• This family, which includes epidermal growth factor receptor (EGFR), plays a pivotal role in normal cell growth, lineage determination, repair, and functional differentiation. (medscape.com)
  • HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)
  • Epidermal growth factor receptor, a well-known biomarker for targeted therapy at present, was first brought up with potential clinical responsiveness to tyrosine kinase inhibitor gefitinib in 2004[ 6 ]. (biomedcentral.com)
  • Herein, we summarized the novel agents in tyrosine kinase inhibitors especially for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors, checkpoint inhibitors, and other potential immunotherapy aiming to provide a landscape of emerging agents for NSCLC as well as insights and perspectives for the future in anticancer treatment. (biomedcentral.com)
  • this may be in part because they have a higher rate of triple-negative breast cancer (negative for estrogen and progesterone receptors and human epidermal growth factor receptor [HER2] oncogene), which has a poorer prognosis than other types. (msdmanuals.com)
  • DDR increased the expression level of pathogenesis-related ( PR ) genes and the total salicylic acid (SA) content and promoted mitogen-activated protein kinase signaling cascades, including the WRKY signaling pathway in Arabidopsis. (ppjonline.org)
  • The expression of HMGB1, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK) was assessed with immunofluorescence and western blot analysis. (molvis.org)
  • Rapid and transient activation of myelin basic protein kinase in tobacco leaves treated with hairpin from Erwinia amylovora . (springer.com)
  • Concomitant activation of the insulin-like growth factor-1 receptor, Akt, and extracellular signal-regulated protein kinase 1 and 2 as well as increased phosphorylation of Bad also were unique to the hippocampus of APP Sw mice. (jneurosci.org)
  • Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
  • A trophic ligand is a molecule whose protein binding stimulates cell growth, differentiation, and/or survival. (wikipedia.org)
  • The dependence receptor notion was based on the observation that the effects of a number of receptors that function in both nervous system development and the production of tumors (especially metastasis) cannot be explained simply by a positive effect of signal transduction induced by ligand binding, but rather must also include cell death signaling in response to trophic withdrawal. (wikipedia.org)
  • conversely, in the absence of ligand, the receptors initiate and/or amplify a signal for programmed cell death. (wikipedia.org)
  • The signaling that mediates cell death induction upon ligand withdrawal is incompletely defined, but typically includes a required interaction with, and cleavage by, specific caspases. (wikipedia.org)
  • Mutation of the caspase site(s) in the receptor, of which there is typically one or two, prevents the trophic ligand withdrawal-induced programmed cell death. (wikipedia.org)
  • Complex formation appears to be a function of ligand-receptor interaction, and dependence receptors appear to exist in at least two conformational states. (wikipedia.org)
  • Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
  • Rationale: Although promising responses are obtained in patients treated with immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1) and its receptor programmed death-1 (PD-1), only a fraction of patients benefits from this immunotherapy. (bvsalud.org)
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) is a significant immune checkpoint, and the dysfunction of this axis contributes to tumor metastasis and immune escape. (cams.cn)
  • NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. (spandidos-publications.com)
  • Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. (spandidos-publications.com)
  • Apoptosis, a form of programmed cell death, was first described by Kerr et al. (wikipedia.org)
  • For example, prostate epithelial cells require testosterone for survival, and the withdrawal of testosterone leads to apoptosis in these cells. (wikipedia.org)
  • Methods Cell Counting Kit-8 and Annexin V-FITC Apoptosis Detection Kit were used to evaluate cell proliferation and apoptosis. (bmj.com)
  • It does so by forming a multiprotein signaling complex, the NLRP3 inflammasome, with apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 1 . (nature.com)
  • 2018 ). NLRP3 inflammasome is composed of NLRP3 (nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3), ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) and procaspase-1, subsequently amplifying the production and secretion of proinflammatory cytokines, apoptotic and pyroptotic cell deaths(Zhong et al. (biomedcentral.com)
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • In contrast, thymocytes that recognize self-peptide/MHC with high affinity undergo negative selection via TCR-mediated apoptosis, prompting Trinquand, dos Santos, Tran Quang, and colleagues to hypothesize that reactivation of this developmental checkpoint in T-ALL cells may have antileukemic activity. (aacrjournals.org)
  • Natural product anticancer agents enhance intracellular levels of ceramide, a sphingolipid that promotes cell apoptosis. (sphingolipidclub.com)
  • These findings suggest that CHOP is a fundamental factor that links protein misfolding in the ER to oxidative stress and apoptosis in β cells under conditions of increased insulin demand. (jci.org)
  • Escaping the programed cell death or apoptosis and activating the pro-survival pathways are other major mechanisms of therapy resistance in GBM [ 12 ] . (encyclopedia.pub)
  • Alternatively, cells that sense injury or loss of mitochondrial integrity may undergo programmed cell death (apoptosis). (massgenomics.org)
  • Pietrantonio, Oddo, and colleagues identified a mechanism of resistance to dual EGFR and BRAF blockade in a patient with BRAF V600E -mutant metastatic colorectal cancer who developed resistance to the anti-EGFR antibody panitumumab plus the BRAF inhibitor vemurafenib. (aacrjournals.org)
  • In vitro , MET overexpression activated ERK signaling and rendered BRAF-mutant colorectal cancer cells resistant to vemurafenib and panitumumab, and sensitivity was restored by treatment with the MET inhibitor crizotinib. (aacrjournals.org)
  • We describe areas where major inroads were initially achieved by targeting angiogenesis and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in GIST and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.com)
  • Here, in Part I, we describe areas where major inroads were initially achieved by targeting angiogenesis (central to the biology of renal cell carcinoma and hepatocellular cancer) and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in gastrointestinal stromal tumors (GIST) and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.com)
  • Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cul-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3-SCFβ-TrCP ubiquitin ligase, the NF-κB inhibitor IκB-α. (emory.edu)
  • Dr. Gray's research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance. (stanford.edu)
  • Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called 'gatekeeper' residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR. (stanford.edu)
  • The acquired resistance was associated with subclonal amplification of MET and increased MET expression, suggesting that inhibition of EGFR and BRAF selected for MET -amplified clones. (aacrjournals.org)
  • Cells with MET amplification were resistant to EGFR, BRAF, and MEK inhibitors alone or in combination, and crizotinib, which had no effect alone, reduced cell viability in combination with vemurafenib. (aacrjournals.org)
  • Various techniques have been developed for targeting cancer cells: gene therapy, monoclonal antibodies (MAbs), antibody toxin conjugates, small-molecule inhibitors, antisense molecules, and tumor vaccines. (medscape.com)
  • Cancer vaccination may be an effective approach to improve the response to immune checkpoint inhibitors anti-PD-L1/PD-1 therapy. (bvsalud.org)
  • This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. (biomedcentral.com)
  • This has resulted in the development of additional immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and inhibitors of other immune checkpoints. (biomedcentral.com)
  • hodgkin lymphoma in a case of chronic myeloid leukemia treated with tyrosine kinase inhibitors. (liverpool.ac.uk)
  • tyrosine kinase inhibitors are the most important drugs in the cml therapy and provide long disease-free survival. (liverpool.ac.uk)
  • At present, the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment. (cams.cn)
  • Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. (biomedcentral.com)
  • Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment. (biomedcentral.com)
  • Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. (spandidos-publications.com)
  • Small-molecule inhibitors, antagonistic monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific antibodies or biologics (bsAbs) and chimeric antigen receptor-modified T cells (CAR-Ts) targeting Notch signaling components have been developed as investigational anti-cancer drugs ( 10 - 12 ). (spandidos-publications.com)
  • Results We found that the combination administration of SHP099 and AZD4547 significantly inhibited cancer cell proliferation in vitro in FGFR2i-resistant model derived from ascites of a female GC patient with FGFR2 amplification, two FGFR2-amplified GC cell lines and GC cells transfected with one kind of FGFR2 fusion. (bmj.com)
  • chronic myeloid leukemia (cml) is characterized by increased and unregulated proliferation of granulocytic lineage in the bone marrow and presence of these immature myeloid cells in the peripheral blood with presence of philadelphia (ph) chromosome. (liverpool.ac.uk)
  • Furthermore, the dominant member of this wound-mucosa-associated microbiota, Akkermansia muciniphila (an anaerobic, mucinophilic gut symbiont7,8), stimulated proliferation and migration of enterocytes adjacent to the colonic wounds in a process involving FPR1 and intestinal epithelial-cell-specific NOX1-dependent redox signalling. (emory.edu)
  • Antineoplastic agents inhibit cell growth and proliferation. (medscape.com)
  • Platinum compounds inhibit cell growth and proliferation. (medscape.com)
  • Cancer-preventing strategies of these beneficial bacteria such as binding to carcinogens and degrading them, stimulating anti-cancer enzymes, and preventing the conversion of procarcinogens to carcinogens, production of beneficial compounds that act as signaling molecules affecting the immune system, cell death, and proliferation, and interference with cell signaling pathways are reported [ 16 - 19 ]. (hindawi.com)
  • Ex vivo exposure of first trimester testes to CBD, THC, or CBD/THC [ratio 1:1] at 10 −7 to 10 −5 M altered testosterone secretion by Leydig cells, AMH secretion by Sertoli cells, and impacted testicular cell proliferation and viability as early as 72 h post-exposure. (biomedcentral.com)
  • Notably, many lncRNAs dysregulation are associated with Oral squamous cell carcinoma (OSCC) and affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. (biomedcentral.com)
  • A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. (lookformedical.com)
  • In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes. (cdc.gov)
  • This task can be accomplished by replacing tumor suppressor genes that have been lost or mutated, selectively inserting genes that produce cytotoxic substances, or modifying the immune system to destroy the tumor cells. (medscape.com)
  • In the presence of Wnt signals, the Wnt proteins bind to (frizzled) frizzled receptors ( FZDs ) and low-density lipoprotein receptor-related protein ( LRP ) receptors, leading to the stabilization of β-catenin , its transfer to the nucleus, and the activation of target genes. (hindawi.com)
  • β-catenin forms a complex with T-cell factor ( TCF ) /lymphoid enhancer factor ( LEF ) transcription factors and cofactors such as histone acetyltransferase p300 (p300), CBP, BCL9, and pygopus, to transcribe Wnt signaling target genes such as Cyclin D1 , C-Myc , and survivin [ 9 , 12 - 15 ]. (hindawi.com)
  • Three jnk genes are expressed in eukaryotes and their products were initially thought to convey cell death signals. (utexas.edu)
  • 1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia. (cancerindex.org)
  • The genes that have been identified to date have been categorized into two broad categories, depending on their normal functions in the cell. (cancerquest.org)
  • Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
  • This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
  • Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
  • Many of these genes are responsible for providing the positive signals that lead to cell division. (cancerquest.org)
  • As stated in the introduction to this section, the defective versions of these genes, known as oncogenes, can cause a cell to divide in an unregulated manner. (cancerquest.org)
  • This is in contrast with tumor suppressor genes which must BOTH be defective to lead to abnormal cell division. (cancerquest.org)
  • Despite the differences in their normal roles, these genes all contribute to unregulated cell division if they are present in a mutant (oncogenic) form. (cancerquest.org)
  • By contrast, somatic alterations in the genes encoding Notch signaling components drive various types of human cancer, such as breast cancer, small-cell lung cancer (SCLC) and T-cell acute lymphoblastic leukemia (T-ALL) ( 6 - 9 ). (spandidos-publications.com)
  • Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. (medscape.com)
  • There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
  • Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness. (uc.edu)
  • Targeting the programmed death-1 pathway in lymphoid neoplasms. (cams.cn)
  • 1991. Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius on chick embryos in ovo and in mouse thymus anlagen in vitro . (cdc.gov)
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
  • The plasma membrane can be envisioned as a central compartment in the cellular adaptation to diverse stress conditions as it shapes the interactions between cells and their environment by harboring an elaborate complement of transmembrane proteins, e.g. transporters, channels, receptors, or adhesion proteins. (cell-stress.com)
  • In cellular biology, dependence receptors are proteins that mediate programmed cell death by monitoring the absence of certain trophic factors (or, equivalently, the presence of anti-trophic factors) that otherwise serve as ligands (interactors) for the dependence receptors. (wikipedia.org)
  • Thus cells that express these proteins at sufficient concentrations manifest a state of dependence on their respective ligands. (wikipedia.org)
  • DDR cascades are activated by ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) proteins, which are DNA damage sensors and members of the phosphatidylinositol-3 kinase-like family that amplify and transmit signals to downstream components ( Meek, 2009 ). (ppjonline.org)
  • The contents of inflammasome proteins were gradually increased after cerebral ischemia/reperfusion (I/R). EA stimulus attenuated NLRP3 inflammasome mediated inflammatory reaction and regulated the balance between proinflammatory factors and anti-inflammatory cytokines. (biomedcentral.com)
  • Specifically, we are interested in post-translational modifications, changes to a protein after it's produced, which add an incredible level of diversity to the underlying proteins within a cell and can control a diverse array of processes, including protein stability, interactions, and activity. (upenn.edu)
  • We focus on a group of proteins known as JNK (c-Jun N-terminal Kinases) which are activated by receptor tyrosine kinases in breast cancer models. (utexas.edu)
  • The plasma membrane is not only the first point of encounter for many types of environmental stress, but given the diversity of receptor proteins and their associated molecules also represents the site at which many cellular signal cascades originate. (cell-stress.com)
  • These cell surface proteins impinge on the vast majority of all cellular functions by mediating nutrient uptake, preserving ion homeostasis and initiating complex signaling cascades in response to extracellular cues. (cell-stress.com)
  • Cell proteins were analysed with 2-dimensional electrophoresis and differentially expressed proteins were identified by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. (who.int)
  • Our preliminary study using 2D isolates were recovered from liq- new cases throughout the world cu- gel electrophoresis in drug sensitive/ uid nitrogen, and sub-cultured in taneous leishmaniasis (CL) remains resistant strains of L. tropica showed RPMI1640 medium (Gibco/BRL) a serious public health problem in that some proteins were differentially supplemented with 10% fetal bovine numerous countries [1,2]. (who.int)
  • Background Fibroblast growth factor receptor 2 (FGFR2) alteration, including gene amplification and fusion, are closely associated with poor prognosis and low response to chemotherapy and immunotherapy in advanced gastric cancer (GC) patients. (bmj.com)
  • One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer. (biomedcentral.com)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022). (biomedcentral.com)
  • Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy[J].Chinese Medical Sciences Journal, 2018, 33(3): 174-182. (cams.cn)
  • The following is the list of known dependence receptors: Notch3 Kremen1 DCC (Deleted in Colorectal Carcinoma) UNC5 receptors (UNC5A, UNC5B, UNC5C, UNC5D) Neogenin p75NTR Ptch1 CDON PLXND1 RET TrkA TrkC EphA4 c-Met Insulin receptor IR Insulin-like growth factor 1 receptor ALK (anaplastic lymphoma kinase) Androgen receptor Some integrins NTRK3 Cells depend for their survival on stimulation that is mediated by various receptors and sensors. (wikipedia.org)
  • Positive survival signals involve classical signal transduction, initiated by interactions between ligands and receptors. (wikipedia.org)
  • Negative survival signals involve an alternative form of signal transduction that is initiated by the withdrawal of ligands from dependence receptors. (wikipedia.org)
  • A novel regulation of PD-1 ligands on mesenchymal stromal cells through MMP-mediated proteolytic cleavage. (cams.cn)
  • Animal modeling and human mechanistic data are summarized to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3 + CD4 + T-regulatory cell and CD4 + T-regulatory cell type 1 (Tr1) cell functions, and a Th1-Tr1 switch. (frontiersin.org)
  • These cells can be activated ex vivo to exhibit a potent antitumor effector function. (biomedcentral.com)
  • The study and/or manipulation of administered cells can potentially result in identification of the exact cell subpopulations and effector functions required for cancer regression in vivo. (biomedcentral.com)
  • The assay uses the Cdc42/Rac Interactive Binding (CRIB) region (also called the p21 Binding Domain, PBD) of the Cdc42 / Rac effector protein, p21 activated kinase 1 (PAK). (cytoskeleton.com)
  • In their review " Natural and Adaptive Immunity to Cancer ", Vesely and colleagues draw from recent mouse models of cancer and human clinical data to describe how cells, effector molecules, and pathways of the immune system act to suppress and control tumor cells. (massgenomics.org)
  • NLRP3/cryopyrin is a member of the NOD-like receptor (NLR) protein family that plays a pivotal role in the inflammatory response against pathogens and cellular damage. (nature.com)
  • Cells depend for their survival on stimulation that is mediated by various receptors and sensors, and integrated via signaling within the cell and between cells. (wikipedia.org)
  • Evidence for CD4 + T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4 + T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. (frontiersin.org)
  • Meanwhile, SHP2 is also an important downstream molecule of Programmed cell death protein-1 (PD-1) signaling. (bmj.com)
  • Given the immunosuppressive role of SHP2 under PD-1 signaling induction, we also proved that SHP099 treatment can significantly increase the secretion level of IFN-γ and downregulated the expression of PD-1 in human CD8+ T cells. (bmj.com)
  • 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)
  • 2009 ) and regulate the Reperfusion Injury Salvage Kinase (RISK) signaling pathway (ERKε, PKC, GSK-3β, STAT3) via cannabinoid receptor 1 (CB1R)(Wang et al. (biomedcentral.com)
  • An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling. (uc.edu)
  • Animal steroid hormones initiate signaling by passive diffusion into cells and binding to their nuclear receptors to regulate gene expression. (biologists.com)
  • Organisms usually contain large numbers of sphingolipid subspecies (for a pathway based compilation, see www.sphingomap.org) and knowledge about the types and amounts is imperative because they influence membrane structure, interactions with the extracellular matrix and neighboring cells, vesicular traffic and the formation of specialized structures such as phagosomes and autophagosomes, as well as participate in intracellular and extracellular signaling. (sphingolipidclub.com)
  • PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3 signalosome and downstream signaling to PKC theta. (cams.cn)
  • Posttranscriptional control of PD-L1 expression by 17β-estradiol via PI3K/Akt signaling pathway in ERα-positive cancer cell lines. (cams.cn)
  • Bystander effects are mediated via cell-to-cell gap junctions or through secreted, diffusible signaling molecules into the local milieu. (amegroups.org)
  • Notch signaling is aberrantly activated in breast cancer, non‑small‑cell lung cancer and hematological malignancies, such as T‑cell acute lymphoblastic leukemia and diffuse large B‑cell lymphoma. (spandidos-publications.com)
  • However, Notch signaling is inactivated in small‑cell lung cancer and squamous cell carcinomas. (spandidos-publications.com)
  • Notch signaling cascades crosstalk with fibroblast growth factor and WNT signaling cascades in the tumor microenvironment to maintain cancer stem cells and remodel the tumor microenvironment. (spandidos-publications.com)
  • While positive survival signals are clearly important, a complementary form of signal transduction is pro-apoptotic, and is activated or propagated by stimulus withdrawal or by the addition of an "anti-trophin. (wikipedia.org)
  • The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. (frontiersin.org)
  • 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)
  • In the absence of Wnt signals, the cytoplasmic catenin beta-1 ( β-catenin ) is associated with a complex including auxin, glycogen synthase kinase 3 ( GSK-3 ), and adenomatous polyposis coli ( APC ) (the APC protein acts as the primary regulator of β-catenin function). (hindawi.com)
  • In normal cells, both internal and external signals control the activity of the oncogenes. (cancerquest.org)
  • What this means for cells is that they divide continuously even in the absence of any signals telling them to divide. (cancerquest.org)
  • These DCs become active via toll-like receptors (TLRs) recognition, in which endogenous danger signals emitted by dying tumor cells are identified. (amegroups.org)
  • 29) analyzed Bis(s) zum effects for the amorphous gene and were how DNA guided in proportional cells of joint and possible protons performed to outcomes of important pairs generally in intracellular results. (scoutconnection.com)
  • With the increased understanding of molecular mechanisms and basic pathways in the pathogenesis of squamous cell cancer of the head and neck , these pathways may be modified, and rational approaches in cancer therapy at the molecular level may be created. (medscape.com)
  • Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. (medscape.com)
  • While certain aspects of stress-elicited adaptive programs such as the heat shock response or the oxidative stress response are very well studied, the contribution of other cellular pathways including endocytosis to cellular adaptation is still elusive. (cell-stress.com)
  • Organ failure in the heart or kidney can initiate various complex metabolic, cell-mediated and humoral pathways affecting distant organs, contributing to the high therapeutic costs and significantly higher morbidity and mortality. (biomedcentral.com)
  • Some of the downstream mediators have been identified, such as DAP kinase and the DRAL gene. (wikipedia.org)
  • Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is the shared downstream of all Receptor tyrosine kinases (RTKs). (bmj.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)
  • Conclusions In general, SHP099 can not only boost the tumor-cytotoxicity effect and overcome the drug resistance of AZD4547, but also activate cytotoxic T lymphocytes to kill tumor cells in FGFR2-alterated gastric cancers. (bmj.com)
  • In contrast to PTI, ETI induces stronger and long-lasting responses, which is frequently accompanied by programmed cell death, a process known as the hypersensitive response (HR), leading to pathogen resistance. (frontiersin.org)
  • Cell-autonomous recognition of the rust pathogen determines Rpl-specified resistance in maize. (springer.com)
  • Four wild-type (drug-sensitive) human breast cancer cell lines (MCF-7, T47D,MDA-MB-231, MDA-MB-435) were used to evaluate the influence of acute and chronic exposure to ceramide and ceramide metabolites on MDR1 mRNA,P-gp, and resistance to chemotherapeutic agents. (sphingolipidclub.com)
  • These cells not only demonstrated a 3-foldincrease in resistance to doxorubicin and a 9-fold increase in resistance to paclitaxel, but also showed increased efflux of rhodamine. (sphingolipidclub.com)
  • Van Den Berg, C.L., von Hoff, D.D. "Use of hydroxyurea to alter drug resistance of human tumor cells" In: Mugia FM, ed. (utexas.edu)
  • These cells play a key role in early resistance to intestinal pathogens. (frontiersin.org)
  • Regulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade. (cams.cn)
  • The progression from insulin resistance to type 2 diabetes is caused by the failure of pancreatic β cells to produce sufficient levels of insulin to meet the metabolic demand. (jci.org)
  • Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in β cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). (jci.org)
  • In both genetic and diet-induced models of insulin resistance, CHOP deficiency improved β cell ultrastructure and promoted cell survival. (jci.org)
  • One of the major hallmarks of GBM is the presence of GBM stem cells (GSCs), which are genetically heterogeneous cells with more distinct properties than primary tumor cells, and they play critical roles in disease recurrence and therapy resistance [ 9 ] [ 10 ] . (encyclopedia.pub)
  • However, multidrug-resistant (MDR) cancer cells may avoid the cytotoxic effects of chemotherapy by glycosylating ceramide. (sphingolipidclub.com)
  • On the other hand, phagosomes are formed when the pathogen is engulfed by macrophages and fuse with lysosomes to release enzymes and toxic substances, resulting in killing or having cytotoxic effects on bacteria and tumor cells. (frontiersin.org)
  • Mitochondrial reactive oxygen species (mtROS) driven by gefitinib stimulated the formation of the NLRP3 (NACHT, LRR and PYD-containing protein 3) inflammasome, leading to mature-IL-1β release. (nature.com)
  • We previously reported that interaction of viable commensal bacteria with mammalian intestinal epithelial cells resulted in a rapid and reversible generation of reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effects on the NF-κB pathway. (emory.edu)
  • We found that SAA not only promotes chemoresistance by inducing cancer stem transformation, but also restricts anti-tumor immunity and promotes tumor fibrosis by driving type 2 immunity, and α-SAA neutralization antibody could restrict treatment resistant and tumor fibrosis. (bvsalud.org)
  • Our data indicate that cancer stem cells secreted SAA have significant biological impact to promote treatment resistant and tumor fibrosis by driving cancer stemness transformation and type 2 immunity polarization via P2X7 receptor. (bvsalud.org)
  • Cancer progression is mainly driven by the expansion of tumor cells, but tumor microenvironment and anti-tumor immunity may also play a role. (amegroups.org)
  • As a consequence, they cannot directly activate the specific CD4+ T cell-mediated tumor immunity, which is essential for the development of adaptive immune responses. (amegroups.org)
  • Cigarette smoke exerts inflammatory and suppressive effects on immune cells, alters mucosal immunity and promotes autoimmunity, resulting in oral cancers [ 10 ]. (biomedcentral.com)
  • Nathanael Gray is the Krishnan-Shah Family Professor of Chemical and Systems Biology at Stanford, Co-Director of Cancer Drug Discovery Co-Leader of the Cancer Therapeutics Research Program, Member of Chem-H, and Program Leader for Small Molecule Drug Discovery for the Innovative Medicines Accelerator (IMA). (stanford.edu)
  • Gooch, J.L., Van Den Berg, C.L., Yee, D. Insulin-like growth factor (IGF)-I rescues breast cancer cells from chemotherapy-induced cell death- proliferative and anti-apoptotic effects. (utexas.edu)
  • The identification of chromosome 1 translocations and deletions is a rare and poorly investigated event in chronic lymphocytic leukemia (CLL). (cancerindex.org)
  • In cells of the mammalian immune system, PI3K is activated by receptors for antigen, cytokines, costimulatory molecules, and so on. (frontiersin.org)
  • The infarct size, neurological deficit score, TUNEL staining and the expression of proinflammatory factors or anti-inflammatory cytokines were evaluated at 72 h after reperfusion in the presence or absence of either α7nAChR antagonist (α-BGT) or agonist (PHA-543,613). (biomedcentral.com)
  • In contrast, α7nAChR antagonist reversed not only the neuroprotective effects, but also the inhibitory effects of NLRP3 inflammasome and the regulatory effects on the balance between proinflammatory factors and anti-inflammatory cytokines. (biomedcentral.com)
  • These cells can produce immunosuppressive cytokines and the recruitment of inhibitory and regulatory cell types, decrease expression of antigens, lose expression of MHC class I molecules, have an aberrant antigen processing, cause anergy or deletion of T cells, and generate the dysfunction of dendritic cells (DCs) ( 5 - 8 ). (amegroups.org)
  • Moreover, gain-of-function mutations in NLRP3 can cause the cryopyrin-associated periodic syndrome (CAPS), resulting in an aberrant oversecretion of IL-1β due to spontaneous activation of NLRP3 inflammasome 3 . (nature.com)
  • For instance, familial AD is linked to mutations in the amyloid precursor protein (APP), presenilin 1, and presenilin 2, all of which lead to increased levels of Aβ. (jneurosci.org)
  • novel mutations in sh2d1a gene in x-linked lymphoproliferative syndrome, diagnosed after b-cell non-hodgkin lymphoma. (liverpool.ac.uk)
  • x-linked lymphoproliferative disease type i (xlp i) is caused by mutations in the sh2d1a gene and characterized mainly by hypogammaglobulinemia and abnormal response to epstein-barr virus with a high predisposition to b-cell non-hodgkin lymphoma development. (liverpool.ac.uk)
  • It is believed that mutations in the deoxyribonucleic acid (DNA) signal the cells related to the esophagus to multiply abnormally [ 4 , 5 ]. (hindawi.com)
  • Loss‑of‑function NOTCH1 mutations are early events during esophageal tumorigenesis, whereas gain‑of‑function NOTCH1 mutations are late events during T‑cell leukemogenesis and B‑cell lymphomagenesis. (spandidos-publications.com)
  • [ 4 , 5 ] Recently, additional mutations have been identified in the GS-domain and kinase domain of ACVR1 in individuals with atypical forms of fibrodysplasia ossificans progressiva. (medscape.com)
  • In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. (nature.com)
  • The activation of DCs is characterized by the upregulation of cell surface molecules involved in antigen presentation and costimulation (e.g. (amegroups.org)
  • Depending on the molecules and testis age, highly deleterious effects of phytocannabinoid exposure were observed on testis tissue after 14 days, including Sertoli and germ cell death. (biomedcentral.com)
  • In 2007, a 15-year-old boy with X-linked agammaglobulinemia (XLA) caused by a missense mutation (Thr35Pro) in the Bruton tyrosine kinase ( Btk ) gene was admitted to a psychiatric facility in Seattle, WA, USA, because of suicidal and homicidal ideation, headache, memory loss, and ataxia. (cdc.gov)
  • To profile genomic and epigenomic of a naïve Chinese non-small cell lung cancer (NSCLC) cohort and investigate the association between tumor mutation burden (TMB) and DNA methylation (DNAm) to explore potential alternative/complimentary biomarkers for NSCLC immunotherapies. (biomedcentral.com)
  • The genetic cause of fibrodysplasia ossificans progressiva was identified as a recurrent missense mutation in the GS activation domain of activin receptor Ia/activinlike kinase 2 ( ACVR1/ALK2 ), a bone morphogenetic protein (BMP) type I receptor, in all individuals with classic fibrodysplasia ossificans progressiva. (medscape.com)
  • A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. (medscape.com)
  • [ 1 ] Early stage head and neck squamous cell carcinoma (HNSCC) is treated relatively well with single-modality therapy (either surgery or radiation alone). (medscape.com)
  • Go to Imaging of Nasopharyngeal and Laryngeal Squamous Cell Carcinoma and Head and Neck Squamous Cell Carcinoma for complete information on these topics. (medscape.com)
  • A phase II study showed that patients with resected local-regionally advanced head and neck squamous cell carcinoma (HNSCC) had improved survival when pembrolizumab was added to adjuvant RT (NCT02641093). (nature.com)
  • This cancer is divided into two types: (1) squamous cell carcinoma, which appears in the middle or top of the esophagus and (2) adenocarcinoma, seen in the glandular cells of the esophagus [ 1 ]. (hindawi.com)
  • We have selected a total of 89 treatment naïve lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) patients from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College who underwent definitive surgical resection before adjuvant therapy, including chemotherapy or radiotherapy. (biomedcentral.com)
  • In 2005, the first-ever trial combining small molecular targeted agent known as bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, with doublet chemotherapy, had shown superiority of overall survival with this treatment modality in advanced non-squamous non-small cell lung cancer patients without brain metastasis [ 2 ]. (biomedcentral.com)
  • Receptor tyrosine kinases (RTKs) convey pro-tumorigenic responses in breast, colon, lung, and prostate cancer. (utexas.edu)
  • We have found that in response to activation of RTKs, JNKs play critical roles in tumorigenesis, DNA damage, cell migration, and metastasis. (utexas.edu)
  • THC and CBD act on specific cannabinoid receptors called CB1 and CB2. (biomedcentral.com)
  • Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
  • Some proto-oncogenes work to regulate cell death. (cancerquest.org)
  • Since these receptors may support either cell death or cell survival, they initiate a new type of tumor suppressor, a conditional tumor suppressor. (wikipedia.org)
  • Together our results reveal the potential ability of gefitinib to initiate sterile inflammation via two distinct mechanisms, and identified IL-1β and HMGB1 as key determinants of gefitinib-induced inflammation that may provide insights into gefitinib-induced interstitial pneumonitis. (nature.com)
  • Cell cycle-specific with activity in the S-phase as single agent and has for many years been combined with biochemical modulator leucovorin.Has activity as single agent that inhibits DNA replication and transcription. (medscape.com)
  • 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. (medscape.com)
  • Here, we provide evidence that gefitinib elicits pro-inflammatory responses by promoting mature-interleukin-1β (IL-1β) and high-mobility group box 1 (HMGB1) release. (nature.com)
  • Furthermore, p53 as a transcription factor in DDRs is involved in innate and adaptive responses through recognizing immune receptors and activating immune cells such as T cells, B cells, NK cells, and macrophages. (ppjonline.org)
  • Our results demonstrate that formyl peptide receptor 1 (FPR1) and neutrophilic NADPH oxidase (NOX2) are required for the rapid depletion of microenvironmental oxygen and compensatory responses, resulting in a dramatic enrichment of an anaerobic bacterial consortium. (emory.edu)
  • Hence, cells have developed sophisticated stress responses to cope with these challenges. (cell-stress.com)
  • This receptor is found in moderate levels on some normal cells and as the gene's name implies, it is involved in cellular responses to growth factors. (cancerquest.org)
  • Bystander effects induced by radiation are characterized by biological responses, which are observed in non-irradiated cells that are in the vicinity of irradiated cells. (amegroups.org)
  • Although chemotherapy (CT) and traditional fractionated radiation have been described as immunosuppressive ( 2 ), recent data suggests that RT can modulate anti-tumor immune responses ( 3 ), modifying tumor and its microenvironment ( 4 ). (amegroups.org)
  • Clinical activity of TIL therapy has also been reported in other cancer types, including human papillomavirus-associated cancers, cholangiocarcinoma, non-small-cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). (biomedcentral.com)
  • Presently, the clinical treatment for diabetic retinopathy is limited to pan-retinal photocoagulation and vitrectomy for late proliferative disease and anti-VEGF therapy for controlling macular edema that impairs vision. (molvis.org)
  • Clinical evidence suggests that tissue injury such as acute kidney injury (AKI) is not an isolated event and it has become apparent that much of the increased risk of death is derived from distant complications [ 5 , 6 ]. (biomedcentral.com)
  • Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia. (lookformedical.com)
  • Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. (spandidos-publications.com)
  • Cancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. (bvsalud.org)
  • These results suggest that the slow progression and lack of full-fledged Alzheimer's disease pathology in the hippocampal neurons of APP Sw mice result from the genetic reprogramming of neural cells to cope with increased levels of Aβ. (jneurosci.org)
  • PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression. (cams.cn)
  • The lamina propria of the small intestine is the main site of the intestinal immune system, which contains a large number of macrophages, CD4 T cells, and dendritic cells. (frontiersin.org)
  • Ionizing radiation therapy (RT), either alone or in combination with additional immune stimulators, can render cancer cells visible to the immune system. (amegroups.org)
  • The interaction of all these factors could lead to cancer cells escaping the immune system ( 6 ). (amegroups.org)
  • The idea that the immune system might recognize and destroy tumor cells was conceived 50-100 years ago. (massgenomics.org)
  • The presence of macrophages, lymphocytes and mast cells in early fibrodysplasia ossificans progressiva lesions, macrophage and lymphocyte-associated death of skeletal muscle, flare-ups following viral infections, the intermittent timing of flare-ups, and the beneficial response of early flare-ups to corticosteroids support involvement of the innate immune system in the pathogenesis of fibrodysplasia ossificans progressiva lesions. (medscape.com)
  • These data are the first evidence that chronic exposure to ceramide and its metabolites enhances expression of the MDR phenotype in cancer cells. (sphingolipidclub.com)
  • Macrophages, which are functional plasticity cells, have the ability to phagocytize and digest foreign substances and acquire pro-(M1-like) or anti-inflammatory (M2-like) phenotypes according to their microenvironment. (frontiersin.org)
  • The targeted intraoperative radiotherapy (TARGIT) method, using INTRABEAM ® , could reduce tumor recurrence, modifying the wound microenvironment, and eradicating residual tumor cells when applied immediately after surgery procedure. (amegroups.org)
  • Besides the direct effects of radiation in reducing viable cancer cells, RT may induce modifications on the local microenvironment that can affect tumor development ( 5 ). (amegroups.org)
  • In mammalian cells, there are three types of PI3K with distinct substrate specificities. (frontiersin.org)
  • ATM and ATR are directly targeted and phosphorylated in mammalian cells by Chk1 and Chk2. (ppjonline.org)
  • The large number of macrophages in the intestinal tract, play a significant role in maintaining the homeostasis of microorganisms on the surface of the intestinal mucosa and in the continuous renewal of intestinal epithelial cells. (frontiersin.org)
  • On the other hand, gefitinib-driven mtROS promoted the accumulation of γH2AX, a hallmark of DNA damage, leading to the activation of poly (ADP-ribose) polymerase-1 (PARP-1) and subsequent active release of HMGB1. (nature.com)
  • In addition to the direct effects of radiation, the ensuing immune response promotes the expression of inflammatory and immunostimulatory mediators, which act on neighboring, non-irradiated, cells. (amegroups.org)