A5037934744- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Vascular Malformations and Hemangiomas
- Cancer Treatment and Pharmacology
- Histone Deacetylase Inhibitors Research
- Synthesis and Reactions of Organic Compounds
- Proteoglycans and glycosaminoglycans research
- Blood Coagulation and Thrombosis Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Platelet Disorders and Treatments
- Sarcoma Diagnosis and Treatment
- Heat shock proteins research
- Antioxidant Activity and Oxidative Stress
- Hippo pathway signaling and YAP/TAZ
- Cancer Mechanisms and Therapy
- ATP Synthase and ATPases Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Galectins and Cancer Biology
- Cancer-related Molecular Pathways
- Gastrointestinal Bleeding Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
Mario Negri Institute for Pharmacological Research
2009-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2021
Background : The importance of matrix metalloproteinases in angiogenesis, tumor growth, and metastasis is well known. However, little known about the role formation hemangiomas possible therapeutic use metalloproteinase inhibitors aggressive vascular tumors. Purpose To study tumors, we tested antineoplastic activity a synthetic inhibitor metalloproteinases, batimastat, on an experimental model hemangioma, formed by murine endothelioma cells transformed polyoma middle-T on-cogene (eEnd.l)....
Tumor angiogenesis is regulated by a dynamic cross-talk between tumor cells and the host microenvironment. Because membrane vesicles shed are known to mediate several tumor-host interactions, we determined whether might also stimulate angiogenesis. Vesicles human ovarian carcinoma cell lines CABA I A2780 stimulated motility invasiveness of endothelial in vitro. Enzyme-linked immunosorbent assay Western blot analysis revealed relevant amounts vascular growth factor (VEGF) two matrix...
Abstract Purpose: The purpose of this study was to investigate the antiangiogenic properties 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; NSC707545), a water-soluble benzoquinone ansamycin. Experimental Design: activity 17-DMAG, in vivo, evaluated for inhibition fibroblast growth factor (FGF)-2-induced angiogenesis s.c. implanted Matrigel mice. In vitro, 17-DMAG on endothelial cells (human umbilical vein cells; HUVEC) tested FGF-2; and vascular (VEGF)-induced proliferation...
Trabectedin is a marine natural product, approved in Europe for the treatment of soft tissue sarcoma and relapsed ovarian cancer. Clinical experimental evidence indicates that trabectedin particularly effective against myxoid liposarcomas where response associated to regression capillary networks. Here, we investigated mechanism antiangiogenic activity liposarcomas. directly targeted endothelial cells, impairing functions relying on extracellular matrix remodeling (invasion branching...
The antineoplastic compound aplidine, a new marine-derived depsipeptide, has shown preclinical activity in vitro on haematological and solid tumour cell lines. It is currently early phase clinical trials. exact mechanism of action this anticancer agent still needs to be clarified. We have previously reported that aplidine blocks the secretion angiogenic factor vascular endothelial growth (VEGF) by human leukaemia cells MOLT-4, suggesting possible effect angiogenesis. This study was designed...
Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All compounds disorganized tubulin cytoskeleton, affected endothelial cell morphology capillary formation in vitro, caused vessel shutdown tumor necrosis vivo, thus confirming their properties. Nonetheless, substitution patterns on imidazole ring, responsible for greater interaction energy with higher cytotoxicity, not associated activity.
Summary Differently from most transformed cells, cutaneous melanoma expresses the pleiotropic factor thrombospondin‐1 ( TSP ‐1). Herein, we show that ‐1 RNA and protein), undetectable in four cultures of melanocytes a RGP melanoma, was variously present 13 cell lines advanced melanomas or metastases. Moreover, microarray analysis 55 human lesions showed higher expression primary metastases than common dysplastic nevi. In functional enrichment analysis, correlated with motility‐related genes....
Trabectedin is a marine-derived antineoplastic drug. Besides targeting the cancer cells, trabectedin has peculiar activity on tumor microenvironment with marked effects vasculature and immune response. Because favorable key factor in progression of cutaneous melanoma, we hypothesized that might affect growth metastasis this highly aggressive cancer. This study shows inhibited subcutaneous murine melanoma B16-BL6 K1735-M2. In line its known activities environment other types, it caused...
The prominent desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a determinant factor in tumor progression and major barrier to the access chemotherapy. PDAC microenvironment therefore appears be promising therapeutic target. CCN2/CTGF profibrotic matricellular protein, highly present associated with disease progression. Here we have investigated value CCN2-targeting BLR100 BLR200, two modified synthetic peptides derived from active regions CCN3, an endogenous inhibitor CCN2....
Abstract Purpose: Different antiangiogenic approaches have been proposed in cancer treatment where therapeutic efficacy has shown with the addition of cytotoxic agents. Here, we used SU6668, a small-molecule receptor tyrosine kinase inhibitor, to investigate combinatorial effect paclitaxel on cellular populations developing vasculature. Experimental Design: The this combination was evaluated vitro 72-hour proliferation assay human umbilical vein endothelial cells (HUVEC) and microvascular...
Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released both KS host cells, as well HHV-8 HIV viral products, have been implicated in the pathogenesis of this lesion. Angiogenesis result imbalance among angiogenesis promoters inhibitors, which disrupts homeostasis. The aim study was to investigate expression mechanism control thrombospondin-1 (TSP), physiological inhibitor...
Taxanes are potent inhibitors of cell motility, a property implicated in their antiangiogenic and antimetastatic activity unrelated to antiproliferative effect. The molecular mechanism this anti-motility is poorly understood. In study, we found that paclitaxel induced tubulin acetylation endothelial tumor cells, at concentrations affected motility but not proliferation (10-8 10-9 M, for 4 hours). Induction correlated with inhibition based on comparison highly cytotoxic taxanes (paclitaxel...
ZD6126 is a vascular targeting agent, developed for the treatment of solid tumors. In vivo, rapidly converted into tubulin-binding agent N-acetylcolchinol. We have previously reported that in vitro N-acetylcolchinol disrupts microtubules and induces rapid changes endothelial cell morphology, which tumor would lead to loss vessel integrity subsequent extensive necrosis. The aim this study was investigate effect cytotoxic antineoplastic drugs-cisplatin, doxorubicin, vincristine, paclitaxel,...