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JOURNAL ARTICLE
Marta B Fernandes, A Margarida Gomes, Mariana L Oliveira, Joana Caldas, Paulo Lúcio, Rathana Kim, Aurélie Caye-Eude, Filomena Pereira, Aida B De Sousa, Alessia De Stefano, Matilde Y Follo, Maria V Soares, João F Lacerda, Joana Desterro, Hélène Cavé, Emmanuelle Clappier, Ximo Duarte, Patrícia Ribeiro, João T Barata
Not available.
April 24, 2024: Haematologica
#2
JOURNAL ARTICLE
Phimmada Hatthakarnkul, Kathryn Pennel, Peter Alexander, Hester van Wyk, Antonia Roseweir, Jitwadee Inthagard, Jennifer Hay, Ditte Andersen, Noori Maka, James Park, Campbell Roxburgh, Chanitra Thuwajit, Donald McMillan, Joanne Edwards
Colorectal cancer (CRC) is a heterogenous malignancy and research is focused on identifying novel ways to subtype patients. In this study, a novel classification system, tumour microenvironment score (TMS), was devised based on Klintrup-Mäkinen grade (KMG), tumour stroma percentage (TSP), and tumour budding. TMS was performed using a haematoxylin and eosin (H&E)-stained section from retrospective CRC discovery and validation cohorts (n = 1,030, n = 787). TMS0 patients had high KMG, TMS1 were low for KMG, TSP, and budding, TMS2 were high for budding, or TSP and TMS3 were high for TSP and budding...
May 2024: Journal of Pathology. Clinical Research
#3
JOURNAL ARTICLE
Xiuli Xu, Zicong Huang, Chenhao Ding, Shiyu Deng, Jiawang Ou, Zihong Cai, Yang Zhou, Haimei Liang, Junjie Chen, ZhiXiang Wang, Xiaoli Liu, Li Xuan, Qifa Liu, Zhongxin Zheng, Zhen Li, Hongsheng Zhou
The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis...
April 19, 2024: British Journal of Haematology
#4
JOURNAL ARTICLE
Jihyun Song, Lucie Lanikova, Soo Jin Kim, Nicolas Papadopoulos, Jessica Meznarich, Stefan N Constantinescu, Brynn Parsegov, Jaroslav F Prchal, Josef T Prchal
Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2V617F or several others in exon 12. A 38-year-old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2V617F and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2R715T in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2R715T mutation...
April 17, 2024: American Journal of Hematology
#5
JOURNAL ARTICLE
Sohini Roy, Geetha Shanmugam, Sudeshna Rakshit, R Pradeep, Melvin George, Koustav Sarkar
Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India's traditional medical system, Ayurveda, where it is recognized as a "medhya rasayana"-a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis...
April 15, 2024: Medical Oncology
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JOURNAL ARTICLE
Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W Zimmerman, Thomas Eder, Diaaeldin I Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Daniel Pölöske, Emina Hubanic, Dennis Jungherz, Tony Andreas Müller, Myint Myat Khine Aung, Anna Orlova, Ha Thi Thanh Pham, Kerstin Zimmel, Thomas Krausgruber, Christoph Bock, Mathias Müller, Maik Dahlhoff, Auke Boersma, Thomas Rülicke, Roman Fleck, Elvin Dominic de Araujo, Patrick Thomas Gunning, Tero Aittokallio, Satu Mustjoki, Takaomi Sanda, Sylvia Hartmann, Florian Grebien, Gregor Hoermann, Torsten Haferlach, Philipp Bernhard Staber, Heidi Anne Neubauer, Alfred Thomas Look, Marco Herling, Richard Moriggl
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR...
April 15, 2024: Journal of Clinical Investigation
#7
REVIEW
Weiyuan Wang, Melanie Cristina Lopez McDonald, Rajashree Hariprasad, Tiara Hamilton, David A Frank
Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases...
March 31, 2024: Cancers
#8
REVIEW
Fauzia Ullah, Mariam Markouli, Mark Orland, Olisaemeka Ogbue, Danai Dima, Najiullah Omar, Moaath K Mustafa Ali
Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disorder characterized by persistent clonal expansion of mature T- or natural killer cells in the blood via chronic antigenic stimulation. LGL leukemia is associated with specific immunophenotypic and molecular features, particularly STAT3 and STAT5 mutations and activation of the JAK-STAT3 , Fas/Fas-L and NF-κB signaling pathways. Disease-related deaths are mainly due to recurrent infections linked to severe neutropenia. The current treatment is based on immunosuppressive therapies, which frequently produce unsatisfactory long-term responses, and for this reason, personalized approaches and targeted therapies are needed...
March 27, 2024: Cancers
#9
JOURNAL ARTICLE
Leona Dold, Sandra Kalthoff, Leonie Frank, Taotao Zhou, Pia Esser, Philipp Lutz, Christian P Strassburg, Ulrich Spengler, Bettina Langhans
INTRODUCTION: Regulatory CD4+ T cells (Tregs) are pivotal for inhibition of autoimmunity. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology where contribution of Tregs is still unclear. Activation of the JAK-STAT pathway critically modifies functions of Tregs. In PSC, we studied activation of STAT proteins and Treg functions in response to cytokines. METHODS: In 51 patients with PSC, 10 disease controls (chronic replicative hepatitis C), and 36 healthy controls we analyzed frequencies of Foxp3+ CD25+ CD127low CD4+ Tregs, their expression of ectonucleotidase CD39, and cytokine-induced phosphorylation of STAT1, 3, 5, and 6 using phospho-flow cytometry...
April 2024: Immunity, Inflammation and Disease
#10
JOURNAL ARTICLE
Xiaofang Xiong, Zheng Yan, Long Yan, Xuexue Yang, Dongsheng Li, Guizhen Lin
T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE-/- ) mice with a high-fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low-density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT-PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay...
May 2024: Scandinavian Journal of Immunology
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JOURNAL ARTICLE
Paula Guerrero, Cristina Bono, María Sobén, Andrea Guiu, Quen J Cheng, M Luisa Gil, Alberto Yáñez
Inflammatory responses must be tightly coordinated with the activation of emergency myelopoiesis to produce potent myeloid cells that fight infection without causing excessive host damage. Here, we show that GM-CSF programs myeloid committed progenitors to produce trained macrophages (increased cytokine response), but programs the upstream non-committed LKS+ progenitors to produce tolerized macrophages (decreased cytokine response). In myeloid progenitors, GM-CSF strongly activates STAT5, ERK and Akt-mTOR signaling pathways, which are essential to establish a training program, whereas in LKS+ progenitors GM-CSF induces NF-κB translocation to the nucleus to establish a tolerization program...
April 11, 2024: Blood
#12
JOURNAL ARTICLE
Christo Tsilifis, Jarmila Stremenova Spegarova, Ross Good, Helen Griffin, Karin R Engelhardt, Sophie Graham, Stephen Hughes, Peter D Arkwright, Sophie Hambleton, Andrew R Gennery
Biallelic null or hypomorphic variants in JAK3 cause SCID and less frequently Omenn syndrome. We investigated homozygous hypomorphic JAK3 mutations in two patients, and expression and function of a novel JAK3R431P variant in Omenn syndrome. Immunophenotyping of PBMC from the patient with the novel JAK3R431P variant was undertaken, by flow cytometry and Phosflow after stimulation with IL-2, IL-7, and IL-15. JAK3 expression was investigated by Western blotting. We report two patients with homozygous hypomorphic JAK3 variants and clinical features of Omenn syndrome...
April 10, 2024: Journal of Clinical Immunology
#13
JOURNAL ARTICLE
María Del Mar Fernández-Arjona, Juan Antonio Navarro, Antonio Jesús López-Gambero, Marialuisa de Ceglia, Miguel Rodríguez, Leticia Rubio, Fernando Rodríguez de Fonseca, Vicente Barrios, Julie A Chowen, Jesús Argente, Patricia Rivera, Juan Suárez
BACKGROUND: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. METHODS: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed...
April 8, 2024: Biology of Sex Differences
#14
JOURNAL ARTICLE
Ting Zhang, Xing-Yan Luo, Lin Jing, Chunfen Mo, Huijie Guo, Shuxia Yang, Yantang Wang, Ketian Zhao, Yi Lai, Yang Liu
In recent years, immunosuppressants have shown significant success in the treatment of autoimmune diseases. Therefore, there is an urgent need to develop additional immunosuppressants that offer more options for patients. Toosendanin has been shown to have immunosuppressive activity in vitro as well as effects on autoimmune hepatitis (AIH) in vivo. Toosendanin did not induce apoptosis in activated T-cells but did affect the survival rate of naive T-cells. Toosendanin did not affect the expression of CD25 or secretion of IL-2 by activated T-cells, and not affect the expression of IL-4 and INF-γ...
April 6, 2024: European Journal of Pharmacology
#15
JOURNAL ARTICLE
Burcin Tezcanli Kaymaz, Nurcan Gumus, Besne Celik, İlayda Alcitepe, Cigir Biray Avci, Cagdas Aktan
Chronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCR::ABL1) oncoprotein; playing a pivotal role in CML molecular pathology, diagnosis, treatment, and possible resistance arising from the success and tolerance of tyrosine kinase inhibitor (TKI)-based therapy. The transcription factor STAT5 constitutive signaling, which is influenced by the cytokine signaling network, triggers BCR::ABL1-based CML pathogenesis and is also relevant to acquired TKI resistance...
April 2024: Journal of Interferon & Cytokine Research
#16
JOURNAL ARTICLE
Ayse Kilic, Arda Halu, Margherita De Marzio, Enrico Maiorino, Melody G Duvall, Thayse Brueggemann, Joselyn J Rojas Quintero, Robert Chase, Hooman Mirzakhani, Ayse Özge Sungur, Janine Koepke, Taiji Nakano, Hong Yong Peh, Nandini Krishnamoorthy, Raja-Elie Abdulnour, Katia Georgopoulos, Augusto A Litonjua, Marie Demay, Harald Renz, Bruce D Levy, Scott T Weiss
Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor ( Vdr ) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21...
April 3, 2024: ELife
#17
JOURNAL ARTICLE
Xiaolei Liu, Jianzhong Han, Qian Wang, Peng Wang, Li Li, Kehe Du, Fengchao Jiang, Pei Zhang, Hongjun Liu, Jian Huang
Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family and has been widely recognized as a master regulator of type 2 inflammatory responses at barrier surfaces. Recent studies found dysregulation of the TSLP-TSLP receptor (TSLPR) pathway is associated with the pathogenesis of not only allergic diseases but also a wide variety of cancers including both solid tumors and hematological tumors. Thus, the blockade of TSLP represents an attractive therapeutic strategy for allergic diseases and cancer...
April 2024: Antibody Therapeutics
#18
JOURNAL ARTICLE
EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.
Zhijie Hou, Yifei Ren, Xuehong Zhang, Dan Huang, Fanzhi Yan, Wentao Sun, Wenjuan Zhang, Qingqing Zhang, Xihui Fu, Zhenghui Lang, Chenyang Chu, Boyang Zou, Beibei Gao, Bilian Jin, Zhijie Kang, Quentin Liu, Jinsong Yan
The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells...
April 2, 2024: Cell Communication and Signaling: CCS
#19
JOURNAL ARTICLE
Qingqing Hu, Ning Dou, Qiong Wu, Yong Gao, Yandong Li, Jingde Chen
Gastric cancer (GC) is one of the most common solid cancers with high incidence and mortality worldwide. Chronic gastritis and consequent inflammatory microenvironment is known as a major cause leading to gastric carcinogenesis. Here we report that PIK3CD that encodes p110δ, a catalytic subunit of the class IA PI3Ks, is overexpressed and tumorigenic in GC and associated with tumor inflammatory microenvironment. By investigating the data from TCGA database and our immunohistochemical staining and quantitative real-time PCR results from clinical samples, we found PIK3CD exhibits higher expression level in GC tissues compared with adjacent non-tumorous stomach tissues...
March 2024: Journal of Cell Communication and Signaling
#20
JOURNAL ARTICLE
Xin Jin, Jiandong Zhu, Haoyun Yu, Shengjun Shi, Kecheng Shen, Jingyu Gu, Ziqian Yin, Zhengquan Yu, Jiang Wu
BACKGROUND: LINC00324 is a long-stranded non-coding RNA, which is aberrantly expressed in various cancers and is associated with poor prognosis and clinical features. It involves multiple oncogenic molecular pathways affecting cell proliferation, migration, invasion, and apoptosis. However, the expression, function, and mechanism of LINC00324 in glioma have not been reported. MATERIAL AND METHODS: We assessed the expression of LINC00324 of LINC00324 in glioma patients based on data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify pathways involved in LINC00324-related glioma pathogenesis...
2024: PloS One
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