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278 results on '"Carlomagno, F"'

4. Pollinator diversity of the food‐deceptive orchids in southern Italy.

Author

Carlomagno, F., Lanzino, M., Mendicino, F., Bonacci, T., and Pellegrino, G.

Subjects
*BIODIVERSITY, *HONEYBEES, *POLLINARIA, *BEETLES, *POLLINATORS, *ORCHIDS, *POLLINATION by bees
Abstract

The orchid family is renowned for its enormous diversity in pollination biology. Many orchid species use deception to attract pollinators, and the main strategy in terrestrial orchids is food deception. Food‐deceptive orchids usually show a low number of pollinator visitations, making field observations of pollinators difficult.In this study visual census, pollinator capture and molecular analysis of pollinaria found on caught insects allowed us to obtain information on species composition of orchid pollinators.A total of 321 insects were caught; most specimens were hymenopterans (Apis mellifera, Bombus ruderatus and Eucera rufa) and coleopterans (Tropinota hirta and T. squalida). The identity of species to which pollinaria found on the insect's body belonged was confirmed by molecular analysis. Moreover, some individuals of Billaea lata (Tachinidae, Diptera) were captured and photographed with the pollinaria on their head.Two new and important results emerged clearly in this work: a dipteran, Billaea lata, pollinator of Anacamptis pyramidalis, and two beetles in the genus Tropinota are pollinators of Orchis italica. Our results confirm that generalized food‐deceptive orchids of the genera Orchis and Anacamptis show weak pollinator specificity. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Calliphora rohdendorfi(Grunin, 1966) (Diptera: Calliphoridae): a new blow fly in the Italian fauna detected in Calabrian Apennines

Author

Pezzi, M., Bonelli, D., Mendicino, F., Carlomagno, F., Munari, C., Mistri, M., Chicca, M., Szpila, K., and Bonacci, T.

Abstract

AbstractWithin the family Calliphoridae, the genus CalliphoraRobineau-Desvoidy, 1830, includes species of medical, veterinary and forensic relevance. This study reports for the first time the presence of Calliphora rohdendorfi(Grunin, 1966) in the Italian territory, namely in Calabrian Apennines (Southern Italy). The adults of the species were captured by bait bottle and yellow pan traps within a monitoring project of Diptera Brachycera involving Parco Nazionale dell’Aspromonte (Aspromonte National Park), Parco Nazionale della Sila (Sila National Park) and Parco Naturale Regionale delle Serre (Natural Regional Park of Serre), between 2018 and 2021. Calliphora rohdendorfiwas identified on detailed morphological bases of both sexes. This was the first description of the general morphology of the female and its terminalia through digital photographs acquired by stereomicroscopy. The species was captured in pine and beech forests at an altitude between 1010 and 1820 m a.s.l. in shaded mountain areas. Prior to the finding in Southern Italy, this species showed an unusually disjointed distribution in Caucasus, Germany and Poland, thus the presence of C. rohdendorfiin Calabrian Apennines provides new and interesting data that require further investigation, because the species could play a role as flower visitor, pollinator and forensic indicator.

Published
2024
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9. Revealing the spacetime hierarchical whole-brain dynamics of auditory predictive coding

Author

Bonetti, L., Fernández Rubio, G., Carlomagno, F., Pantazis, D., Vuust, P., and Kringelbach, M.L.

Subjects
Recognition memory, Temporal sequences, Predictive coding (PC), Magnetoencephalography (MEG)
Abstract

The full analysis pipeline used in this study is available at the following link: https://github.com/leonardob92/HierarchicalPredictiveCoding_Music_MEG.git Additional in-house-built codes and functions used in this study are part of the LBPD repository and are available at the following link: https://github.com/leonardob92/LBPD-1.0.git. Abstract To survive the brain must extract and predict information from key spacetime features of the physical world. While neural processing of visuospatial patterns has been extensively studied, much remains to be discovered about the hierarchical brain mechanisms underlying recognition of auditory sequences with associated prediction errors. Using magnetoencephalography (MEG), we studied the temporal unfolding over milliseconds of brain activity in 83 participants recognising original melodies and systematic variations. The results showed a hierarchy of processing in networks from the auditory to the ventromedial prefrontal and inferior temporal cortices, hippocampus and medial cingulate gyrus. Both original melodies and variations engaged the pathway from auditory cortex at the bottom of the hierarchy to upstream processing in hippocampus and ventromedial prefrontal cortex, but differed in terms of temporal dynamics, where the recognition of originals elicited stronger gamma power. Our results provide detailed spacetime insights into the hierarchical brain mechanisms underlying auditory sequence recognition. The data is provided after pre-processing (Maxfilter, ICA for removing eye blink and heart beat, co-registration with the individual MRI T1) and epoching.

Published
2022
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11. An Automatically-Retargetable Time-Constraint-Driven Instruction Scheduler for Post-compiling Optimization of Embedded Code

Author

Carlomagno F., José O., Santos, Luiz F. P., dos Santos, Luiz C. V., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Vassiliadis, Stamatis, editor, Bereković, Mladen, editor, and Hämäläinen, Timo D., editor

Published
2007
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16. 360 ° - wenn funktionelle Rohstoffe auf Formulierungsschutz treffen.

Author

Zanzottera, S. and Carlomagno, F.

Subjects
*RAW materials, *STAPHYLOCOCCUS aureus, *PRODUCT safety, *SURFACE active agents, *ASPERGILLUS
Abstract

The article "360 ° - when functional raw materials meet formulation protection" deals with the relationship between preservation systems and functional ingredients in cosmetic formulations. It emphasizes that the use of a preservation system is essential to ensure the safety of the products. An example of a mild surfactant of natural origin is BeauSens ® PG4, which was developed as a gentle cleanser for cosmetic applications. The surfactant has shown promising results in combating Staphylococcus aureus and Aspergillus brasiliensis and exhibits antimicrobial properties under real conditions. It has been found that the surfactant maintains product protection at a high level and can replace the primary preservative. [Extracted from the article]

Published
2022

17. Family Pediatrician and Public Health collaboration, an alliance to increase vaccination coverage: an experience with MenB vaccination in Italy.

Author

D’Avino, A., Aloi, G., Argo, G., Bozza, L., Canale, P., Carlomagno, F., Carpino, A., Castaldo, E., Castiglione, O., Chianese, P., Cioffi, L., Coppola, G., Costigliola, C., D’Onofrio, A., de Franchis, R., De Giovanni, M., De Magistris, T., De Prosperis, A., Ercolini, P., and Esposito, A.

Subjects
NEISSERIA meningitidis, VACCINATION, PEDIATRICIANS, BOOSTER vaccines, ROTAVIRUS vaccines
Abstract

Background. Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named “Progetto Via”) with the aim of increasing Meningococcal B vaccination coverage. Study design. Source of data is the regional platform “GE.VA.”. Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/ Vaccination Center. Methods. Time: January 2019 – December 2019. The Federation of Italian Primary Care Pediatricians/ Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics. Results. A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians’ counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations’ status check. Conclusions. The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians’ clinics were key elements for the success of this project and were also recognized by parents. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Bioisosteric discovery of NPA101.3, a second generation RET/VEGFR2 inhibitor optimized for single-agent polypharmacology

Author

Moccia, M., Frett, B., Zhang, L., Lakkaniga, R., Briggs, D.C., Chauhan, R., Brescia, A., Federico, G., Santoro, M., McDonald, Neil Q., Li, H., and Carlomagno, F.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, endocrine system diseases, bcs
Abstract

RET receptor tyrosine kinase is a driver oncogene in human cancer. We recently identified the clinical drug candidate Pz-1, which targets RET and VEGFR2. A key in vivo metabolite of Pz-1 is its less active demethylated pyrazole analogue. Using bioisosteric substitution methods, here, we report the identification of NPA101.3, lacking the structural liability for demethylation. NPA101.3 showed selective inhibitory profile and an inhibitory concentration 50 (IC50) of

Published
2020

20. Presence of the endangered saproxylic species Cucujus haematodes(Coleoptera: Cucujidae) in Aspromonte National Park (Southern Italy)

Author

Bonacci, T., Biscaccianti, A. B., Siclari, A., Carlomagno, F., Bonelli, D., Mendicino, F., Plewa, R., Jaworski, T., and Pezzi, M.

Abstract

AbstractThe knowledge of the ecological preferences of threatened species is critical to all conservation programs. Analyses of habitats and ecological parameters of species are necessary to predict future distribution and responses to climate change. Cucujus haematodesErichson, 1845 (Coleoptera: Cucujidae) is a threatened obligate saproxylic species, listed in the IUCN European Red List of Saproxylic Beetles. After a few decades of apparent absence, the species was recently found in Calabria (Southern Italy) in some good quality biotopes of the Sila National Park in association with Cucujus cinnaberinus(Scopoli, 1763) and Cucujus tulliaeBonacci, Mazzei, Horák & Brandmayr, 2012 (Coleoptera: Cucujidae). Field surveys carried out from 2014 to 2020 in Aspromonte National Park (Calabria) revealed large populations of C. haematodes. Larvae of C. haematodeswere collected from under the bark of dead trees in 11 sampling areas within Aspromonte National Park. The presence of larvae of C. haematodeson the non-autochthonous conifer Pseudotsuga menziesii(Mirb.) Franco (Pinales: Pinaceae) was also reported for the first time in Italy.

Published
2022
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25. 360° -- When Functional Ingredients Meet Formula Protection.

Author

Zanzottera, S. and Carlomagno, F.

Subjects
*COSMETICS additives, *SURFACE active agents, *MISINFORMATION, *ANTI-infective agents, *AMPHIPHILES
Abstract

All ingredients in a cosmetic formula can influence, positively or negatively, the degree of possible contamination of a product by external microorganisms. What if a key ingredient like a surfactant could also help the preservation system and act as a multifunctional? What if it's also mild, comfortable on the skin and natural-derived? Result: 360° of safety! [ABSTRACT FROM AUTHOR]

Published
2022

26. NCOA4 Links Iron Bioavailability to DNA Metabolism

Author

Federico, G, Bellelli, R, Nai, A, Silvestri, L, Camaschella, C, Iolascon, A, Santoro, M, Carlomagno, F, Federico, G, Bellelli, R, Nai, A, Silvestri, L, Camaschella, C, Iolascon, A, Santoro, M, and Carlomagno, F

Published
2017

27. Insights into Current Tropomyosin Receptor Kinase (TRK) inhibitors:\ud development and clinical application

Author

Yan, W., Lakkaniga, N.R., Gunaganti, N., Lv, F., Carlomagno, F., Santoro, M., McDonald, Neil Q., Frett, B., and Li, H.-Y.

Subjects
enzymes and coenzymes (carbohydrates), animal structures, nervous system, embryonic structures, bcs
Abstract

The use of kinase-directed precision medicine has been heavily pursued since the discovery and development of\ud imatinib. Annually, it is estimated that around ∼20 000 new cases of tropomyosin receptor kinase (TRK) cancers are diagnosed,\ud with the majority of cases exhibiting a TRK genomic rearrangement. In this Perspective, we discuss current development and\ud clinical applications for TRK precision medicine by providing the following: (1) the biological background and significance of\ud the TRK kinase family, (2) a compilation of known TRK inhibitors and analysis of their cocrystal structures, (3) an overview of\ud TRK clinical trials, and (4) future perspectives for drug discovery and development of TRK inhibitors.

Published
2018

28. RET/PTC activation in human thyroid carcinomas

Author

Fusco, A., Santoro, M., Grieco, M., Carlomagno, F., Dathan, N., Fabien, N., Berlingieri, M. T., Li, Z., De Franciscis, V., Salvatore, D., Melillo, R. M., Portella, G., Cerrato, A., Colantuoni, V., and Vecchio, G.

Published
1995
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29. Molecular biology of the MEN2 gene

Author

SANTORO, M., MELILLO, R. M., CARLOMAGNO, F., VISCONTI, R., DE VITA, G., SALVATORE, G., LUPOLI, G., FUSCO, A., and VECCHIO, G.

Published
1998

30. Correlates of sexual functioning in Italian menopausal women

Author

Donati Sarti, C, Graziottin, A, Mincigrucci, M, Ricci, E, Chiaffarino, F, Bonaca, S, Becorpi, A, Cipriani, S, Parazzini, F, Gruppo di studio IperAOGOI, Agostinelli, D, Alpinelli, P, Angeloni, C, Arienzo, R, Bacchi Modena, A, Baldaccini, E, Barese, G, Barretta, R, Belloni, C, Bergamini, E, Bocchin, E, Bongiovanni, F, Bonomo, A, Boninfante, Ce, Borsellino, G, Bassi Carla, M, Brun, A, Buonerba, M, Cancellieri, F, Cappa, F, Cardone, A, Colacurci, N, Carlomagno, F, Casarella, G, Ceccarelli, P, Cecchini, G, Chiantera, A, Persia, A, Cicchetti, C, Cocca, Eb, D'Amore, A, Comitini, G, Coppola, A, Cordapatri, A, Corrado Tonti, G, Christiani, P, Curiel, P, D'Andrea, A, D'Angelo, N, D'Asta, S, De Carlo, G, De Leo, V, De Placido, G, De Silvio MG, Del Pup, L, Di Donato, P, Di Nisio, Q, di Prisco, L, Dolfin, G, Raspagliesi, F, Ercolano, Vb, Esposito, E, Fabiani, M, Fasolino, A, Fiorillo, F, Fischetti, G, Gacci, G, Galati, G, Gallo, M, Garbarino, G, Garzarelli, S, Genazzani, Andrea, Gambacciani, M, Giannola, C, Graziano, R, Giannone, G, Giulini, Ns, Golinelli, S, Gullo, D, Lai, Gr, Lai, R, Laneve, Mr, Levi D'Ancona, V, Li Calsi, L, Luerti, M, Lupo, A, Marchesoni, D, Marino, L, Masellis, G, Massi, Gb, Mazzola, V, Melani, A, Meli, G, Mucci, M, Nocera, F, Orlando, A, Palumbo, G, Papotto, A, Penotti, M, Pirillo, P, Pisaturo, G, Procaccioli, P, Quaranta, S, Rastelli, S, Rattazzi, Pd, Rossaro, D, Santeufemia, G, Santilli, C, Scarpello, F, Scarselli, G, Schiliro, S, Schonauer, S, Trojano, V, Scopelliti, A, Senatore, G, Spagnuolo, L, Stellin, G, Stigliano, Cm, Storace, A, Tamburrino, A, Tesauro, R, Todaro, Pa, Trombetta, G, Vadala, P, Valentino, G, Zandonini, G, Zompicchiatti, C, Zullo, F., Donati Sarti, C., Graziottin, A., Mincigrucci, M., Ricci, E., Chiaffarino, F., Bonaca, S., Becorpi, A., Cipriani, S., Parazzini, F., Colacurci, N., Carlomagno, F., Casarella, G., Ceccarelli, P., Cecchini, G., Chiantera, A., Persia, A., Cicchetti, C., Cocca, E. B., D'Amore, A., Comitini, G., Coppola, A., Cordapatri, A., Corrado Tonti, G., Christiani, P., Curiel, P., D'Andrea, A., D'Angelo, N., D'Asta, S., De Carlo, G., De Leo, V., DE PLACIDO, Giuseppe, De Silvio, M. G., Del Pup, L., Di Donato, P., Di Nisio, Q., di Prisco, L., Dolfin, G., Raspagliesi, F., Ercolano, V. B., Esposito, E., Fabiani, M., Fasolino, A., Fiorillo, F., Fischetti, G., Gacci, G., Galati, G., Gallo, M., Garbarino, G., Garzarelli, S., Sarti, C. Donati, and Colacurci, Nicola

Subjects
Adult, medicine.medical_specialty, MENOPAUSE, Cross-sectional study, media_common.quotation_subject, Libido, Sexual Behavior, SEXUAL FUNCTIONING, Human sexuality, Orgasm, QUALITY OF LIFE, CROSS-SECTIONAL STUDY, Surveys and Questionnaires, Medicine, Surveys and Questionnaire, Humans, Sexual Dysfunctions, Psychological, Life Style, media_common, Gynecology, Cross-Sectional Studie, HORMONE THERAPY, business.industry, Obstetrics and Gynecology, General Medicine, Odds ratio, Middle Aged, medicine.disease, Menopause, Sexual intercourse, Sexual desire, Cross-Sectional Studies, Italy, Women's Health, Female, business, Demography, Human
Abstract

To analyze the sexuality of Italian menopausal women.Cross-sectional study.Menopausal women consecutively observed during the study period in menopause clinics.Women were interviewed about their current and premenopausal sexual activity: sexual intercourse frequency and self-rated sexual desire, capacity for orgasm and sexual satisfaction were recorded. Women were defined as having poor sexual functioning if they had one or less sexual intercourses per week or answered 'absent/poor' to the questions about the sexual domains.Oral hormone therapy (HT) use (odds ratio (OR) 0.43 for desire, 0.54 for orgasm and 0.56 for overall sexual satisfaction, all p0.001) and transdermal HT (OR 0.38, 0.53 and 0.53, respectively, all p0.001) were significantly associated with lower risk of poor sexual functioning. Higher physical and mental component scores (PCS and MCS, range 0-100) of the Short Form-12 are inversely related to poor sexual functioning (OR by point 0.96, 0.95, 0.95 for PCS and 0.96, 0.96 and 0.95, for MCS, respectively, all p0.001). Pain during and symptoms after sexual intercourse were significantly related to desire (OR 1.96 and 1.78, respectively), orgasm (OR 2.22 and 2.06, respectively) and sexual satisfaction (OR 2.02 and 1.79, respectively). The partner's health problems were associated with low sexual intercourse frequency (OR 4.18, p0.001) and absent/poor overall satisfaction (OR 2.61, p0.001).This study shows that, in menopausal Italian women attending menopause clinics, sexual function is associated with the quality of sexual life in reproductive age, partner's health status, current quality of life, HT and occurrence of pain during and symptoms after sexual intercourse.

Published
2010

31. I geni oncosoppressori in 'Patologia Generale' IV Ed, Pontieri-Russo-Frati

Author

SANTORO, MASSIMO, VECCHIO, GIANCARLO, Carlomagno F, Santoro, Massimo, Carlomagno, F, and Vecchio, Giancarlo

Subjects
geni oncosoppressori, trasformazione neoplastica, cancro
Abstract

Il cancro e’ causato dall’accumulo di molteplici mutazioni a carico di specifici geni: gli oncogeni ed i geni oncosoppressori. Nel caso degli oncogeni, le mutazioni determinano un’acquisizione di funzione (gain-of-function), viceversa gli oncosoppressori sono colpiti da mutazioni inattivanti (loss-of-function). Le mutazioni che colpiscono gli oncogeni, dovendo causare attivazione della funzione della proteina, sono in genere estremamente specifiche e dominanti (come ad esempio la mutazione dei codoni 12, 13, 61 dei geni RAS) Al contrario, le mutazioni inattivanti dei geni oncosoppressori possono essere molto eterogenee ed il piu’ delle volte sono recessive.

Published
2009

33. Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study

Author

Di Donato, P, Giulini, N. A, Bacchi Modena, A, Cicchetti, G, Comitini, G, Gentile, G, Cristiani, P, Careccia, A, Esposito, E, Gualdi, F, Golinelli, S, Bergamini, E, Masellis, G, Rastelli, S, Gigli, C, Elia, A, Marchesoni, D, Sticotti, F, Del Frate, G, Zompicchiatti, C, Marino, L, Costa, M. R, Pinto, P, Dodero, D, Storace, A, Spinelli, G, Quaranta, S, Bossi, C. M, Ollago, A, Omodei, U, Vaccari, M, Luerti, M, Repetti, F, Zandonini, G, Raspagliesi, F, Dolci, F, Gambarino, G, De Pasquale, B, Polizzotti, G, Borsellino, G, Alpinelli, P, Natale, N, Colombo, D, Belloni, C, Viani, A, Cecchini, G, Vinci, G. W, Samaja, B. A, Pasinetti, E, Penotti, M, Ognissanti, F, Pesando, P, Malanetto, C, Gallo, M, Dolfin, G, Tartaglino, P, Mossotto, D, Pistoni, A, Tarani, A, Rattazzi, P. D, Rossaro, D, Campanella, M, Arisi, E, Gamper, M, Salvatores, D, Bocchin, E, Stellin, G, Meli, G, Azzini, V, Tirozzi, F, Buoso, G, Fraioli, R, Marsoni, V, Cetera, C, Sposetti, R, Candiotto, E, Pignalosa, R, Del Pup, L, Bellati, U, Angeloni, C, Buonerba, M, Garzarelli, S, Santilli, C, Mucci, M, Di Nisio, Q, Cappa, F, Pierangeli, I, Cordone, A, Falasca, L, Ferrante, D, Serra, G. B, Cirese, E, Todaro, P. A, Romanini, C, Spagnuolo, L, Lanzone, A, Donadio, C, Fabiani, M, Baldaccini, E, Votano, S, Bellardini, P, Favale, W, Monti, V, Bonomo, A, Boninfante, C. E, Pietrobattista, P, Massacesi, L, Donini, G, Del Savio, F, Palombi, L, Procaccioli, P, Romani, A, Romagnoli, G, Genazzani, A. R, Gambacciani, M, Scarselli, G, Curiel, P, De Leo, V, Melani, A, Levi D'Ancona, V, Giarrè, G, Di Gioia, E, Ceccarelli, P, Massi, G. B, Cosci, S, Gacci, G, Cascianini, A, Donati Sarti, C, Bircolotti, S, Pupita, P, Mincigrucci, M, Spadafora, A, Santeufemia, G, Marongiu, G, Lai, G. R, Lai, R, Dessole, S, D'Andrea, S. A, Coppola, Null, Chiantera, A, De Placido, Null, Arienzo, R, Pastore, A. R, Tamburrino, A, Cardone, A, Izzo, S, Tesauro, R, Pascarella, A, De Silvio, M. G, Di Prisco, L, Lauda, N, Sirimarco, F, Agrimi, C, Casarella, G, Senatore, G, Ronzini, S, Ruccia, G, De Carlo, G, Pisaturo, G, Carlomagno, F, Fasolino, A, Fiorillo, F, Sorrentino, R, Ercolano, V. B, Panariello, S, Brun, A, Tropea, P, Stigliano, C. M, Amoroso, A, Vadalà, P, Coco, A, Galati, G, Barese, G, Masciari, G, Pirillo, P, Gioffrè, T, Mastrantonio, P, Cardamone, A, D'Angelo, N, Valentino, G, Barretta, R, Ferraro, G, Ferruccio, C, Agostinelli, D, Corrado, G, Scopelliti, A, Schonauer, S, Trojano, V, Bongiovanni, F, Tinelli, F, Poddi, E. R, Scarpello, F, Colonna, L, Fischetti, G, Doria, R, Trombetta, G, Cocca, E. B, D'Amore, A, Di Masi, M, Liguori, R, Dimaggio, A, Laneve, M. R, Maolo, M. C, Gravina, G, Nacci, G, Nocera, F, Lupo, A, Giannola, C, Graziano, R, Mezzatesta, M, Vegna, G, Giannone, G, Palumbo, G, Cancellieri, F, Mondo, A, Cordopatri, A, Carrubba, M, Mazzola, V, Cincotta, L, D'Asta, S, Bono, A, Li Calsi, L, Cavallaro Nigro, S, Schilirò, S, Repici, A, Gullo, D, Orlando, A, Specchiale, F, Papotto, A, Abruzzo, Null, Basilicata, Null, Calabria, Null, Campania, Null, Emilia, Null, Romagna, Null, Giulia, Friuli Venezia, Lazio, Null, Liguria, Null, Lombardia, Null, Marche, Null, Molise, Null, Piemonte, Null, Puglia, Null, Sardegna, Null, Sicilia, Null, Toscana, Null, Adige, Trentino Alto, Umbria, Null, D'Aosta, Valle, Veneto, Null, Massacesi, A, De Aloysio, P, Campagnoli, C, Gambacciani, A, Graziottin, A, Baldi, C, Colacurci, N, Corrado Tonti, G, Parazzini, F, Chatenoud, L., COLACURCI, Nicola, Di Donato, P, Giulini, N. A, Bacchi Modena, A, Cicchetti, G, Comitini, G, Gentile, G, Cristiani, P, Careccia, A, Esposito, E, Gualdi, F, Golinelli, S, Bergamini, E, Masellis, G, Rastelli, S, Gigli, C, Elia, A, Marchesoni, D, Sticotti, F, Del Frate, G, Zompicchiatti, C, Marino, L, Costa, M. R, Pinto, P, Dodero, D, Storace, A, Spinelli, G, Quaranta, S, Bossi, C. M, Ollago, A, Omodei, U, Vaccari, M, Luerti, M, Repetti, F, Zandonini, G, Raspagliesi, F, Dolci, F, Gambarino, G, De Pasquale, B, Polizzotti, G, Borsellino, G, Alpinelli, P, Natale, N, Colombo, D, Belloni, C, Viani, A, Cecchini, G, Vinci, G. W, Samaja, B. A, Pasinetti, E, Penotti, M, Ognissanti, F, Pesando, P, Malanetto, C, Gallo, M, Dolfin, G, Tartaglino, P, Mossotto, D, Pistoni, A, Tarani, A, Rattazzi, P. D, Rossaro, D, Campanella, M, Arisi, E, Gamper, M, Salvatores, D, Bocchin, E, Stellin, G, Meli, G, Azzini, V, Tirozzi, F, Buoso, G, Fraioli, R, Marsoni, V, Cetera, C, Sposetti, R, Candiotto, E, Pignalosa, R, Del Pup, L, Bellati, U, Angeloni, C, Buonerba, M, Garzarelli, S, Santilli, C, Mucci, M, Di Nisio, Q, Cappa, F, Pierangeli, I, Cordone, A, Falasca, L, Ferrante, D, Serra, G. B, Cirese, E, Todaro, P. A, Romanini, C, Spagnuolo, L, Lanzone, A, Donadio, C, Fabiani, M, Baldaccini, E, Votano, S, Bellardini, P, Favale, W, Monti, V, Bonomo, A, Boninfante, C. E, Pietrobattista, P, Massacesi, L, Donini, G, Del Savio, F, Palombi, L, Procaccioli, P, Romani, A, Romagnoli, G, Genazzani, A. R, Gambacciani, M, Scarselli, G, Curiel, P, De Leo, V, Melani, A, Levi D'Ancona, V, Giarrè, G, Di Gioia, E, Ceccarelli, P, Massi, G. B, Cosci, S, Gacci, G, Cascianini, A, Donati Sarti, C, Bircolotti, S, Pupita, P, Mincigrucci, M, Spadafora, A, Santeufemia, G, Marongiu, G, Lai, G. R, Lai, R, Dessole, S, D'Andrea, S. A, Coppola, Null, Chiantera, A, De Placido, Null, Arienzo, R, Pastore, A. R, Tamburrino, A, Cardone, A, Colacurci, Nicola, Izzo, S, Tesauro, R, Pascarella, A, De Silvio, M. G, Di Prisco, L, Lauda, N, Sirimarco, F, Agrimi, C, Casarella, G, Senatore, G, Ronzini, S, Ruccia, G, De Carlo, G, Pisaturo, G, Carlomagno, F, Fasolino, A, Fiorillo, F, Sorrentino, R, Ercolano, V. B, Panariello, S, Brun, A, Tropea, P, Stigliano, C. M, Amoroso, A, Vadalà, P, Coco, A, Galati, G, Barese, G, Masciari, G, Pirillo, P, Gioffrè, T, Mastrantonio, P, Cardamone, A, D'Angelo, N, Valentino, G, Barretta, R, Ferraro, G, Ferruccio, C, Agostinelli, D, Corrado, G, Scopelliti, A, Schonauer, S, Trojano, V, Bongiovanni, F, Tinelli, F, Poddi, E. R, Scarpello, F, Colonna, L, Fischetti, G, Doria, R, Trombetta, G, Cocca, E. B, D'Amore, A, Di Masi, M, Liguori, R, Dimaggio, A, Laneve, M. R, Maolo, M. C, Gravina, G, Nacci, G, Nocera, F, Lupo, A, Giannola, C, Graziano, R, Mezzatesta, M, Vegna, G, Giannone, G, Palumbo, G, Cancellieri, F, Mondo, A, Cordopatri, A, Carrubba, M, Mazzola, V, Cincotta, L, D'Asta, S, Bono, A, Li Calsi, L, Cavallaro Nigro, S, Schilirò, S, Repici, A, Gullo, D, Orlando, A, Specchiale, F, Papotto, A, Abruzzo, Null, Basilicata, Null, Calabria, Null, Campania, Null, Emilia, Null, Romagna, Null, Giulia, Friuli Venezia, Lazio, Null, Liguria, Null, Lombardia, Null, Marche, Null, Molise, Null, Piemonte, Null, Puglia, Null, Sardegna, Null, Sicilia, Null, Toscana, Null, Adige, Trentino Alto, Umbria, Null, D'Aosta, Valle, Veneto, Null, Massacesi, A, De Aloysio, P, Campagnoli, C, Gambacciani, A, Graziottin, A, Baldi, C, Colacurci, N, Corrado Tonti, G, Parazzini, F, and Chatenoud, L.

Subjects
medicine.medical_specialty, Cross-sectional study, Hormone Replacement Therapy, medicine.medical_treatment, Type 2 diabetes, Motor Activity, Ambulatory Care Facilities, Age Distribution, Risk Factors, Diabetes mellitus, medicine, Odds Ratio, Humans, Obesity, Multivariate Analysi, menopausal status, Gynecology, Cross-Sectional Studie, diabetes, business.industry, Obstetrics, Risk Factor, Obstetrics and Gynecology, Hormone replacement therapy (menopause), General Medicine, Odds ratio, Middle Aged, medicine.disease, Educational Statu, Confidence interval, Menopause, Ambulatory Care Facilitie, women, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Italy, Multivariate Analysis, Educational Status, Female, business, Human
Abstract

To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause.Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms.Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year.Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women agedor = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73).This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Published
2005

34. Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy

Author

Parazzini, Fabio, Di Donato, P., Giulini, N. A., Bacchi Modena, A., Cicchetti, G., Comitini, G., Gentile, G., Cristiani, P., Careccia, A., Esposito, E., Gualdi, F., Golinelli, S., Bergamini, E., Masellis, G., Rastelli, S., Gigli, C., Elia, A., Marchesoni, D., Sticotti, F., Del Frate, G., Zompicchiatti, C., Marino, L., Costa, M. R., Pinto, P., Dodero, D., Storace, A., Spinelli, G., Quaranta, S., Bossi, C. M., Ollago, A., Omodei, U., Vaccari, M., Luerti, M., Repetti, F., Zandonini, G., Raspagliesi, F., Dolci, F., Gambarino, G., De Pasquale, B., Polizzotti, G., Borsellino, G., Alpinelli, P., Natale, N., Colombo, D., Belloni, C., Viani, A., Cecchini, G., Vinci, G. W., Samaja, B. A., Pasinetti, E., Penotti, M., Ognissanti, F., Pesando, P., Malanetto, C., Gallo, M., Dolfin, G., Tartaglino, P., Mossotto, D., Pistoni, A., Tarani, A., Rattazzi, P. D., Rossaro, D., Campanella, M., Arisi, E., Gamper, M., Salvatores, D., Bocchin, E., Stellin, G., Meli, G., Azzini, V., Tirozzi, F., Buoso, G., Fraioli, R., Marsoni, V., Cetera, C., Sposetti, R., Candiotto, E., Pignalosa, R., Del Pup, L., Bellati, U., Angeloni, C., Buonerba, M., Garzarelli, S., Santilli, C., Mucci, M., Di Nisio, Q., Cappa, F., Pierangeli, I., Cordone, A., Falasca, L., Ferrante, D., Cirese, E., Todaro, P. A., Spagnuolo, L., Lanzone, A., Donadio, C., Fabiani, M., Baldaccini, E., Votano, S., Bellardini, P., Favale, W., Monti, V., Bonomo, A., Boninfante, C. E., Pietrobattista, P., Massacesi, L., Donini, G., Del Savio, F., Palombi, L., Procaccioli, P., Romani, A., Romagnoli, G., Genazzani, A. R., Gambacciani, M., Scarselli, G., Curiel, P., De Leo, V., Melani, A., Levi D'Ancona, V., Giarrè, G., Di Gioia, E., Ceccarelli, P., Massi, G. B., Cosci, S., Gacci, G., Cascianini, A., Donati Sarti, C., Bircolotti, S., Pupita, P., Mincigrucci, M., Spadafora, A., Santeufemia, G., Marongiu, G., Lai, G. R., Lai, R., Dessole, S., D'Andrea, S. A., Coppola, Null, Chiantera, A., De Placido, Null, Arienzo, R., Pastore, A. R., Tamburrino, A., Cardone, A., Izzo, S., Tesauro, R., Pascarella, A., De Silvio, M. G., Di Prisco, L., Lauda, N., Sirimarco, F., Agrimi, C., Casarella, G., Senatore, G., Ronzini, S., Ruccia, G., De Carlo, G., Pisaturo, G., Carlomagno, F., Fasolino, A., Fiorillo, F., Sorrentino, R., Ercolano, V. B., Panariello, S., Brun, A., Tropea, P., Stigliano, C. M., Amoroso, A., Vadalà, P., Coco, A., Galati, G., Barese, G., Masciari, G., Pirillo, P., Gioffrè, T., Mastrantonio, P., Cardamone, A., D'Angelo, N., Valentino, G., Barretta, R., Ferraro, G., Ferruccio, C., Agostinelli, D., Corrado, G., Scopelliti, A., Schonauer, S., Trojano, V., Bongiovanni, F., Tinelli, F., Poddi, E. R., Scarpello, F., Colonna, L., Fischetti, G., Doria, R., Trombetta, G., Cocca, E. B., D'Amore, A., Di Mas, M., Liguori, R., Dimaggio, A., Laneve, M. R., Maolo, M. C., Gravina, G., Nacci, G., Nocera, F., Lupo, A., Giannola, C., Graziano, R., Mezzatesta, M., Vegna, G., Giannone, G., Palumbo, G., Cancellieri, F., Mondo, A., Cordopatri, A., Carrubba, M., Mazzola, V., Cincotta, L., D'Asta, S., Bono, A., Li Calsi, L., Cavallaro Nigro, S., Schilirò, S., Repici, A., Gullo, D., Orlando, A., Specchial, F., Papotto, A., Abruzzo, Angeloni, Basilicata, D'Andrea, Calabria, Stigliano, Campania, Arienzo, Emilia, Di Donato, Romagna, Giulini, Friuli Venezia Giulia, Gigli, Lazio, Todaro, Liguria, Marino, Lombardia, Luerti, Marche, Donini, Molise, Ferrante, Piemonte, Dolfin, Puglia, Poddi, Sardegna, Santeufemia, Sicilia, Nocera, Toscana, Melani, Trentino Alto Adige, Arisi, Umbria, Mincigrucci, Valle D'Aosta, Salvatores, Veneto, Bocchin, Massacesi, A., De Aloysio, P., Campagnoli, C., Gambacciani, A., Graziottin, A., Baldi, C., Colacurci, N., Corrado Tonti, G., Chatenoud, L., COLACURCI, Nicola, Parazzini, Fabio, Di Donato, P., Giulini, N. A., Bacchi Modena, A., Cicchetti, G., Comitini, G., Gentile, G., Cristiani, P., Careccia, A., Esposito, E., Gualdi, F., Golinelli, S., Bergamini, E., Masellis, G., Rastelli, S., Gigli, C., Elia, A., Marchesoni, D., Sticotti, F., Del Frate, G., Zompicchiatti, C., Marino, L., Costa, M. R., Pinto, P., Dodero, D., Storace, A., Spinelli, G., Quaranta, S., Bossi, C. M., Ollago, A., Omodei, U., Vaccari, M., Luerti, M., Repetti, F., Zandonini, G., Raspagliesi, F., Dolci, F., Gambarino, G., De Pasquale, B., Polizzotti, G., Borsellino, G., Alpinelli, P., Natale, N., Colombo, D., Belloni, C., Viani, A., Cecchini, G., Vinci, G. W., Samaja, B. A., Pasinetti, E., Penotti, M., Ognissanti, F., Pesando, P., Malanetto, C., Gallo, M., Dolfin, G., Tartaglino, P., Mossotto, D., Pistoni, A., Tarani, A., Rattazzi, P. D., Rossaro, D., Campanella, M., Arisi, E., Gamper, M., Salvatores, D., Bocchin, E., Stellin, G., Meli, G., Azzini, V., Tirozzi, F., Buoso, G., Fraioli, R., Marsoni, V., Cetera, C., Sposetti, R., Candiotto, E., Pignalosa, R., Del Pup, L., Bellati, U., Angeloni, C., Buonerba, M., Garzarelli, S., Santilli, C., Mucci, M., Di Nisio, Q., Cappa, F., Pierangeli, I., Cordone, A., Falasca, L., Ferrante, D., Cirese, E., Todaro, P. A., Spagnuolo, L., Lanzone, A., Donadio, C., Fabiani, M., Baldaccini, E., Votano, S., Bellardini, P., Favale, W., Monti, V., Bonomo, A., Boninfante, C. E., Pietrobattista, P., Massacesi, L., Donini, G., Del Savio, F., Palombi, L., Procaccioli, P., Romani, A., Romagnoli, G., Genazzani, A. R., Gambacciani, M., Scarselli, G., Curiel, P., De Leo, V., Melani, A., Levi D'Ancona, V., Giarrè, G., Di Gioia, E., Ceccarelli, P., Massi, G. B., Cosci, S., Gacci, G., Cascianini, A., Donati Sarti, C., Bircolotti, S., Pupita, P., Mincigrucci, M., Spadafora, A., Santeufemia, G., Marongiu, G., Lai, G. R., Lai, R., Dessole, S., D'Andrea, S. A., Coppola, Null, Chiantera, A., De Placido, Null, Arienzo, R., Pastore, A. R., Tamburrino, A., Cardone, A., Colacurci, Nicola, Izzo, S., Tesauro, R., Pascarella, A., De Silvio, M. G., Di Prisco, L., Lauda, N., Sirimarco, F., Agrimi, C., Casarella, G., Senatore, G., Ronzini, S., Ruccia, G., De Carlo, G., Pisaturo, G., Carlomagno, F., Fasolino, A., Fiorillo, F., Sorrentino, R., Ercolano, V. B., Panariello, S., Brun, A., Tropea, P., Stigliano, C. M., Amoroso, A., Vadalà, P., Coco, A., Galati, G., Barese, G., Masciari, G., Pirillo, P., Gioffrè, T., Mastrantonio, P., Cardamone, A., D'Angelo, N., Valentino, G., Barretta, R., Ferraro, G., Ferruccio, C., Agostinelli, D., Corrado, G., Scopelliti, A., Schonauer, S., Trojano, V., Bongiovanni, F., Tinelli, F., Poddi, E. R., Scarpello, F., Colonna, L., Fischetti, G., Doria, R., Trombetta, G., Cocca, E. B., D'Amore, A., Di Mas, M., Liguori, R., Dimaggio, A., Laneve, M. R., Maolo, M. C., Gravina, G., Nacci, G., Nocera, F., Lupo, A., Giannola, C., Graziano, R., Mezzatesta, M., Vegna, G., Giannone, G., Palumbo, G., Cancellieri, F., Mondo, A., Cordopatri, A., Carrubba, M., Mazzola, V., Cincotta, L., D'Asta, S., Bono, A., Li Calsi, L., Cavallaro Nigro, S., Schilirò, S., Repici, A., Gullo, D., Orlando, A., Specchial, F., Papotto, A., Abruzzo, Angeloni, Basilicata, D'Andrea, Calabria, Stigliano, Campania, Arienzo, Emilia, Di Donato, Romagna, Giulini, Friuli Venezia Giulia, Gigli, Lazio, Todaro, Liguria, Marino, Lombardia, Luerti, Marche, Donini, Molise, Ferrante, Piemonte, Dolfin, Puglia, Poddi, Sardegna, Santeufemia, Sicilia, Nocera, Toscana, Melani, Trentino Alto Adige, Arisi, Umbria, Mincigrucci, Valle D'Aosta, Salvatore, Veneto, Bocchin, Massacesi, A., De Aloysio, P., Campagnoli, C., Gambacciani, A., Graziottin, A., Baldi, C., Colacurci, N., Corrado Tonti, G., and Chatenoud, L.

Subjects
Aging, Epidemiology, Cross-sectional study, Marital Statu, Ambulatory Care Facilities, Body Mass Index, Age Factor, Reproductive History, Depression (differential diagnoses), Depression, Smoking, Age Factors, Headache, Obstetrics and Gynecology, Middle Aged, Menopause, Italy, Educational Status, Female, medicine.symptom, Climacteric, Human, Adult, medicine.medical_specialty, Hot Flashe, Logistic Model, Symptom, Irritability, General Biochemistry, Genetics and Molecular Biology, medicine, Humans, Aged, Cross-Sectional Studie, Marital Status, business.industry, Odds ratio, medicine.disease, Educational Statu, Diet, Ambulatory Care Facilitie, Cross-Sectional Studies, Logistic Models, Risk factors, Hot Flashes, Symptoms, Physical therapy, Risk factor, business, Body mass index, Demography
Abstract

OBJECTIVE To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Published
2005

35. Antitumor effects of ZD6474, a small molecule Vascular Endothelial Growth Factor receptor tyrosine kinase inhibitor, with additional activity against Epidermal Growth Factor

Author

Ciardiello, F, Caputo, R, Damiano, V, Troiani, T, Vitagliano, D, Carlomagno, F, Veneziani, Bm, Fontanini, G, Bianco, Ar, Tortora, Giampaolo, Ciardiello, F, Caputo, R, Damiano, Vincenzo, Troiani, T, Vitagliano, D, Carlomagno, F, Veneziani, BIANCA MARIA, Fontanini, G, Bianco, Ar, and Tortora, Giampaolo

Subjects
angiogenesis, ZD6474, EGFR
Published
2003

36. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase

Author

Ciardiello F, Caputo R, Damiano V, Troiani T, Vitagliano D, Carlomagno F, Bianca Maria VENEZIANI, Fontanini G, Ar, Bianco, Tortora G, Ciardiello, Fortunato, Caputo, R, Damiano, V, Troiani, Teresa, Vitagliano, D, Carlomagno, F, Veneziani, Bm, Fontanini, G, Bianco, Ar, Tortora, G., Ciardiello, F, Troiani, T, Carlomagno, Francesca, Veneziani, BIANCA MARIA, Fortunato, Ciardiello, Rosa, Caputo, Vincenzo, Damiano, Roberta, Caputo, Teresa, Troiani, Donatella, Vitagliano, Gabriella, Fontanini, A., Raffaele Bianco, and Giampaolo, Tortora

Subjects
Time Factors, Paclitaxel, Blotting, Western, Apoptosis, Mice, Piperidines, Cell Line, Tumor, Neoplasms, Animals, Humans, Enzyme Inhibitors, Phosphorylation, Mice, Inbred BALB C, Dose-Response Relationship, Drug, Antibodies, Monoclonal, Protein-Tyrosine Kinases, Flow Cytometry, Immunohistochemistry, Vascular Endothelial Growth Factor Receptor-2, ErbB Receptors, Agar, Receptors, Vascular Endothelial Growth Factor, NIH 3T3 Cells, Quinazolines, Electrophoresis, Polyacrylamide Gel, Cell Division, Neoplasm Transplantation
Abstract

PURPOSE: Vascular endothelial growth factor (VEGF) is a major mitogen for endothelial cells and enhances vascular permeability. Enhanced VEGF secretion is found in human cancers and correlates with increased tumor neovascularization. ZD6474 is a p.o. bioavailable, VEGF flk-1/KDR receptor (VEGFR-2) tyrosine kinase inhibitor with antitumor activity in many human cancer xenografts and is currently in Phase I clinical development. EXPERIMENTAL DESIGN: We tested the effects of ZD6474 on EGFR phosphorylation in cell expressing functional epidermal growth factor receptor (EGFR) and the antiproliferative and the proapoptotic activity of ZD6474 alone or in combination taxanes in human cancer cell lines with functional EGFR but lacking VEGFR-2. The antitumor activity of this drug was also tested in nude mice bearing established GEO colon cancer xenografts. RESULTS: ZD6474 causes a dose-dependent inhibition of EGFR phosphorylation in mouse NIH-EGFR fibroblasts and human MCF-10A ras breast cancer cells, two cell lines that overexpress the human EGFR. ZD6474 treatment resulted in a dose-dependent inhibition of soft agar growth in seven human cell lines (breast, colon, gastric, and ovarian) with functional EGFR but lacking VEGFR-2. A dose-dependent supra-additive effect in growth inhibition and in apoptosis in vitro was observed by the combined treatment with ZD6474 and paclitaxel or docetaxel. ZD6474 treatment of nude mice bearing palpable GEO colon cancer xenografts (which are sensitive to inhibition of EGFR signaling) induced dose-dependent tumor growth inhibition. Immunohistochemical analysis revealed a significant dose-dependent reduction of neoangiogenesis. The antitumor activity of ZD6474 in GEO tumor xenografts was also found to be enhanced when combined with paclitaxel. Tumor regression was observed in all mice after treatment with ZD6474 plus paclitaxel, and it was accompanied by a significant potentiation in inhibition of angiogenesis. Six of 20 mice had no histological evidence of tumors after treatment with ZD6474 plus paclitaxel. CONCLUSIONS: This study suggests that in addition to inhibiting endothelial cell proliferation by blocking VEGF-induced signaling, ZD6474 may also be able to inhibit cancer cell growth by blocking EGFR autocrine signaling. These results provide also a rationale for the clinical evaluation of ZD6474 combined with taxanes in cancer patients.

Published
2003

37. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases

Author

Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G, Aj, Ryan, Gabriella Fontanini, Fusco A, Santoro M, Carlomagno, Francesca, Vitagliano, Donata, Guida, Teresa, Ciardiello, Fortunato, Tortora, Giampaolo, Vecchio, Giancarlo, Ryan, A. J., Fontanini, G., Fusco, Alfredo, Santoro, Massimo, Carlomagno, F, Vitagliano, D, Guida, T, Tortora, G, Vecchio, G, Ryan, Aj, Fontanini, G, Fusco, A, and Santoro, M.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, endocrine system diseases, Mice, Nude, ZD6474, Mice, Piperidines, KDR, Proto-Oncogene Proteins, Animals, Drosophila Proteins, TKI, RET, Thyroid Neoplasms, Enzyme Inhibitors, Phosphorylation, neoplasms, Mice, Inbred BALB C, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, 3T3 Cells, Vascular Endothelial Growth Factor Receptor-2, Carcinoma, Papillary, Cell Transformation, Neoplastic, Quinazolines, Signal Transduction
Abstract

RET/papillary thyroid carcinoma (PTC) oncogenes, generated by recombination of the tyrosine kinase-encoding domain of RET with different heterologous genes, are prevalent in papillary carcinomas of the thyroid. Point mutations of RET cause multiple endocrine neoplasia type 2 (MEN2) familial cancer syndrome and are found in sporadic medullary thyroid carcinomas. Here, we show that ZD6474, a low molecular weight tyrosine kinase inhibitor, blocks the enzymatic activity of RET-derived oncoproteins at a one-half maximal inhibitory concentration of 100 nM. ZD6474 blocked in vivo phosphorylation and signaling of the RET/PTC3 and RET/MEN2B oncoproteins and of an epidermal growth factor (EGF)-activated EGF-receptor/RET chimeric receptor. RET/PTC3-transformed cells-treated ZD6474 lost proliferative autonomy and showed morphological reversion. ZD6474 prevented the growth of two human PTC cell lines that carry spontaneous RET/PTC1 rearrangements. Finally, it blocked anchorage-independent growth of RET/PTC3-transformed NIH3T3 fibroblasts and the formation of tumors after injection of NIH-RET/PTC3 cells into nude mice. Thus, targeting RET oncogenes with ZD6474 might offer a potential treatment strategy for carcinomas sustaining oncogenic activation of RET.

Published
2002

39. Molecular mechanisms of RET activation in human cancer

Author

SANTORO, MASSIMO, FUSCO, ALFREDO, VECCHIO, GIANCARLO, MELILLO, ROSA MARINA, CARLOMAGNO F, CASTAGNETTA L, AGOSTARA B, MASSIMO L, MONTALTO G, BRADLOW L., Santoro, Massimo, Melillo, ROSA MARINA, Carlomagno, F, Fusco, Alfredo, and Vecchio, Giancarlo

Subjects
kinase, oncogene, papillary, receptor, chromosome, carcinoma, thyroidendocrine
Abstract

Mutations that produce oncogenes with dominant gain of function target receptor protein tyrosine kinases (PTKs) in cancer and confer uncontrolled proliferation, impaired differentiation, or unrestrained survival to the cancer cell. However, insufficient PTK signaling may be responsible for developmental diseases. Gain of function of the RET receptor PTK is associated with human cancer. At the germline level, point mutations of RET are responsible for multiple endocrine neoplasia type 2 (MEN2A, MEN2B, and FMTC). Mutations of extracellular cysteines are found in MEN2A patients, and a Met918Thr mutation is responsible for most MEN2B cases. At the somatic level, gene rearrangements juxtaposing the tyrosine kinase domain of RET to heterologous gene partners are found in papillary carcinomas of the thyroid. These rearrangements generate the chimeric RET/PTC oncogenes. Both MEN2 mutations and PTC gene rearrangements potentiate the intrinsic tyrosine kinase activity of RET and, ultimately, the RET downstream signaling events. A multidocking site of the C-tail of RET is essential for both mitogenic and survival RET signaling. Such a site is involved in the recruitment of several intracellular molecules, such as the Shc, FRS2, IRS1, Gab1/2, and Enigma. The different activating mutations not only potentiate the enzymatic activity of the RET kinase but also may alter qualitatively RET signaling properties by: (1) altering RET autophosphorylation (in the case of the MEN2B mutation), (2) modifying the subcellular distribution of the active kinase, and (3) providing the active kinase with a scaffold for novel protein-protein interactions (as in the case of RET/PTC oncoproteins). This review describes the molecular mechanisms by which the different genetic alterations cause the conversion of RET into a dominant transforming oncogene.

Published
2002

40. Molecular Mechianism of RET Activation In Human Neoplasia

Author

SANTORO, MASSIMO, VECCHIO, GIANCARLO, FUSCO, ALFREDO, Carlomagno F., MELILLO, ROSA MARINA, T.Akamuzu,M.Kasuga,T.Davies, Santoro, Massimo, Carlomagno, F., Melillo, ROSA MARINA, Vecchio, Giancarlo, and Fusco, Alfredo

Published
2002

41. Molecular Mechanism of RET in Human Cancer

Author

SANTORO, MASSIMO, FUSCO, ALFREDO, VECCHIO, GIANCARLO, MELILLO, ROSA MARINA, Carlomagno F., L.Castagnetta,B.Agostara,L.Massimo,G.Montalto,H.Bradlow, Santoro, Massimo, Melillo, ROSA MARINA, Carlomagno, F., Fusco, Alfredo, and Vecchio, Giancarlo

Published
2002

42. Ereditarietà dei Tumori

Author

VECCHIO, GIANCARLO, CARLOMAGNO F., SANTORO M., AMADORI D., GRILLI S., Vecchio, Giancarlo, Carlomagno, F., and Santoro, M.

Published
2001

43. Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and mitogen-activated protein kinase pathways leading to PC12 cell survival

Author

Vita, G., Rosa Marina MELILLO, Carlomagno, F., Visconti, R., Castellone, M. D., Bellacosa, A., Billaud, M., Fusco, A., Tsichlis, P. N., Santoro, M., DE VITA, Gabriella, Melillo, ROSA MARINA, Carlomagno, F, Visconti, R, Castellone, Md, Bellacosa, A, Billaud, M, Fusco, Alfredo, Tsichlis, Pn, Santoro, M., and Carlomagno, Francesca

Subjects
Glial Cell Line-Derived Neurotrophic Factor Receptors, Cell Survival, MAP Kinase Signaling System, Morpholines, Blotting, Western, Multiple Endocrine Neoplasia Type 2a, DNA Fragmentation, Protein Serine-Threonine Kinases, Ligands, Transfection, PC12 Cells, Culture Media, Serum-Free, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins, In Situ Nick-End Labeling, Animals, Drosophila Proteins, Protein Isoforms, Enzyme Inhibitors, Flavonoids, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Precipitin Tests, Rats, Enzyme Activation, Chromones, Tyrosine, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

The RET tyrosine kinase is a functional receptor for neurotrophic ligands of the glial cell line-derived neurotrophic factor (GDNF) family. Loss of function of RET is associated with congenital megacolon or Hirschsprung's disease, whereas germ-line point mutations causing RET activation are responsible for multiple endocrine neoplasia type 2 (MEN2A, MEN2B, and familial medullary thyroid carcinoma) syndromes. Here we show that the expression of a constitutively active RET-MEN2A oncogene promotes survival of rat pheochromocytoma PC12 cells upon growth factor withdrawal. Moreover, we show that the RET-MEN2A-mediated survival depends on signals transduced by the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) cascades. Thus, in PC12 cells, RET-MEN2A associates with the PI3K regulatory subunit p85 and promotes activation of Akt (also referred to as protein kinase B) in a PI3K-dependent fashion; in addition, RET-MEN2A promotes MAPK activation. PI3K recruitment and Akt activation as well as MAPK activation depend on RET-MEN2A tyrosine residue 1062. As a result, tyrosine 1062 of RET-MEN2A is essential for RET-MEN2A-mediated survival of PC12 cells cultured in growth factor-depleted media.

Published
2000

44. RET is a heat shock protein 90 (HSP90) client protein and is knocked down upon HSP90 pharmacological block

Author

Alfano L, Guida T, Provitera L, Vecchio G, Billaud M, Santoro M, and Carlomagno F.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, endocrine system diseases, polycyclic compounds, neoplasms
Abstract

CONTEXT: Mutations of the RET receptor tyrosine kinase are associated to multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinoma (MTC). The heat shock protein (HSP) 90 chaperone is required for folding and stability of several kinases. HSP90 is specifically inhibited by 17-allyl-amino-17-demethoxygeldanamycin (17-AAG). OBJECTIVE: Our aim was to investigate whether RET protein half-life depends on HSP90 and to dissect the molecular pathway responsible for the degradation of RET upon HSP90 inhibition by 17-AAG. DESIGN: 17-AAG effects were studied in RAT1 fibroblasts exogenously expressing MEN2-associated RET mutants and human MTC-derived cell lines. RESULTS: 17-AAG induced a 26S proteasome-dependent degradation of wild-type RET and MEN2-associated RET mutants. The compound hampered HSP90/RET interaction and stabilized RET binding to HSP70, leading to the recruitment of the HSP70-associated E3 ligase C-terminus of Hsc70-interacting protein. In turn, C-terminus of Hsc70-interacting protein polyubiquitinated RET, promoting its proteasomal degradation. 17-AAG blocked RET downstream effectors and RET-dependent transcriptional activation of gene promoters. In human MTC cells carrying oncogenic RET mutants, HSP90 inhibition induced receptor degradation and signaling hindrance leading to cell cycle arrest. CONCLUSION: RET and MEN2-associated RET mutants rely on HSP90 for protein stability, and HSP90 blockade by 17-AAG promotes RET degradation.

Published
2010

45. Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal Protein Kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret

Author

CHIARIELLO, M, VISCONTI, R, CARLOMAGNO, F, R. M, BUCCI, C, DE FRANCISCIS, V, FOX, G. M, JING, S, COSO, O. M, GUTKIND, S. J, FUSCO, A, AND SANTORO, MELILLO, ROSA MARINA, Chiariello, M, Visconti, R, Carlomagno, F, Melillo, ROSA MARINA, R. M, Bucci, De, Francisci, V, Fox, G. M, Jing, S, Coso, O. M, Gutkind, S. J, Fusco, A, and And, Santoro

Published
1998

48. Intracellular signaling by RET tyrosine Kynase

Author

FUSCO, ALFREDO, VECCHIO, GIANCARLO, SANTORO, MASSIMO, Dathan N., Carlomagno F., Di Fiore P., B.D.Nelkin, Fusco, Alfredo, Vecchio, Giancarlo, Dathan, N., Carlomagno, F., Di Fiore, P., and Santoro, Massimo

Published
1996

49. Activation of the Erk8 MAP kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene

Author

Iavarone C., Acunzo M., Carlomagno F., Catania A., Melillo R.M., Carlomagno M.S., Santoro M., and Chiariello M.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, endocrine system diseases, neoplasms
Abstract

Mitogen-activated protein (MAP) kinases have a central role in several biological functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation, and apoptosis. Extracellular signal-regulated kinase 8 (Erk8) is a large MAP kinase whose activity is controlled by serum and the c-Src non-receptor tyrosine kinase. Here, we show that RET/PTC3, an activated form of the RET proto-oncogene, was able to activate Erk8, and we demon- strate that such MAP kinase participated in RET/PTC3-dependent stimulation of the c-jun promoter. By using RET/PTC3 molecules mutated in specific tyrosine autophosphorylation sites, we charac- terized Tyr981, a known binding site for c-Src, as a major determi- nant of RET/PTC3-induced Erk8 activation, although, surprisingly, the underlying mechanism did not strictly depend on the activity of Src. In contrast, we present evidence that RET/PTC3 acts on Erk8 through Tyr981-mediated activation of c-Abl. Furthermore, we localized the region responsible for the modulation of Erk8 activity by the RET/PTC3 and Abl oncogenes in the Erk8 C-terminal domain. Altogether, these results support a role for Erk8 as a novel effector of RET/PTC3 and, therefore, RET biological functions.

Published
2006
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