• 10. Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone destruction. (nih.gov)
  • Stattic also suppressed RANKL-induced upregulation of osteoclast-related genes tartrate-resistant acid phosphatase, matrix metalloproteinase 9, cathepsin K, RANK, tumor necrosis factor receptor-associated factor 6, and osteoclast-associated receptor in RAW264.7 cells. (pdgfreceptor.com)
  • Following successful antigen-specific activation in secondary lymphoid tissues, T cells begin to produce numerous pro-inflammatory cytokines such as interleukin (IL)-2, -4, -5, -6 and -8, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon γ (IFN-γ), etc. (3). (biochemia-medica.com)
  • 5 ] RANKL, a member of the tumor necrosis factor (TNF) family, plays crucial roles in osteoclast differentiation and activation. (e-jbm.org)
  • This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. (nih.gov)
  • This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. (nih.gov)
  • Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis. (ima-press.net)
  • Binding of RANKL to its receptor, RANK, recruits TNF receptor-associated factor 6 (TRAF6) to sequentially activate NF-κB, nuclear factor of activated T cells (NFATc1) and c-Fos, which are master regulators of osteoclast differ- entiation [2,3]. (pdgfreceptor.com)
  • 3 , 6 ] The binding of RANKL to its receptor RANK in osteoclast precursor cells induces TNF receptor-associated factor 6 (TRAF6) recruitment and the sequential activation of multiple intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38 MAPK, and the NF-kB pathway. (e-jbm.org)
  • Cathepsin K, among other cathepsins, plays a role in cancer metastasis through the degradation of the extracellular matrix. (wikipedia.org)
  • However, unlike other hematologic malignancies diffusely infiltrating the marrow, it behaves like a tumor metastasis with the involvement of the bone. (tmeresearch.org)
  • First, however, it is important to discuss some of the newer information on the biology of tumor metastasis that has been derived from the methods of molecular pathology. (basicmedicalkey.com)
  • and (5) form deposits capable of surviving in the new environment 10 ( Fig. 19-1, A ). The basic biology, molecular mechanisms, and genetic and epigenetic changes that drive these steps are extremely complex and probably differ depending on the source of the metastasis and specific type of tumor. (basicmedicalkey.com)
  • Major biologic phenomena associated with tumor progression and metastasis. (basicmedicalkey.com)
  • Although biologic phenomena associated with tumor progression and metastasis are usually present as sequence of orderly events, in reality tumor cells may develop these properties in a virtually haphazard pattern. (basicmedicalkey.com)
  • B, Summary of molecular changes associated with tumor cell interaction with various stromal components essential for invasive growth and metastasis. (basicmedicalkey.com)
  • Muc16 depletion diminishes KRAS-induced tumorigenesis and metastasis by altering tumor microenvironment factors in pancreatic ductal adenocarcinoma. (unmc.edu)
  • The expression of cathepsin K in cultured endothelial cells is regulated by shear stress. (wikipedia.org)
  • A complex interaction between osteoclasts, endothelial cells, BM matrix, myeloid as well as the lymphoid elements and the malignant PCs occurs at the level of the microenvironment favoring the expansion of latter cells and their spread. (tmeresearch.org)
  • A, To metastasize, tumor cells must gain several unique biologic properties such as invasive growth, induction of vascular growth, vascular invasion, adherence to endothelial cells or thrombosis of peripheral sinusoids, continuation of invasive growth with extravasation, and formation of primary and secondary metastatic foci. (basicmedicalkey.com)
  • Cathepsin B has also been implicated in the progression of various human tumors including ovarian cancer. (wikipedia.org)
  • 15. Human C-reactive protein binds activating Fcgamma receptors and protects myeloma tumor cells from apoptosis. (nih.gov)
  • Bisphosphonates inhibit osteoclast recruitment and maturation, prevent the development of monocytes into osteoclasts, induce osteoclast apoptosis and interrupt their attachment to the bone. (medscape.com)
  • 10 , 11 , 12 ] NFATc1 then translocates to the nucleus and activates the expression of multiple osteoclastogenesis-related genes, such as cathepsin K (CTK), c-Src, and tartrate-resistant acid phosphatase (TRAP). (e-jbm.org)
  • [ 1 ] This article focuses on cutaneous paraneoplastic syndromes caused by solid tumors. (medscape.com)
  • The maladaptive nature of myeloma PCs and the BM microenvironment niche has been recognized to play a crucial role in the pathogenesis and progression of the disease which behaves in a manner similar to solid tumors in their growth and dissemination. (tmeresearch.org)
  • It has been shown that some pro-inflammatory cytokines could possess osteoclastogenic and/or anti-osteoclastogenic properties and can target osteoclasts directly or via receptor activator of nuclear factor κB (RANK)/RANK ligand(RANKL)/osteoprotegerin (OPG) system. (biochemia-medica.com)
  • 6 , 9 By modulating hematopoietic cells to increase fibronectin production and by directly producing factors that render the bone microenvironment receptive, tumors are able to prepare the bone for metastases. (basicmedicalkey.com)
  • SAR114137, a Cathepsin S inhibitor, did not progress past phase I for chronic pain. (wikipedia.org)
  • In 2022, STI-1558, a Cathepsin L inhibitor, received FDA clearance to begin phase I studies to treat COVID-19. (wikipedia.org)
  • Microfluidic Platform for Microparticle Fabrication and Release of a Cathepsin Inhibitor. (nih.gov)
  • Thus, Stattic represents a novel type of osteoclast inhibitor that could be useful for conditions such as osteoporosis and rheumatoid arthritis. (pdgfreceptor.com)
  • Matrix metalloproteinase 2 (MMP2) is a well‑characterized protein that is indispensable for extracellular matrix remodeling and other pathological processes, such as tumor progression and skeletal dysplasia. (nih.gov)
  • Here we discuss the mechanisms by which macrophages get activated and their important role in tumor progression. (molcells.org)
  • Cathepsin B may function as a beta-secretase 1, cleaving amyloid precursor protein to produce amyloid beta. (wikipedia.org)
  • Overexpression of the encoded protein, which is a member of the peptidase C1 family, has been associated with esophageal adenocarcinoma and other tumors. (wikipedia.org)
  • Osteoclasts are the bone resorbing cells of the body, and they secrete cathepsin K in order to break down collagen, the major component of the non-mineral protein matrix of the bone. (wikipedia.org)
  • 8. Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma. (nih.gov)
  • 11. The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors. (nih.gov)
  • 16. C-reactive protein (CRP) up-regulates expression of receptor for advanced glycation end products (RAGE) and its inflammatory ligand EN-RAGE in THP-1 cells: inhibitory effects of atorvastatin. (nih.gov)
  • Under the assumption that the primary mechanism http://www.selleckchem.com/products/Perifosine.html of tumor eradication is, in fact, the protein kinase inhibition enacted by these targeted drugs, a natural consequence would be the existence of a relationship between the IC50 and EC50 values. (screeninglibraries.com)
  • Tumor cells home in to bone via the same protein interactions that hematopoietic stem cells use, relying on integrins, chemokines, bone morphogenetic proteins, and osteopontin, among others, to settle in bone. (basicmedicalkey.com)
  • This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. (nih.gov)
  • However, the encoded protein is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. (nih.gov)
  • 2. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma. (nih.gov)
  • 3. p38 MAPK in myeloma cells regulates osteoclast and osteoblast activity and induces bone destruction. (nih.gov)
  • 5. Gene silencing of the BDNF/TrkB axis in multiple myeloma blocks bone destruction and tumor burden in vitro and in vivo. (nih.gov)
  • 19. Interactions of myeloma cells with osteoclasts promote tumour expansion and bone degradation through activation of a complex signalling network and upregulation of cathepsin K, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). (nih.gov)
  • Several families of MMPs are involved in atherogenesis, myocardial infarction, angiogenesis and tumor invasion and metastases ( 8-11 ). (nih.gov)
  • Once the primary site is established, tumor development is spurred by angiogenesis. (molcells.org)
  • In reality, high sensitivity to a drug is often attributed to a family of related kinases or several independent kinases working synergistically over one or multiple pathways to induce tumor death. (screeninglibraries.com)
  • Forty years ago, before the development of tamoxifen, high-dose estrogen was used to induce tumor regression of hormone-dependent breast cancer in post-menopausal women. (biomedcentral.com)
  • Morphological, biochemical and chromosomal characterization of breast tumor lines from pleural effusions. (fuxiangbio.com)
  • Mutually exclusive genetic signatures of human breast tumor cell lines with a common chromosomal marker. (fuxiangbio.com)
  • Breast tumor cell lines from pleural effusions. (fuxiangbio.com)
  • Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBP expression and contributes to transformation of breast tumor cells. (tamu.edu)
  • Stattic inhibited osteoclast differentiation and bone resorption in RANKL-induced RAW264.7 cells in a dose-dependent manner. (pdgfreceptor.com)
  • Although the effects of Stattic in cancer and autoimmune diseases have been widely studied [8,9], its effects on RANKL-mediated osteoclast differ- entiation remain unknown. (pdgfreceptor.com)
  • We found that Stattic markedly in- hibited RANKL-mediated multinucleated osteoclast formation, and that this inhibitory effect was achieved through suppression of STAT3 and NF-κB signaling pathways. (pdgfreceptor.com)
  • This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. (e-jbm.org)
  • In mammals, receptor activator of NF-κB ligand (Rankl) is a regulator of osteoclast formation and activation: its misexpression causes osteoclast stimulation and osteoporotic bone loss. (biologists.com)
  • We generated transgenic medaka lines that express GFP under control of the cathepsin K promoter in osteoclasts starting at 12 days post-fertilization (dpf), or Rankl together with CFP under control of a bi-directional heat-shock promoter. (biologists.com)
  • Upon Rankl induction, GFP-positive osteoclasts are first observed in the intervertebral regions and then quickly migrate to the surface of mineralized neural and haemal arches, as well as to the centra of the vertebral bodies. (biologists.com)
  • Osteoclasts, derived from hematopoietic precursors of the monocyte/macrophage lineage, are bone-specialized multinucleated cells. (e-jbm.org)
  • 3 , 4 ] M-CSF is important for the proliferation and survival of the osteoclast precursors and upregulates RANK expression, which is a prerequisite for osteoclastogenesis. (e-jbm.org)
  • The genetic knockout for cathepsin S and K in mice with atherosclerosis was shown to reduce the size of atherosclerotic lesions. (wikipedia.org)
  • Mouse cathepsin L is homologous to human cathepsin V. Mouse cathepsin L has been shown to play a role in adipogenesis and glucose intolerance in mice. (wikipedia.org)
  • Cathepsin L-deficient mice were shown to have less adipose tissue, lower serum glucose and insulin levels, more insulin receptor subunits, more glucose transporter (GLUT4) and more fibronectin than wild type controls. (wikipedia.org)
  • Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S. (nih.gov)
  • Sickle cell disease promotes sex-dependent pathological bone loss through enhanced cathepsin proteolytic activity in mice. (nih.gov)
  • Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. (nih.gov)
  • these experiments showed enhanced CT contrast of the vasculature, kidneys, and tumor in mice. (nih.gov)
  • High levels of this enzyme in tumor cells seems to be associated with greater invasiveness. (wikipedia.org)
  • Overexpression of matrix metalloproteinases (MMPs) and other proteases by tumor cells allows intravasation of tumor cells into the circulatory system after degrading the basement membrane and ECM ( 3 ). (nih.gov)
  • Osteoclasts (OCs), derived from monocyte/macrophage lineage, are deifferentiated into mature, multinucleated OCs (a process also known as osteoclastogenesis) via a series of osteoclastogenic signaling pathways, are responsible for resorbing bone. (asmepress.com)
  • ETHNOPHARMACOLOGICAL RELEVANCE: Wear particle-induced inflammatory osteoclast activation is a master contributor to periprosthetic osteolysis, which can cause pathological bone loss and destruction. (bvsalud.org)
  • Cathepsin A increased in muscles moderately affected by muscular dystrophy and denervating diseases. (wikipedia.org)
  • Thus, targeting STAT3 may be an inspiring strategy for treating osteoclast-related diseases such as rheumatoid arthritis. (pdgfreceptor.com)
  • Initially, the interplay between immune cells and osteoclasts has been observed in clinical settings of increased bone resorption following glucocorticoid therapy and in typical inflammatory bone diseases, such as rheumatoid arthritis (RA) and periodontal disease. (biochemia-medica.com)
  • Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. (e-jbm.org)
  • Cy5.5-MMP-AuNPs are being developed for NIR fluorescence imaging of MMPs expressed in tumors, atherosclerosis, myocardial infarction, and other diseases. (nih.gov)
  • In other words, Inhibitors,Modulators,Libraries if 50% inhibition of a kinase target directly correlates with 50% of the tumor cells losing viability, then inhibition of the kinase target is most likely one of the causes of cell death. (screeninglibraries.com)
  • Cathepsin D (an aspartyl protease) appears to cleave a variety of substrates such as fibronectin and laminin. (wikipedia.org)
  • Cathepsin L degrades fibronectin, insulin receptor (IR), and insulin-like growth factor 1 receptor (IGF-1R). (wikipedia.org)
  • Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. (nih.gov)
  • The present data suggest that ELL has an inhibitory effect on osteoclast differentiation and function via downregulation of the p38/c-Fos/NFATc1 signaling pathways. (e-jbm.org)
  • Stroke Traumatic brain injury Alzheimer's disease Arthritis Ebola, Cathepsin B and to a lesser extent cathepsin L have been found to be necessary for the virus to enter host cells. (wikipedia.org)
  • Now days, we have firm evidence on the influence of numerous pro-inflammatory cytokines on bone cells, with the majority of data focused on osteoclasts, the bone resorbing cells. (biochemia-medica.com)
  • Depending on their influence on osteoclast differentiation, activation or survival, the pro-inflammatory cytokines can roughly be divided into osteoclastogenic, if they stimulate osteoclasts, or anti-osteoclastogenic, if they inhibit these unique bone-resorbing cells. (biochemia-medica.com)
  • Invasive tumor cells adhere to the ECM, which provides a matrix environment for permeation of tumor cells through the basal lamina and underlying interstitial stroma of the connective tissue. (nih.gov)
  • The ability of tumor cells to invade within their host organ and their ability to metastasize to distant sites are two biologic hallmarks of malignancy. (basicmedicalkey.com)
  • Before metastasizing, tumor cells prepare distant sites to receive metastatic deposits by creating a premetastatic niche. (basicmedicalkey.com)
  • 5 Once tumor cells have become disseminated, the local environment within the metastatic site, or metastatic niche, is important in determining whether tumor cells are able to survive. (basicmedicalkey.com)
  • After induction neovascularization by tumor cells in the primary organ, the tumor cells invade into the vessels and are embolized to distant sites. (basicmedicalkey.com)
  • Those tumor cells that are able to survive in transit become lodged in capillaries within a secondary site such as bone, adhere to the endothelium, and eventually extravasate through the capillary wall and into the stroma, where they proliferate and ultimately form clinically significant masses. (basicmedicalkey.com)
  • Osteoclasts are macrophage-related bone resorbing cells of hematopoietic origin. (biologists.com)
  • Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells. (tamu.edu)
  • In vivo delivery of TK-NTR and administration of prodrugs led to the effective killing of both targeted cells and surrounding tumor cells via TK-NTR-mediated conversion of co-delivered prodrugs into active cytotoxic agents. (regenerativemedicine.net)
  • In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR-encoding MCs. (regenerativemedicine.net)
  • The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. (wikipedia.org)
  • The general surgical pathologist is far more likely to encounter a skeletal focus of metastatic cancer than any of the primary malignant bone tumors. (basicmedicalkey.com)
  • Elevated levels of MMPs have been found in tumors associated with a poor prognosis for cancer patients ( 12 ). (nih.gov)
  • Tumor Microenviron [serial online] 2018 [cited 2023 Dec 3];1:1-8. (tmeresearch.org)
  • The two main causes of osteoporosis are an increase in osteoclast activity or quantity and a decrease in osteoblast viability. (frontiersin.org)
  • Bone homeostasis is delicately regulated by osteoclast-mediated bone resorption and osteoblast-induced bone formation. (e-jbm.org)
  • Lastly, Aplidin alone, or suboptimal doses of Aplidin combined with Dex or Btz, decreased tumor growth and bone resorption in ex vivo bone organ cultures that reproduce the 3D-organization and the cellular diversity of the MM/bone marrow niche. (oncotarget.com)
  • Cathepsins B and L are involved in matrix degradation and cell invasion. (wikipedia.org)
  • Further, Aplidin markedly decreased osteoclast precursor numbers and differentiation, and reduced mature osteoclast number and resorption activity. (oncotarget.com)
  • http://www.selleckchem.com/products/Cisplatin.html 8% of mutations identified from the screening of 141 tumor samples, while 10. (screeninglibraries.com)
  • Patients frequently present with signs and symptoms related to metastatic bone lesions before a primary tumor has come to clinical attention, and severe pain or a pathologic fracture is commonly the presenting complaint. (basicmedicalkey.com)
  • Prediction of clinical benefits of somatostatin analogues in patients with neuroendocrine tumors (NET) is very important prior to their administration. (almclinmed.ru)
  • Cathepsin K is the most potent mammalian collagenase. (wikipedia.org)
  • Expressions of SMAD3 and SMAD4 are up regulated in breast carcinoma Using publically available online tissue expression data, SMAD3 and SMAD4 expression in breast tumors versus normal breast tissue were assessed using two independent samples t test and Levins test for the equality of variance. (screeninglibraries.com)
  • SMAD3 and SMAD4 mRNA expression levels were found to be significantly elevated in the tumor tissues compared to normal tissues for four of five probes and one of two probes. (screeninglibraries.com)
  • TAMs can typically be identified by low expression of tumor necrosis factors (TNF) and high expression of IL-1 and IL-6. (molcells.org)
  • Because fine-needle aspiration cytology plays a major role in diagnosing metastatic lesions affecting the skeleton, we include in this chapter a brief description of cytologic features of metastatic tumors in bone. (basicmedicalkey.com)
  • These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy. (regenerativemedicine.net)