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Article ; Online: Structure-activity characteristics of phenylalanine analogs selectively transported by L-type amino acid transporter 1 (LAT1).

Chen, Sihui / Jin, Chunhuan / Ohgaki, Ryuichi / Xu, Minhui / Okanishi, Hiroki / Kanai, Yoshikatsu

2024 Volume 14, Issue 1, Page(s) 4651

Abstract: L-type amino acid transporter 1 (LAT1) is a transmembrane protein responsible for transporting large neutral amino acids. While numerous LAT1-targeted compound delivery for the brain and tumors have been investigated, their LAT1 selectivity often remains ...

Abstract	L-type amino acid transporter 1 (LAT1) is a transmembrane protein responsible for transporting large neutral amino acids. While numerous LAT1-targeted compound delivery for the brain and tumors have been investigated, their LAT1 selectivity often remains ambiguous despite high LAT1 affinity. This study assessed the LAT1 selectivity of phenylalanine (Phe) analogs, focusing on their structure-activity characteristics. We discovered that 2-iodo-L-phenylalanine (2-I-Phe), with an iodine substituent at position 2 in the benzene ring, markedly improves LAT1 affinity and selectivity compared to parent amino acid Phe, albeit at the cost of reduced transport velocity. L-Phenylglycine (Phg), one carbon shorter than Phe, was found to be a substrate for LAT1 with a lower affinity, exhibiting a low level of selectivity for LAT1 equivalent to Phe. Notably, (R)-2-amino-1,2,3,4-tetrahydro-2-naphthoic acid (bicyclic-Phe), with an α-methylene moiety akin to the α-methyl group in α-methyl-L-phenylalanine (α-methyl-Phe), a known LAT1-selective compound, showed similar LAT1 transport maximal velocity to α-methyl-Phe, but with higher LAT1 affinity and selectivity. In vivo studies revealed tumor-specific accumulation of bicyclic-Phe, underscoring the importance of LAT1-selectivity in targeted delivery. These findings emphasize the potential of bicyclic-Phe as a promising LAT1-selective component, providing a basis for the development of LAT1-targeting compounds based on its structural framework.
MeSH term(s)	Phenylalanine/metabolism ; Amino Acids/metabolism ; Brain/metabolism ; Large Neutral Amino Acid-Transporter 1/metabolism ; Biological Transport
Chemical Substances	Phenylalanine (47E5O17Y3R) ; Amino Acids ; Large Neutral Amino Acid-Transporter 1
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55252-w
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Article ; Online: Inhibition of amino acid transporter LAT1 in cancer cells suppresses G0/G1-S transition by downregulating cyclin D1 via p38 MAPK activation.

Zhou, Xinyu / Ohgaki, Ryuichi / Jin, Chunhuan / Xu, Minhui / Okanishi, Hiroki / Endou, Hitoshi / Kanai, Yoshikatsu

Journal of pharmacological sciences

2024 Volume 154, Issue 3, Page(s) 182–191

Abstract: L-type amino acid transporter 1 (LAT1, SLC7A5) is upregulated in various cancers and associated with disease progression. Nanvuranlat (Nanv; JPH203, KYT-0353), a selective LAT1 inhibitor, suppresses the uptake of large neutral amino acids required for ... ...

Abstract	L-type amino acid transporter 1 (LAT1, SLC7A5) is upregulated in various cancers and associated with disease progression. Nanvuranlat (Nanv; JPH203, KYT-0353), a selective LAT1 inhibitor, suppresses the uptake of large neutral amino acids required for rapid growth and proliferation of cancer cells. Previous studies have suggested that the inhibition of LAT1 by Nanv induces the cell cycle arrest at G0/G1 phase, although the underlying mechanisms remain unclear. Using pancreatic cancer cells arrested at the restriction check point (R) by serum deprivation, we found that the Nanv drastically suppresses the G0/G1-S transition after release. This blockade of the cell cycle progression was accompanied by a sustained activation of p38 mitogen-activated protein kinase (MAPK) and subsequent phosphorylation-dependent proteasomal degradation of cyclin D1. Isoform-specific knockdown of p38 MAPK revealed the predominant contribution of p38α. Proteasome inhibitors restored the cyclin D1 amount and released the cell cycle arrest caused by Nanv. The increased phosphorylation of p38 MAPK and the decrease of cyclin D1 were recapitulated in xenograft tumor models treated with Nanv. This study contributes to delineating the pharmacological activities of LAT1 inhibitors as anti-cancer agents and provides significant insights into the molecular basis of the amino acid-dependent cell cycle checkpoint at G0/G1 phase.
MeSH term(s)	Humans ; Cyclin D1/genetics ; Cyclin D1/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; G1 Phase ; Phosphorylation ; Cell Cycle Checkpoints ; Cell Proliferation/genetics ; Neoplasms
Chemical Substances	Cyclin D1 (136601-57-5) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2024-01-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2104264-0
ISSN	1347-8648 ; 1347-8613
ISSN (online)	1347-8648
ISSN	1347-8613
DOI	10.1016/j.jphs.2024.01.007
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Article ; Online: Identification of tumor-suppressive miRNAs that target amino acid transporter LAT1 and exhibit anti-proliferative effects on cholangiocarcinoma cells.

Liu, Xingming / Nishikubo, Kou / Ohgaki, Ryuichi / Okanishi, Hiroki / Okuda, Suguru / Xu, Minhui / Kanai, Yoshikatsu

Journal of pharmacological sciences

2024 Volume 154, Issue 4, Page(s) 301–311

Abstract: Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the ... ...

Abstract	Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the pathological upregulation of LAT1 remain largely unknown. This study pursued the possibility of miRNA-mediated regulation of the LAT1 expression in CHOL cells. Using online target prediction methods, we extracted five candidate miRNAs commonly predicted to regulate the LAT1 expression. Three of them, miR-194-5p, miR-122-5p, and miR-126-3p, were significantly downregulated in CHOL cancer compared to normal tissues. Correlation analysis revealed weak-to-moderate negative correlations between the expression of these miRNAs and LAT1 mRNA in CHOL cancer tissues. We selected miR-194-5p and miR-122-5p for further analyses and found that both miRNAs functionally target 3'UTR of LAT1 mRNA by a luciferase-based reporter assay. Transfection of the miRNA mimics significantly suppressed the LAT1 expression at mRNA and protein levels and inhibited the proliferation of CHOL cells, with a trend of affecting intracellular amino acids and amino acid-related signaling pathways. This study indicates that the decreased expression of these LAT1-targeting tumor-suppressive miRNAs contributes to the upregulation of LAT1 and the proliferation of CHOL cells, highlighting their potential for developing novel cancer therapeutics and diagnostics.
MeSH term(s)	Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Cell Line, Tumor ; Bile Ducts, Intrahepatic/metabolism ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; RNA, Messenger/genetics ; Gene Expression Regulation, Neoplastic ; Cell Proliferation/genetics
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2024-02-24
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2104264-0
ISSN	1347-8648 ; 1347-8613
ISSN (online)	1347-8648
ISSN	1347-8613
DOI	10.1016/j.jphs.2024.02.012
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Article ; Online: Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells.

Ma, Yu / Okuda, Suguru / Okanishi, Hiroki / Xu, Minhui / Jin, Chunhuan / Endou, Hitoshi / Ohgaki, Ryuichi / Kanai, Yoshikatsu

Journal of pharmacological sciences

2024 Volume 155, Issue 1, Page(s) 14–20

Abstract: L-type amino acid transporter 1 (LAT1) is recognized as a promising target for cancer therapy; however, the cellular adaptive response to its pharmacological inhibition remains largely unexplored. This study examined the adaptive response to LAT1 ... ...

Abstract	L-type amino acid transporter 1 (LAT1) is recognized as a promising target for cancer therapy; however, the cellular adaptive response to its pharmacological inhibition remains largely unexplored. This study examined the adaptive response to LAT1 inhibition using nanvuranlat, a high-affinity LAT1 inhibitor. Proteomic analysis revealed the activation of a stress-induced transcription factor ATF4 following LAT1 inhibition, aligning with the known cellular responses to amino acid deprivation. This activation was linked to the GCN2-eIF2α pathway which regulates translation initiation. Our results show that ATF4 upregulation counteracts the suppressive effect of nanvuranlat on cell proliferation in pancreatic ductal adenocarcinoma cell lines, suggesting a role for ATF4 in cellular adaptation to LAT1 inhibition. Importantly, dual targeting of LAT1 and ATF4 exhibited more substantial anti-proliferative effects in vitro than individual treatments. This study underscores the potential of combining LAT1 and ATF4 inhibition as a therapeutic strategy in cancer treatment.
MeSH term(s)	Humans ; Up-Regulation ; Proteomics ; Amino Acids/metabolism ; Pancreatic Neoplasms/drug therapy ; Carcinoma, Pancreatic Ductal/drug therapy ; Large Neutral Amino Acid-Transporter 1/genetics ; Large Neutral Amino Acid-Transporter 1/metabolism ; Cell Line, Tumor ; Activating Transcription Factor 4/genetics ; Activating Transcription Factor 4/metabolism
Chemical Substances	Amino Acids ; Large Neutral Amino Acid-Transporter 1 ; ATF4 protein, human ; Activating Transcription Factor 4 (145891-90-3)
Language	English
Publishing date	2024-03-13
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2104264-0
ISSN	1347-8648 ; 1347-8613
ISSN (online)	1347-8648
ISSN	1347-8613
DOI	10.1016/j.jphs.2024.03.001
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Article: Combination effects of amino acid transporter LAT1 inhibitor nanvuranlat and cytotoxic anticancer drug gemcitabine on pancreatic and biliary tract cancer cells.

Nishikubo, Kou / Ohgaki, Ryuichi / Liu, Xingming / Okanishi, Hiroki / Xu, Minhui / Endou, Hitoshi / Kanai, Yoshikatsu

Cancer cell international

2023 Volume 23, Issue 1, Page(s) 116

Abstract: Background: Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous cancer tissues. ... ...

Abstract	Background: Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous cancer tissues. Combination therapies of cytotoxic anticancer drugs with molecularly targeted drugs have been pursued to solve such fundamental problems. Nanvuranlat (JPH203 or KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), has novel mechanisms of action to suppress the cancer cell proliferation and tumor growth by inhibiting the transport of large neutral amino acids into cancer cells. This study investigated the potential of the combined use of nanvuranlat and cytotoxic anticancer drugs. Methods: The combination effects of cytotoxic anticancer drugs and nanvuranlat on cell growth were examined by a water-soluble tetrazolium salt assay in two-dimensional cultures of pancreatic and biliary tract cancer cell lines. To elucidate the pharmacological mechanisms underlying the combination of gemcitabine and nanvuranlat, we investigated apoptotic cell death and cell cycle by flow cytometry. The phosphorylation levels of amino acid-related signaling pathways were analyzed by Western blot. Furthermore, growth inhibition was examined in cancer cell spheroids. Results: All the tested seven types of cytotoxic anticancer drugs combined with nanvuranlat significantly inhibited the cell growth of pancreatic cancer MIA PaCa-2 cells compared to their single treatment. Among them, the combined effects of gemcitabine and nanvuranlat were relatively high and confirmed in multiple pancreatic and biliary tract cell lines in two-dimensional cultures. The growth inhibitory effects were suggested to be additive but not synergistic under the tested conditions. Gemcitabine generally induced cell cycle arrest at the S phase and apoptotic cell death, while nanvuranlat induced cell cycle arrest at the G0/G1 phase and affected amino acid-related mTORC1 and GAAC signaling pathways. In combination, each anticancer drug basically exerted its own pharmacological activities, although gemcitabine more strongly influenced the cell cycle than nanvuranlat. The combination effects of growth inhibition were also verified in cancer cell spheroids. Conclusions: Our study demonstrates the potential of first-in-class LAT1 inhibitor nanvuranlat as a concomitant drug with cytotoxic anticancer drugs, especially gemcitabine, on pancreatic and biliary tract cancers.
Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2091573-1
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-023-02957-z
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Article: Phosphoproteomics revealed cellular signals immediately responding to disruption of cancer amino acid homeostasis induced by inhibition of L-type amino acid transporter 1.

Okanishi, Hiroki / Ohgaki, Ryuichi / Xu, Minhui / Endou, Hitoshi / Kanai, Yoshikatsu

Cancer & metabolism

2022 Volume 10, Issue 1, Page(s) 18

Abstract: Background: Cancer-upregulated L-type amino acid transporter 1 (LAT1; SLC7A5) supplies essential amino acids to cancer cells. LAT1 substrates are not only needed for cancer rapid growth, but involved in cellular signaling. LAT1 has been proposed as a ... ...

Abstract	Background: Cancer-upregulated L-type amino acid transporter 1 (LAT1; SLC7A5) supplies essential amino acids to cancer cells. LAT1 substrates are not only needed for cancer rapid growth, but involved in cellular signaling. LAT1 has been proposed as a potential target for cancer treatment-its inhibitor, JPH203, is currently in clinical trials and targets biliary tract cancer (BTC). Here, we revealed to what extent LAT1 inhibitor affects intracellular amino acid content and what kind of cellular signals are directly triggered by LAT1 inhibition. Methods: Liquid chromatography assay combined with o-phthalaldehyde- and 9-fluorenyl-methylchloroformate-based derivatization revealed changes in intracellular amino acid levels induced by LAT1 inhibition with JPH203 treatment in three BTC cell lines. Tandem mass tag-based quantitative phosphoproteomics characterized the effect of JPH203 treatment on BTC cells, and suggested key regulators in LAT1-inhibited cells. We further studied one of the key regulators, CK2 protein kinase, by using Western blot, enzymatic activity assay, and co-immunoprecipitation. We evaluated anticancer effects of combination of JPH203 with CK2 inhibitor using cell growth and would healing assay. Results: JPH203 treatment decreased intracellular levels of LAT1 substrates including essential amino acids of three BTC cell lines, immediately and drastically. We also found levels of some of these amino acids were partially recovered after longer-time treatment. Therefore, we performed phosphoproteomics with short-time JPH203 treatment prior to the cellular compensatory response, and revealed hundreds of differentially phosphorylated sites. Commonly downregulated phosphorylation sites were found on proteins involved in the cell cycle and RNA splicing. Our phosphoproteomics also suggested key regulators immediately responding to LAT1 inhibition. Focusing on one of these regulators, protein kinase CK2, we revealed LAT1 inhibition decreased phosphorylation of CK2 substrate without changing CK2 enzymatic activity. Furthermore, LAT1 inhibition abolished interaction between CK2 and its regulatory protein NOLC1, which suggests regulatory mechanism of CK2 substrate protein specificity controlled by LAT1 inhibition. Moreover, we revealed that the combination of JPH203 with CK2 inhibitor resulted in the enhanced inhibition of proliferation and migration of BTC cells. Conclusion: This study provides new perspectives on LAT1-dependent cellular processes and a rationale for therapeutics targeting reprogrammed cancer metabolism.
Language	English
Publishing date	2022-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2700141-6
ISSN	2049-3002
ISSN	2049-3002
DOI	10.1186/s40170-022-00295-8
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Article ; Online: Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models.

Shi, Zitong / Kaneda-Nakashima, Kazuko / Ohgaki, Ryuichi / Xu, Minhui / Okanishi, Hiroki / Endou, Hitoshi / Nagamori, Shushi / Kanai, Yoshikatsu

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13943

Abstract: Metastasis is the leading cause of mortality in cancer patients. L-type amino acid transporter 1 (LAT1, SLC7A5) is a ... ...

Abstract	Metastasis is the leading cause of mortality in cancer patients. L-type amino acid transporter 1 (LAT1, SLC7A5) is a Na
MeSH term(s)	Animals ; Mice ; Amino Acid Transport Systems ; Disease Models, Animal ; Integrin alphaVbeta3 ; Large Neutral Amino Acid-Transporter 1/genetics ; Lung Neoplasms/genetics ; Melanoma, Experimental/genetics ; Neoplasms, Second Primary
Chemical Substances	Amino Acid Transport Systems ; Integrin alphaVbeta3 ; Large Neutral Amino Acid-Transporter 1 ; Slc7a7 protein, mouse
Language	English
Publishing date	2023-08-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41096-3
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Article ; Online: External genitalia phenotypes of a Mab21l1-null mouse model for cerebellar, ocular, craniofacial, and genital (COFG) syndrome.

Promsut, Watcharapon / Yamada, Ryuichi / Takami, Shohei / Miyazaki, Nanae / Uemura, Mami / Hiramatsu, Ryuji / Takahashi, Naoki / Kanai, Yoshiakira

Anatomical record (Hoboken, N.J. : 2007)

2023 Volume 307, Issue 5, Page(s) 1943–1959

Abstract: The cerebellar, ocular, craniofacial, and genital (COFG) syndrome is a human genetic disease that is caused by MAB21L1 mutations. A COFG mouse model with Mab21l1-null mutation causes severe microphthalmia and fontanelle dysosteogenesis, similar to the ... ...

Abstract	The cerebellar, ocular, craniofacial, and genital (COFG) syndrome is a human genetic disease that is caused by MAB21L1 mutations. A COFG mouse model with Mab21l1-null mutation causes severe microphthalmia and fontanelle dysosteogenesis, similar to the symptoms in human patients. One of the typical symptoms is scrotal agenesis in male infants, while male Mab21l1-null mice show hypoplastic preputial glands, a rodent-specific derivative of the cranial scrotal fold. However, it is still unclear where and how MAB21Ll acts in the external genitalia in both mice and humans. Here we show that, at the neonatal stage, MAB21L1 expression in the external genitalia was restricted to two mesenchymal cell populations-underneath the scrotal and labial skin and around the preputial and clitoral glands (PG/CG). Morphometric analyses of the Mab21l1
MeSH term(s)	Animals ; Female ; Male ; Mice ; Genitalia ; Homeodomain Proteins/genetics ; Mice, Knockout ; Mutation ; Phenotype ; Vulva
Chemical Substances	Homeodomain Proteins ; MAB21L1 protein, human
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2269667-2
ISSN	1932-8494 ; 1932-8486
ISSN (online)	1932-8494
ISSN	1932-8486
DOI	10.1002/ar.25330
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Article ; Online: Pharmacologic inhibition of LAT1 predominantly suppresses transport of large neutral amino acids and downregulates global translation in cancer cells.

Nishikubo, Kou / Ohgaki, Ryuichi / Okanishi, Hiroki / Okuda, Suguru / Xu, Minhui / Endou, Hitoshi / Kanai, Yoshikatsu

Journal of cellular and molecular medicine

2022 Volume 26, Issue 20, Page(s) 5246–5256

Abstract: L-type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral amino acids, is highly upregulated in various cancers. LAT1 supplies cancer cells with amino acids as substrates for enhanced biosynthetic and bioenergetic ... ...

Abstract	L-type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral amino acids, is highly upregulated in various cancers. LAT1 supplies cancer cells with amino acids as substrates for enhanced biosynthetic and bioenergetic reactions and stimulates signalling networks involved in the regulation of survival, growth and proliferation. LAT1 inhibitors show anti-cancer effects and a representative compound, JPH203, is under clinical evaluation. However, pharmacological impacts of LAT1 inhibition on the cellular amino acid transport and the translational activity in cancer cells that are conceptually pivotal for its anti-proliferative effect have not been elucidated yet. Here, we demonstrated that JPH203 drastically inhibits the transport of all the large neutral amino acids in pancreatic ductal adenocarcinoma cells. The inhibitory effects of JPH203 were observed even in competition with high concentrations of amino acids in a cell culture medium. The analyses of the nutrient-sensing mTORC1 and GAAC pathways and the protein synthesis activity revealed that JPH203 downregulates the global translation. This study demonstrates a predominant contribution of LAT1 to the transport of large neutral amino acids in cancer cells and the suppression of protein synthesis by JPH203 supposed to underly its broad anti-proliferative effects across various types of cancer cells.
MeSH term(s)	Amino Acids ; Amino Acids, Neutral ; Cell Line, Tumor ; Large Neutral Amino Acid-Transporter 1/genetics ; Large Neutral Amino Acid-Transporter 1/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Neoplasms
Chemical Substances	Amino Acids ; Amino Acids, Neutral ; Large Neutral Amino Acid-Transporter 1 ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.17553
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Article ; Online: Impact of JSS-PCS on the In-Hospital Workflow and Outcomes of Reperfusion Therapy for Acute Ischemic Stroke: Cases of a Metropolitan Secondary Emergency Facility.

Shinoda, Jun / Ichimura, Saeko / Kanai, Ryuichi / Majima, Takamasa / Azami, Shumpei / Inoue, Kouji / Shirai, Toshitaka

Journal of neuroendovascular therapy

2022 Volume 17, Issue 2, Page(s) 37–46

Abstract: Objective: Protected code stroke has been widely introduced in the emergency medical system for acute stroke in the current coronavirus disease 2019 (COVID-19) pandemic. This study aims to confirm the effects of protected code stroke formulated by the ... ...

Abstract	Objective: Protected code stroke has been widely introduced in the emergency medical system for acute stroke in the current coronavirus disease 2019 (COVID-19) pandemic. This study aims to confirm the effects of protected code stroke formulated by the Japan Stroke Society (JSS-PCS) on the quality and outcomes of reperfusion therapy for acute ischemic stroke (AIS), followed by evaluating its validity. Methods: The subjects were 109 consecutive patients with AIS who underwent reperfusion therapy between January 2016 and July 2021, excluding in-hospital onset cases. Patients were classified according to the treatment date into the pre-COVID-19 (n = 82) and the with-COVID-19 (n = 27) groups. JSS-PCS was applied to all patients in the latter group. Statistical comparisons were made between groups on time indicators for initial treatment (onset-to-door time, door-to-imaging time [DTI], door-to-needle time [DTN], door-to-puncture time [DTP], door-to-reperfusion time, and puncture-to-reperfusion time [PTR]). The time indicator transition over the entire period was also evaluated by subgroup analysis. Subsequently, the outcomes at discharge were statistically compared between the two periods, followed by a subgroup comparison. Finally, univariate and multivariate analyses examined whether the application of JSS-PCS affected clinical outcomes. Results: Slight delays were revealed in DTI, DTN, DTP, and PTR in the with-COVID-19 group with no statistical significance. The time indicators were delayed once entering the period of the COVID-19 pandemic and then shortened again. The outcomes at discharge tended to worsen slightly in the with-COVID-19 group with no significance. Subgroup analysis depicted a transient deterioration of outcomes early in the pandemic. Applying JSS-PCS did not significantly affect clinical outcomes in univariate and multivariate analyses. Conclusion: Regarding reperfusion therapy at our facility, the introduction and application of JSS-PCS during the COVID-19 pandemic significantly affected neither time indicators nor outcomes. Infection control should be a top priority in the first medical practice for AIS in today's world, where COVID-19 shows no signs of termination.
Language	English
Publishing date	2022-12-14
Publishing country	Japan
Document type	Journal Article
ISSN	2186-2494
ISSN (online)	2186-2494
DOI	10.5797/jnet.oa.2022-0031
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