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Article ; Online: Ephedrine enhances HIV-1 reactivation from latency through elevating tumor necrosis factor receptor II (TNFRII) expression

Jutatip Panaampon / Eriko Kudo / Ryusho Kariya / Seiji Okada

Heliyon, Vol 5, Iss 9, Pp e02490- (2019)

2019

Abstract: HIV-1 persists during antiretroviral therapy (ART) due to long-lived and proliferating latently-infected host cells, with the outcome being an incomplete cure. The latently-infected cells, or reservoir cells, are transcriptionally absent and invisible to ...

Abstract	HIV-1 persists during antiretroviral therapy (ART) due to long-lived and proliferating latently-infected host cells, with the outcome being an incomplete cure. The latently-infected cells, or reservoir cells, are transcriptionally absent and invisible to the immune response. Elimination of latency is one strategy in activating virus production, making it visible to immune clearance. We previously showed that Ephedrae herba reactivated HIV-1 from latency. In this study, we used ephedrine, a major component of Ephedra herba, to reactivate HIV-1 from latency. The results showed that ephedrine enhances HIV-1 reactivation in the presence of TNFα. Combination treatment demonstrates a synergistic effect of HIV-1 reactivation compared to TNFα alone. Ephedrine treatment shows a higher TNFRII expression level, which is related to increased HIV-1 reactivation. However, the mechanism of ephedrine in HIV-1 reactivation is still unclear, and may be related to TNFRII receptor expression. Our results indicate that ephedrine enhances HIV-1 reactivation from latency in combination with TNFα treatment. This new reagent could be a promising latency reversal agent (LRA).
Keywords	Cell biology ; Microbiology ; Molecular biology ; Hematological system ; Infectious disease ; Ephedrine ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	570
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Seiji Okada / Kulthida Vaeteewoottacharn / Ryusho Kariya

Cells, Vol 8, Iss 8, p

2019 Volume 889

Abstract: Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. Since a PDX model retains the characteristics of the primary patient tumor including gene expression profiles and drug responses, it has ...

Abstract	Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. Since a PDX model retains the characteristics of the primary patient tumor including gene expression profiles and drug responses, it has become the most reliable in vivo human cancer model. The engraftment rate increases with the introduction of Non-obese diabetic Severe combined immunodeficiency (NOD/SCID)-based immunocompromised mice, especially the NK-deficient NOD strains NOD/SCID/interleukin-2 receptor gamma chain(IL2Rγ) null ( NOG/NSG) and NOD/SCID/Jak3(Janus kinase 3) null (NOJ). Success rates differ with tumor origin: gastrointestinal tumors acquire a higher engraftment rate, while the rate is lower for breast cancers. Subcutaneous transplantation is the most popular method to establish PDX, but some tumors require specific environments, e.g., orthotropic or renal capsule transplantation. Human hormone treatment is necessary to establish hormone-dependent cancers such as prostate and breast cancers. PDX mice with human hematopoietic and immune systems (humanized PDX) are powerful tools for the analysis of tumor−immune system interaction and evaluation of immunotherapy response. A PDX biobank equipped with patients’ clinical data, gene-expression patterns, mutational statuses, tumor tissue architects, and drug responsiveness will be an authoritative resource for developing specific tumor biomarkers for chemotherapeutic predictions, creating individualized therapy, and establishing precise cancer medicine.
Keywords	patient-derived xenograft ; immunocompromised mice ; precision medicine ; drug screening ; cancer ; cell line ; cancer immunotherapy ; humanized mice ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ribosome induces transdifferentiation of A549 and H-111-TC cancer cell lines

Mohammad Badrul Anam / Arif Istiaq / Ryusho Kariya / Mikiko Kudo / Shah Adil Ishtiyaq Ahmad / Naofumi Ito / Seiji Okada / Kunimasa Ohta

Biochemistry and Biophysics Reports, Vol 26, Iss , Pp 100946- (2021)

2021

Abstract: Previously we reported that, lactic acid bacteria (LAB) can induce human dermal fibroblast (HDF) cells to form multipotent cell clusters which are able to transdifferentiate into three germ layer derived cell lineages. Later on, we confirmed that ... ...

Abstract	Previously we reported that, lactic acid bacteria (LAB) can induce human dermal fibroblast (HDF) cells to form multipotent cell clusters which are able to transdifferentiate into three germ layer derived cell lineages. Later on, we confirmed that ribosome is responsible for the LAB-induced transdifferentiation and ribosomes from diverse organisms can mimic the LAB effect on HDF cells. In our present study we have shown that, upon incorporation of ribosomes, non-small cell lung cancer cell line A549 and gastric tubular adenocarcinoma cell line H-111-TC are transformed into spheroid like morphology those can be transdifferentiated into adipocytes and osteoblast. Our qPCR analysis has revealed that, during the formation of ribosome induced cancer cell spheroids, the expression of the cancer cell associated markers and cell cycle/proliferation markers were altered at different time point. Through our investigation, here we report a novel and a non-invasive approach for cancer cell reprogramming by incorporating ribosomes.
Keywords	Cancer ; Ribosome ; Reprogramming ; Transdifferentiation ; Cancer cell spheroids ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Homophilic Interaction of CD147 Promotes IL-6-Mediated Cholangiocarcinoma Invasion via the NF-κB-Dependent Pathway

Paweena Dana / Ryusho Kariya / Worachart Lert-itthiporn / Wunchana Seubwai / Saowaluk Saisomboon / Chaisiri Wongkham / Seiji Okada / Sopit Wongkham / Kulthida Vaeteewoottacharn

International Journal of Molecular Sciences, Vol 22, Iss 13496, p

2021 Volume 13496

Abstract: Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The ... ...

Abstract	Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The role of CD147 on cytokine production has been observed in inflammation-related diseases, but not in CCA. Therefore, this study was focused on CD147-promoting proinflammatory cytokine production and functions. Proinflammatory cytokine profiles were compared between CD147 expressing CCA cells and CD147 knockout cells (CD147 KO). Three cytokines, namely interleukin (IL)-6, IL-8, and granulocyte–monocyte colony-stimulating factor (GM-CSF), were dramatically diminished in CD147 KO clones. The involvement of the CD147-related cytokines in CCA invasion was established. CD147-promoted IL-6, IL-8, and GM-CSF secretions were regulated by NF-κB nuclear translocation, Akt activation, and p38 phosphorylation. CD147-fostering IL-6 production was dependent on soluble CD147, CD147 homophilic interaction, and NF-κB function. The overexpression of specific genes in CCA tissues compared to normal counterparts emphasized the clinical importance of these molecules. Altogether, CD147-potentiated proinflammatory cytokine production leading to CCA cell invasion is shown for the first time in the current study. This suggests that modulation of CD147-related inflammation might be a promising choice for advanced CCA treatment.
Keywords	cholangiocarcinoma (CCA) ; cluster of differentiation 147 (CD147) ; extracellular matrix metalloproteinase inducer (EMMPRIN) ; proinflammatory cytokines ; cancer invasion ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antitumor effects of flavopiridol, a cyclin-dependent kinase inhibitor, on human cholangiocarcinoma in vitro and in an in vivo xenograft model

Saowaluk Saisomboon / Ryusho Kariya / Kulthida Vaeteewoottacharn / Sopit Wongkham / Kanlayanee Sawanyawisuth / Seiji Okada

Heliyon, Vol 5, Iss 5, Pp e01675- (2019)

2019

Abstract: Flavopiridol, a pan-cyclin-dependent kinase (CDK) inhibitor, was recently identified as an effective antitumor agent for several cancers. We investigated the antitumor effect of flavopiridol on cholangiocarcinoma (CCA), in vitro and in vivo. A ... ...

Abstract	Flavopiridol, a pan-cyclin-dependent kinase (CDK) inhibitor, was recently identified as an effective antitumor agent for several cancers. We investigated the antitumor effect of flavopiridol on cholangiocarcinoma (CCA), in vitro and in vivo. A methylthiotetrazole assay revealed that the proliferation of certain CCA cells was inhibited by flavopiridol, which induced the caspase-dependent apoptosis of CCA cells. Although increased cell cycle arrest was observed at the G2/M phase, caspase activation occurred earlier than 24 h, indicating that caspase-dependent apoptosis is the major pathway for the suppression of cell proliferation. Flavopiridol potently reduced the CCA tumor growth in a xenograft model without observable adverse effects. These findings indicated that flavopiridol could be a potential antitumor agent for the treatment of CCA.
Keywords	Biochemistry ; Cancer research ; Molecular biology ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	570
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice

Naoto Yoshimura / Ryusho Kariya / Masaki Shimada / Makoto Tateyama / Hideto Matsunaga / Yuto Shibata / Shuntaro Tanimura / Kosei Takata / Takahiro Arima / Junki Kawakami / Kazuya Maeda / Yuko Fukuma / Masaru Uragami / Katsumasa Ideo / Kazuki Sugimoto / Ryuji Yonemitsu / Kozo Matsushita / Satoshi Hisanaga / Masaki Yugami /

Yusuke Uehara / Tetsuro Masuda / Takayuki Nakamura / Takuya Tokunaga / Tatsuki Karasugi / Takanao Sueyoshi / Hiro Sato / Yoichiro Iwakura / Kimi Araki / Eisuke Kobayashi / Seiji Okada / Takeshi Miyamoto

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued ... ...

Abstract	Abstract Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment approaches is needed. Here, we report that IL-17, a proinflammatory cytokine, increases osteosarcoma mortality in a mouse model with AX osteosarcoma cells. AX cell transplantation into wild-type mice resulted in 100% mortality due to ectopic ossification and multi-organ metastasis. However, AX cell transplantation into IL-17-deficient mice significantly prolonged survival relative to controls. CD4-positive cells adjacent to osteosarcoma cells express IL-17, while osteosarcoma cells express the IL-17 receptor IL-17RA. Although AX cells can undergo osteoblast differentiation, as can patient osteosarcoma cells, IL-17 significantly inhibited that differentiation, indicating that IL-17 maintains AX cells in the undifferentiated state seen in malignant tumors. By contrast, IL-17RA-deficient mice transplanted with AX cells showed survival comparable to wild-type mice transplanted with AX cells. Biopsy specimens collected from osteosarcoma patients showed higher expression of IL-17RA compared to IL-17. These findings suggest that IL-17 is essential to maintain osteosarcoma cells in an undifferentiated state and could be a therapeutic target for suppressing tumorigenesis.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Terminal fucose mediates progression of human cholangiocarcinoma through EGF/EGFR activation and the Akt/Erk signaling pathway

Somsiri Indramanee / Kanlayanee Sawanyawisuth / Atit Silsirivanit / Paweena Dana / Chatchai Phoomak / Ryusho Kariya / Nathakan Klinhom-on / Supannika Sorin / Chaisiri Wongkham / Seiji Okada / Sopit Wongkham

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 13

Abstract: Abstract Aberrant glycosylation is recognized as a cancer hallmark that is associated with cancer development and progression. In this study, the clinical relevance and significance of terminal fucose (TFG), by fucosyltransferase-1 (FUT1) in ... ...

Abstract	Abstract Aberrant glycosylation is recognized as a cancer hallmark that is associated with cancer development and progression. In this study, the clinical relevance and significance of terminal fucose (TFG), by fucosyltransferase-1 (FUT1) in carcinogenesis and progression of cholangiocarcinoma (CCA) were demonstrated. TFG expression in human and hamster CCA tissues were determined using Ulex europaeus agglutinin-I (UEA-I) histochemistry. Normal bile ducts rarely expressed TFG while 47% of CCA human tissues had high TFG expression and was correlated with shorter survival of patients. In the CCA-hamster model, TFG was elevated in hyperproliferative bile ducts and gradually increased until CCA was developed. This evidence indicates the involvement of TFG in carcinogenesis and progression of CCA. The mechanistic insight was performed in 2 CCA cell lines. Suppression of TFG expression using siFUT1 or neutralizing the surface TFG with UEA-I significantly reduced migration, invasion and adhesion of CCA cells in correlation with the reduction of Akt/Erk signaling and epithelial-mesenchymal transition. A short pulse of EGF could stimulate Akt/Erk signaling via activation of EGF-EGFR cascade, however, decreasing TFG using siFUT1 or UEA-I treatment reduced the EGF-EGFR activation and Akt/Erk signaling. This evidence provides important insight into the relevant role and molecular mechanism of TFG in progression of CCA.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model

Kulthida Vaeteewoottacharn / Chawalit Pairojkul / Ryusho Kariya / Kanha Muisuk / Kanokwan Imtawil / Yaovalux Chamgramol / Vajarabhongsa Bhudhisawasdi / Narong Khuntikeo / Ake Pugkhem / O-Tur Saeseow / Atit Silsirivanit / Chaisiri Wongkham / Sopit Wongkham / Seiji Okada

Cells, Vol 8, Iss 5, p

2019 Volume 496

Abstract: Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. ... ...

Abstract	Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. Recent multi-omics studies revealed the promising targets for CCA treatment; however, limited models for drug discovery are available. This study aimed to develop a patient-derived xenograft (PDX) model as well as PDX-derived cell lines of CCA for future drug screening. From a total of 16 CCA frozen tissues, 75% (eight intrahepatic and four extrahepatic subtypes) were successfully grown and subpassaged in Balb/c Rag-2 -/- /Jak3 -/- mice. A shorter duration of PDX growth was observed during F0 to F2 transplantation; concomitantly, increased Oct-3/4 and Sox2 were evidenced in 50% and 33%, respectively, of serial PDXs. Only four cell lines were established. The cell lines exhibited either bile duct (KKK-D049 and KKK-D068) or combined hepatobiliary origin (KKK-D131 and KKK-D138). These cell lines acquired high transplantation efficiency in both subcutaneous (100%) and intrasplenic (88%) transplantation models. The subcutaneously transplanted xenograft retained the histological architecture as in the patient tissues. Our models of CCA PDX and PDX-derived cell lines would be a useful platform for CCA precision medicine.
Keywords	cholangiocarcinoma ; patient-derived xenograft ; cell line ; cancer model ; precision medicine ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inflammation-driven senescence-associated secretory phenotype in cancer-associated fibroblasts enhances peritoneal dissemination

Tadahito Yasuda / Mayu Koiwa / Atsuko Yonemura / Keisuke Miyake / Ryusho Kariya / Sho Kubota / Takako Yokomizo-Nakano / Noriko Yasuda-Yoshihara / Tomoyuki Uchihara / Rumi Itoyama / Luke Bu / Lingfeng Fu / Kota Arima / Daisuke Izumi / Shiro Iwagami / Kojiro Eto / Masaaki Iwatsuki / Yoshifumi Baba / Naoya Yoshida /

Hiroto Ohguchi / Seiji Okada / Keisuke Matsusaki / Goro Sashida / Akiko Takahashi / Patrick Tan / Hideo Baba / Takatsugu Ishimoto

Cell Reports, Vol 34, Iss 8, Pp 108779- (2021)

2021

Abstract: Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression ... ...

Abstract	Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.
Keywords	cancer-associated fibroblasts ; senescence-associated secretory phenotype ; EZH2 ; gastric cancer ; peritoneal dissemination ; H3K27me3 marks ; Biology (General) ; QH301-705.5
Subject code	616 ; 610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative Study of Human Hematopoietic Cell Engraftment into Balb/c and C57BL/6 Strain of Rag-2/Jak3 Double-Deficient Mice

Ayumi Ono / Shinichiro Hattori / Ryusho Kariya / Sumako Iwanaga / Manabu Taura / Hideki Harada / Shinya Suzu / Seiji Okada

Journal of Biomedicine and Biotechnology, Vol

2011 Volume 2011

Abstract: Immunodeficient mice are becoming invaluable tools in human stem cell and tumor research. In this study, we generated Rag-2/Jak3 double-deficient (Rag-2−/−Jak3−/−) mice with a C57/BL6 and Balb/c genetic background and compared the human ... ...

Abstract	Immunodeficient mice are becoming invaluable tools in human stem cell and tumor research. In this study, we generated Rag-2/Jak3 double-deficient (Rag-2−/−Jak3−/−) mice with a C57/BL6 and Balb/c genetic background and compared the human lymphohematopoietic cell engraftment rate. Human cord blood-derived CD34+ hematopoietic stem cells were successfully engrafted into Balb/c Rag-2−/−Jak3−/− mice; however, the engraftment rate was far lower in C57/BL6 Rag-2−/−Jak3−/− mice. Transplantation of human peripheral blood mononuclear cells resulted in the same tendency. Thus, a Balb/c background offers superior engraftment capacity than a C57/BL6 background and provides an attractive model for human hematopoietic cell engraftment.
Keywords	Biotechnology ; TP248.13-248.65 ; Medicine ; R
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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