- |||||||||| Journal: Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism. (Pubmed Central) - Nov 13, 2024
Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.
- |||||||||| Journal: Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function. (Pubmed Central) - Aug 17, 2024
Further, GDE2 deficits are evident in human neural cell models of ALS, which display erroneous Wnt activation that, when inhibited, increases mRNA levels of genes regulated by TDP-43. Our study identifies GDE2 as a critical physiological regulator of Wnt signaling in adult neurons and highlights Wnt pathway activation as an unappreciated mechanism contributing to nucleocytoplasmic transport and TDP-43 abnormalities in disease.
- |||||||||| gemcitabine / Generic mfg.
Journal: Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer. (Pubmed Central) - Jun 14, 2024 This paper discusses the potential utility of the LGR5+ pig model in exploring the role of LGR5+ cells in tissue development and regeneration with the goal of translating these findings into human and animal clinical applications. These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.
- |||||||||| nintedanib / Generic mfg.
Understanding the Dynamics of Pro-Fibrotic Biomarkers in Precision-Cut Lung Slices: Implications for Preclinical Studies (PS-29; Poster board no. 9) - May 31, 2024 - Abstract #ERS2024ERS_3389; Nintedanib treatment decreased SFTPD by up to 44% and MMP9 up to 64%, with limited effect on PDGFB after 48h of culture. Our study underscores the value of PCLS for unraveling the complex molecular landscape of PF and provides insights into the dynamics of pro-fibrotic markers, Wnt pathway activation, and Nintedanib treatment, highlighting the PCLS as an important approach to advance our understanding of PF pathogenesis.
- |||||||||| Biomarker, Retrospective data, Journal: Utility of LEF1 to differentiate desmoid fibromatosis from its histologic mimics. (Pubmed Central) - May 20, 2024
Positivity for LEF1 and ?-catenin in combination showed sensitivity of 89%, lower than the sensitivity of ?-catenin alone (94%); however, the combination of both LEF1 and ?-catenin improved specificity (96%) compared to the specificity of ?-catenin alone (88%). Although LEF1 has imperfect specificity in isolation, this stain has diagnostic utility when used in combination with ?-catenin.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
DRUG RESISTANCE IN ACUTE LYMPHOBLASTIC LEUKEMIA IS ASSOCIATED WITH INCREASED WNT-SIGNALING ACTIVITY AND CAN BE OVERCOME BY CO-TARGETING BCL-2 (Poster Area (Hall 7)) - May 15, 2024 - Abstract #EHA2024EHA_3402; A shRNA library screen was performed in the ALL cell line NALM-6 exposed to vincristine, dexamethasone andasparaginase...Most interestingly, no increased resistance for the BCL-2 inhibitor venetoclax (VEN) was found inWnt-high ALL lines as compared to Wnt-low cells... Taken together, resistance to induction therapy drugs in ALL is associated withincreased Wnt signaling activity and can be overcome by co-targeting Wnt signaling and anti-apoptotic BCL-2resulting in synergistic anti-leukemia activity.
- |||||||||| PREVOTELLA COPRI PROMOTES INTESTINAL CARCINOGENESIS BY ACTIVATING THE WNT SIGNALING PATHWAY (Hall A) - Mar 14, 2024 - Abstract #DDW2024DDW_5407;
Butyricicoccus was negatively correlated with the expression of Sirt Mmp7 and Il1b while Harryflintia was positively relevant with Ldha Klf4 B nip 3 l Wnt9a etc. Conclusions : P. copri drives colorectal tumorigenesis through inducing gut barrier dysfunction the Wnt pathway activation and gut microbial dysbiosis with SCFAs-producing bacteria decreased. This confirms the close relationship between gut microbiota dysbiosis and CRC suggesting that novel strategies targeting the gut microbiota may be effective against CRC.
- |||||||||| Review, Journal: Wnt signaling in cell adhesion, development, and colon cancer. (Pubmed Central) - Jan 17, 2024
The main conclusion that emerges from these studies is that in basal cell conditions, the activity of the key protein kinase GSK3, which is inhibited by Wnt pathway activation, normally represses the actin machinery that orchestrates macropinocytosis with implications in cancer. These contributions expand our understanding of the multifaceted roles of Wnt signaling in cellular processes, development, and cancer, providing insights into potential therapeutic targets and strategies.
- |||||||||| Journal: Resveratrol's Impact on the Chondrogenic Reagents' Effects in Cell Sheet Cultures of Wharton's Jelly-Derived MSCs. (Pubmed Central) - Dec 26, 2023
The mouse knee defect model experiment revealed that hWJ-MSC sheets grown with the addition of resveratrol and Y27632 were well integrated with the surrounding tissues; however, after 3 months, the restored tissue was identical to that of the naturally healed cartilage injury. Thus, the combination of chondrogenic supplements may not always have additive effects on the progress of cell culture and could be neutralized by the microenvironment after transplantation.
- |||||||||| RG2833 / BioMarin, Johns Hopkins University
Schlafen11 is a powerful biomarker of chemosensitivity in medulloblastomas (Room 121-122) - Nov 11, 2023 - Abstract #SNO2023SNO_1515; Importantly, markedly increased sensitivity to cisplatin and SN-38 was seen in initially SLFN11-negative medulloblastoma cells also treated with RG2833, suggesting an approach by which more aggressive medulloblastoma subtypes might be targeted. Our findings suggest a novel mechanism for the increased chemosensitivity of some medulloblastoma subtypes linked to a specific biomarker, as well as a novel combinatorial chemotherapeutic strategy for the treatment of more aggressive medulloblastoma subtypes (Groups 3 and 4) lacking SLFN11.
- |||||||||| Exploring the role of Wnt pathway inhibition on glioma stem cells progression and brain endothelial integrity (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_630;
Future studies will evaluate orthotopic Wnt inhibitor overexpressing transplant rodent models to assess changes in BBB integrity, drug permeability, model survival, and treatment response. Further understanding of the Wnt pathway in both GSCs and the BBB has the potential for improved central nervous system treatment penetration and prolonged disease response.
- |||||||||| Journal, Tumor cell, Metastases: Cadherin-11 increases tumor cell proliferation and metastatic potential via Wnt pathway activation. (Pubmed Central) - Oct 6, 2023
Binding of ?-catenin to CTFs preserved ?-catenin activity, whereas inhibiting CDH11 cleavage led to ?-catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidates a previously unknown role of CDH11, which serves to stabilize ?-catenin in the cytoplasm and facilitate its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential.
- |||||||||| Journal: Sema3C Signaling is an Alternative Activator of the Canonical WNT Pathway in Glioblastoma. (Pubmed Central) - Oct 3, 2023
Since Sema3C is overexpressed in >85% glioblastoma and is used to maintain GSCs but not normal neural progenitor cells, this pathway may represent a major mechanism of Wnt pathway activation and resistance to upstream Wnt pathway inhibitors in GSCs. Our data provide a therapeutic strategy to achieve clinically significant Wnt pathway inhibition in GSCs potentially without the toxicity of currently available WNT inhibitors.
- |||||||||| Wnt Signaling Drives Pathogenic Stromal Inflammation in Inflammatory Arthritis (Room 29A-D; in person) - Sep 23, 2023 - Abstract #ACRConvergence2023ACR_Convergence_1969;
This work provides evidence supporting a new molecular target for treatments directed at synovial fibroblasts in RA. Figure 1: Stromal Wnt activation observed in rheumatoid arthritis is recapitulated in a murine model of inflammatory arthritis.
- |||||||||| Sema3C Signaling is an Alternative Activator of the Canonical WNT Pathway in Glioblastoma (Room 8) - Aug 22, 2023 - Abstract #ASTRO2023ASTRO_1683;
Since Sema3C is overexpressed in >85% glioblastoma and is used to maintain GSCs but not normal neural progenitor cells, this pathway may represent a major mechanism of Wnt pathway activation and resistance to upstream Wnt pathway inhibitors in GSCs. Our data provide a therapeutic strategy to achieve clinically significant Wnt pathway inhibition in GSCs potentially without the toxicity of currently available WNT inhibitors.
- |||||||||| RXC004 / Redx
Therapeutic opportunities for porcupine inhibition in gastrointestinal cancer () - Jul 27, 2023 - Abstract #ESMO2023ESMO_1851; Preclinically, GI tumors with upstream Wnt pathway variants (RNF43 loss of function (LoF), RSPO gain of function (GoF)) are Wnt ligand dependent and exquisitely sensitive to RXC004, a small molecule Porcupine inhibitor...Conclusions Upstream Wnt pathway variants are enriched in GI cancer, in particular Small Bowel cancer, a rare subtype of high unmet need. In MSS CRC cancer, the poor prognosis and high BRAF_V600E co-occurrence with upstream Wnt pathway variants suggests benefit of co-targeting Wnt and MAPK pathways in this population.
- |||||||||| Journal: Wnt signaling preserves progenitor cell multipotency during adipose tissue development. (Pubmed Central) - Jun 27, 2023
We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.
- |||||||||| Review, Journal: Wnt Signaling in Brain Tumors: A Challenging Therapeutic Target. (Pubmed Central) - May 27, 2023
Finally, the latest anti-cancer therapeutic approaches employing the specific targeting of Wnt signaling are extensively reviewed and discussed. In conclusion, here we provide evidence that Wnt signaling, due to its pleiotropic involvement in several brain tumor features, may represent a relevant target in this context, although additional efforts will be needed to: (i) demonstrate the real clinical impact of Wnt inhibition in these tumors; (ii) overcome some still unsolved concerns about the potential systemic effects of such approaches; (iii) achieve efficient brain penetration.
- |||||||||| foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
Targeting WNT Signaling for Improved Glioma Immunotherapy (Board No. 581) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1371; Furthermore, we found that in a syngeneic mouse model of glioma (K-luc), ICG-001 treatment enhances tumor infiltration by CD3+ and CD8+ cells with increased expression of the vascular endothelial marker CD31 (PECAM-1) on days 7, 14 and 21 post tumor engraftment. We conclude that reprogramming the glioma tumor microenvironment by means of differentiation of glioma stem cells, modulation of the stroma and immune cell activation and recruitment, utilizing the pleiotropic effects of biochemically specific Wnt/CBP/?-catenin antagonists, may enhance immunotherapy in glioma patients.
- |||||||||| Journal: Role of Wnt signaling in the maintenance and regeneration of the intestinal epithelium. (Pubmed Central) - Mar 31, 2023
We extensively discuss the contribution of the stem cell niche in maintaining Wnt signaling in the intestinal crypts that support ISC functions. The integration of these findings highlights the complex interplay of multiple niche signals and cellular components sustaining ISC behavior and maintenance, which together supports the immense plasticity of the intestinal epithelium.
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