A5090431998- Retinoids in leukemia and cellular processes
- Antioxidant Activity and Oxidative Stress
- Estrogen and related hormone effects
- Synthesis of Organic Compounds
- Synthesis and biological activity
- Drug Transport and Resistance Mechanisms
- Retinal Development and Disorders
- Systemic Lupus Erythematosus Research
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Cancer therapeutics and mechanisms
- Growth Hormone and Insulin-like Growth Factors
- Oral Health Pathology and Treatment
- Retinal Diseases and Treatments
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Cancer Risks and Factors
- Chronic Lymphocytic Leukemia Research
- NF-κB Signaling Pathways
- Drug-Induced Ocular Toxicity
- RNA Research and Splicing
Fondazione IRCCS Istituto Nazionale dei Tumori
2007-2024
University of Milan
2009-2012
European Institute of Oncology
2001-2007
Tumori Foundation
2003-2006
Italian Association for Cancer Research
1999
Background: The identification and management of hemolyzed samples are crucial issues in the development new blood-based biomarkers. Results: Using experiments controlled hemolysis lipemia two plasma series from cancer patients, we developed validated a lipemia-independent score (HS). HS resulted strictly associated with amount lysed erythrocytes serum index measurement (reference method), highly reproducible, able to identify as plasma/serum containing ≥6.1 mg/dl free hemoglobin....
We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision oral leukoplakia. In a controlled multicenter study, 170 patients operated on for leukoplakias with benign postoperative histology were randomized to 200 mg daily 1 year vs. no intervention. Preliminary analysis indicated that had good tolerability was effective relapses during treatment. Analysis 5-year follow-up suggested protected against up 19 months randomization, both...
Purpose High endogenous testosterone is associated with increased breast cancer (BC) risk. We designed this study specifically to assess the long-term prognostic role of in a cohort postmenopausal BC patients. Patients and Methods considered 194 women, operated on for early (T1-2N0M0), who never received chemotherapy or hormonal therapy, participated fenretinide prevention trial as untreated controls. Blood samples were collected 3 months (median) after surgery; plasma samples, stored at...
Fenretinide [ N -(4-hydroxyphenyl)-retinamide (4HPR)] is a synthetic retinoid with antitumor activity that induces apoptosis in various types of cancer cell. We showed previously 4HPR upregulates the proapoptotic gene placental bone morphogenetic protein (PLAB), which mediator 4HPR-induced ovarian cells. Here, we investigated signaling cascade involving PLAB mediates apoptotic effect. In 4HPR-sensitive cells, reactive oxygen species (ROS) are involved upregulation and apoptosis, both events...
Fenretinide, a retinoid with low-toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer young women. Fenretinide exhibits apoptotic and antiinvasive properties it improves insulin sensitivity overweight premenopausal women resistance. This study aimed further characterize its role prevention by measuring circulating biomarkers related risk.Sixty-two women, ages 20 46 years, healthy or who had already undergone surgery, known BRCA1/2 mutation...
Abstract 4-Oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) is a recently identified metabolite of fenretinide (4-HPR). We explored the effectiveness 4-oxo-4-HPR in inducing cell growth inhibition ovarian, breast, and neuroblastoma tumor lines; moreover, we investigated molecular events mediating this effect two ovarian carcinoma lines, one sensitive (A2780) resistant (A2780/HPR) to 4-HPR. 4-Oxo-4-HPR was four times more effective than 4-HPR most both 4-HPR–sensitive 4-HPR–resistant cells,...
The role of retinoic acid receptor (RAR) expression in sensitivity to N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide) as well on the tumorigenicity human ovarian carcinoma cells was examined. Two cancer cell lines, A2780 and IGROV-1, with a 10-fold difference 4HPR were chosen study RAR involvement response 4HPR. To determine which effective, RARα, β γ individually overexpressed cells, are most sensitive Sensitivity increased RARβ-overexpressing clones, whereas it slightly decreased RARα...
Abstract Purpose: The synthetic retinoid fenretinide (4-HPR) exhibits preventive and therapeutic activity against ovarian tumors. An unidentified polar metabolite was previously found in 4-HPR-treated subjects A2780 human carcinoma cells continuously treated with 4-HPR (A2780/HPR). the enzyme involved its formation tumor are herein identified. Experimental Design: identified by mass spectrometry A2780/HPR cell extracts plasma from 11 women participating a phase III trial 200 mg/d for 5...
Abstract Purpose: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 cytomorphometric biomarkers cells collected from ascitic fluid before after treatment. Methods: Twenty-two naive patients with were treated 4-HPR at 0, 400, 600, 800 mg/d for 1 to 4 weeks surgery. Changes proportion proliferating expressed Ki67 computer-assisted...
The role of retinol (vitamin A) in breast cancer prognosis has never been investigated postmenopausal women. We prospectively assessed the long-term prognostic plasma levels a cohort patients.We 208 women self-reported as operated on for T(1-2)N(0)M(0) who participated chemoprevention trial controls and received chemotherapy or hormone therapy. Plasma samples were collected 3 months (median) after surgery assayed within weeks retinol. Minimum median potential follow-up 12 15 years,...
Background Fenretinide (4-HPR) is a synthetic retinoid that exhibits potent antitumor and chemopreventive activities against different malignancies, including ovarian tumors. We previously showed in cancer cells, 4-HPR induces apoptosis through signaling cascade starting from reactive oxygen species (ROS) generation involving endoplasmic reticulum (ER) stress response, Jun N-terminal Kinase (JNK) activation, induction of the proapoptotic PLAcental Bone morphogenetic protein (PLAB). Since...
We investigated whether the efficacy of fenretinide (HPR) against ovarian tumours may be limited by induction resistance. The human carcinoma cell line A2780, which is sensitive to a pharmacologically achievable HPR concentration (IC50=1 μM), became 10-fold more resistant after exposure increasing concentrations. cells (A2780/HPR) did not show cross-resistance synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and were sensitive, similarly parent line,...
Abstract The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), a metabolite of fenretinide (4-HPR) present in plasma 4-HPR–treated patients, is very effective inducing growth inhibition and apoptosis several cancer cell lines. 4-Oxo-4-HPR 4-HPR have different mechanisms action because 4-oxo-4-HPR, unlike 4-HPR, causes marked accumulation G2-M phase. Here, we investigated the molecular events involving 4-oxo-4-HPR–induced cycle perturbation ovarian (A2780 IGROV-1) breast (T47D,...
Background The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) is a polar metabolite of fenretinide (4-HPR) very effective in killing cancer cells different histotypes, able to inhibit 4-HPR-resistant cell growth and act synergistically combination with the parent drug. Unlike 4-HPR other retinoids, 4-oxo-4-HPR inhibits tubulin polymerization, leading multipolar spindle formation mitotic arrest. Here we investigated whether 4-oxo-4-HPR, like 4-HPR, triggered death also via...
The functional role of AF1q/MLLT11, an oncogenic factor involved in a translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been investigated hematological and solid malignancies its expression was found to be linked tumor progression poor clinical outcome. In addition function, AF1q shown play the onset basal drug-induced apoptosis cancer cells different histotypes, including ovarian cancer. Through vitro, ex vivo, silico approaches, we demonstrated here that is also...