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  • ||||||||||  CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers (Section 13) -  Mar 5, 2024 - Abstract #AACR2024AACR_9547;    
    We find that inhibition of CRIPTO with A4Fc suppresses cancer associated fibroblast (CAF) activation and collagen remodeling in vivo. Further, by modeling tumor cell:fibroblast crosstalk in vitro, we have demonstrated mechanistically that CRIPTO expression in tumor cells mediates subsequent extracellular vesicle (EV) uptake by fibroblasts, as well as fibroblast SMAD pathway activation and priming for reciprocal signaling back to tumor cells to promote transcriptional reprogramming and cellular invasion.The significance of these findings lies in their elucidation of key EV control mechanisms that could be exploited to intervene in essential tumor cell:fibroblast crosstalk or to enhance targeting of therapeutic moieties based on EV architecture and function in cancer and/or normative regenerative processes.
  • ||||||||||  CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers (Hall 2-3) -  Nov 4, 2023 - Abstract #SABCS2023SABCS_1317;    
    The significance of these findings lies in their potential to pave the way for the development of new therapies specifically targeting crucial tumor cell:fibroblast crosstalk mechanisms at primary and metastatic sites. Plasticity targeting therapies are urgently needed in the treatment of TNBC and other malignancies, and hold great promise for improving patient outcomes.
  • ||||||||||  [VIRTUAL] miR299a-5p Is a Novel Mediator of Fibrosis in Diabetic Kidney Disease () -  Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_2005;    
    Through suppression of two important antifibrotic proteins, CR-1 and FST, miR299a-5p potentiates the action of TGFβ family profibrotic cytokines. Future studies will determine whether inhibition of this miR can attenuate DKD.
  • ||||||||||  thapsigargin / University of Nottingham, Pirbright Institute
    Journal:  Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response. (Pubmed Central) -  Jul 14, 2021   
    In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume...Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.
  • ||||||||||  Journal:  Role of Oncofetal Protein CR-1 as a Potential Tumor Marker for Oral Squamous Cell Carcinoma. (Pubmed Central) -  Jul 6, 2021   
    This study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.
  • ||||||||||  Journal:  Evidence that activin A directly modulates early human male germline differentiation status. (Pubmed Central) -  Jun 22, 2021   
    This study showed that activin A can directly modulate germline markers in this human gonocyte-like cell, promoting a less-differentiated phenotype. Additional findings indicate evidence of signaling crosstalk between activin A and NODAL, leading to target-specific effects on gonocyte differentiation.
  • ||||||||||  Journal:  CRIPTO antagonist ALK4-Fc inhibits breast cancer cell plasticity and adaptation to stress. (Pubmed Central) -  Jun 22, 2021   
    Identifying mechanisms that govern cellular adaptation, plasticity, and the emergence of stem-like cancer cells may be key to effective anticancer therapies. Results presented here indicate that targeting CRIPTO with ALK4-Fc may have potential as such a therapy since it inhibits breast cancer cell adaptation to microenvironmental challenges and associated stem-like and EMT phenotypes.
  • ||||||||||  Journal:  The Role of Nodal and Cripto-1 in Human Oral Squamous Cell Carcinoma. (Pubmed Central) -  Jun 16, 2021   
    Further investigation showed that the combination treatment with both Nodal and CR-1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR-1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.
  • ||||||||||  Review, Journal, Cancer stem cells:  Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy. (Pubmed Central) -  Jun 3, 2021   
    In recent years, it has been reported that Cripto-1 could be a potential therapeutic target in CSCs. Here, we review the accumulated literature on the molecular mechanisms by which Cripto-1 functions in CSCs and discuss the potential of Cripto-1 as an immunotherapeutic target in CSCs.
  • ||||||||||  Journal:  Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer (Pubmed Central) -  May 11, 2021   
    Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ =4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.
  • ||||||||||  Journal:  Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle. (Pubmed Central) -  Apr 28, 2021   
    This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206 anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.
  • ||||||||||  Journal:  A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth. (Pubmed Central) -  Apr 13, 2021   
    Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.
  • ||||||||||  Biomarker, Journal:  An evaluation of different Cripto-1 antibodies and their variable results. (Pubmed Central) -  Mar 19, 2021   
    The cripto-1 expression was varied for the different antibodies with respect to cellular localization and fixation methods. To further elaborate on these findings, we present a systematic review of cripto-1 antibodies found in the literature and highlight some possible cross reactants with data on sequence alignments and structural comparison of EGF domains.
  • ||||||||||  Journal:  PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins. (Pubmed Central) -  Feb 24, 2021   
    In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the CFC (Cripto-1/FRL1/Cryptic) domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4 and contactin-1 in addition to CRIPTO are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.
  • ||||||||||  Journal:  Structure-based design of small bicyclic peptide inhibitors of Cripto-1 activity. (Pubmed Central) -  Dec 17, 2020   
    The functional effects of B3 on the Cripto-1-positive NTERA cancer cell line have been evaluated showing that both CFC and B3 are cytotoxic for the cells and block the Cripto-1 intracellular signaling. Altogether, the data suggest that administration of the soluble CFC and of the structurally related analogue has the potential to inhibit tumor growth.
  • ||||||||||  Biomarker, Journal:  Beneficial effects of Cripto-1 for transarterial chemoembolization in hepatocellular carcinoma. (Pubmed Central) -  Jun 19, 2020   
    In different subgroups of vascular invasion, larger tumor size or liver cirrhosis, patients with adjuvant TACE had longer TTR and OS times than those without TACE in patients with high Cripto-1 expression, while they could not obtain benefits from adjuvant TACE in patients with low-expressed Cripto-1 expression. In conclusion, Cripto-1 may be a potential prognostic factor in predicting outcome of HCC patients with TACE therapy, and combined with Cripto-1 and tumor features may be helpful to stratify patients with respect to prognosis and response to adjuvant TACE.
  • ||||||||||  Biomarker, Journal:  The function and prognostic significance of Cripto-1 in colorectal cancer. (Pubmed Central) -  May 11, 2020   
    Cripto-1-silenced colorectal cancer cell lines had reduced cell proliferation, migration, and activation of Akt and MAPK signaling pathways in vitro, and decreased tumor growth and lymph node metastasis in vivo. Cripto-1 could be a useful prognostic biomarker and therapeutic target in colorectal cancer.
  • ||||||||||  Biomarker, Clinical, Journal:  Cripto-1 expression in patients with clear cell renal cell carcinoma is associated with poor disease outcome. (Pubmed Central) -  Mar 13, 2020   
    We have provided the largest dataset of evaluation of CRIPTO in serum and seminal plasma of GCTs, showing its potential value as a biomarker of the disease. These results suggest that CR-1 is likely to play important roles in ccRCC development and progression, and that CR-1 is a prognostic biomarker and a promising therapeutic target for ccRCC.
  • ||||||||||  Journal:  Investigating the oxidative refolding mechanism of Cripto-1 CFC domain. (Pubmed Central) -  Feb 7, 2020   
    Data altogether support a mechanism whereby the Cripto-1 CFC domain refolds by virtue of long-range intramolecular interactions that involve residues close to cysteines of the second and third bridge. These findings are supported by the in silico study that shows how distant parts of the molecules come into contact on a long time scale.