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Article ; Online: Monitoring of leucine-rich alpha-2-glycoprotein and assessment by small bowel capsule endoscopy are prognostic for Crohn's disease patients.

Ito, Takahiro / Dai, Kazuki / Horiuchi, Masashi / Horii, Toshiki / Furukawa, Shigeru / Maemoto, Atsuo

JGH open : an open access journal of gastroenterology and hepatology

2023 Volume 7, Issue 9, Page(s) 645–651

Abstract: Background and aim: Endoscopy is important to determine the effectiveness of treatment for Crohn's disease (CD), but searching the entire small intestine is difficult. Thus, we investigated the usefulness of leucine-rich alpha-2 glycoprotein (LRG), a ... ...

Abstract	Background and aim: Endoscopy is important to determine the effectiveness of treatment for Crohn's disease (CD), but searching the entire small intestine is difficult. Thus, we investigated the usefulness of leucine-rich alpha-2 glycoprotein (LRG), a new biomarker for predicting mucosal activity, in evaluating the activity of CD small intestinal lesions. This will further determine whether the results of small bowel capsule endoscopy (SBCE) affect the prognosis of patients with CD. Methods: A total of 114 patients with CD who underwent SBCE were included. We analyzed the correlation between LRG and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). The cutoff value of LRG to achieve mucosal healing was calculated using the receiver operating characteristic curve. Then, we compared the presence or absence of intervention and the relapse rate of patients who could not achieve mucosal healing. Results: The CECDAI correlated with LRG. The calculated LRG value for achieving mucosal healing was ≤11.9. Ninety-one patients were in clinical remission at the time of SBCE. During the follow-up period, 17 patients relapsed. As a result of SBCE, when no treatment intervention was performed in the case of CECDAI ≥3.5, the relapse rate was significantly higher than when CECDAI <3.5 or intervention was performed in the case of CECDAI ≥3.5. Conclusions: The results reveal that LRG correlates with the activity of the entire small intestine and that SBCE assessment and therapeutic intervention can influence patient prognosis.
Language	English
Publishing date	2023-09-05
Publishing country	Australia
Document type	Journal Article
ISSN	2397-9070
ISSN (online)	2397-9070
DOI	10.1002/jgh3.12964
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Article ; Online: Solid-State Schikorr Reaction from Ferrous Chloride to Magnetite with Hydrogen Evolution as the Kinetic Bottleneck.

Yamamoto, Masanori / Takamura, Yota / Kokubo, Yoshiaki / Urushihara, Makoto / Horiuchi, Nobutake / Dai, Wenbin / Hayasaka, Yuichiro / Kita, Eiji / Takao, Koichiro

Inorganic chemistry

2023 Volume 62, Issue 36, Page(s) 14580–14589

Abstract: The selective formation of meta-stable ... ...

Abstract	The selective formation of meta-stable Fe
Language	English
Publishing date	2023-08-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1484438-2
ISSN	1520-510X ; 0020-1669
ISSN (online)	1520-510X
ISSN	0020-1669
DOI	10.1021/acs.inorgchem.3c01676
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Article ; Online: S100A8/A9 predicts response to PIM kinase and PD-1/PD-L1 inhibition in triple-negative breast cancer mouse models.

Begg, Lauren R / Orriols, Adrienne M / Zannikou, Markella / Yeh, Chen / Vadlamani, Pranathi / Kanojia, Deepak / Bolin, Rosemary / Dunne, Sara F / Balakrishnan, Sanjeev / Camarda, Roman / Roth, Diane / Zielinski-Mozny, Nicolette A / Yau, Christina / Vassilopoulos, Athanassios / Huang, Tzu-Hsuan / Kim, Kwang-Youn A / Horiuchi, Dai

Communications medicine

2024 Volume 4, Issue 1, Page(s) 22

Abstract: Background: Understanding why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well remains a challenge. This study aims to understand the potential underlying mechanisms distinguishing early- ... ...

Abstract	Background: Understanding why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well remains a challenge. This study aims to understand the potential underlying mechanisms distinguishing early-stage TNBC tumors that respond to clinical intervention from non-responders, as well as to identify clinically viable therapeutic strategies, specifically for TNBC patients who may not benefit from existing therapies. Methods: We conducted retrospective bioinformatics analysis of historical gene expression datasets to identify a group of genes whose expression levels in early-stage tumors predict poor clinical outcomes in TNBC. In vitro small-molecule screening, genetic manipulation, and drug treatment in syngeneic mouse models of TNBC were utilized to investigate potential therapeutic strategies and elucidate mechanisms of drug action. Results: Our bioinformatics analysis reveals a robust association between increased expression of immunosuppressive cytokine S100A8/A9 in early-stage tumors and subsequent disease progression in TNBC. A targeted small-molecule screen identifies PIM kinase inhibitors as capable of decreasing S100A8/A9 expression in multiple cell types, including TNBC and immunosuppressive myeloid cells. Combining PIM inhibition and immune checkpoint blockade induces significant antitumor responses, especially in otherwise resistant S100A8/A9-high PD-1/PD-L1-positive tumors. Notably, serum S100A8/A9 levels mirror those of tumor S100A8/A9 in a syngeneic mouse model of TNBC. Conclusions: Our data propose S100A8/A9 as a potential predictive and pharmacodynamic biomarker in clinical trials evaluating combination therapy targeting PIM and immune checkpoints in TNBC. This work encourages the development of S100A8/A9-based liquid biopsy tests for treatment guidance.
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00444-8
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Article ; Online: A retrospective comparison between digital to conventional drainage systems for secondary spontaneous pneumothorax related to diffuse interstitial lung disease.

Shikano, Kohei / Abe, Mitsuhiro / Hirama, Ryutaro / Kitahara, Shinsuke / Maruyama, Kanae / Horiuchi, Dai / Sakuma, Noriko / Ishii, Daisuke / Kawasaki, Takeshi / Nakamura, Hidenori / Suzuki, Takuji

The clinical respiratory journal

2023 Volume 17, Issue 8, Page(s) 733–739

Abstract: Introduction: Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP-IP) is ...

Abstract	Introduction: Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP-IP) is frequently not curable by chest drainage only. A digital drainage system (DDS) provides an objective evaluation of air leakage and maintains a pre-determined negative pressure, compared to an analog drainage system (ADS). Few studies have reported the effectiveness of DDS in the treatment of SSP-IP. This study aimed to assess the usefulness of DDS for SSP-IP. Methods: This retrospective study included patients with SSP-IP who had undergone chest drainage. We reviewed the included patients' medical records, laboratory data, computed tomography findings, and pulmonary function data. Results: DDS was used in 24 patients and ADS in 49 patients. The mean duration of chest drainage was 11.4 ± 1.9 days in the DDS group and 14.2 ± 1.3 days in the ADS group, which was not significantly different (p = 0.218). Surgery, pleurodesis, and/or factor XIII administration were performed in 40 patients. Additionally, five (20.8%) patients in the DDS group and nine (18.4%) in the ADS group had a recurrence of pneumothorax within 4 weeks (p = 1.000). One patient (14%) in the DDS group and six (12.2%) in the ADS group (p = 0.414) were cured of pneumothorax but later died. Conclusion: DDS did not demonstrate a significant difference in the shortening of chest drainage duration. Further study is needed to validate the results of this study.
MeSH term(s)	Humans ; Chest Tubes ; Drainage/methods ; Lung Diseases, Interstitial/complications ; Lung Diseases, Interstitial/therapy ; Pleurodesis/methods ; Pneumothorax/therapy ; Pneumothorax/surgery ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2442214-9
ISSN	1752-699X ; 1752-6981
ISSN (online)	1752-699X
ISSN	1752-6981
DOI	10.1111/crj.13654
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Article ; Online: Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer.

Callmann, Cassandra E / Cole, Lisa E / Kusmierz, Caroline D / Huang, Ziyin / Horiuchi, Dai / Mirkin, Chad A

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 30, Page(s) 17543–17550

Abstract: Highly heterogenous cancers, such as triple-negative breast cancer (TNBC), remain challenging immunotherapeutic targets. Herein, we describe the synthesis and evaluation of immunotherapeutic liposomal spherical nucleic acids (SNAs) for TNBC therapy. The ... ...

Abstract	Highly heterogenous cancers, such as triple-negative breast cancer (TNBC), remain challenging immunotherapeutic targets. Herein, we describe the synthesis and evaluation of immunotherapeutic liposomal spherical nucleic acids (SNAs) for TNBC therapy. The SNAs comprise immunostimulatory oligonucleotides (CpG-1826) as adjuvants and encapsulate lysates derived from TNBC cell lines as antigens. The resulting nanostructures (Lys-SNAs) enhance the codelivery of adjuvant and antigen to immune cells when compared to simple mixtures of lysates with linear oligonucleotides both in vitro and in vivo, and reduce tumor growth relative to simple mixtures of lysate and CpG-1826 (Lys-Mix) in both Py230 and Py8119 orthotopic syngeneic mouse models of TNBC. Furthermore, oxidizing TNBC cells prior to lysis and incorporation into SNAs (OxLys-SNAs) significantly increases the activation of dendritic cells relative to their nonoxidized counterparts. When administered peritumorally in vivo in the EMT6 mouse mammary carcinoma model, OxLys-SNAs significantly increase the population of cytotoxic CD8+ T cells and simultaneously decrease the population of myeloid derived suppressor cells (MDSCs) within the tumor microenvironment, when compared with Lys-SNAs and simple mixtures of oxidized lysates with CpG-1826. Importantly, animals administered OxLys-SNAs exhibit significant antitumor activity and prolonged survival relative to all other treatment groups, and resist tumor rechallenge. Together, these results show that the way lysates are processed and packaged has a profound impact on their immunogenicity and therapeutic efficacy. Moreover, this work points toward the potential of oxidized tumor cell lysate-loaded SNAs as a potent class of immunotherapeutics for cancers lacking common therapeutic targets.
MeSH term(s)	Adjuvants, Immunologic ; Animals ; Antigens, Neoplasm/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Humans ; Immunomodulation ; Immunotherapy ; Mice ; Nucleic Acids/immunology ; Oligodeoxyribonucleotides/immunology ; Oligonucleotides/immunology ; Oxidation-Reduction ; Treatment Outcome ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/immunology ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	Adjuvants, Immunologic ; Antigens, Neoplasm ; Cancer Vaccines ; CpG ODN 1826 ; Nucleic Acids ; Oligodeoxyribonucleotides ; Oligonucleotides
Language	English
Publishing date	2020-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2005794117
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Zs.A 1148: Show issues

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Article ; Online: Changes in Emergency Medical Services Before and During the COVID-19 Pandemic in the United States, January 2018-December 2020.

Handberry, Maya / Bull-Otterson, Lara / Dai, Mengtao / Mann, N Clay / Chaney, Eric / Ratto, Jeff / Horiuchi, Kalanthe / Siza, Charlene / Kulkarni, Aniket / Gundlapalli, Adi V / Boehmer, Tegan K

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue Suppl 1, Page(s) S84–S91

Abstract: Background: As a result of the continuing surge of coronavirus disease 2019 (COVID-19), many patients have delayed or missed routine screening and preventive services. Medical conditions, such as coronary heart disease, mental health issues, and ... ...

Abstract	Background: As a result of the continuing surge of coronavirus disease 2019 (COVID-19), many patients have delayed or missed routine screening and preventive services. Medical conditions, such as coronary heart disease, mental health issues, and substance use disorder, may be identified later, leading to increases in patient morbidity and mortality. Methods: National Emergency Medical Services Information System data were used to assess 911 emergency medical services (EMS) activations during 2018-2020. For specific activation types, the percentage of total activations was calculated per week, and Joinpoint analysis was used to identify changes over time. Results: Since March 2020, the number of 911 EMS activations has decreased, while the percentages of on-scene death, cardiac arrest, and opioid use/overdose EMS activations were higher than prepandemic levels. During the early pandemic period, percentages of total EMS activations increased for on-scene death (from 1.3% to 2.4% during weeks 11-15), cardiac arrest (from 1.3% to 2.2% during weeks 11-15), and opioid use/overdose (from 0.6% to 1.1% during weeks 8-18). The percentages then declined but remained above prepandemic levels through calendar week 52. Conclusions: The COVID-19 pandemic has indirect consequences, such as relative increases in EMS activations for cardiac events and opioid use/overdose, possibly linked to disruptions is healthcare access and health-seeking behaviors. Increasing telehealth visits and other opportunities for patient-provider touch points for chronic disease and substance use disorders that emphasize counseling, preventive care, and expanded access to medications can disrupt delayed care-seeking during the pandemic and potentially prevent premature death.
MeSH term(s)	COVID-19 ; Drug Overdose/drug therapy ; Drug Overdose/epidemiology ; Emergency Medical Services ; Humans ; Pandemics ; SARS-CoV-2 ; United States/epidemiology
Language	English
Publishing date	2021-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab373
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: S100A8/A9 predicts triple-negative breast cancer response to PIM kinase and PD-1/PD-L1 inhibition.

bioRxiv : the preprint server for biology

2023

Abstract: It remains elusive why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well. Our retrospective analysis of historical gene expression datasets reveals that increased expression of ... ...

Abstract	It remains elusive why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well. Our retrospective analysis of historical gene expression datasets reveals that increased expression of immunosuppressive cytokine S100A8/A9 in early-stage tumors is robustly associated with subsequent disease progression in TNBC. Although it has recently gained recognition as a potential anticancer target, S100A8/A9 has not been integrated into clinical study designs evaluating molecularly targeted therapies. Our small molecule screen has identified PIM kinase inhibitors as capable of decreasing S100A8/A9 expression in multiple cell types, including TNBC and immunosuppressive myeloid cells. Furthermore, combining PIM inhibition and immune checkpoint blockade induces significant antitumor responses, especially in otherwise resistant S100A8/A9-high PD-1/PD-L1-positive tumors. Importantly, serum S100A8/A9 levels mirror those of tumor S100A8/A9 in a syngeneic mouse model of TNBC. Thus, our data suggest that S100A8/A9 could be a predictive and pharmacodynamic biomarker in clinical trials evaluating combination therapy targeting PIM and immune checkpoints in TNBC and encourage the development of S100A8/A9-based liquid biopsy tests.
Language	English
Publishing date	2023-09-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.21.558870
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Article ; Online: Taking on challenging targets: making MYC druggable.

Horiuchi, Dai / Anderton, Brittany / Goga, Andrei

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2014 , Page(s) e497–502

Abstract: The transcription factor proto-oncogene c-MYC (hereafter MYC) was first identified more than 3 decades ago and has since been found deregulated in a wide variety of the most aggressive human malignancies. As a pleiotropic transcription factor, MYC ... ...

Abstract	The transcription factor proto-oncogene c-MYC (hereafter MYC) was first identified more than 3 decades ago and has since been found deregulated in a wide variety of the most aggressive human malignancies. As a pleiotropic transcription factor, MYC directly or indirectly controls expression of hundreds of coding and noncoding genes, which affect cell cycle entry, proliferation, differentiation, metabolism, and death/survival decisions of normal and cancer cells. Tumors with elevated MYC expression often exhibit highly proliferative, aggressive phenotypes, and elevated MYC expression has been correlated with diminished disease-free survival for a variety of human cancers. The use of MYC overexpression or MYC-dependent transcriptional gene signatures as clinical biomarkers is currently being investigated. Furthermore, preclinical animal and cell-based model systems have been extensively utilized in an effort to uncover the mechanisms of MYC-dependent tumorigenesis and tumor maintenance. Despite our ever-growing understanding of MYC biology, currently no targeted therapeutic strategy is clinically available to treat tumors that have acquired elevated MYC expression. This article summarizes the progresses being made to discover and implement new therapies to kill MYC over-expressing tumors-a target that was once deemed undruggable.
MeSH term(s)	Animals ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Predisposition to Disease ; Humans ; Molecular Targeted Therapy/adverse effects ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction/drug effects ; Transcription, Genetic/drug effects ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Proto-Oncogene Proteins c-myc
Language	English
Publishing date	2014-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review ; Video-Audio Media
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.14694/EdBook_AM.2014.34.e497
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Article ; Online: Changes in Colonic Inflammation Related with Takayasu Arteritis during a 10-year Observation Period.

Wada, Akinori / Higashiyama, Masaaki / Hirata, Dai / Ito, Suguru / Tanemoto, Rina / Nishii, Shin / Mizoguchi, Akinori / Inaba, Kenichi / Sugihara, Nao / Hanawa, Yoshinori / Horiuchi, Kazuki / Akita, Yoshihiro / Narimatsu, Kazuyuki / Komoto, Shunsuke / Tomita, Kengo / Hokari, Ryota

Internal medicine (Tokyo, Japan)

2021 Volume 61, Issue 4, Page(s) 475–480

Abstract: Takayasu arteritis (TA) sometimes presents with colitis, which may be diagnosed as inflammatory bowel disease unclassified (IBDU) because of atypical or mixed findings of ulcerative colitis (UC) and Crohn's disease. We herein report an 18-year-old girl ... ...

Abstract	Takayasu arteritis (TA) sometimes presents with colitis, which may be diagnosed as inflammatory bowel disease unclassified (IBDU) because of atypical or mixed findings of ulcerative colitis (UC) and Crohn's disease. We herein report an 18-year-old girl presenting with colitis with an occasional high fever eventually diagnosed as TA with IBDU. Colonic inflammation was initially discontinuous and stronger in the proximal colon, atypical of UC. However, over 10-year observation, the distribution of colonic inflammation varied and became UC-like. Variations in TA-related colonic inflammations over time have been unclear. Our long-term observation might help clarify the details of TA-related colonic inflammation.
MeSH term(s)	Adolescent ; Colitis, Ulcerative/complications ; Colitis, Ulcerative/diagnosis ; Female ; Humans ; Inflammation ; Retrospective Studies ; Takayasu Arteritis/complications ; Takayasu Arteritis/diagnosis
Language	English
Publishing date	2021-08-13
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.7287-21
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Zs.A 240: Show issues

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Article ; Online: Immunoglobulin G4-related disease accompanying a small intestinal ulcer: A case.

Yoshidome, Yuta / Mizoguchi, Akinori / Narimatsu, Kazuyuki / Takahashi, Shun / Hirata, Dai / Ono, Shinji / Onoyama, Yusuke / Suzuki, Seiya / Horiuchi, Tomoaki / Chiya, Nanoka / Ikeyama, Keisuke / Tahara, Hiroyuki / Tomioka, Akira / Ito, Suguru / Tanemoto, Rina / Nishii, Shin / Inaba, Kenichi / Sugihara, Nao / Hanawa, Yoshinori /

Horiuchi, Kazuki / Wada, Akinori / Akita, Yoshihiro / Higashiyama, Masaaki / Komoto, Shunsuke / Tomita, Kengo / Yoshimatsu, Shinya / Matsukuma, Susumu / Hokari, Ryota

DEN open

2021 Volume 2, Issue 1, Page(s) e76

Abstract: Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that ... ...

Abstract	Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that IgG4-RD affects a variety of organs but uncommonly affects the gastrointestinal tract. In particular, there are few cases of lesions in the small intestine, except for sclerosing mesenteritis, which were mostly diagnosed from surgical specimens. Herein, we describe the case of a 70-year-old man who initially presented with abdominal pain, headache, later cognitive decline, and gait disturbance caused by IgG4-RD. Colonoscopy revealed irregular ulcers in the terminal ileum, and computed tomography of the head showed hypertrophic pachymeningitis. Numerous IgG4-positive cells were detected in the ileal and dural biopsies. We diagnosed the patient with IgG4-RD and started steroid pulse therapy. After initiation of treatment, the symptoms quickly improved. The patient was discharged from the hospital after starting oral prednisolone treatment (30 mg). The dosage was gradually reduced to 10 mg. A follow-up colonoscopy revealed scarring of the ileal ulcers. This case may provide valuable information regarding the endoscopic findings of small intestinal lesions in IgG4-RD.
Language	English
Publishing date	2021-11-24
Publishing country	Australia
Document type	Case Reports
ISSN	2692-4609
ISSN (online)	2692-4609
DOI	10.1002/deo2.76
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