The Tokushima journal of experimental medicine最新文献_第2页

Altered glycosylation in pancreatic cancer and beyond. 胰腺癌及其他疾病中的糖基化改变

The Tokushima journal of experimental medicine Pub Date : 2022-06-06 Epub Date: 2022-05-06 DOI: 10.1084/jem.20211505

Jan C Lumibao, Jacob R Tremblay, Jasper Hsu, Dannielle D Engle

{"title":"Altered glycosylation in pancreatic cancer and beyond.","authors":"Jan C Lumibao, Jacob R Tremblay, Jasper Hsu, Dannielle D Engle","doi":"10.1084/jem.20211505","DOIUrl":"10.1084/jem.20211505","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers and is projected to soon be the second leading cause of cancer death. Median survival of PDA patients is 6-10 mo, with the majority of diagnoses occurring at later, metastatic stages that are refractory to treatment and accompanied by worsening prognoses. Glycosylation is one of the most common types of post-translational modifications. The complex landscape of glycosylation produces an extensive repertoire of glycan moieties, glycoproteins, and glycolipids, thus adding a dynamic and tunable level of intra- and intercellular signaling regulation. Aberrant glycosylation is a feature of cancer progression and influences a broad range of signaling pathways to promote disease onset and progression. However, despite being so common, the functional consequences of altered glycosylation and their potential as therapeutic targets remain poorly understood and vastly understudied in the context of PDA. In this review, the functionality of glycans as they contribute to hallmarks of PDA are highlighted as active regulators of disease onset, tumor progression, metastatic capability, therapeutic resistance, and remodeling of the tumor immune microenvironment. A deeper understanding of the functional consequences of altered glycosylation will facilitate future hypothesis-driven studies and identify novel therapeutic strategies in PDA.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86207784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer. 抑制FGF受体可阻断CCDC6-RET重排甲状腺癌对RET抑制的适应性抵抗。

The Tokushima journal of experimental medicine Pub Date : 2022-06-06 Epub Date: 2022-05-05 DOI: 10.1084/jem.20210390

Renuka Raman, Jacques A Villefranc, Timothy M Ullmann, Jessica Thiesmeyer, Viviana Anelli, Jun Yao, James R Hurley, Chantal Pauli, Rohan Bareja, Kenneth Wha Eng, Princesca Dorsaint, David C Wilkes, Shaham Beg, Sarah Kudman, Reid Shaw, Michael Churchill, Adnan Ahmed, Laurel Keefer, Ian Misner, Donna Nichol, Naveen Gumpeni, Theresa Scognamiglio, Mark A Rubin, Carla Grandori, James Patrick Solomon, Wei Song, Juan Miguel Mosquera, Noah Dephoure, Andrea Sboner, Olivier Elemento, Yariv Houvras

{"title":"Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.","authors":"Renuka Raman, Jacques A Villefranc, Timothy M Ullmann, Jessica Thiesmeyer, Viviana Anelli, Jun Yao, James R Hurley, Chantal Pauli, Rohan Bareja, Kenneth Wha Eng, Princesca Dorsaint, David C Wilkes, Shaham Beg, Sarah Kudman, Reid Shaw, Michael Churchill, Adnan Ahmed, Laurel Keefer, Ian Misner, Donna Nichol, Naveen Gumpeni, Theresa Scognamiglio, Mark A Rubin, Carla Grandori, James Patrick Solomon, Wei Song, Juan Miguel Mosquera, Noah Dephoure, Andrea Sboner, Olivier Elemento, Yariv Houvras","doi":"10.1084/jem.20210390","DOIUrl":"10.1084/jem.20210390","url":null,"abstract":"Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer. Using a combination of drug screening and proteomic and biochemical profiling, we identified an adaptive resistance to RET inhibitors that reactivates ERK signaling within hours of drug exposure. We found that activation of FGFR signaling is a mechanism of adaptive resistance to RET inhibitors that activates ERK signaling. Combined inhibition of FGFR and RET prevented the development of adaptive resistance to RET inhibitors, reduced cell viability, and decreased tumor growth in cellular and animal models of CCDC6-RET-rearranged thyroid cancer.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75805630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Null IFNAR1 and IFNAR2 alleles are surprisingly common in the Pacific and Arctic. 在太平洋和北极地区，IFNAR1 和 IFNAR2 等位基因无效的现象非常普遍。

The Tokushima journal of experimental medicine Pub Date : 2022-06-06 Epub Date: 2022-04-29 DOI: 10.1084/jem.20220491

Isabelle Meyts

引用次数: 0

Hypoxia induces adrenomedullin from lung epithelia, stimulating ILC2 inflammation and immunity. 缺氧诱导肺上皮细胞分泌肾上腺髓质素，刺激 ILC2 发炎和免疫。

The Tokushima journal of experimental medicine Pub Date : 2022-06-06 Epub Date: 2022-05-09 DOI: 10.1084/jem.20211985

Jihye Han, Qingqing Wan, Goo-Young Seo, Kenneth Kim, Sarah El Baghdady, Jee H Lee, Mitchell Kronenberg, Yun-Cai Liu

{"title":"Hypoxia induces adrenomedullin from lung epithelia, stimulating ILC2 inflammation and immunity.","authors":"Jihye Han, Qingqing Wan, Goo-Young Seo, Kenneth Kim, Sarah El Baghdady, Jee H Lee, Mitchell Kronenberg, Yun-Cai Liu","doi":"10.1084/jem.20211985","DOIUrl":"10.1084/jem.20211985","url":null,"abstract":"Hypoxia contributes to airway inflammation and remodeling in several lung diseases; however, exactly how hypoxic pulmonary epithelium regulates allergic inflammation remains to be fully characterized. Here, we report that conditional deletion of the E3 ubiquitin ligase VHL in lung epithelial cells resulted in exacerbated type 2 responses accompanied by selective increase of group 2 innate lymphoid cells (ILC2s) at steady state and following inflammation or helminth infection. Ablation of expression of the hypoxia-inducible factor 2α (HIF2α) significantly reversed VHL-mediated ILC2 activation. VHL deficiency in lung epithelial cells caused increased expression of the peptide hormone adrenomedullin (ADM), and our data suggest that HIF2α controls Adm expression. ADM directly promoted ILC2 activation both in vitro and in vivo. Our findings indicate that the hypoxic response mediated by the VHL-HIF2α axis is critical for control of pulmonary type 2 responses by increasing ADM expression in lung epithelia, causing ILC2 activation.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84546841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD4+ T helper 2 cells suppress breast cancer by inducing terminal differentiation CD4+ T辅助2细胞通过诱导终末分化抑制乳腺癌

The Tokushima journal of experimental medicine Pub Date : 2022-06-03 DOI: 10.1084/jem.20201963

M. Boieri, A. Malishkevich, R. Guennoun, E. Marchese, Sanne Kroon, Kathryn E Trerice, Mary E. Awad, Jong Ho Park, Sowmya Iyer, J. Kreuzer, W. Haas, M. Rivera, S. Demehri

引用次数: 15

Dietary intervention preserves β cell function in mice through CTCF-mediated transcriptional reprogramming 饮食干预通过ctcf介导的转录重编程保持小鼠β细胞功能

The Tokushima journal of experimental medicine Pub Date : 2022-06-02 DOI: 10.1084/jem.20211779

Ruo-Ran Wang, Xinyuan Qiu, Ran Pan, Hongxing Fu, Ziyin Zhang, Qintao Wang, Haide Chen, Qing-Qian Wu, Xiaowen Pan, Yanping Zhou, Pengfei Shan, Shusen Wang, Guoji Guo, Min Zheng, Lingyun Zhu, Z. Meng

引用次数: 12

Lysophosphatidylserines derived from microbiota in Crohn’s disease elicit pathological Th1 response 来自克罗恩病微生物群的溶血磷脂酰丝氨酸引起病理性Th1反应

The Tokushima journal of experimental medicine Pub Date : 2022-05-24 DOI: 10.1084/jem.20211291

Yuriko Otake-Kasamoto, H. Kayama, T. Kishikawa, S. Shinzaki, T. Tashiro, Takahiro Amano, M. Tani, T. Yoshihara, Bo Li, Haruka Tani, Li Liu, Akio Hayashi, D. Okuzaki, D. Motooka, S. Nakamura, Y. Okada, H. Iijima, K. Takeda, T. Takehara

引用次数: 8

Realigning the LIGHT signaling network to control dysregulated inflammation 重新调整光信号网络以控制失调的炎症

The Tokushima journal of experimental medicine Pub Date : 2022-05-23 DOI: 10.1084/jem.20220236

C. Ware, M. Croft, G. Neil

引用次数: 10

SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly SARS-CoV-2刺突蛋白通过抑制免疫突触组装抑制ctl介导的杀伤

The Tokushima journal of experimental medicine Pub Date : 2022-05-20 DOI: 10.1101/2022.05.20.492764

A. Onnis, Emanuele Andreano, Chiara Cassioli, Elisa Pantano, Valentina Abbiento, G. Marotta, R. Rappuoli, C. Baldari

{"title":"SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly","authors":"A. Onnis, Emanuele Andreano, Chiara Cassioli, Elisa Pantano, Valentina Abbiento, G. Marotta, R. Rappuoli, C. Baldari","doi":"10.1101/2022.05.20.492764","DOIUrl":"https://doi.org/10.1101/2022.05.20.492764","url":null,"abstract":"CTL-mediated killing of virally infected or malignant cells is orchestrated at a specialized intercellular junction, the immune synapse (IS). We hypothesized that SARS-CoV-2 may target IS assembly in CTLs to escape killing. We show that primary human CD8+ T cells strongly upregulate the expression of ACE2, the Spike protein receptor, during differentiation to CTLs. CTL pre-incubation with the Wuhan or Omicron Spike variants inhibits IS assembly and function, as shown by defective synaptic accumulation of TCRs and tyrosine phosphoproteins as well as defective centrosome and lytic granule polarisation to the IS, resulting in impaired target cell killing. These defects were reversed by anti-Spike antibodies that interfere with ACE2 binding and were reproduced by ACE2 engagement with Angiotensin-II or an anti-ACE2 antibody, but not by the ACE2 product Ang (1-7). These results highlight a new strategy of immune evasion by SARS-CoV-2 based on the Spike-dependent, ACE2-mediated targeting of the lytic IS to prevent the elimination of infected cells. Summary statement We report a new mechanism of immune evasion by SARS-CoV-2 based on direct disabling CTLs to form immune synapses through Spike protein binding to ACE2. This mechanism could contribute to the failure of the immune system to control SARS-CoV-2 infection.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89612763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Interleukin-4 receptor signaling modulates neuronal network activity 白细胞介素-4受体信号传导调节神经网络活动

The Tokushima journal of experimental medicine Pub Date : 2022-05-19 DOI: 10.1084/jem.20211887

Nicholas Hanuscheck, Carine Thalman, M. Domingues, Samantha Schmaul, M. Muthuraman, Florian Hetsch, Manuela Ecker, Heiko Endle, Mohammadsaleh Oshaghi, G. Martino, T. Kuhlmann, K. Bozek, Tim van Beers, S. Bittner, Jakob von Engelhardt, J. Vogt, C. Vogelaar, F. Zipp

引用次数: 7