A5079462145- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Prostate Cancer Treatment and Research
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Acute Myeloid Leukemia Research
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Cancer-related Molecular Pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Retinoids in leukemia and cellular processes
- MicroRNA in disease regulation
- Mast cells and histamine
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Science, Research, and Medicine
- Protist diversity and phylogeny
- Proteoglycans and glycosaminoglycans research
University of Trento
2020-2024
Bambino Gesù Children's Hospital
2024
Istituti di Ricovero e Cura a Carattere Scientifico
2024
Kettering University
2008-2020
Memorial Sloan Kettering Cancer Center
2008-2020
Beth Israel Deaconess Medical Center
2008-2015
Cancer Genetics (United States)
2008-2013
Dana-Farber Cancer Institute
2011-2013
Harvard University
2011-2013
Technion – Israel Institute of Technology
2013
Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may therapeutic potential. In this study, we show its analogs activate the MAPK pathway in human cancer, what represents novel mTORC1-MAPK feedback loop. We found tumor samples from patients with biopsy-accessible solid tumors advanced disease treated RAD001, derivative, showed an administration schedule–dependent increase...
There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in MMTV-CreBrca1(f/f)Trp53(+/-) mouse model When treated with pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 26 days. NVP-BKM120 reduced AKT phosphorylation, cell proliferation, angiogenesis. Resistant tumors maintained suppression phosphorylation but exhibited MAPK pathway at...
Irreversible cell growth arrest, a process termed cellular senescence, is emerging as an intrinsic tumor suppressive mechanism. Oncogene-induced senescence thought to be invariably preceded by hyperproliferation, aberrant replication, and activation of DNA damage checkpoint response (DDR), rendering therapeutic enhancement this unsuitable for cancer treatment. We previously demonstrated in mouse model prostate that inactivation the suppressor phosphatase tensin homolog deleted on chromosome...
Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine (CRPC-NE) distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE challenging relies on metastatic biopsy. We developed targeted methylation assay detect using plasma cell-free (cfDNA). quantifies tumor content provides...
The mammalian target of rapamycin (mTOR) represents a critical signaling crossroad where pathways commonly disrupted in cancer converge. We report here that Rheb GTPase, the upstream activator mTOR complex 1 (mTORC1) is amplified human prostate cancers. demonstrate overexpression promotes hyperplasia and low-grade neoplastic phenotype mouse while eliciting concomitant senescence response negative feedback loop limiting Akt activation. Importantly, we show Pten haploinsufficiency cooperates...
Prostate cancer is the most prevalent in males, and treatment options are limited for advanced forms of disease. Loss PTEN TP53 tumor suppressor genes commonly observed prostate cancer, whereas their compound loss often cancer. Here, we show that PARP inhibition triggers a p53-dependent cellular senescence PTEN-deficient setting prostate. Surprisingly, also find PARP-induced morphed into an apoptotic response upon p53. We further superactivation prosurvival PI3K-AKT signaling pathway limits...
Conditional inactivation of mTor has little effect in adult mouse prostate, but suppresses tumor initiation and progression.
The aim of this study was to investigate the mechanism activation human heparanase, a key player in heparan sulfate degradation, thought be involved normal and pathologic cell migration processes. Active heparanase arises as product series proteolytic processing events. Upon removal signal peptide, resulting, poorly active 65 kDa species undergoes excision an intervening 6 fragment generating 8 polypeptide 50 polypeptide, forming fully heterodimer. By engineering tobacco etch virus protease...
Abstract Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 secreted, oncogenic mucin that expressed aberrantly in AML blasts, but its potential uses to target have not been explored. Here, we report highly on CD34+/lineage−/CD38− as compared their normal cell counterparts. expression was restricted CD34+ populations similar results were obtained leukemic from patients CD34− disease. Engraftment express (MUC1high) led development...
ABSTRACT The NS2-NS3 region of the hepatitis C virus polyprotein encodes a proteolytic activity that is required for processing NS2/3 junction. Membrane association NS2 and autocatalytic nature event have so far constituted hurdles to detailed investigation this reaction. We now report first biochemical characterization self-processing purified precursor. Using multiple sequence alignments, we were able define minimal domain, devoid membrane-anchoring sequences, which was still capable...
Abstract Expression of oncogenic K‐RAS in primary cells elicits oncogene‐induced cellular senescence (OIS), a form growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms depend on the p53 tumour suppressor protein. The PML was initially identified as component PML‐RARα oncoprotein acute promyelocytic leukaemia (APL). PML, critical OIS mediator, is upregulated by vivo and vitro . We demonstrate here induces protein...
The ETS family of transcription factors has been repeatedly implicated in tumorigenesis. In prostate cancer, members, such as ERG, ETV1, ETV4, and ETV5, are frequently overexpressed due to chromosomal translocations, but the molecular mechanisms by which they promote tumorigenesis remain largely undefined. Here, we show that ERG directly repress expression checkpoint kinase 1 (CHK1), a key DNA damage response cell-cycle regulator essential for maintenance genome integrity. Critically, find...
Abstract Multi‐analyte liquid biopsies represent an emerging opportunity for non‐invasive cancer assessment. We developed ONCE (One Aliquot Circulating Elements), approach the isolation of extracellular vesicles (EV) and cell‐free DNA (cfDNA) from a single aliquot blood. assessed performance to classify HER2‐positive early‐stage breast (BrCa) patients by combining EV‐associated RNA (EV‐RNA) cfDNA signals on n = 64 healthy donors (HD) non–metastatic BrCa patients. Specifically, we isolated...
Abstract The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed discuss quantitative strategies and harmonized wet computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) vesicle analyses with a special focus on emerging technologies. covered key issues in different EV‐associated molecular components EV biophysical features, which are considered core biomarker discovery validation for their clinical translation. in‐person‐only...
Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1-APS4. APS1 is caused by