A5086731068- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Renal cell carcinoma treatment
- Chromatin Remodeling and Cancer
- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Renal and related cancers
- HER2/EGFR in Cancer Research
- Microtubule and mitosis dynamics
- Genetic and rare skin diseases.
- Extracellular vesicles in disease
- Cancer Treatment and Pharmacology
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Mass Spectrometry Techniques and Applications
- Breast Cancer Treatment Studies
- Genetics and Neurodevelopmental Disorders
- Analytical Chemistry and Chromatography
- Genetic and Kidney Cyst Diseases
- MicroRNA in disease regulation
- Prostate Cancer Treatment and Research
Istituto Superiore di Sanità
2018-2025
Sapienza University of Rome
2013-2018
Agostino Gemelli University Polyclinic
2018
Istituto Pasteur
2015-2017
Article4 December 2014Open Access Source Data Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors Paola Infante Center Life [email protected], Istituto Italiano di Tecnologia, Rome, Italy Search more papers by this author Mattia Mori Romina Alfonsi Department of Molecular Medicine, University La Sapienza, Francesca Ghirga Dipartimento Chimica e Tecnologie del Farmaco, Federica Aiello Chemistry and Industrial Chemistry, Pisa, Sara Toscano Cinzia Ingallina Mariangela Siler...
Abstract The pressure towards innovation and creation of new model systems in regenerative medicine cancer research has fostered the development novel potential therapeutic applications. Kidney injuries provoke a high request organ transplants making it most demanding system field medicine. Furthermore, renal frequently threaten patients’ life aggressive forms still remain difficult to treat. Ethical issues related use embryonic stem cells, fueled on adult, patient-specific pluripotent cells...
We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding colchicine tubulin, cancer cell growth. ARAP 22 showed strong P-glycoprotein-overexpressing NCI-ADR-RES Messa/Dx5MDR lines. Compounds 27 suppressed in vitro Hedgehog signaling pathway, strongly reducing...
Abstract Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust sensitive molecular tests by liquid biopsy. Prostate (PCa) is still one the most frequent deadly tumor in men analysis EVs from biological fluids PCa patients has proven feasibility unprecedented potential such approach. Here, we exploited antibody-based proteomic technology, i.e. Reverse-Phase Protein microArrays (RPPA), to measure key antigens activated signaling...
We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of indole and halogen methoxy substituent(s) positions 4-7. Compounds 33 44 strongly inhibited growth P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES Messa/Dx5. At 10 nM, stimulated cytotoxic activity NK cells. 20-50 arrested >80% HeLa cells in G2/M phase cycle, stable arrest mitotic...
Abstract Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range cancers. Indeed, aberrant activation Hh pathway occurring either by ligand-dependent or -independent mechanisms is key driver tumorigenesis. The smoothened (Smo) receptor one main upstream transducers signaling and validated target for development anticancer compounds, underlined FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) basal cell carcinoma. However, mutations that confer...
Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is central player Hh signalling, pathway crucial for development and deregulated cancer. Although the control Gli transcription factors by SuFu critical our understanding mechanism regulating this key event remains limited. Here, we show that Itch/β-arrestin2 complex binds induces its Lys63-linked polyubiquitylation without affecting stability. This process increases association with Gli3, promoting conversion Gli3...
This work aims at elucidating the mechanism and kinetics of hydrolysis GANT61, first most-widely used inhibitor Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, confirming chemical nature its bioactive form. GANT61 is poorly stable under physiological conditions rapidly hydrolyses into an aldehyde species (GANT61-A), which devoid biological activity against Hh signalling, a diamine derivative (GANT61-D), has shown inhibition Gli-mediated...
A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of chiral active pharmaceutical ingredient silodosin. The simultaneous separation enantiomers silodosin its main organic related substances listed in Japanese Pharmacopoeia (JP) monograph drug substance achieved on Chiralpak AD-3 (250 mm × 4.6 mm, 3 μm) column under normal-phase isocratic conditions. optimized conditions employed mixture...
2-Substituted 3-aroylquinolin-4(1H)-ones, prepared through a palladium-catalyzed carbonylative cyclization of N-(2-iodoaryl)enaminones, proved to inhibit efficiently the Hedgehog pathway direct antagonism wild-type and drug-resistant form Smoothened receptor. Notably, these compounds repressed Hh-dependent growth events proliferation tumor cells with aberrant activation Hh pathway, which plays crucial role in development tumorigenesis.
Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be best efficacious approach majority patients. However, a consistent fraction (30%) cases progress after surgery with curative intent. It is currently largely debated use adjuvant therapy high-risk patients and clinical molecular parameters stratifying beneficiary categories. In addition, advanced forms lacks reliable driver biomarkers appropriated therapeutic choice. Thus, patient...
Abstract The design and the preparation of a small library 1,4‐diphenyl‐1,2,3‐triazole derivatives is reported, with aim to obtain new class Hedgehog pathway inhibitors. smoothened protein part hedgehog signaling that inhibited by lead compound Vismodegib. Based on molecular modeling simulations, seven triazole Vismodegib are synthesized their biological effect different endothelial, cancer, cancer stem cell lines reported.
Aberrant activation of the Hedgehog (Hh) signaling pathway is implicated in pathogenesis many cancers, including medulloblastoma and basal cell carcinoma (BCC). In this study, using neonatally irradiated Ptch1(+/-) mice as a model Hh-dependent tumors, we investigated vivo effects MK-4101, novel SMO antagonist, for treatment BCC. Results clearly demonstrated robust antitumor activity achieved through inhibition proliferation induction extensive apoptosis tumor cells. Of note, beside on...
Abstract The Sonic Hedgehog (SHH) pathway is crucial regulator of embryonic development and stemness. Its alteration leads to medulloblastoma (MB), the most common malignant pediatric brain tumor. SHH-MB subgroup best genetically characterized, however molecular mechanisms responsible for its pathogenesis are not fully understood therapeutic benefits still limited. Here, we show that pro-oncogenic stemness Spalt-like transcriptional factor 4 (SALL4) re-expressed in mouse models, high levels...
Abstract BACKGROUND Medulloblastoma (MB) is the most common malignant pediatric brain tumor arising from alterations in cerebellum development. The Sonic Hedgehog variant (SHH MB) best genetically characterized, however molecular mechanisms responsible for its pathogenesis are not fully understood and therapeutic benefits still limited. Mutations key components of SHH pathway cytogenetic (such as chromosome 17p deletion) lay pathogenetic foundation MB subgroup. RENKCTD11 (here REN) a...