Soft tissue sarcomas (STS) have a strong propensity for aggressive growth and metastasis. We showed that the secreted Wnt antagonist Frzb exhibited potent antitumor activity against prostate cancer, an epithelial type of malignancy. In this study, we further showed the antitumor efficacy of Frzb in STS, a mesenchymal group of cancer. Frzb transfection of HT1080 (fibrosarcoma) and SW872 (liposarcoma) cell lines and their conditioned media resulted in a significant reduction in cellular invasion, motility, and colony formation in soft agar compared with vector control-transfected cells. In a xenograft mouse model, Frzb dramatically suppressed tumor growth of HT1080 cells in nude mice. In a tail-vein injection metastatic model, Frzb-transfected HT1080 cells formed fewer and smaller lung nodules than vector control cells. In addition, we identified new mechanisms for Frzb antitumor activities. Frzb reduced c-Met expression and inhibited Met-mediated signaling, associated with up-regulation of epithelial markers (i.e., keratins 8 and 18) and down-regulation of mesenchymal markers (i.e., vimentin, N-cadherin, fibronectin, Slug, and Twist). Similar to Frzb, silencing of c-Met by short hairpin RNA or using a dominant-negative LRP5 receptor also suppressed Met signaling, leading to reduced cellular motility, invasion, and in vivo tumor growth. Given recent studies indicating an important role of c-Met in sarcoma development and progression, our data showed that Frzb expression was significantly inversely correlated with Met expression in both STS cell lines and tissues. These results suggested the usefulness of Frzb in modulating Met signaling as a new treatment strategy for STS.
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http://dx.doi.org/10.1158/0008-5472.CAN-07-3220 | DOI Listing |
Expert Opin Drug Saf
January 2025
Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Background: Faricimab is predominantlyprescribed for conditions such as age-related macular degeneration (AMD),diabetic macular edema (DME), and macular edema related to retinal veinocclusion (RVO-ME). Currently, a notable absence of large-scale, real-worldstudies focusing on the adverse reactions of faricimab exists.
Methods: Thisstudy assesses the side effects of faricimab by analyzing reports of adverseevents (AEs) from the FDA's AEReporting System (FAERS) database.
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Seoul Korean Medicine Hospital of Daejeon University, Seoul, Republic of Korea.
In this study, we investigated the synergistic effect of co-administration of osimertinib and HAD-B1 using gefitinib-resistant non-small cell lung cancer cells, HCC827-GR. HAD-B1 is composed of 4 natural drugs, Panax Notoginseng Radix, Panax ginseng C. A.
View Article and Find Full Text PDFBackground: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
The RNase activity of MCPIP1 is essential for regulating cellular homeostasis, proliferation, and tumorigenesis. Our study elucidates the effects of downregulation of MCPIP1 expression and an RNase-inactivating mutation (D141N) on normal epithelial kidney cells, indicating that MCPIP1 expression is a key factor that suppresses neoplastic transformation. We observed that either expression downregulation or mutation of MCPIP1 significantly increased its clonogenicity and altered the expression of cancer stem cell (CSC) markers and factors involved in epithelial-to-mesenchymal transition (EMT).
View Article and Find Full Text PDFInt Urol Nephrol
January 2025
Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, University of Mansoura, Mansoura, 35516, Egypt.
Aim: Although the relief of ureteral obstruction seems to be a radical treatment for obstructive uropathy (OU), progressive kidney damage is the result because of the associated increased apoptosis and fibrosis. Therefore, it is urgent to find a complementary renoprotective therapy against partially obstructed uropathy cascades. Thus, this study investigated the renoprotective effects of both losartan (LOS) and zinc oxide nanoparticles (ZnONPs) in partial unilateral ureteral obstruction (PUUO).
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