Biological & pharmaceutical bulletin最新文献_第5页

Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval. 基于美国批准与本土批准间隔的日韩肿瘤药物滞后性比较

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00555

Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa

{"title":"Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval.","authors":"Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa","doi":"10.1248/bpb.b24-00555","DOIUrl":"10.1248/bpb.b24-00555","url":null,"abstract":"Drug lag is a serious issue for patients with life-threatening diseases such as cancer. Japan and Korea have been facing a large drug lag, despite having a large market and a good clinical trial environment. We analyzed drug lags for anticancer drugs between these countries, using the information on 82 anticancer drugs approved in the United States between 2017 and 2022. The national health insurance coverage status was also investigated. The approval lag, defined as the number of days from the date of approval in the United States to the date of approval in the country of interest, was used as the indicator of drug lag and was calculated for each drug. The median for all drugs was estimated using the Kaplan-Meier method, with the lag for locally unapproved drugs treated as censored data. The median approval lag in Japan and Korea for all drugs, including locally unapproved drugs, were 1547 d (4.2 years) and 1000 d (2.7 years), respectively. The approval lags for the approved drugs were 216 and 655 d in Japan and Korea, respectively. All drugs approved in Japan were covered by national health insurance whereas many drugs recently approved in Korea were not yet covered. The overall drug lag in Japan was greater than that in Korea due to the high number of unapproved drugs in Japan. In Korea, more drugs have been approved; however, it generally takes longer for them to become widely available to the public.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"11-16"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977468","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

Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations. 维生素D受体rs2228570基因多态性与哮喘严重程度和恶化有关

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00684

Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh

{"title":"Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations.","authors":"Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh","doi":"10.1248/bpb.b24-00684","DOIUrl":"10.1248/bpb.b24-00684","url":null,"abstract":"Vitamin D plays a crucial role in immune system function. Several studies have indicated that genetic variations in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP, encoded by GC gene) increase the risk of developing asthma. However, the effect of these variations on the prognosis and clinical outcomes of asthma remains unclear. This study, involving 152 adult patients with asthma, aimed to assess the influence of VDR and GC polymorphisms on asthma severity and its exacerbation. Gene polymorphisms previously associated with asthma risk were analyzed, and VDR mRNA expression levels were evaluated in peripheral blood mononuclear cells. The AA genotype of the VDR rs2228570 polymorphism was associated with an elevated risk of severe asthma compared to the AG/GG genotype (odds ratio, 3.20; 95% confidence interval [CI], 1.24-8.28). Furthermore, patients with the rs2228570 AA genotype showed an elevated risk of exacerbation during the 1-year follow-up period (hazard ratio, 4.01; 95% CI, 1.75-9.15). VDR mRNA expression was significantly reduced in patients with the AA genotype. Furthermore, the mRNA expression levels of GLCCI1, HDAC2, NR3C1, and NFE2L2, which are associated with steroid response, were reduced in patients with the AA genotype. Our findings indicate that patients with the AA genotype of VDR rs2228570 are more likely to experience severe asthma and exacerbations. This polymorphism has the potential to reduce vitamin D efficacy by altering VDR function and expression, potentially resulting in increased inflammation and reduced steroid responsiveness in patients with asthma.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"86-92"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078582","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

Development of Research Foundation for Comprehensive Articulation of Drug Effects. 药物效应综合表达研究基金的建立。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00509

Tadahaya Mizuno

{"title":"Development of Research Foundation for Comprehensive Articulation of Drug Effects.","authors":"Tadahaya Mizuno","doi":"10.1248/bpb.b24-00509","DOIUrl":"https://doi.org/10.1248/bpb.b24-00509","url":null,"abstract":"As unexpected adverse events and successful drug repositioning have shown, drug effects are complex and include aspects not recognized by developers. How can we understand these unrecognized drug effects? Drug effects can be numerized by encompassing biological responses to drugs. For instance, the transcriptome data of cultured cells and toxicopathological images of mice treated with a compound represent the effects of the compound in vitro and in vivo, respectively. As a next step, we focused on pattern recognition, a data science framework to extract essentially important low-dimensional latent variables from high-dimensional observed data such as latent variable models. Latent variables are low-dimensional, allowing us to visualize drug effects in an easily recognizable form, such as a radar chart. This bird's-eye view of drug effects enables us to compare them with existing knowledge, potentially articulating the effects of drugs as the known knowns and known unknowns. We believe that the three-step strategy of numerization, visualization, and articulation will allow us to understand drug effects comprehensively, and we are currently verifying this approach. In this review, we will introduce these candidate studies and hope to share our interest in \"pattern recognition of biological responses,\" the pillar of our group.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930619","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

Role of Companion Diagnostics in Advancing Patient-Centered Anticancer Drug Treatment. 伴随诊断在推进以患者为中心的抗癌药物治疗中的作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00240

Nanaki Shingyo, Manaka Taguchi, Mizuki Matsubara, Michitaka Shichijo, Naoki Matsumaru, Katsura Tsukamoto

{"title":"Role of Companion Diagnostics in Advancing Patient-Centered Anticancer Drug Treatment.","authors":"Nanaki Shingyo, Manaka Taguchi, Mizuki Matsubara, Michitaka Shichijo, Naoki Matsumaru, Katsura Tsukamoto","doi":"10.1248/bpb.b25-00240","DOIUrl":"https://doi.org/10.1248/bpb.b25-00240","url":null,"abstract":"Cancer is an age-related disease that affects one in two Japanese individuals, placing a significant burden on both patients and caregivers due to its clinical characteristics, high treatment costs, and associated adverse events (AEs). Consequently, cancer treatment remains a major public concern. In recent years, patient-centered medical care has gained increasing attention and is strongly desired in cancer treatment. Companion diagnostics (CDx) are expected to facilitate personalized treatment; however, their current status remains unclear. In this study, we evaluated the role of CDx in anticancer drug treatment based on data available at the time of drug approval. Our analysis revealed that the benefit-risk ratio, defined as the objective response rate of an anticancer drug divided by the incidence of severe AEs, was significantly higher for anticancer drugs requiring CDx (wCDx) in Japanese patients (1.54-fold, p < 0.0135) than for anticancer drugs not requiring CDx. Although the objective response rate did not differ between the 2 groups, the incidence of severe AEs was lower in the wCDx group. These findings suggest that CDx helps identify patients who are better suited for specific anticancer treatments and/or that active pharmaceutical ingredients in wCDx therapies carry a lower risk of severe AEs. To further promote patient-centered medical care, the active development of CDx alongside new anticancer drugs should be encouraged, despite the higher development hurdles, through regulatory support, particularly since drug pricing does not differ between the 2 groups.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 8","pages":"1255-1259"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941541","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

Anti-osteoporosis Activity of Sodium Glucuronate in Preosteo-blast MC3T3-E1 Cells and an Ovariectomized Rat Model. 葡萄糖酸钠对成骨前细胞MC3T3-E1和去卵巢大鼠模型的抗骨质疏松活性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00885

Anqi Wang, Biyao Liu, Qingkai Zeng, Xiuhua Zhang, Yihong Xu, Xiao Zhang, Lei Chen, Juzheng Sheng, Huarong Shao, Fei Liu

{"title":"Anti-osteoporosis Activity of Sodium Glucuronate in Preosteo-blast MC3T3-E1 Cells and an Ovariectomized Rat Model.","authors":"Anqi Wang, Biyao Liu, Qingkai Zeng, Xiuhua Zhang, Yihong Xu, Xiao Zhang, Lei Chen, Juzheng Sheng, Huarong Shao, Fei Liu","doi":"10.1248/bpb.b24-00885","DOIUrl":"https://doi.org/10.1248/bpb.b24-00885","url":null,"abstract":"The purpose of this study was to explore the potential therapeutic effect of sodium glucuronate (SG) on osteoporosis (OP). To achieve this aim, the optimal concentration of SG for stimulating MC3T3-E1 osteoblast cells derived from the calvaria of neonatal mice was determined using cell counting kit-8 and alkaline phosphatase (ALP) activity assays. Osteogenic markers were analyzed by qRT-PCR and Western blotting. The histopathological morphology of the tibial tissues was performed using hematoxylin and eosin staining. The levels of bone turnover markers (BTMs) were assessed using enzyme-linked immunosorbent assay (ELISA). SG treatment was found to effectively promote osteoblastic differentiation and mineralization in MC3T3-E1 cells, evidenced by enhanced ALP activity, increased calcium deposition, and upregulated expression of key osteogenic markers including runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN). Moreover, in ovariectomized rats, a model of postmenopausal OP, SG treatment significantly promoted bone formation, regulated the levels of BTMs, and augmented bone mineral density. Consistently, SG upregulated the expression of osteogenic genes (RUNX2, OCN, and OPN) in bone tissue, further supporting its osteogenic potential. Collectively, these findings suggest that SG possesses the ability to stimulate bone formation and may hold promise as a potential agent for the management of OP.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"895-907"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504815","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

FLG249 Exhibits FXR Antagonist Activity by Inducing Dissociation of Both Corepressors and Coactivators from FXR. FLG249通过诱导辅抑制因子和辅激活因子从FXR中解离而表现出FXR拮抗剂活性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00095

Yusuke Iguchi, Yukiko Yamashita, Keigo Gohda, Ko Fujimori, Yukihiro Sera, Tsuneo Imanaka, Masafumi Yamaguchi, Mizuho Une, Naoki Teno

{"title":"FLG249 Exhibits FXR Antagonist Activity by Inducing Dissociation of Both Corepressors and Coactivators from FXR.","authors":"Yusuke Iguchi, Yukiko Yamashita, Keigo Gohda, Ko Fujimori, Yukihiro Sera, Tsuneo Imanaka, Masafumi Yamaguchi, Mizuho Une, Naoki Teno","doi":"10.1248/bpb.b25-00095","DOIUrl":"https://doi.org/10.1248/bpb.b25-00095","url":null,"abstract":"The farnesoid X receptor (FXR), a nuclear receptor activated by endogenous bile acids, regulates not only bile acid synthesis but also lipid and carbohydrate metabolism. Therefore, FXR ligands, including FXR antagonists, show potential as therapeutic agents for various metabolic diseases. However, the mechanism by which FXR antagonists influence FXR activity is unclear. We previously synthesized an FXR antagonist, FLG249, which reduced the expression of several FXR target genes in the mouse ileum when orally administered and improved lipid metabolism in the liver and ileum of high-fat diet-induced obese mice. In the present study, we aimed to characterize the mechanism by which FLG249 inhibits the interaction of FXR with its coactivators and corepressors. The LanthaScreenTM time-resolved fluorescence energy transfer assay and two-hybrid assay were used to evaluate the effect of FLG249 on FXR. We found that, upon binding, FLG249 reduced the interaction of FXR with both coactivators and corepressors. This result suggests that the mechanism of FLG249 as a nuclear receptor modulator is distinct from that of previously reported neutral antagonists and inverse agonists of nuclear receptors.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1016-1021"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648427","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

Pentadecyl, an Active Component of Microalgae, Ameliorates Endoplasmic Reticulum Stress and Blue Light-Induced Cell Death in Mouse Retina-Derived 661W Cells. 微藻活性成分Pentadecyl改善小鼠视网膜源性661W细胞内质网应激和蓝光诱导的细胞死亡

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00889

Mayuna Obayashi, Wataru Otsu, Kanta Yamazaki, Shinsuke Nakamura, Hideaki Ishikawa, Yasuko Sakata, Makoto Tsuboi, Hideshi Tsusaki, Masamitsu Shimazawa

{"title":"Pentadecyl, an Active Component of Microalgae, Ameliorates Endoplasmic Reticulum Stress and Blue Light-Induced Cell Death in Mouse Retina-Derived 661W Cells.","authors":"Mayuna Obayashi, Wataru Otsu, Kanta Yamazaki, Shinsuke Nakamura, Hideaki Ishikawa, Yasuko Sakata, Makoto Tsuboi, Hideshi Tsusaki, Masamitsu Shimazawa","doi":"10.1248/bpb.b24-00889","DOIUrl":"https://doi.org/10.1248/bpb.b24-00889","url":null,"abstract":"Light stress is a risk factor leading to retinal diseases such as age-related macular degeneration. However, the mechanism underlying the stress response to light in the retina has yet to be elucidated. We have reported that exposure to blue light-emitting diode light induces excessive production of reactive oxygen species and activates the unfolded protein response, robustly increasing activating transcription factor 4 (ATF4) expression. These processes result in photoreceptor cell death. This study investigates the effects of Pentadecyl, a bioactive product obtained from Aurantiochytrium limacinum, on either chemical-induced or blue light-induced endoplasmic reticulum (ER) stress. Pentadecyl suppressed cell death induced by either thapsigargin or tunicamycin in a concentration-dependent manner. Pentadecyl also suppressed the expression of unfolded protein response target genes, including Atf4 and ER chaperones. Consistently, immunoblotting revealed that Pentadecyl suppressed the increased expression of ATF4 at the protein level. Pentadecyl also protected 661W cells from blue light-induced damage but did not protect against hydrogen peroxide (H2O2)-induced oxidative stress. These results indicated that Pentadecyl has a novel function that protects against ER stress induced by photodamage.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"791-800"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246249","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

Quercetin, a Natural Dietary Flavonoid, Emerges a Novel USP7 Inhibitor with Anti-colorectal Cancer Effects. 槲皮素，一种天然的膳食类黄酮，发现一种新的USP7抑制剂，具有抗结直肠癌的作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00435

Xue Li, Qiyan Li, Ying Huang, Heyang Zhou, Qianqing Yang, Lingmei Kong

{"title":"Quercetin, a Natural Dietary Flavonoid, Emerges a Novel USP7 Inhibitor with Anti-colorectal Cancer Effects.","authors":"Xue Li, Qiyan Li, Ying Huang, Heyang Zhou, Qianqing Yang, Lingmei Kong","doi":"10.1248/bpb.b25-00435","DOIUrl":"https://doi.org/10.1248/bpb.b25-00435","url":null,"abstract":"The human deubiquitinating enzyme ubiquitin-specific peptidase 7 (USP7) has emerged as a promising anti-tumor target, particularly in colorectal cancer, due to its regulation of the MDM2/p53 axis. Through a combination of ubiquitin C-terminal 7-amido-4-methylcoumarin hydrolysis assay and ubiquitin-propargylamide protease profiling, we identified the natural dietary flavonoid quercetin as a potent USP7 inhibitor in both cell-free and cellular contexts. Cellular thermal shift and surface plasmon resonance analyses demonstrated that quercetin is directly bound to USP7. Consistent with USP7 target engagement in cells, quercetin decreased MDM2 levels and subsequently increased the levels of p53. Moreover, quercetin also suppressed colorectal cancer cell proliferation by inducing G2/M cell cycle arrest and inhibiting cell migration. Collectively, our study identified quercetin as a novel and effective USP7 inhibitor with potent anti-colorectal cancer activity, highlighting its therapeutic potential for targeting the USP7-MDM2-p53 axis and warranting further exploration as a promising therapeutic agent in colorectal cancer treatment.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 10","pages":"1485-1492"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249527","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

Placental Extract Inhibits Melanogenesis by Inducing the Proteasome-Dependent Degradation of Tyrosinase and TRP-1. 胎盘提取物通过诱导酪氨酸酶和TRP-1的蛋白酶体依赖性降解来抑制黑色素生成。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00101

Mie Moriya

{"title":"Placental Extract Inhibits Melanogenesis by Inducing the Proteasome-Dependent Degradation of Tyrosinase and TRP-1.","authors":"Mie Moriya","doi":"10.1248/bpb.b25-00101","DOIUrl":"https://doi.org/10.1248/bpb.b25-00101","url":null,"abstract":"Placental extract (PE) is employed as a skin-whitening agent in Japan, where this material is used in cosmetics and dietary supplements. However, the mechanism of PE's anti-melanogenic activity remains poorly understood. The goal of the present study was to elucidate the mechanism of PE's inhibitory effect on melanogenesis in B16 murine melanoma cells. Specifically, the activity of equine PE (EPE) against tyrosinase and melanogenic proteins was evaluated. The effects of EPE on tyrosinase activity and melanin content were assessed spectrophotometrically. This analysis showed that EPE inhibits melanogenesis in melanoma cells in a dose-dependent manner without affecting cell proliferation. EPE did not directly inhibit the enzymatic activity of tyrosinase. Western blot analysis demonstrated that EPE exposure also led to decreases in the protein levels of tyrosinase and tyrosinase-related protein 1 (TRP-1) in melanoma cells, without affecting the levels of the mRNAs encoding these proteins. This analysis further demonstrated that the EPE-induced depletion of tyrosinase and TRP-1 resulted from the induction, by EPE, of proteasome-mediated proteolytic degradation. Notably, the EPE-induced depletion of tyrosinase and TRP-1 was prevented by joint exposure to EPE and the proteasome inhibitor MG132. Similar experiments showed that the exposure of melanoma cells to MG132 abrogates the inhibition of melanogenesis by EPE. Immunoprecipitation analysis further revealed that EPE induces the ubiquitination of tyrosinase and TRP-1. Taken together, these results suggested that EPE induces proteasomal degradation of tyrosinase and TRP-1 by enhancing the ubiquitination of these targets, leading to the depletion of these proteins and the inhibition of melanogenesis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 10","pages":"1472-1484"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249546","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

Extracellular CD30 Regulates Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line. 细胞外CD30调控Brentuximab vedotin诱导的成人t细胞白血病细胞系细胞死亡

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00508

Keisuke Sato, Tomohiro Kozako, Akira Nakano, Naho Kato, Kentaro Ogata, Hidetoshi Kamimura, Hidenori Sasaki, Yasushi Takamatsu, Shigeki Takemoto, Shin-Ichiro Honda

{"title":"Extracellular CD30 Regulates Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line.","authors":"Keisuke Sato, Tomohiro Kozako, Akira Nakano, Naho Kato, Kentaro Ogata, Hidetoshi Kamimura, Hidenori Sasaki, Yasushi Takamatsu, Shigeki Takemoto, Shin-Ichiro Honda","doi":"10.1248/bpb.b24-00508","DOIUrl":"https://doi.org/10.1248/bpb.b24-00508","url":null,"abstract":"Adult T-cell leukemia/lymphoma (ATL) is a malignant tumor of mature T lymphocytes induced by human T-cell leukemia virus 1, and it has a poor prognosis. Brentuximab vedotin (BV) is included in the treatment of CD30-positive ATL, but there are no predictive biomarkers for the treatment effects of BV. Serum soluble CD30 (sCD30) concentrations are increased in aggressive ATL at the time of diagnosis, but the effect of extracellular CD30 on BV-induced cell death in ATL is unknown. Similarly, a disintegrin and metalloproteinase 10 (ADAM10) and ADAM17 possess CD30 sheddase activity in anaplastic large cell lymphoma, but this activity is unclear in ATL. In this study, we showed that sCD30 concentrations were associated with BV activity in ATL-associated cell lines. Extracellular vesicles, such as exosomes containing CD30, also inhibited BV activity. Furthermore, knockdown of ADAM10/17 significantly reduced sCD30 concentrations and increased BV-induced cell death. These results suggest that ADAM10 and ADAM17 are involved in sCD30 production in ATL. Furthermore, endogenous extracellular CD30, such as sCD30 and CD30-positive extracellular vesicles shed by ADAM10/17, may be involved in BV-induced cell death. Taken together, our findings suggest that extracellular CD30 concentrations, including CD30 on extracellular vesicles, are a useful biomarker for BV therapy in ATL.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 9","pages":"1375-1383"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074391","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