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  1. Article ; Online: Clinical predictors of cardiac toxicity in HER2-positive early breast cancer patients treated with adjuvant s.c. versus i.v. trastuzumab.

    De Sanctis, Rita / Giordano, Laura / D'Antonio, Federica / Agostinetto, Elisa / Marinello, Arianna / Guiducci, Daniela / Masci, Giovanna / Losurdo, Agnese / Zuradelli, Monica / Torrisi, Rosalba / Santoro, Armando

    Breast (Edinburgh, Scotland)

    2021  Volume 57, Page(s) 80–85

    Abstract: Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v ... neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received ... s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v ...

    Abstract Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors.
    Patients and methods: We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity.
    Results: Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups.
    Conclusion: Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Cardiotoxicity/epidemiology ; Chemotherapy, Adjuvant ; Female ; Heart/drug effects ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Trastuzumab/adverse effects ; Trastuzumab/therapeutic use ; Ventricular Function, Left/drug effects
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2021-03-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1143210-x
    ISSN 1532-3080 ; 0960-9776
    ISSN (online) 1532-3080
    ISSN 0960-9776
    DOI 10.1016/j.breast.2021.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1.

    Ju, Xiaoming / Jiao, Xuanmao / Ertel, Adam / Casimiro, Mathew C / Di Sante, Gabriele / Deng, Shengqiong / Li, Zhiping / Di Rocco, Agnese / Zhan, Tingting / Hawkins, Adam / Stoyanova, Tanya / Andò, Sebastiano / Fatatis, Alessandro / Lisanti, Michael P / Gomella, Leonard G / Languino, Lucia R / Pestell, Richard G

    Cancer research

    2016  Volume 76, Issue 22, Page(s) 6723–6734

    Abstract: ... which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine ... by gene expression, epitope characteristics, and prostatosphere formation. Cyclin D1 was induced by v-Src, and Src ... Cyclin D1, therefore, serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance ...

    Abstract Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine prostate epithelial cells increased the proportion of prostate cancer stem cells as characterized by gene expression, epitope characteristics, and prostatosphere formation. Cyclin D1 was induced by v-Src, and Src kinase induction of Trop2 ICD nuclear accumulation required cyclin D1. Cyclin D1 induced abundance of the Trop2 proteolytic cleavage activation components (PS2, TACE) and restrained expression of the inhibitory component of the Trop2 proteolytic complex (Numb). Patients with prostate cancer with increased nuclear Trop2 ICD and cyclin D1, and reduced Numb, had reduced recurrence-free survival probability (HR = 4.35). Cyclin D1, therefore, serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. Cancer Res; 76(22); 6723-34. ©2016 AACR.
    MeSH term(s) Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cyclin D1/metabolism ; Humans ; Mice ; Signal Transduction ; Transfection ; src-Family Kinases/metabolism
    Chemical Substances Antigens, Neoplasm ; Cell Adhesion Molecules ; TROP2 protein, mouse ; Cyclin D1 (136601-57-5) ; src-Family Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2016-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-15-3327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Advances in Use of Capsule-Based Fluorescent Sensors for Measuring Acidification of Endocytic Compartments in Cells with Altered Expression of V-ATPase Subunit V1G1.

    De Luca, Maria / Ferraro, Marzia M / Hartmann, Raimo / Rivera-Gil, Pilar / Klingl, Andreas / Nazarenus, Moritz / Ramirez, Agnese / Parak, Wolfgang J / Bucci, Cecilia / Rinaldi, Rosaria / del Mercato, Loretta L

    ACS applied materials & interfaces

    2015  Volume 7, Issue 27, Page(s) 15052–15060

    Abstract: Acidification of eukaryotic cell compartments is accomplished by vacuolar H+-ATPases (V-ATPases ... medium. V-ATPases are involved in a number of physiological cellular processes, and thus regulation of V ... ATPase activity is of crucial importance for the cell. Indeed, dysfunction of V-ATPase or alterations ...

    Abstract Acidification of eukaryotic cell compartments is accomplished by vacuolar H+-ATPases (V-ATPases), large multisubunit complexes able to pump protons into the lumen of organelles or in the extracellular medium. V-ATPases are involved in a number of physiological cellular processes, and thus regulation of V-ATPase activity is of crucial importance for the cell. Indeed, dysfunction of V-ATPase or alterations of acidification have been recently recognized as key factors in a variety of human diseases. In this study, we applied capsule-based pH sensors and a real-time tracking method for investigating the role of the V1G1 subunit of V-ATPases in regulating the activity of the proton pump. We first constructed stable cell lines overexpressing or silencing the subunit V1G1. Second, we used fluorescent capsule-based pH sensors to monitor acidification before and during internalization by modified and control living cells. By using a simple real-time method for tracking capsule internalization, we were able to identify different capsule acidification levels with respect to each analyzed cell and to establish the kinetics for each. The intracellular pH measurements indicate a delay in acidification in either V1G1-overexpressing or V1G1-silenced cells compared to controls. Finally, in an independent set of experiments, we applied transmission electron microscopy and confocal fluorescence microscopy to further investigate the internalization of the capsules. Both analyses confirm that capsules are engulfed in acidic vesicular structures in modified and control cell lines. The use of capsule-based pH sensors allowed demonstration of the importance of the V1G1 subunit in V-ATPase activity concerning intravesicular acidification. We believe that the combined use of these pH-sensor system and such a real-time method for tracking their internalization path would contribute to systematically measure the proton concentration changes inside the endocytic compartments in various cell systems. This approach would provide fundamental information regarding molecular mechanisms and factors that regulate intracellular acidification, vesicular trafficking, and cytoskeletal reorganizations.
    MeSH term(s) Endosomes/chemistry ; Endosomes/metabolism ; Fluorescent Dyes/chemistry ; Hydrogen-Ion Concentration ; Microscopy, Fluorescence/methods ; Molecular Imaging/methods ; Nanocapsules/chemistry ; Vacuolar Proton-Translocating ATPases/metabolism
    Chemical Substances Fluorescent Dyes ; Nanocapsules ; ATP6V1G1 protein, human (EC 3.6.1.-) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-)
    Language English
    Publishing date 2015-07-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.5b04375
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Perceptual Training as Means to Assess the Effect of Alpha Frequency on Temporal Binding Window.

    Venskus, Agnese

    Journal of cognitive neuroscience

    2023  Volume 36, Issue 4, Page(s) 706–711

    Abstract: ... B., Northoff, G., Romei, V., & Costantini, M. Individual alpha frequency predicts perceived ... Biology, 27, 2344-2351, 2017; Cecere, R., Rees, G., & Romei, V. Individual differences in alpha frequency ...

    Abstract For decades, it has been shown that alpha frequency is related to temporal binding window, and currently, such is the mainstream viewpoint [Noguchi, Y. Individual differences in beta frequency correlate with the audio-visual fusion illusion. Psychophysiology, 59, e14041, 2022; Gray, M. J., & Emmanouil, T. A. Individual alpha frequency increases during a task but is unchanged by alpha-band flicker. Psychophysiology, 57, e13480, 2020; Hirst, R. J., McGovern, D. P., Setti, A., Shams, L., & Newell, F. N. What you see is what you hear: Twenty years of research using the sound-induced flash illusion. Neuroscience & Biobehavioral Reviews, 118, 759-774, 2020; Keil, J. Double flash illusions: Current findings and future directions. Frontiers in Neuroscience, 14, 298, 2020; Migliorati, D., Zappasodi, F., Perrucci, M. G., Donno, B., Northoff, G., Romei, V., & Costantini, M. Individual alpha frequency predicts perceived visuotactile simultaneity. Journal of Cognitive Neuroscience, 32, 1-11, 2020; Keil, J., & Senkowski, D. Individual alpha frequency relates to the sound-induced flash illusion. Multisensory Research, 30, 565-578, 2017; Minami, S., & Amano, K. Illusory jitter perceived at the frequency of alpha oscillations. Current Biology, 27, 2344-2351, 2017; Cecere, R., Rees, G., & Romei, V. Individual differences in alpha frequency drive crossmodal illusory perception. Current Biology, 25, 231-235, 2015]. However, recently, this stance has been challenged [Buergers, S., & Noppeney, U. The role of alpha oscillations in temporal binding within and across the senses. Nature Human Behaviour, 6, 732-742, 2022]. Moreover, both stances appear to have their limitations regarding the reliability of results. Therefore, it is of paramount importance to develop new methodology to gain more reliable results. Perceptual training seems to be such a method that also offers significant practical implications.
    MeSH term(s) Humans ; Visual Perception/physiology ; Auditory Perception/physiology ; Illusions/physiology ; Reproducibility of Results ; Hearing ; Acoustic Stimulation/methods ; Photic Stimulation/methods
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1007410-7
    ISSN 1530-8898 ; 0898-929X ; 1096-8857
    ISSN (online) 1530-8898
    ISSN 0898-929X ; 1096-8857
    DOI 10.1162/jocn_a_01982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Advances in Use of Capsule-Based Fluorescent Sensors for Measuring Acidification of Endocytic Compartments in Cells with Altered Expression of V-ATPase Subunit V1G1

    De Luca, Maria / Bucci Cecilia / del Mercato Loretta L / Ferraro Marzia M / Hartmann Raimo / Klingl Andreas / Nazarenus Moritz / Parak Wolfgang J / Ramirez Agnese / Rinaldi Rosaria / Rivera-Gil Pilar

    ACS Applied Materials & Interfaces. 2015 July 15, v. 7, no. 27

    2015  

    Abstract: Acidification of eukaryotic cell compartments is accomplished by vacuolar H⁺-ATPases (V-ATPases ... medium. V-ATPases are involved in a number of physiological cellular processes, and thus regulation of V ... ATPase activity is of crucial importance for the cell. Indeed, dysfunction of V-ATPase or alterations ...

    Abstract Acidification of eukaryotic cell compartments is accomplished by vacuolar H⁺-ATPases (V-ATPases), large multisubunit complexes able to pump protons into the lumen of organelles or in the extracellular medium. V-ATPases are involved in a number of physiological cellular processes, and thus regulation of V-ATPase activity is of crucial importance for the cell. Indeed, dysfunction of V-ATPase or alterations of acidification have been recently recognized as key factors in a variety of human diseases. In this study, we applied capsule-based pH sensors and a real-time tracking method for investigating the role of the V₁G₁ subunit of V-ATPases in regulating the activity of the proton pump. We first constructed stable cell lines overexpressing or silencing the subunit V₁G₁. Second, we used fluorescent capsule-based pH sensors to monitor acidification before and during internalization by modified and control living cells. By using a simple real-time method for tracking capsule internalization, we were able to identify different capsule acidification levels with respect to each analyzed cell and to establish the kinetics for each. The intracellular pH measurements indicate a delay in acidification in either V₁G₁-overexpressing or V₁G₁-silenced cells compared to controls. Finally, in an independent set of experiments, we applied transmission electron microscopy and confocal fluorescence microscopy to further investigate the internalization of the capsules. Both analyses confirm that capsules are engulfed in acidic vesicular structures in modified and control cell lines. The use of capsule-based pH sensors allowed demonstration of the importance of the V₁G₁ subunit in V-ATPase activity concerning intravesicular acidification. We believe that the combined use of these pH-sensor system and such a real-time method for tracking their internalization path would contribute to systematically measure the proton concentration changes inside the endocytic compartments in various cell systems. This approach would provide fundamental information regarding molecular mechanisms and factors that regulate intracellular acidification, vesicular trafficking, and cytoskeletal reorganizations.
    Keywords acidification ; cytoskeleton ; eukaryotic cells ; fluorescence ; fluorescence microscopy ; H-transporting ATP synthase ; human diseases ; pH ; proton pump ; transmission electron microscopy ; vacuoles
    Language English
    Dates of publication 2015-0715
    Size p. 15052-15060.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1944-8252
    DOI 10.1021%2Facsami.5b04375
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Leaving the parental home during the COVID-19 pandemic: the case of Southern Europe.

    Ferraretto, Valeria / Vitali, Agnese / Billari, Francesco C

    Advances in life course research

    2024  Volume 59, Page(s) 100594

    Abstract: In 2020, COVID-19-related governmental restrictions forced individuals to radically change their habits, possibly impacting on their living arrangements. Whether COVID-19 affected young adults' propensity to leave the parental home is still unknown; ... ...

    Abstract In 2020, COVID-19-related governmental restrictions forced individuals to radically change their habits, possibly impacting on their living arrangements. Whether COVID-19 affected young adults' propensity to leave the parental home is still unknown; Southern Europe is of particular interest, as youth experience the "latest-late" transition to adulthood, face uncertainty in the labor market, and receive low welfare support. Using EU-SILC longitudinal data from Greece, Spain, Italy, and Portugal, this study examines how home-leaving rates evolved in the short-term and explores the relationship between governmental restrictions, economic characteristics of households and young adults, and leaving home behaviors. Descriptive analyses reveal that the share of young adults leaving the parental home in Southern Europe between 2019 and 2020 slightly increased compared to previous years. Discrete-time event history models show that the propensity to leave the parental home increases with the stringency of policy measures. Young adults with the highest likelihood to leave home are employed individuals whose households are in the lowest income quintile as well as students from the highest income quintile, suggesting that, in these countries, residential independence is associated with either the acquisition of economic resources in the labor market or the availability of family resources. We interpret this result in favor of an "independence effect" exerted by COVID-19-related restrictions on young adults; future research might establish whether this trend is temporary or persistent over time.
    MeSH term(s) Adolescent ; Humans ; Pandemics ; COVID-19/epidemiology ; Europe/epidemiology ; Income ; Parents
    Language English
    Publishing date 2024-02-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2474504-2
    ISSN 1879-6974 ; 1569-4909
    ISSN (online) 1879-6974
    ISSN 1569-4909
    DOI 10.1016/j.alcr.2024.100594
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Genetic diversity of a cichlid fish population after 100 years of isolation

    Ndiwa, Titus Chemandwa / Wanja, Dorothy Nyingi / Agnèse, Jean‐François

    African Journal of Ecology. 2023 Sept., v. 61, no. 3 p.595-605

    2023  

    Abstract: High rates of species radiation have been recorded in Cichlids of East African lakes. The current study focused on a population of Nile tilapia (Oreochromis niloticus) found in a crater lake (Lake Crocodile) that occurs within the Central Island of Lake ... ...

    Abstract High rates of species radiation have been recorded in Cichlids of East African lakes. The current study focused on a population of Nile tilapia (Oreochromis niloticus) found in a crater lake (Lake Crocodile) that occurs within the Central Island of Lake Turkana. The population separated from Lake Turkana about 100 years ago and has since then existed in isolation. This study aimed at assessing the existence of genetic differences between the Lake Crocodile Nile tilapia population and other closely related Nile tilapia populations from Lake Turkana, Lake Baringo and River Suguta. Genetic differences between the populations were evaluated using two mtDNA markers, and 16 microsatellite markers. Significant genetic differences (p > 0.05) were observed between the Lake Crocodile population and the other studied populations within the region. Despite the shared ancestry between Lake Crocodile and Lake Turkana, genetic differences were observed between the two populations. This can mostly be attributed to the lack of gene flow and environmental differences between the two populations.
    Keywords Oreochromis niloticus ; ancestry ; crocodiles ; fish communities ; gene flow ; genetic variation ; lakes ; microsatellite repeats ; rivers
    Language English
    Dates of publication 2023-09
    Size p. 595-605.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 2019879-6
    ISSN 1365-2028 ; 0141-6707
    ISSN (online) 1365-2028
    ISSN 0141-6707
    DOI 10.1111/aje.13144
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Emerging role of lysosomal calcium store as a hub of neuroprotection.

    Tedeschi, Valentina / Secondo, Agnese

    Neural regeneration research

    2021  Volume 17, Issue 6, Page(s) 1259–1260

    Language English
    Publishing date 2021-11-15
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.327340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.

    Bighinati, Andrea / Adani, Elisa / Stanzani, Agnese / D'Alessandro, Sara / Marigo, Valeria

    Frontiers in cellular neuroscience

    2024  Volume 18, Page(s) 1343544

    Abstract: Retinitis pigmentosa (RP) is a form of retinal degeneration characterized by primary degeneration of rod photoreceptors followed by a secondary cone loss that leads to vision impairment and finally blindness. This is a rare disease with mutations in ... ...

    Abstract Retinitis pigmentosa (RP) is a form of retinal degeneration characterized by primary degeneration of rod photoreceptors followed by a secondary cone loss that leads to vision impairment and finally blindness. This is a rare disease with mutations in several genes and high genetic heterogeneity. A challenging effort has been the characterization of the molecular mechanisms underlying photoreceptor cell death during the progression of the disease. Some of the cell death pathways have been identified and comprise stress events found in several neurodegenerative diseases such as oxidative stress, inflammation, calcium imbalance and endoplasmic reticulum stress. Other cell death mechanisms appear more relevant to photoreceptor cells, such as high levels of cGMP and metabolic changes. Here we review some of the cell death pathways characterized in the RP mutant retina and discuss preclinical studies of therapeutic approaches targeting the molecular outcomes that lead to photoreceptor cell demise.
    Language English
    Publishing date 2024-02-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2024.1343544
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  10. Article ; Online: New Improved cGMP Analogues to Target Rod Photoreceptor Degeneration.

    Pérez, Oswaldo / Stanzani, Agnese / Huang, Li / Schipper, Nicolaas / Loftsson, Thorsteinn / Bollmark, Martin / Marigo, Valeria

    Journal of medicinal chemistry

    2024  

    Abstract: Retinitis pigmentosa (RP) is a form of retinal degeneration affecting a young population with an unmet medical need. Photoreceptor degeneration has been associated with increased guanosine 3',5'-cyclic monophosphate (cGMP), which reaches toxic levels for ...

    Abstract Retinitis pigmentosa (RP) is a form of retinal degeneration affecting a young population with an unmet medical need. Photoreceptor degeneration has been associated with increased guanosine 3',5'-cyclic monophosphate (cGMP), which reaches toxic levels for photoreceptors. Therefore, inhibitory cGMP analogues attract interest for RP treatments. Here we present the synthesis of dithio-CN03, a phosphorodithioate analogue of cGMP, prepared using the H-phosphonothioate route. Two crystal modifications were identified as a trihydrate and a tetrahydrofuran monosolvates. Dithio-CN03 featured a lower aqueous solubility than its
    Language English
    Publishing date 2024-04-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.4c00586
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