Biological & pharmaceutical bulletin最新文献_第10页

Estradiol Regulates the Expression of Type 3 Deiodinase in a Chondrocyte Cell Line. 雌二醇调控软骨细胞3型脱碘酶的表达。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00825

Mana Mitsutani, Mei Yokoyama, Hiromi Hano, Midori Matsushita, Misa Hayashi, Ichiro Yamauchi, Tetsuya Tagami, Kenji Moriyama

{"title":"Estradiol Regulates the Expression of Type 3 Deiodinase in a Chondrocyte Cell Line.","authors":"Mana Mitsutani, Mei Yokoyama, Hiromi Hano, Midori Matsushita, Misa Hayashi, Ichiro Yamauchi, Tetsuya Tagami, Kenji Moriyama","doi":"10.1248/bpb.b24-00825","DOIUrl":"10.1248/bpb.b24-00825","url":null,"abstract":"Although accelerated growth is observed in both sexes upon reaching puberty, the growth of girls ceases around menarche (the average age at menarche is 12-13 years in Japan). However, the molecular basis of the action of estrogen remains unclear. In this study, we investigated whether estrogen is involved in the differences in growth between males and females while focusing on thyroid hormone metabolic enzymes. We analyzed the promoters of iodothyronine deiodinase (DIO)2 and DIO3 by 17β-estradiol (E2). ATDC5 cells (mouse chondrocytes cell line) were treated with E2, and the expression of DIO2 and DIO3 mRNA and proteins was evaluated. Sham-operated (sham) or ovariectomized (OVX) female mice were treated daily with E2 or vehicle for three consecutive weeks. Subsequently, the left femur was removed to evaluate the effect of E2 on DIO2/DIO3 gene and protein expression. E2 increased the transcriptional activity of DIO3 in a concentration-dependent manner. On the DIO3 promoter indicates the presence of an estrogen response element. DIO2 and DIO3 mRNA and protein expression in ATDC5 cells in the presence of E2 was significantly increased, while DIO2 expression was unchanged. In vivo, we used OVX mice and E2 supplementation as a model of amenorrhea for further investigation. DIO3 expression was significantly increased in mice treated with E2 in OVX compared to that in mice treated with vehicle in sham. E2 increases DIO3 expression in chondrocytes and long bone tissues, suggesting that E2 may affect bone growth and cause sexual dimorphism during puberty.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"267-278"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Severe Neutropenia Caused by S-1 Adjuvant Chemotherapy on Pancreatic Cancer Prognosis. S-1辅助化疗所致严重中性粒细胞减少对胰腺癌预后的影响。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00602

Yusuke Noguchi, Ryo Inose, Tatsuya Ohtsubo, Daisuke Kobayashi, Yoshitaka Kato, Yuichi Muraki, Kanji Tomogane

{"title":"Effect of Severe Neutropenia Caused by S-1 Adjuvant Chemotherapy on Pancreatic Cancer Prognosis.","authors":"Yusuke Noguchi, Ryo Inose, Tatsuya Ohtsubo, Daisuke Kobayashi, Yoshitaka Kato, Yuichi Muraki, Kanji Tomogane","doi":"10.1248/bpb.b24-00602","DOIUrl":"10.1248/bpb.b24-00602","url":null,"abstract":"In Japan, S-1 is used as adjuvant chemotherapy for pancreatic cancer. Neutropenia during S-1 chemotherapy is reported to be an independent predictor of prolonged survival in patients with advanced gastric cancer. However, this is unclear in pancreatic cancer. This study aimed to examine the effect of severe neutropenia caused by S-1 adjuvant chemotherapy on pancreatic cancer prognosis: overall survival (OS) and recurrence-free survival (RFS), and the potential effect of the duration from surgery to S-1 administration on OS and RFS. This single-center, retrospective, observational study included patients who newly received S-1 adjuvant chemotherapy after curative resection of pancreatic cancer at the Japanese Red Cross Kyoto Daini Hospital between January 1, 2016, and September 30, 2020. Of the 43 patients, 9 had grade 3 or higher neutropenia (G3 group) and had a significantly longer median OS than the other 34 (non-G3 group) did. The median RFS of the G3 group was longer than that of the non-G3 group. The median time from surgery to S-1 administration was significantly shorter in the G3 group than in the non-G3 group. Cox proportional hazards regression analysis revealed that duration from surgery to S-1 administration <51 d (hazard ratio: 0.375, 95% confidence interval: 0.154-0.914, p = 0.031) and occurrence of grade 3 neutropenia (hazard ratio: 0.198, 95% confidence interval: 0.046-0.860, p = 0.031) were significantly associated with prolonged OS. In conclusion, initiating S-1 adjuvant chemotherapy early after surgery and the occurrence of grade 3 neutropenia may improve pancreatic cancer prognosis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"132-136"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety Assessment of Medications during Pregnancy and Breastfeeding Based on Quantitative and Toxicological Analyses. 基于定量和毒理学分析的妊娠和哺乳期药物安全性评估。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00016

Ayako Furugen

{"title":"Safety Assessment of Medications during Pregnancy and Breastfeeding Based on Quantitative and Toxicological Analyses.","authors":"Ayako Furugen","doi":"10.1248/bpb.b25-00016","DOIUrl":"10.1248/bpb.b25-00016","url":null,"abstract":"The potential risks to the fetus or infant should be evaluated before initiating pharmacotherapy during pregnancy and breastfeeding. However, safety information and experiences during pregnancy and breastfeeding are often lacking because these populations are generally excluded from clinical drug development studies. Perinatal mental health is important. Based on quantitative and toxicological analyses, we focused on medications used in psychiatry and neurology during the perinatal period. As the placenta serves as a temporary but crucial organ for ensuring successful pregnancy and appropriate fetal growth, we assessed the effects of antiepileptic drugs (AEDs) on placental functions such as transport mechanisms, nutrient transport, and trophoblast differentiation. Several AEDs have been suggested to be transported to the placenta via carrier-mediated pathways in a series of studies. Valproic acid, known to pose several risks to the fetus, affects the gene expression of nutrient transporters and trophoblast differentiation. Furthermore, we established several quantitative methods, such as those for antianxiety and hypnotic drugs, to evaluate the safety of pharmacotherapy during breastfeeding using liquid chromatography-tandem mass spectrometry. The validated methods were applied to clinical samples donated by lactating women. In a series of studies, the importance of choosing a suitable method for sample preparation for each biological matrix has been highlighted. The results obtained from the clinical samples suggest the possibility of differences in transfer properties among drugs categorized in the same class. Furthermore, this research emphasizes the critical need to assess breast milk transfer in human studies because species differences have been suggested in some cases.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"337-343"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simple Cytosolic and Nuclear Introduction of Boron Compounds Using Cationic Lipids to Enhance Cancer Cell-Killing Activity in Boron Neutron Capture Therapy. 在硼中子俘获治疗中，利用阳离子脂质引入简单的细胞质和核硼化合物以增强癌细胞杀伤活性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00651

Shiori Hirase, Yurina Araki, Yoshihide Hattori, Ayako Aoki, Daisuke Fujiwara, Masataka Michigami, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki, Mitsunori Kirihata, Ikuhiko Nakase

{"title":"Simple Cytosolic and Nuclear Introduction of Boron Compounds Using Cationic Lipids to Enhance Cancer Cell-Killing Activity in Boron Neutron Capture Therapy.","authors":"Shiori Hirase, Yurina Araki, Yoshihide Hattori, Ayako Aoki, Daisuke Fujiwara, Masataka Michigami, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki, Mitsunori Kirihata, Ikuhiko Nakase","doi":"10.1248/bpb.b24-00651","DOIUrl":"10.1248/bpb.b24-00651","url":null,"abstract":"Boron neutron capture therapy (BNCT), a type of nuclear capture-based radiotherapy, has received extensive attention because of its strong anticancer effects, especially in head and neck cancers. This therapy was approved for clinical use in 2020 in Japan. This study demonstrated a technique that effectively uses the electrostatic interactions of negatively charged borane cage (polyhedral borane anion) of disodium mercaptoundecahydro-closo-dodecaborate (BSH) and positively charged cationic lipids or arginine-rich cell-penetrating peptides as carriers to enhance the efficiency of cellular uptake. Mixing of fluorescein isothiocyanate (FITC)-labeled BSH (FITC-BSH) with the cationic lipids led to increased cytosolic release and nuclear accumulation of FITC-BSH, resulting in superior cancer cell-killing activity following thermal neutron irradiation. This simple technique and our experimental results provide essential insights for the further development of BNCT.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"344-354"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RasGRP2 Attenuates TAGE Modification of eNOS in Vascular Endothelial Cells. RasGRP2减弱血管内皮细胞中eNOS的age修饰。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00730

Shouhei Miyazaki, Jun-Ichi Takino, Kentaro Nagamine, Masayoshi Takeuchi, Takamitsu Hori

{"title":"RasGRP2 Attenuates TAGE Modification of eNOS in Vascular Endothelial Cells.","authors":"Shouhei Miyazaki, Jun-Ichi Takino, Kentaro Nagamine, Masayoshi Takeuchi, Takamitsu Hori","doi":"10.1248/bpb.b24-00730","DOIUrl":"10.1248/bpb.b24-00730","url":null,"abstract":"Toxic advanced glycation end-products (TAGEs) are glyceraldehyde (GA)-derived AGEs with strong cytotoxic effects. TAGEs are also involved in lifestyle-related diseases. Notably, modification of TAGEs by GA causes protein dysfunction. As endothelial nitric oxide synthase (eNOS) is constitutively expressed in vascular endothelial cells and is a source of nitric oxide (NO), we focused on it as a TAGE modification-targeting protein. Our laboratory has reported that Ras guanyl nucleotide-releasing protein 2 (RasGRP2) activates Rap1 and R-Ras, among other small GTPases, and suppresses apoptosis and TAGE-induced vascular hyperpermeability in vascular endothelial cells. Therefore, in this study, we investigated the effects of RasGRP2 on cell death, TAGE formation, and TAGE modification of eNOS in vascular endothelial cells following GA treatment using RasGRP2-overexpressing (R) cells and mock (M) immortalized human umbilical vein endothelial cells. GA treatment decreases the viability of both cell types in a concentration-dependent manner. In M cells, GA treatment increased the formation of TAGEs and TAGE modification of eNOS in a concentration-dependent manner, but this increase was suppressed in R cells. Additionally, co-treatment with aminoguanidine, an inhibitor of AGEs formation, suppressed cell death and TAGE modification of eNOS induced by GA. These results indicate that GA induces cell death, the formation of TAGEs, and TAGE modification of eNOS in vascular endothelial cells. Additionally, RasGRP2 is a protective factor that suppresses TAGE formation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"262-266"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance. 5-羟色胺通过调节Th17/Treg平衡限制肺动脉高压进展。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00831

Junli Han, Lianghe Wang, Li Wang, Hua Lei

{"title":"5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance.","authors":"Junli Han, Lianghe Wang, Li Wang, Hua Lei","doi":"10.1248/bpb.b24-00831","DOIUrl":"https://doi.org/10.1248/bpb.b24-00831","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"555-562"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid Synthesis of Oversulfated Chondroitin Sulfate. 过硫酸软骨素的快速合成。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00117

Hiroshi Akiyama, Hiori Misu, Yume Tsuruyama, Sanami Isaka, Utano Makiyama, Mayumi Ikegami-Kawai, Natsuko Miki, Yukari Nakagawa, Hideki Tamura, Yusuke Iwasaki, Rie Ito

引用次数: 0

Adipose-Derived Mesenchymal Stromal/Stem Cells Reduce Inflammatory Responses and Partially Alleviate Skin Symptoms in Imiquimod-Induced Psoriasis-Like Dermatitis Model Mice. 脂肪来源的间充质基质/干细胞可减轻吡喹莫德诱导的银屑病样皮炎模型小鼠的炎症反应并部分缓解皮肤症状

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00060

Ryohei Ogino, Mayu Tokunaga, Kenji Hayashida, Takanori Taogoshi, Tomoharu Yokooji, Hiroaki Matsuo

{"title":"Adipose-Derived Mesenchymal Stromal/Stem Cells Reduce Inflammatory Responses and Partially Alleviate Skin Symptoms in Imiquimod-Induced Psoriasis-Like Dermatitis Model Mice.","authors":"Ryohei Ogino, Mayu Tokunaga, Kenji Hayashida, Takanori Taogoshi, Tomoharu Yokooji, Hiroaki Matsuo","doi":"10.1248/bpb.b25-00060","DOIUrl":"https://doi.org/10.1248/bpb.b25-00060","url":null,"abstract":"Transplantation of adipose-derived mesenchymal stromal/stem cells (ASCs) has successfully alleviated the severity of psoriasis. Although several therapeutic mechanisms of mesenchymal stromal/stem cells (MSCs) for psoriasis have been elucidated using the imiquimod (IMQ)-induced psoriasis-like dermatitis model, the effects of MSC transplantation on pathways other than the interleukin (IL)-23/T helper 17 (Th17) axis, including the IL-36 pathway, remain unclear. In this study, we aimed to investigate the efficacy of ASC transplantation for the IMQ-induced psoriasis-like dermatitis in male C57BL/6J mice, and to elucidate its effects on the IL-36 pathway as well as the IL23/Th17 axis. ASCs (2.0 × 106 cells) from mouse inguinal white adipose tissue were subcutaneously injected into the dorsal skin of mice. After the topical application of IMQ cream for 5 consecutive days, objective severity scores, cytokine gene expression levels, and neutrophil infiltration grade were determined to evaluate their efficacy. Anti-IL-23p19 antibody treatment was used for comparison. ASCs slightly ameliorated IMQ-induced epidermal thickening, although anti-IL-23p19 antibodies had no effect on any skin manifestations. Anti-IL-23p19 antibody and ASC suppressed the expressions of Il17a, Il17f, and Il22 mRNAs and neutrophil infiltration in IMQ-applied skin, but not the expression of Il1f6 and Il1f9. ASC also suppressed the expressions of Il23, Il6, Il1b, Tnfa, Lipocalin-2, and Cxcl5 mRNAs, which were not suppressed by anti-IL-23p19 antibody treatment. In conclusion, ASC transplantation suppressed activation of the IL-23/Th17 axis and neutrophil infiltration, and inhibited the activation of a broader range of inflammatory mediators except for IL-36 expression in IMQ-applied skin compared with anti-IL-23p19 antibody treatment.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"812-824"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effective Location of the Plantar Surface of the Hind Paw for the Evaluation of Mechanical Hyperalgesia Using von Frey Filaments in Mice Treated with Paclitaxel. 紫杉醇治疗小鼠后足跖面有效定位评价冯氏纤维对机械性痛觉过敏的影响。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00242

Tsugunobu Andoh, Hirari Takahashi

{"title":"Effective Location of the Plantar Surface of the Hind Paw for the Evaluation of Mechanical Hyperalgesia Using von Frey Filaments in Mice Treated with Paclitaxel.","authors":"Tsugunobu Andoh, Hirari Takahashi","doi":"10.1248/bpb.b25-00242","DOIUrl":"https://doi.org/10.1248/bpb.b25-00242","url":null,"abstract":"Mechanical hyperalgesia is commonly evaluated using von Frey filaments (vFFs) in the rodent hind paw plantar. However, it is difficult to select the plantar location to stimulate with the vFFs. In the present study, we investigated the effective location of the plantar surface for the evaluation of mechanical hyperalgesia using vFFs in mice treated with paclitaxel (PTX). PTX or vehicle was injected intraperitoneally once daily, 4 times every other day. On Day 14, mechanical hyperalgesia was evaluated using vFFs. The evaluation was performed by stimulation with vFFs on the skin directly under the 3rd and 4th paw pads (base of the index and middle fingers) from closest to the heel on the thumb side, in the central skin surrounded by the pads, and in the plantar skin one-third of the way down from the heel toward the toe. In comparison to vehicle-treated mice, mechanical hyperalgesia was significantly observed in the skin directly under the 3rd and 4th paw pads counted from closest to the heel, and in the plantar skin one-third of the way down from the heel toward the toe. However, this was not significant in the central skin surrounded by the pads. Interestingly, in vehicle-treated mice, the paw withdrawal threshold varied for each location evaluated. In contrast, in PTX-treated mice, the thresholds were similar across all evaluated locations. These results suggest that the selection of the location on the plantar surface to be stimulated is important for pain evaluation using vFFs.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"835-837"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteasome Inhibition Induces IRF1 Downstream Molecules Independently of JAK Activity in Cancers. 蛋白酶体抑制在癌症中诱导IRF1下游分子独立于JAK活性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00006

Kaito Takahashi, Atsushi Takahashi, Nana Takahashi, Yue Zhou, Hiroaki Sakurai, Satoru Yokoyama

{"title":"Proteasome Inhibition Induces IRF1 Downstream Molecules Independently of JAK Activity in Cancers.","authors":"Kaito Takahashi, Atsushi Takahashi, Nana Takahashi, Yue Zhou, Hiroaki Sakurai, Satoru Yokoyama","doi":"10.1248/bpb.b25-00006","DOIUrl":"https://doi.org/10.1248/bpb.b25-00006","url":null,"abstract":"Loss-of-function mutations in Janus kinase 1/2 (JAK1/2) cause low tumor immunogenicity through defects in the induction of the transcription factor interferon regulatory factor 1 (IRF1), resulting in non-responsiveness to cancer immunotherapy reagents. Therefore, the discovery of reagents that increase IRF1 expression independent of JAK activity is clinically important for the success of cancer immunotherapy reagents. We herein demonstrated that proteasome inhibitors activated IRF1 downstream pathways in a JAK-independent manner in various cancer types. Proteasome inhibitors increased IRF1 expression by inhibiting the degradation of IRF1 in melanoma. Furthermore, proteasome inhibitors induced the expression of the IRF1 downstream molecules, programmed death-ligand 1 (PD-L1), PD-L2, and human leukocyte antigen class I molecules. The induction of IRF1 expression by proteasome inhibitors was also detected in cancer types other than melanoma. Moreover, we showed that the induction of IRF1 expression was independent of JAK activity by genetic or chemical inhibition of JAK. Therefore, proteasome inhibitors may serve as adjuvants that potentiate the efficacy of cancer immunotherapy reagents by enhancing cancer immunogenicity.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"864-871"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0