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- | Journal: Perilipin1 inhibits Nosema bombycis proliferation by promoting Domeless- and Hop-mediated JAK-STAT pathway activation in Bombyx mori. (Pubmed Central) - May 1, 2024
The present study found that a surface protein of insect lipid droplets could not only regulate the morphological changes of lipid droplets but also inhibit the proliferation of a microsporidian pathogen Nosema bombycis (Nb) by activating the JAK-STAT signaling pathway. This is the first discovery of the relationship between microsporidian pathogen and insect lipid surface protein perilipin and insect immunity.
- | dexmedetomidine / Generic mfg.
Journal: Dexmedetomidine hydrochloride plus sufentanil citrate inhibits glucose metabolism and epithelial?mesenchymal transition in human esophageal squamous carcinoma KYSE30 cells by modulating the JAK/STAT3/HIF?1? axis. (Pubmed Central) - Apr 30, 2024
Demonstrating a reduction in Hexokinase 2, matrix metallopeptidase 2 and 9, N-cadherin and lactate dehydrogenase A protein expression levels. The effects of DEX-HCl and SFC combined treatment were counteracted by the addition of JAK/STAT pathway activator RO8191, which suggested that DEX-HCl and SFC could serve a role in mediating the JAK/STAT signaling pathway in KYSE30 cells.
- | Journal: Potential diagnostic and drug target markers in glioblastoma. (Pubmed Central) - Apr 1, 2024
We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.
- || Review, Journal: Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer. (Pubmed Central) - Mar 23, 2024
Furthermore, we summarize the latest advancements in targeting the JAK-STAT pathway for LC treatment. The insights presented in this review aim to underscore the necessity of research into the JAK-STAT signaling pathway as a promising avenue for LC therapy.
- tofacitinib / Generic mfg.
Tofacitinib Suppresses JAK/STAT Pathway Hyperactivity ex vivo in Pediatric Focal Segmental Glomerulosclerosis (Convention Center Exhibit Hall) - Mar 16, 2024 - Abstract #PAS2024PAS_2337;
The level of STAT3 phosphorylation in T cells predicts lower kidney function, lower serum albumin, and increased proteinuria 1 year later. IL6 and IL17 which stimulate STAT3 phosphorylation are increased in patient plasma.
- Cilcane (cilengitide) / Iceni Pharma, Jakafi (ruxolitinib) / Incyte, Targretin oral (bexarotene oral) / ReXceptor
Integrin ?V?3 activation by thyroid hormones triggers JAK/STAT oncogenic pathways that promote T cell lymphoma dissemination (Section 26) - Mar 5, 2024 - Abstract #AACR2024AACR_2541;
Although the FDA approved the use of inhibitors to target this pathway (Ruxolitinib), significant toxic effects have been reported and their use is limited...We found that THs induced STAT1, 3 and 5 phosphorylation in TCL cells and that the integrin ?V?3 inhibitor, Cilengitide (Cile) blunted these effects (p<0.05)...Finally, we evaluated the dissemination of TCL in an in vivo model (by vain tail) and found that BexT4+Cile reduced EL4 cell implantation into the liver and kidneys (p<0.05). These results described the mechanisms by which THs induce the activation of JAK/STAT oncogenic pathway and showed how the inhibition of integrin ?v?3 in combination with bexarotene has therapeutic potential for TCL.
- | Journal: Computational simulation of JAK/STAT signaling in somatic versus germline stem cells. (Pubmed Central) - Dec 21, 2023
These results described the mechanisms by which THs induce the activation of JAK/STAT oncogenic pathway and showed how the inhibition of integrin ?v?3 in combination with bexarotene has therapeutic potential for TCL. The simulation suggests that the duration of ligand exposure could explain the observed opposite effects of JAK/STAT activation on heterochromatin in somatic versus GSCs.
- | Journal, IO biomarker: Higher BST2 Expression Promotes the Anti-HBV Effect of IFN-? and BST2 Genetic Variant Predicts PegIFN? Treatment Response of HBeAg-positive Chronic Hepatitis B Patients. (Pubmed Central) - Nov 29, 2023
The PGS possesses the potential to boost the ability of PegIFN? therapy response.
- Gene Expression Profiling Reveals Two Overarching Types of Anaplastic Large Cell Lymphoma with Distinct Targetable Biology: An L.L.M.P.P. Study (SDCC - Room 6DE) - Nov 3, 2023 - Abstract #ASH2023ASH_5002;
Distinct GEP signatures exist for ALK+ ALCL and BIA-ALCL (predominantly Type I), and DUSP22- R ALCL and TP63- R ALCL (predominantly Type II). TN ALCLs lacking ALK- R, DUSP22- R, and TP63- R can be stratified into TN-I and TN-II subtypes.
- BMS-986158 / BMS
Modulation of Biomarkers By BET Inhibitor, BMS-986158, Including JAK2 Variant Allele Frequency (VAF), Bone Marrow (BM) Fibrosis, and Reversal of Abnormal Cytokine Production in Intermediate- or High-Risk Myelofibrosis (MF) (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_4090;
P1/2
2023) were observed as expected. Conclusions Preliminary data suggest combination treatment with BMS-986158 and JAKi in MF may modulate JAK2 VAF, BM microenvironment, circulatory cytokines, and other SF, providing evidence of early disease modifying potential of these drug combinations.
- Jakafi (ruxolitinib) / Novartis, Incyte
Ruxolitinib Promotes Clinical Responses in Large Granular Lymphocytic Leukemia Via Suppression of JAK/STAT-Dependent Inflammatory Cascades (Grand Hyatt - Grand Hall B) - Nov 3, 2023 - Abstract #ASH2023ASH_1201;
P2
STAT3 mutation status was predictive of EFS and responses were associated with JAK/STAT pathway down-regulation, demonstrating on-target effects. Integrated immune profiling suggests that ruxolitinib may interrupt JAK/STAT-dependent paracrine inflammatory signals that promote bone marrow suppression.
- Dependence of IL-7R-Mediated Signaling on Sphingosine Kinase Activity in Acute Lymphoblastic Leukemia, but Not Healthy Lymphoid Cells, Is an Exploitable Therapeutic Vulnerability (Marriott Marquis - Marriott Grand) - Nov 3, 2023 - Abstract #ASH2023ASH_936;
Overall, our studies demonstrate that SKs are key players in oncogenic, but not in physiological, IL-7/IL-7R-mediated signaling. We uncover the importance of the SK-IL7R signaling crosstalk in ALL and pinpoint the therapeutic potential of SK inhibitors for IL-7R-dependent ALL.
- | selisistat (SEN-196) / AOP Orphan Pharma
Journal: Silencing SIRT1 promotes the anti-HBV action of IFN-? by regulating Pol expression and activating the JAK-STAT signaling pathway. (Pubmed Central) - Nov 1, 2023
This would be a promising therapeutic target to improve the efficacy of IFN-? in the treatment of CHB.
- | Journal: Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation. (Pubmed Central) - Sep 23, 2023
Thus, we propose that noncanonical receptor complexes may participate in endogenous type III IFN signaling to confer TYK2-independent signaling downstream of IFN-? stimulation.
- | Journal, PD(L)-1 Biomarker, IO biomarker: MTHFD2 promotes PD-L1 expression via activation of the JAK/STAT signalling pathway in bladder cancer. (Pubmed Central) - Jul 22, 2023
Moreover, addition of a JAK/STAT pathway activator partially reduced the effect of MTHFD2 knockdown on BC cells. Collectively, our findings suggest that MTHFD2 promotes the expression of PD-L1 through the JAK/STAT signalling pathway in BC.
- | Journal: KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway. (Pubmed Central) - Jul 18, 2023
Furthermore, GH treatment increased both the nuclear content of KLF13 and Klf13 mRNA levels, suggesting that KLF13 could be part of the mechanisms that maintain the homeostatic state of this pathway. These findings support the notion that KLF13 is a regulator of JAK/STAT activity.
- | Journal, PD(L)-1 Biomarker, IO biomarker: Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing. (Pubmed Central) - Jul 7, 2023
TARA infiltration might promote glioma tumor progression and can be used as a diagnostic, predictive and prognostic marker in gliomas. Prevention of TARA infiltration might be a new therapeutic strategy for glioma.
- Jakafi (ruxolitinib) / Novartis, Incyte
First experience of the JAK 1/2 inhibitor ruxolitinib for the treatment of primary cutaneous gamma-delta T-cell lymphoma (PCGDTL) and molecular insights into treatment response and relapse () - Jul 3, 2023 - Abstract #WCD2023WCD_5320;
We report the first case treated with ruxolitinib monotherapy with near-complete but short-lived response. Unexpectedly, molecular analysis at time of relapse revealed re-activation of JAK/STAT signaling suggesting its vital importance.
- tofacitinib / Generic mfg.
mtDNA OXIDATIVE DAMAGE IS PROINTERFEROGENIC AND PRONETOTIC, AND RELATES TO ANTIPHOSPHOLIPID ANTIBODY POSITIVITY IN SLE () - May 19, 2023 - Abstract #EULAR2023EULAR_3708;
Tofacitinib, a JAK1-JAK3 inhibitor, was utilised to assess the JAK-STAT pathway activation...Circulatory ox-mtDNA might promote endothelial damage and vasculitis in SLE. A significant link between aPL, namely aCL IgG, and circulating mtDNA in SLE patients was evident, potentially aggravating the inflammatory state linked to disease severity and promoting thrombotic events.
- Selective inhibition of the JAK-STAT3 pathway activated by interleukin-6 in PMBCs of systemic sclerosis patients: bench clues for new therapeutic perspectives (TBSI Level -1) - Mar 29, 2023 - Abstract #EWRR2023EWRR_201;
- bleomycin / Generic mfg.
Mesenchymal Stem Cell-derived Humoral Factor STC-1 Suppresses Il-6 Auto-amplification in Bleomycin-induced Pulmonary Fibrosis Model (Walter E. Washington Convention Center, Area J, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_5581;
STC1 has inhibitory effects on bleomycin-induced ACE2 and TMPRSS2 (required for SARS-CoV2 infection) expression depends on SOCS1. (Conclusion) STC1 i.t. may be a novel therapeutic method to control IL-6 amp related pathology such as pulmonary fibrosis and CRS.
- Degos disease is characterized by cytotoxic transcriptome centering on CD8 T cells () - Mar 4, 2023 - Abstract #ISID2023ISID_1705;
These results suggest Degos disease is an immune-mediated disease involving cytotoxic CD8 T cells across multiple organs. The upregulation of JAK-STAT genes and type I and II IFN-responsive genes highlight the cytokine receptor signaling pathways, such as the JAK- STAT pathway, may be attractive therapeutic targets in Degos disease.
- | Xalkori (crizotinib) / Pfizer, Jakafi (ruxolitinib) / Novartis, Incyte
Preclinical, Journal: Crizotinib has Preclinical Efficacy in Philadelphia-negative Myeloproliferative Neoplasms. (Pubmed Central) - Mar 2, 2023
In summary, we demonstrate that crizotinib has preclinical efficacy in MPN patient cells, JAK2-mutated cell lines, and a JAK2-mutated mouse model, and that the combination of crizotinib with JAK inhibitors suppresses JAK inhibitor persistence. Our work suggests that crizotinib should be investigated for the treatment of MPN patients.
- | Journal: Antimicrobial Peptide LCN2 Inhibited Uropathogenic Escherichia coli Infection in Bladder Cells in a High-Glucose Environment through JAK/STAT Signaling Pathway. (Pubmed Central) - Dec 24, 2022
These findings may provide a rationale for targeting LCN2/TLR-4/JAK/STAT regulation in bacterial cystitis treatment. Further studies should explore specific mechanisms by which the LCN2, TLR-4, and JAK/STAT pathways participate in UPEC-induced inflammation to facilitate the development of effective therapies for cystitis.
- | Inrebic (fedratinib) / BMS, Jakafi (ruxolitinib) / Novartis, Incyte, Vonjo (pacritinib) / CTI BioPharma
Journal: New approaches to tackle cytopenic myelofibrosis. (Pubmed Central) - Dec 10, 2022
The first approved Jak inhibitors, ruxolitinib and fedratinib, can both improve constitutional symptoms and splenomegaly but carry on-target risks of worsening anemia and thrombocytopenia, limiting their use in patients with cytopenic MF...Pacritinib, selective Jak2 inhibitor, was approved in 2022 to treat patients with symptomatic MF and a platelet count lower than 50 × 109/L...As a result, significant unmet needs remain for cytopenic MF. Here, we discuss clinical implications of the cytopenic MF phenotype and present existing and future strategies to tackle this challenging disease.
- | Journal: Methylation of the suppressor of Cytokine Signaling 1 Gene (SOCS1) in Philadelphia-negative myeloproliferative neoplasms. (Pubmed Central) - Dec 3, 2022
Here, we discuss clinical implications of the cytopenic MF phenotype and present existing and future strategies to tackle this challenging disease. We concluded that the activation of the JAK/STAT signaling pathway in alternative or with JAK2 mutations leads to SOCS1 hypermethylation, which could represent a potential therapeutic target.
- golidocitinib (DZD4205) / Dizal Pharma
Preliminary Biomarker Data from a Phase 1/2 Study of Golidocitinib Demonstrates Targeting JAK/STAT Pathway to Treat Peripheral T-Cell Lymphoma (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4292;
P2
No apparent correlation between mutations in JAK/STAT pathway and clinical response was observed while baseline high pSTAT level seems to predict clinical benefit. Larger sample size is needed to confirm the findings.
- PRDM1 Deletion and STAT3 Mutations Cooperatively Promote CD8+ T-Cell and NK-Cell Growth in Vitro (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4052;
We are currently investigating the adoptive transfer of modified mouse or human cells into littermates or NSG-Tg(huIL15) mice respectively to observe the in vivo development and evolution of the transferred cells. The detailed mechanistic interactions between these two genetic abnormalities in lymphoma development will be further investigated.
- Jakafi (ruxolitinib) / Novartis, Incyte, Mekinist (trametinib) / Novartis
JAK Inhibition Mediates Clonal Selection of RAS Pathway Mutations in Myeloproliferative Neoplasms (ENMCC - 275-277) - Nov 4, 2022 - Abstract #ASH2022ASH_1747;
The clinical use of JAK inhibitors like ruxolitinib (rux) was introduced a decade ago for treatment (trt) of myeloproliferative neoplasms (MPN) driven by JAK/STAT pathway activation...This effect was rescued by trametinib trt confirming its dependence on the MAPK pathway activation...From a more fundamental perspective, the enhanced oncogenic potential of RAS mutations after inactivation of the oncogenic JAK/STAT pathway, pinpoints an intriguing paradoxical oncogenic mechanism and highlights the complexity of the combinatorial mutational landscape in cancer. NM BR and JJK BC LB: equal contribution
- | Trial completion date, Trial primary completion date: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction (clinicaltrials.gov) - Oct 26, 2022
P2, N=56, Recruiting, Sponsor: Stanford University
NM BR and JJK BC LB: equal contribution Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
- JAK/STAT Inhibition and Beyond in Ph Negative MPNs (ENMCC - 293-294) - Sep 4, 2022 - Abstract #ASH2022ASH_26;
Raajit Rampal will review the clinical features of accelerated or blast phase MPNs, and discuss pathologic drivers of MPN evolution towards these more aggressive disease states. He will discuss current treatment options for accelerated of blast phase MPNs, highlighting novel therapeutic options as well as the need for more effective therapies.
- Mesenchymal Stromal Cell Delivery via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Surgical Model (S103D) - Aug 11, 2022 - Abstract #AHA2022AHA_2214;
He will discuss current treatment options for accelerated of blast phase MPNs, highlighting novel therapeutic options as well as the need for more effective therapies. BM-MSC delivery via CPB minimizes inflammatory/oxidative stress and reduces neuronal caspase and microglial activation, with subsequent rescue of behavioral/structural impairments in children undergoing cardiac surgery.
- | Trial completion date, Trial primary completion date: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction (clinicaltrials.gov) - May 26, 2021
P2, N=56, Recruiting, Sponsor: Stanford University
BM-MSC delivery via CPB minimizes inflammatory/oxidative stress and reduces neuronal caspase and microglial activation, with subsequent rescue of behavioral/structural impairments in children undergoing cardiac surgery. Trial completion date: Dec 2021 --> Jun 2023 | Trial primary completion date: Dec 2021 --> Jun 2023
- | Phase classification: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction (clinicaltrials.gov) - Mar 19, 2020
P2, N=56, Recruiting, Sponsor: Stanford University
Trial completion date: Dec 2021 --> Jun 2023 | Trial primary completion date: Dec 2021 --> Jun 2023 Phase classification: P1 --> P2
- | Enrollment open: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction (clinicaltrials.gov) - Sep 27, 2019
P1, N=56, Recruiting, Sponsor: Stanford University
Phase classification: P1 --> P2 Not yet recruiting --> Recruiting
- | New P1 trial: Janus Kinase Inhibition to Prevent Ventilator-induced Diaphragm Dysfunction (clinicaltrials.gov) - Sep 24, 2018
P1, N=56, Not yet recruiting, Sponsor: Stanford University