• Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. (jacobiopharma.com)
  • 1) We study Cbl proteins, a family of ubiquitin ligases that negatively regulate signaling by receptor tyrosine kinases. (cancer.gov)
  • Cbl proteins belong to the RING finger class of ubiquitin protein ligases (E3s) and function as E3s for activated tyrosine kinases. (cancer.gov)
  • GSK-3 is therefore a part of the canonical Beta-catenin/Wnt pathway, which signals the cell to divide and proliferate. (wikipedia.org)
  • In the receptor tyrosine kinase (RTK) pathway, SHP2 effects are upstream of RAS, in mediating tumor proliferation and downstream of the immune checkpoint regulator, Programmed cell death protein 1 (PD-1), in inhibiting the anti-tumor effect of T cells. (jacobiopharma.com)
  • Ingenuity pathway analysis was performed to integrate elevated kinase activity and gene over-expression with coexisting missense mutations at DNA level. (oncotarget.com)
  • We found that 125 I seeds radiation activated PI3K/AKT signaling pathway and could trigger paraptosis-like cell death. (hindawi.com)
  • Moreover, inhibitor of PI3K/AKT signaling pathway could inhibit paraptosis-like cell death induced by 125 I seeds radiation. (hindawi.com)
  • Our data suggest that 125 I seeds radiation can induce paraptosis-like cell death via PI3K/AKT signaling pathway. (hindawi.com)
  • This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1). (biomedcentral.com)
  • The purpose of the research is to investigate the roles of Jak-STAT3 signaling pathway in bufalin-induced apoptosis in colon cancer SW620 cells. (biomedcentral.com)
  • Western Blot was used to determine the protein expression of the apoptosis inhibitors livin and caspase-3, the apoptosis-related proteins Bax and Bcl-2, as well as the key protein kinases in the Jak-stat3 signaling pathway, stat3 and p-stat3. (biomedcentral.com)
  • Title: Inflammatory-pathway.indd Created Date: 7/18/2018 1:38:17 PM Small-diameter sensory neurons express a variety of sodium channel transcripts as well as a repertoire of electrophysiological and pharmacologically distinct type of sodium currents. (newmedia1.net)
  • Biochemical data suggest that SA potentiates the signal pathway for HR by affecting an early phosphorylation-sensitive step preceding the generation of pro-death signals, including those derived from the oxidative burst. (springer.com)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase related kinase family is a well-known player in repairing DNA double strand break through non-homologous end joining pathway. (molcells.org)
  • We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. (hopkinsmedicine.org)
  • The inactivation of GSK3B by various protein kinases also affects the adaptive immune response by inducing cytokine production and proliferation in naïve and memory CD4+ T cells. (wikipedia.org)
  • In a second project we are investigating the induction of apoptosis by activation of death receptors for the ligand TRAIL in breast and ovarian cancer cells. (cancer.gov)
  • We have shown that most breast and ovarian cancer cell lines are resistant to the induction of apoptosis by TRAIL, the ligand for the death receptors DR4 and DR5. (cancer.gov)
  • Our current work utilizes biochemical and genetic approaches to identify mechanisms that regulate the induction of death by TRAIL ligand in breast and ovarian cancer cells. (cancer.gov)
  • The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). (frontiersin.org)
  • CHICAGO, June 5, 2023 - The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from an interim analysis of Cohort 1 of the Phase 3 THOR study, evaluating treatment with BALVERSA ® (erdafitinib) versus chemotherapy in patients with metastatic or unresectable urothelial carcinoma (UC) and selected fibroblast growth factor receptor (FGFR) gene alterations who had received prior treatment with an anti-programmed death ligand 1 (PD-[L]1) agent. (janssen.com)
  • Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. (frontiersin.org)
  • The apoptosis rate was 34.63 ± 2.57% (vs 19.69 ± 1.63%, P = 0.002) in JAK kinase inhibitor AG490 plus bufalin treatment group. (biomedcentral.com)
  • ASP1570 is a novel inhibitor against DGKz and has the potential to enhance DAG downstream signaling which can activate T cells regardless of PD-1 signaling and lead to tumor killing. (providence.org)
  • Our previous studies have shown that the free fatty acid extract (FFAE) of krill oil inhibits the proliferation of both CRC and osteosarcoma cells, and induces the apoptosis of CRC cells [ 17 , 18 ]. (biomedcentral.com)
  • In T cells, DGK (such as DGKz) inhibits DAG-mediated signals following T-cell receptor engagement by catalyzing the conversion of DAG to PA.2 Even when PD-1 is blocked by anti-PD-1 antibodies, there may be partial inactivation by DGK. (providence.org)
  • In influenza viruses, the nonstructural protein 1 inhibits the interferon-mediated antiviral response. (cdc.gov)
  • First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. (wikipedia.org)
  • GSK-3 is also integrally tied to pathways of cell proliferation and apoptosis. (wikipedia.org)
  • JAB-3312 is highly selective, allosteric inhibitors of SHP2 that can block the RTK/RAS/MAPK signaling pathways and inhibit the growth and proliferation of tumor cells driven by RTK or with KRAS, BRAF Class 3 and NF1 loss of function (LOF) mutations. (jacobiopharma.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Top pathways upregulated in both the kinase activity and gene expression platforms were PTEN, STAT3, GNRH, IL-8 and B cell receptor signaling. (oncotarget.com)
  • Potentially relevant missense mutations were seen in 176 kinase genes, with the top altered pathways overlapping with gene overexpression being GNRH, NF-kB and STAT3 signaling. (oncotarget.com)
  • My laboratory studies signal transduction pathways that regulate growth and programmed cell death in epithelial cancer cells, with a focus on breast and ovarian cancer. (cancer.gov)
  • The potential anti-cancer properties of krill oil are likely to be associated with the downregulation of EGFR, pEGFR and their downstream pERK/ERK1/2 and pAKT/AKT signalling pathways along with the downregulation of PD-L1. (biomedcentral.com)
  • Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. (hopkinsmedicine.org)
  • Network mapping was done with GeneGo MetaCore™ and upstream kinase prediction was performed with BioNavigator and the Kinexus database. (oncotarget.com)
  • Accordingly, the epistatic relationship between cell death and SA accumulation, analyzed in crosses between lesion-mimic mutants (spontaneous lesion formation) and the transgenic nahG line (depleted in SA) places the SA activity in a feedback loop downstream and upstream of cell death. (springer.com)
  • In a phosphatidylinositol 3-kinase-dependent way. (wikipedia.org)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), encoded by PRKDC gene, is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, which also includes the two DNA damage repair proteins, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein (ATR). (molcells.org)
  • It has been established that approximately 60% to 70% of patients who receive anti-programmed cell death protein-1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) do not respond to treatment.1 Furthermore, acquired resistance is common, causing some patients who initially responded to the therapy to later experience disease progression. (providence.org)
  • Next Generation Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture and run on the Illumina MiSeq at PE150bp. (oncotarget.com)
  • The NanoString nCounter® platform analyzed the expression of 519 kinase genes. (oncotarget.com)
  • 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. (hopkinsmedicine.org)
  • 100 genes ( 1 ). (cdc.gov)
  • ERBB2, ERBB3 and SYK were altered on NGS and also exhibited elevated kinase activity. (oncotarget.com)
  • However our results showed some unique morphological features such as cell swelling, cytoplasmic vacuolation, and plasma membrane integrity, which is obviously different to apoptosis. (hindawi.com)
  • Paraptosis is a kind of caspase-independent programmed cell death and is characterized by distinct cytoplasmic vacuolization derived from swelling endoplasmic reticulum and/or mitochondria. (hindawi.com)
  • All IFNαs and IFNβ bind to the same receptor and as a result, the cytoplasmic kinases JAK1 and TYK2 become activated and phosphorylate the STAT1 and STAT2 molecules. (cdc.gov)
  • citation needed] As of 2019[update], GSK-3 is the only type of glycogen synthase kinase named and recognized. (wikipedia.org)
  • [1] Following the accelerated approval of BALVERSA ® in 2019, these confirmatory data were featured in a Late-Breaking Presentation Session (Abstract # LBA4619 ) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. (janssen.com)
  • In this area, our recent research has included studying cutaneous shave biopsies for diagnosing primary colonic adenocarcinoma as well as growth inhibition and apoptosis in human brain tumor cell lines using selenium. (hopkinsmedicine.org)
  • Rapid and transient activation of myelin basic protein kinase in tobacco leaves treated with hairpin from Erwinia amylovora . (springer.com)
  • Also promising are synergistic effects for SHP2 inhibitors used in combination with a variety of targeted therapies and immunotherapies, such as KRAS/EGFR/ALK inhibitors, and PD-1 antibody, that would expand this potential benefit to even more patients. (jacobiopharma.com)
  • Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. (biomedcentral.com)
  • The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry. (biomedcentral.com)
  • A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. (mdpi.com)
  • The inhibitory effects of bufalin on cell proliferation were determined by MTT (Methyl thiazolyltetrazolium) assay. (biomedcentral.com)
  • 1) Bufalin inhibited the proliferation of SW620 cells. (biomedcentral.com)
  • Human epithelial malignancies frequently display deregulated tyrosine kinase activity. (cancer.gov)
  • Due to the change in people's diet, the incidence of colon cancer is rising and becoming one of the most common malignancies and the leading cause of death from cancer. (biomedcentral.com)
  • More than 30 company-sponsored abstracts have been accepted, supporting the data from clinical development programs investigating innovative treatments for prostate cancer, hematologic malignancies and solid tumors. (jnj.com)
  • IgEs conversation Ginsenoside Rg3 with CD23 modulates both IgE production and functional activities.CD23 is a noncanonical immunoglobulin receptor, unrelated to receptors of other antibody isotypes. (treatmentforprostatecancer.info)
  • Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. (hopkinsmedicine.org)
  • Both JAB-3312 have been granted orphan drug designation for esophageal cancer (including esophageal squamous cell carcinoma) by the U.S. FDA. (jacobiopharma.com)
  • Results from studies to date suggest that JAB-3312 may be effective in patients with non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, colorectal cancer, pancreatic cancer harboring specific gene mutations, and patients with Class 3 BRAF-mutated, or NF1 LOF mutated solid tumors. (jacobiopharma.com)
  • Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. (oncotarget.com)
  • The biology and drivers of penile squamous cell carcinoma (PSCC), an orphan disease, are poorly understood. (oncotarget.com)
  • We further focused our interest on the molecular mechanisms that underlie 125 I seeds radiation-induced paraptosis on colorectal cancer cells. (hindawi.com)
  • Breast cancer tumors that do not express hormone receptors or have amplification of Her2/Neu (so called triple-negative tumors) have a poor prognosis and no validated molecular targets. (cancer.gov)
  • Taken together, ASP1570 treatment as a single agent and/or in combination with anti-PD-1 therapy for locally advanced or metastatic solid tumors may result in clinical benefit. (providence.org)
  • Methods This is a phase 1/2, open-label, multicenter, multipledose, dose-escalation/expansion study of ASP1570 in participants with locally advanced or metastatic solid tumors. (providence.org)
  • Understanding the mechanisms that regulate signaling by these kinases should uncover new ways to inhibit cancer cell growth. (cancer.gov)
  • Cancer cells avoid apoptosis by a variety of genetic and epigenetic mechanisms. (cancer.gov)
  • Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. (hopkinsmedicine.org)
  • Different cell subtypes appear to employ different mechanisms to recognize viral products ( 8 ). (cdc.gov)
  • We are investigating the function of Cbl proteins, a family of proteins that regulate tyrosine kinase activity. (cancer.gov)
  • Ongoing work is focused on understanding the biochemical and physiologic functions of the three mammalian Cbl proteins in epithelial cells and elucidating the differences in their specificity and/or function. (cancer.gov)
  • We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). (hopkinsmedicine.org)
  • Binding to dsRNA by these proteins may result in initiation of helicase activity, concomitant with a conformational change that leads to recruiting additional cellular factors, including the recently identified IPS-1/MAVS protein ( 5 , 6 ). (cdc.gov)
  • SHP2 also functions downstream of Colony Stimulating Factor 1 Receptor (CSF1R), in promoting tumor-associated macrophage activity. (jacobiopharma.com)
  • Therefore, DGK inhibitors have the potential to enhance DAG downstream signaling, leading to T-cell activation regardless of the PD-1 signal. (providence.org)
  • Diacylglycerol kinase (DGK) is a large enzyme family of 10 mammalian isoenzymes that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). (providence.org)
  • Particularly, viral infection triggers specific signaling programs within the infected cells that results in substantial changes in host gene expression. (cdc.gov)
  • The study also revealed increased risk of death from RCC in patients who did not undergo surgical resection of metastasis. (medscape.com)
  • The ASCO Annual Meeting represents an important venue to present the very latest from our research and development programs, and showcase our commitment to improve the lives of patients who have been diagnosed with cancer through breakthrough science and innovative medicines. (jnj.com)
  • Janssen partners directly with patients and caregivers as we develop medicines, improve clinical trials, and create educational materials and support programs. (janssen.com)
  • Patients were categorized to one of two cohorts based on the type of prior therapy they had received: prior treatment with an anti-PD-(L)1 agent (Cohort 1) or prior treatment not containing an anti-PD-(L)1 agent (Cohort 2). (janssen.com)
  • In humans, CD23 is usually expressed on a range of cells including B cells, T cells, monocytes, follicular dendritic cells, intestinal epithelial cells, bone marrow stromal cells and respiratory epithelial cells. (treatmentforprostatecancer.info)
  • The active site, at residues 181, 200, 97, and 85, binds the terminal phosphate of ATP and transfers it to the target location on the substrate (see figure 1). (wikipedia.org)
  • FcRI is usually primarily expressed on the surface of mast cells and basophils, binds to IgE with high affinity (KD? (treatmentforprostatecancer.info)
  • Once IFNα/β has been synthesized, it is secreted and binds to the IFNα/β receptor. (cdc.gov)
  • Given that kinases may be drivers and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor and normal tissue. (oncotarget.com)
  • After macrodissection to demarcate tumor from normal tissue, the samples underwent multiplatform analysis of kinases. (oncotarget.com)
  • Kinase activity of tissue lysates was measured using PamStation®12 high-content phospho-peptide substrate microarray system. (oncotarget.com)
  • Augmenting the synthesis and/or secretion of opioid peptides and opioid receptor numbers within injured tissue may be accomplished by gene therapy: delivery of PENK, POMC, and of μ receptor cDNAs have been shown to decrease chronic pain and inflammation (Braz, J. et al. (newmedia1.net)
  • In addition, insulin-like growth factor I receptor- (IGFIR-) induced paraptosis has been reported to be inhibited by MEK-2-specific inhibitors and by antisense oligonucleotides directed against JNK-1 [ 15 ]. (hindawi.com)
  • Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level. (molcells.org)
  • We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell. (mdpi.com)
  • Many studies on the cancer-killing activity of 125 I seeds radiation mainly focused on its ability to trigger apoptosis, which is the most well-known and dominant type of cell death induced by radiation. (hindawi.com)
  • Colorectal cancer remains one of the most common causes of cancer-related deaths worldwide [ 1 ]. (hindawi.com)
  • We found besides apoptosis that 125 I seed radiation killed colorectal cancer cell via inducing paraptosis. (hindawi.com)
  • 2) We investigate induction of apoptosis in breast cancer cells by TRAIL receptor agonists. (cancer.gov)
  • Our goal is to selectively trigger apoptosis in the cancer cells. (cancer.gov)
  • In our third project we are using functional genomic approaches and tumor genetics to identify new therapeutic targets in triple-negative breast cancer cells. (cancer.gov)
  • ONC201 kills breast cancer cells in vitro by targeting mitochondria. (cancer.gov)
  • Bufalin not only inhibited the growth of colon cancer SW620 cells, but also induced apoptosis of SW620 cells. (biomedcentral.com)
  • Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. (hopkinsmedicine.org)
  • Systemic therapy for metastatic PSCC yields poor outcomes, with a median overall survival (OS) of 6 to 9 months [ 1 - 10 ]. (oncotarget.com)
  • In this cohort, the study met its primary endpoint of overall survival (OS) and reduced the risk of death by 36 percent. (janssen.com)
  • Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. (wikipedia.org)
  • Our previous studies have shown that the free fatty acid extract (FFAE) of krill oil exhibits anti-proliferative and pro-apoptotic properties. (biomedcentral.com)
  • found that HBO could significantly relieve abdominal pain in the acute inflammatory abdominal pain mouse model induced by intraperitoneal injection of 1% acetic acid. (newmedia1.net)
  • Although extensive data has described the key role of salicylic acid (SA) in signaling pathogen-induced disease resistance, its function in physiological processes related to cell death is still poorly understood. (springer.com)
  • While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. (molcells.org)
  • Defective cell death programs cause disease states. (hopkinsmedicine.org)
  • Moreover, the expression of AIP1 is specifically inhibited in paraptosis cells, while it is not affected in apoptotic cells [ 15 ]. (hindawi.com)
  • This form of cell death is fundamentally different from apoptosis and lacks some distinct characteristics of apoptosis such as DNA fragmentation, pyknosis, or caspase activation and cleavage [ 14 ]. (hindawi.com)
  • Curcumin-induced paraptosis has been reported to be positively associated with ERK2 and JNK (c-jun N-terminal kinase-1) activation [ 16 ]. (hindawi.com)
  • After being primed by casein kinase 2 (CK2), glycogen synthase gets phosphorylated at a cluster of three C-terminal serine residues, reducing its activity. (wikipedia.org)
  • To summarize, multiplatform comprehensive analysis of kinases discovered potential drivers of PSCC and actionable therapeutic targets. (oncotarget.com)
  • have reported that increased DNA-PKcs activity can suppress HR repair in G1 phase of cells through increasing RBX1 protein expression, which prompts the neddylation and activity of cullin 1, a key component of the Skp1-Cullin1-F-box ubiquitin 3 ligase, consequently mediating ubiquitination and degradation of EXO1. (molcells.org)
  • Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. (hopkinsmedicine.org)
  • We have demonstrated that resistance to TRAIL-induced apoptosis can be overcome by co-incubation of the cells with chemotherapeutic agents, semi-synthetic retinoids (such as 4HPR), or molecularly targeted agents (such as anti-ErbB-2 antibodies). (cancer.gov)
  • Cell-autonomous recognition of the rust pathogen determines Rpl-specified resistance in maize. (springer.com)
  • ASP1570 restored T-cell functions suppressed by multiple immunosuppressive signals (PD-1, transforming growth factor beta, prostaglandin E2, and adenosine) and induced tumor growth inhibition in mice models of MC38 (anti-PD1 sensitive) and B16-F1 (tumor-infiltrating lymphocyte poor, anti-PD1 insensitive). (providence.org)
  • The morphological changes of cells were measured by Wright-Giemsa staining. (biomedcentral.com)
  • Anti-PD-1 and PD-L1 antibodies in metastatic melanoma. (providence.org)
  • Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro , however BMS-777607 was far superior to LCRF-0004. (frontiersin.org)
  • In addition to its role in regulating glycogen synthase, GSK-3 has been implicated in other aspects of glucose homeostasis, including the phosphorylation of insulin receptor IRS1 and of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6 phosphatase. (wikipedia.org)
  • In addition, JAB-3312 can block PD-1 signaling, enhancing the tumor-killing functions of CD8+ T cells, and relieve immunosuppression in the tumor microenvironment from tumor-associated macrophages resulting in overall anti-tumor effects. (jacobiopharma.com)
  • The transcription factors c-myc and c-fos (also S phase promoters ), which are primarily phosphorylated by the dual-specificity tyrosine phosphorylation-regulated kinase, are also phosphorylated by GSK3, causing them to be degraded. (wikipedia.org)