変を認めた。発作頻度が増したため、17歳時に病変とその直下のてんかん焦点を含む左前頭葉部分切除術が施行された。脳表側では砂粒体と渦巻き状に紡錘形細胞が認められ、移行性髄膜腫であった。大脳側では血管が網目状に増生し、血管周囲には髄膜皮細胞が取り巻く髄膜血管腫症であった。症状や画像の経過より髄膜血管腫症が先行し、その後髄膜腫が合併したと考えられた。(著者抄録)

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naïve Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2-deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

DOI： 10.1038/srep37531

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

We describe a rare case of thyroidal Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly (EBV⁺DLBCLe) in which diagnosis was difficult and spontaneous esophageal fistula developed. A 79-year-old woman presented with acute swelling of the anterior neck with tenderness, general fatigue, and continual fever. Malignant lymphoma of the thyroid was suspected. Histologically, the thyroid lesion showed extensive necrosis, including a few Ziehl–Neelsen-positive substances. No evidence of tuberculosis was detected by any other examinations. While performing examinations, left recurrent nerve palsy and a tumorous lesion in the pharynx appeared. Computed tomography and gastrointestinal fiberscopy revealed esophageal fistula. Biopsy specimens from the pharyngeal lesion showed diffuse proliferation of large atypical lymphoid cells that were strongly positive for CD20 and EBV early RNAs. The final diagnosis was thyroidal EBV⁺DLBCLe with infiltration of surrounding organs. The esophageal fistula had healed 6 months after beginning treatment of EBV⁺DLBCLe.

DOI： 10.1007/s10388-013-0408-2

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We describe an extremely rare case of tracheal stenosis caused by unnoticed microscopic fiber-like foreign bodies. A 66-year-old woman complained of dyspnea with inspiratory stridor. Magnifying electroendoscopy and computed tomography revealed stenosis involving the entire circumference of the tracheal lumen. Tracheotomy and biopsy were performed. Histologically, the lesion showed chronic inflammation with a deposition of fiber-like foreign bodies. The patient had no history of trauma or inhalation injury, but had undergone intratracheal intubation on 4 occasions. The lesion was incised using semiconductor laser photoresection, and the postoperative course was good. To the best of our knowledge, this represents the first report in the English literature of tracheal stenosis caused by unnoticed foreign bodies. The origin of these fiber-like foreign bodies remains unclear but might be related to chronic inflammation resulting from intratracheal intubations. © 2014 by Okayama University Medical School.

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MAO.0b013e3182a361cd

Scopus

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

Cervical tuberculous lymphadenitis is mainly diagnosed by analyzing tissue samples obtained by fine-needle aspiration (FNA). However, some cases remain diagnostic challenges even after polymerase chain reaction analysis of FNA specimens. To delineate differences between cases that are relatively easy to diagnose and those for which diagnosis is difficult, 22 patients with cervical tuberculous lymphadenitis were studied retrospectively. FNA tissues were used to diagnose 14 cases (group A), whereas excisional biopsy was required for accurate diagnosis of 8 cases (group B). These two groups were compared with regard to results of blood examinations, ultrasound appearance, and various other procedures required to reach the final diagnosis. The results indicated that diagnosis of cervical tuberculous lymphadenitis was more difficult for patients with lower white blood cell counts, lower serum C-reactive protein levels, and absence of lymph node fusion or abscess formation on ultrasonography. The possibility of tuberculosis as a cause of cervical lymphadenopathy should always be considered, even when the presenting symptoms are not typical of this disease. © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.

DOI： 10.1007/s10156-013-0615-8

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Oxaliplatin-based chemotherapy is widely used for advanced colorectal cancer treatment, but it occasionally induces liver injury that is characterized histologically by sinusoidal dilatation, hepatic plate atrophy and/or venular obstruction. Most of the patients do not reveal apparent radiological abnormalities, however. Here, we report the case of a 47-year-old man with a radiologically detectable mass-forming oxaliplatin-induced sinusoidal injury that mimicked multiple liver tumors. These mass lesions were found on computed tomography images after the administration of six cycles of folinic acid, fluorouracil and oxaliplatin therapy as adjuvant chemotherapy for Stage III rectal cancer. The patient had to undergo liver resection because imaging studies could not exclude metastases. The histological examination revealed that a resected mass lesion was composed of severe sinusoidal dilatation. Milder dilatation was also seen in the surrounding parenchyma. We diagnosed the patient as having an oxaliplatin-induced sinusoidal injury with severe deviation. As oxaliplatin is a standard agent in colorectal cancer therapy today, all clinicians and pathologists should be aware of such non-neoplastic lesions as one of the rare differential diagnoses of metastatic liver tumor, to prevent overtreatment.

DOI： 10.1093/jjco/hyt113

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

The histopathology of submandibular gland tumors is varied, and in many cases, it is also difficult to make a diagnosis preoperatively. A clinical study was performed on 38 cases of submandibular gland tumor surgically resected between 1995 and 2011. There were 33 benign and 5 malignant tumors. The most common benign tumor was pleomorphic adenoma (97. 0%). Three of the 5 malignant tumors were low-grade mucoepidermoid carcinomas, and two were adenoid cystic carcinomas. We compared the preoperative diagnosis with final diagnosis. We considered that fine-needle aspiration (FNA) biopsy was very useful for the surgical management of submandibular gland tumor, and in malignant cases, the use of both FNA and frozen section biopsy (FSB) could improve the precision of the preoperative diagnosis. We performed supraomohyoid neck dissection in patients with clinically negative neck metastasis, and total neck dissection in patients with clinically positive neck metastasis. Postoperative radiotherapy was performed in patients with perineural invasion, a narrow safety margin, high-grade malignancy, multiple neck metastasis and extranodal extension. Following extirpation of the submandibular gland and tumor, facial paresis occurred in 8 (27. 6%) cases. We compared postoperative complications following the non-identified method with the identified method. Facial paresis occurred in 1 (5. 9%) cases following the non-identified method, and occurred in 7 (50. 0%) cases following the identified method. Our results suggested that the non-identified method was safer and more useful in preventing postoperative complications following extirpation of the submandibular gland and associated tumors.

DOI： 10.5631/jibirin.106.723

Scopus

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Publishing type：Research paper (scientific journal)  

Thyroid carcinomas arising from ectopic thyroid tissue are uncommon; most of them arise from thyroid tissuein thyroglossal cysts. A rare case of a 66-year-old woman with papillary thyroid carcinoma arising from median ectopic thyroid tissue lacking a thyroglossal duct remnant is reported. The tumor was resected by Sistrunks procedure, and the patient's postoperative course was good. © 2013 by Okayama University Medical School.

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Bentham Science Publishers B.V.  

Autoimmune pancreatitis (AIP) is pathologically characterized by lymphoplasmacytic infiltration and fibrosis. However, AIP is not a single entity, but rather includes two histological types-lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric chronic pancreatitis (IDCP)- of which the former constitutes the pancreatic manifestation of IgG4-related disease. The inflammation seen in peripancreatic adipose tissue and the interlobular area in LPSP, such as dense lymphoplasmacytic infiltration with fibrosis, storiform fibrosis, and obliterative phlebitis, is common among the various lesions that belong to IgG4-related disease. However, some lesions in the family of IgG4-related disease, such as IgG4-related sclerosing sialadenitis and lymphadenopathy, often lack prominent fibrosis, suggesting the histological variation of this entity. Nonetheless, histological features are important in the formation of a pathological diagnosis of IgG4-related disease because the presence of numerous IgG4-positive plasma cells is not necessarily specific to this disease. © 2011 Bentham Science Publishers Ltd.

DOI： 10.2174/157339511795194884

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to survey Cdx2 expression in pyloric gland adenoma (PGA) of the gallbladder. We reviewed 29 PGA cases, ten (34.4%) and seven (24.1%) of which showed intestinal metaplasia (IM) and squamous morule (SM), respectively. The immunostaining for Cdx2, beta-catenin, MUC5AC, MUC2, MUC6, and M-GGMC-1 was performed and scored (0 = negative, 1+ = &lt
10%, 2+ = 10% to &lt
30%, 3+ = 30% to &lt
50%, 4+ = 50% to &lt
70%, 5+ = 70-100%). Although its scores were relatively low (1+ or 2+), Cdx2 was frequently expressed in 27 cases (93.1%). Not only goblet and/or Paneth cells were positive but also non-IM cells in PGAs, as opposed to the lack of staining in the background mucosa. Cdx2 scores were not correlated with those of IM (p = 0.485) and MUC2 (p = 0.868). Of note, Cdx2 was positive in foci of SM in all seven cases, and there was a significant difference in Cdx2 scores between PGAs with and without SM. Furthermore, the p value of scores between Cdx2 and beta-catenin was 0.051, and both mean labeling indices (LIs) were correlated (r = 0.736). With Cdx2, higher morular LIs than glandular LIs were observed (p = 0.001). Finally, we concluded that aberrant Cdx2 expression in PGAs is closely associated with nuclear beta-catenin expression and SM in contrast with IM. © 2008 Springer-Verlag.

DOI： 10.1007/s00428-008-0680-z

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumour with low malignant potential. It is clinically distinct from other pancreatic tumours, and the proper diagnosis is crucial for patient management. However, the histological features of SPN are variable and its diagnosis is not always straightforward. Finger-like extension of the tumour into the surrounding pancreatic parenchyma, a perpendicular cell arrangement around blood vessels and indented vesicular nuclei are characteristic histological features of SPN. The lobulated solid cell pattern seen in SPN is easily mistaken for pancreatic endocrine tumour. Immunohistochemically, SPN is consistently positive for vimentin and CD56, negative or focally positive for cytokeratin and synaptophysin, and always negative for chromogranin. Diffuse nuclear expression of β-catenin is useful for the diagnosis. The distinction of SPN from other solid cellular neoplasms can be made by careful histological observation as well as using a panel of immunohistochemical markers. © 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.mpdhp.2008.04.003

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

A 71-year-old woman with type 2 diabetes mellitus complained of generalized fatigue. A 36-mm tumor in the pancreatic tail was detected with ultrasonography. The tumor was found to have marked hypervascularity with contrast-enhanced computed tomography (CT) and magnetic resonance. Combined 18F-fluorodeoxyglucose positron emission tomography and CT ( 18F-FDG PET/CT) showed 18F-FDG by the tumor with a maximal standardized uptake value of 2.98 at 50 min and 3.29 at 100 min following injection of 18F-FDG. 18F-FDG PET/CT suggested no extrapancreatic spread of the tumor. The patient had no pancreatic hormone-associated symptoms. Distal pancreatectomy was performed, and a well-differentiated endocrine tumor was diagnosed. The resected specimen showed neither infiltration of adjacent structures nor metastasis to regional lymph nodes. The present case suggests that 18F-FDG PET/CT is a reliable modality for staging endocrine pancreatic tumors. © 2008 The Japanese Society of Nuclear Medicine.

DOI： 10.1007/s12149-007-0085-0

Scopus

PubMed

researchmap

Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/32811

CiNii Article

CiNii Books

researchmap

Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/31687

CiNii Article

CiNii Books

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：English  

DOI： 10.1038/s41598-022-11823-3

PubMed

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English  

BACKGROUND: Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. METHODS: Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. RESULTS: The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). CONCLUSIONS: Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates.

DOI： 10.1007/s11605-021-05197-6

PubMed

researchmap

J-GLOBAL

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：Elsevier {BV}  

DOI： 10.1016/j.healun.2018.01.509

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(公社)日本臨床細胞学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publisher：(一社)日本病理学会  

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publishing type：Book review, literature introduction, etc.  

Autoimmune pancreatitis (AIP) is a unique inflammatory disorder of the pancreas. Two histological types are recognized: lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic pancreatitis, with the former representing the pancreatic manifestation of IgG4-related disease. Presented here is a 64-year-old man who was incidentally found to have a mass in the pancreatic tail. The resected specimen revealed typical histological features of lymphoplasmacytic sclerosing pancreatitis, consisting of storiform fibrosis, obliterative phlebitis, and characteristic lobular and ductal inflammation. IgG4-positive plasma cells were numerous, and his serum IgG4 level was elevated (436 mg/dL). He also had systemic lesions, such as hypophysitis, bilateral eyelid lesions and bilateral pleural thickening, that most likely represented IgG4-related disease. Sometimes the distinction of AIP from cancer is clinically difficult, especially in cases with a localized lesion and/or without serological abnormalities
thus, pancreatic resection may be carried out. Pancreas biopsy is attracting attention as a diagnostic tool, and pathologists may play an important role in diagnosing AIP in the future. © 2010 by Lippincott Williams &amp
Wilkins.

DOI： 10.1097/PCR.0b013e3181ffb6d0

Scopus

researchmap

researchmap