19 results on '"Garbo V"'
Search Results
2. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis
- Author
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Avellone, G, Di Garbo, V, Campisi, D, De Simone, R, Raneli, G, Scaglione, R, and Licata, G
- Published
- 2006
- Full Text
- View/download PDF
3. Relationship between transforming growth factor β1 and progression of hypertensive renal disease
- Author
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Scaglione, R, Argano, C, Parrinello, G, Colomba, D, Di Chiara, T, Ferrante, A, Di Garbo, V, Avellone, G, and Licata, G
- Published
- 2002
- Full Text
- View/download PDF
4. 57P Functional inactivation of E-cadherin by Trop-2 drives cancer metastasis
- Author
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Alberti, S., primary, Guerra, E., additional, Lattanzio, R., additional, Boujnah, K., additional, Garbo, V., additional, Moschella, A., additional, Altomare, D., additional, Depalo, R., additional, and Trerotola, M., additional
- Published
- 2020
- Full Text
- View/download PDF
5. 1977O Functional inactivation of E-cadherin drives EMT-less metastasis
- Author
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Alberti, S., primary, Guerra, E., additional, Lattanzio, R., additional, Ceci, M., additional, Boujnah, K., additional, Briguori, S., additional, Garbo, V., additional, Moschella, A., additional, Altomare, D.F., additional, Depalo, R., additional, Rotelli, M.T., additional, Picciariello, A., additional, and Trerotola, M., additional
- Published
- 2020
- Full Text
- View/download PDF
6. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis
- Author
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Avellone, G, primary, Di Garbo, V, additional, Campisi, D, additional, De Simone, R, additional, Raneli, G, additional, Scaglione, R, additional, and Licata, G, additional
- Published
- 2005
- Full Text
- View/download PDF
7. CIVIL LIABILITY OF DOCTORS AND THEIR INSURANCE (MALPRACTICE)
- Author
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Gârbo Viorica Irina
- Subjects
doctors, liability insurance, malpractice, indemnity, compensation. ,Business ,HF5001-6182 ,Finance ,HG1-9999 - Abstract
Malpractice insurance of medical staff is probably the oldest professional liability insurance underwritten in the insurance market in Romania. The aim of our research is to theoretically examine in a qualitative inquiry the usefulness of insurance completion by the practitioners from the Romanian health system at both state and private, in order to improve a best practice medical insurance. The medical profession is practiced in Romania under the Code of Medical Ethics 30 March 2012 prepared in code that complies with international standards contained in the Geneva Declaration of 1948, as amended by the World Medical Association and the International Code of Medical Ethics. The forms of medical liability are: disciplinary, administrative, civil and criminal and only the civil liability can be taken into insurance because only it meets the conditions of insurability. Once we explain in general and the insurance liability in particular we show articles of the Romanian Civil Code which establishes the obligation the one that caused an injury to a third person for the repair or indemnify and conditions provided by the Civil Code as an act to be considered liability. Then we refer to situations where the patient may be damaged through the fault of the doctor or the doctor unit operates. The object of malpractice insurance is loss of money that the insured would have to pay a patient whom he caused injury as a result of acts or deeds of negligence committed to, during and in relation to professional activity. Risks taken in the insurance are personal injury, illness or death of the patient and / or moral damages. Regarding the excluded risks we have presented an overview of the more common contracts underwritten by Romanian insurance companies. We show the way of underwriting, the insured sums of the standard insurance and the additional one which subscribes moral damages, to companies in Romania agreed by bodies which organize and supervise the Romanian medical system. The current procedure for determining the guilt of a doctor and his patient complained of the amount of damages is a long and difficult. The procedure for determining the guilt of a doctor reported by his patient and the amount of compensation is a long and arduous one. In conclusions we have shown that along with the reform and reorganization of the Romanian medical system, the civil liability insurance of the medical staff, the way of contracting, the way of establishing the guilt of the applicant and the amount of compensation need to be reformed.
- Published
- 2013
8. Impact of atorvastatin plus n-3 PUFA on metabolic, inflammatory and coagulative parameters in metabolic syndrome without and with type 2 diabetes mellitus.
- Author
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Avellone G, Guarnotta V, di Garbo V, Abruzzese G, Campisi D, Pinto A, Pizzo G, and Licata G
- Published
- 2009
9. Granulicatella spp., a Causative Agent of Infective Endocarditis in Children
- Author
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Chiara Albano, Sara Bagarello, Salvatore Giordano, Maria Fiorella Sanfilippo, Calogero Comparato, Giuseppe Scardino, Valeria Garbo, Giovanni Boncori, Anna Condemi, Antonio Cascio, Claudia Colomba, Albano C., Bagarello S., Giordano S., Sanfilippo M.F., Comparato C., Scardino G., Garbo V., Boncori G., Condemi A., Cascio A., and Colomba C.
- Subjects
Microbiology (medical) ,nutritionally variant streptococci ,pediatric ,Infectious Diseases ,General Immunology and Microbiology ,infective endocarditi ,Immunology and Allergy ,Molecular Biology ,Granulicatella - Abstract
Granulicatella spp. are non-motile, non-sporulating, facultatively anaerobic Gram-positive cocci. Throughout the literature, these organisms have been referred to by several names, such as “nutritionally deficient streptococci”, “vitamin-B dependent streptococci” and “pyridoxal-dependent streptococci”, because of their fastidious nutritional requirements, which can often make culture isolation challenging. Known to be a member of the normal microbiota of the human oral cavity and urogenital and intestinal tracts, similar to other streptococci, Granulicatella spp. can cause bacteremia, sepsis and infective endocarditis. Considering the difficulty in growing this organism on culture medium, the fact that it is now included among the bacteria known to be responsible for culture-negative infective endocarditis suggests that its pathogenic role could be highly underestimated. Moreover, being considered such a rare causative agent, it is not a target of standard antibiotic empiric treatment. We present a rare case of G. elegans endocarditis in a young child and review the medical literature on Granulicatella endocarditis in the pediatric population, with the aim of sharing knowledge about this microorganism, which can be challenging for a clinician who is not familiar with it.
- Published
- 2022
10. Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer
- Author
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Martina Ceci, Giuseppe Pizzicannella, Carla Di Loreto, Patrizia Querzoli, Raffaella Depalo, Maria Teresa Rotelli, Marco Trerotola, Laura Antolini, Valeria Garbo, Arcangelo Picciariello, Khouloud Boujnah, Ulrich H. Weidle, Domenico Angelucci, Pasquale Simeone, Xiao-Feng Sun, Robert de Lange, Altomare Donato, Romina Tripaldi, Giovanna Vacca, Valeria Relli, Enzo Bianchini, Rossano Lattanzio, Romina Zappacosta, Emanuela Guerra, Saverio Alberti, Massimo Pedriali, Antonino Moschella, Mauro Piantelli, Guerra, E, Trerotola, M, Relli, V, Lattanzio, R, Tripaldi, R, Vacca, G, Ceci, M, Boujnah, K, Garbo, V, Moschella, A, Zappacosta, R, Simeone, P, de Lange, R, Weidle, U, Rotelli, M, Picciariello, A, Depalo, R, Querzoli, P, Pedriali, M, Bianchini, E, Angelucci, D, Pizzicannella, G, Di Loreto, C, Piantelli, M, Antolini, L, Sun, X, Altomare, D, and Alberti, S
- Subjects
Cancer Research ,Colorectal cancer ,proteolytic cleavage ,Metastasi ,Metastasis ,CDH1 ,ADAM10 Protein ,Mice ,Δcyto, cytoplasmic-tail deletion mutant ,RC254-282 ,Original Research ,GFP, green fluorescent protein ,CF, change factor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell migration ,Cadherins ,Epithelial-mesenchymal transition ,Metastatic breast cancer ,Survival Rate ,Colonic Neoplasms ,Female ,EMT, epithelial-mesenchymal transition ,HT29 Cells ,IHC, immunohistochemistry ,Trop-2 ,Mice, Nude ,Mice, Transgenic ,E-cadherin ,Signaling networks ,β-catenin ,Biology ,Signaling network ,Antigens, CD ,Antigens, Neoplasm ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,mAb, monoclonal antibody ,Transcription factor ,Cancer och onkologi ,Cadherin ,beta-catenin ,Gene Expression Profiling ,Membrane Proteins ,medicine.disease ,HCT116 Cells ,ΔHIKE, HIKE deletion mutant ,Xenograft Model Antitumor Assays ,SC, subcutaneous ,Cancer and Oncology ,Cancer research ,biology.protein ,Amyloid Precursor Protein Secretases ,Cell Adhesion Molecules ,SV, voxels - Abstract
We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAMIO underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated Delta cytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from beta-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of beta-catenin signaling, which were further enhanced by the Delta cytoTrop-2 mutant. This Trop-2/E-cadherin/beta-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer. Funding Agencies|grants of Fondazione of the Cassa di Risparmio della Provincia di Chieti; Compagnia di San PaoloCompagnia di San Paolo [2489IT]; Italian Ministry of Development [MI01_00424]; Region Abruzzo (POR FESR) [C78C14000100005]; Oncoxx Biotech (Italian Ministry of University and Research, Smart Cities and Communities) [SCN_00558]; Programma Per Giovani Ricercatori "Rita Levi Montalcini", Italian Ministry of University and Research [PGR12I7N1Z]
- Published
- 2021
11. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis
- Author
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G. Raneli, R. De Simone, Rosario Scaglione, D. Campisi, Licata G, Gino Avellone, V. Di Garbo, AVELLONE G, DI GARBO V, CAMPISI D, DE SIMONE R, RANELI G, SCAGLIONE R, and LICATA G
- Subjects
Adult ,Male ,medicine.medical_specialty ,Settore MED/09 - Medicina Interna ,Mediterranean diet ,Medicine (miscellaneous) ,Wine ,Clinical nutrition ,Fibrinogen ,Diet, Mediterranean ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,Aged ,Nutrition and Dietetics ,Cross-Over Studies ,Factor VII ,business.industry ,Vascular disease ,food and beverages ,red wine ,Middle Aged ,medicine.disease ,Atherosclerosis ,Lipid Metabolism ,Settore MED/11 - Malattie Dell'Apparato Cardiovascolare ,Crossover study ,Surgery ,hs-CRP ,Endocrinology ,C-Reactive Protein ,Cholesterol ,risk factor ,chemistry ,Italy ,TGFb1 ,risk factors ,Female ,Inflammation Mediators ,business ,Oxidation-Reduction ,Biomarkers ,medicine.drug - Abstract
Objective: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. Methods: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d’Avola or Etna Torrepalino) during meals: Group A (n ¼ 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n ¼ 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFb1, D-Dimer, Factor VII , PAI Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. Results: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFb1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. Conclusions: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet. European Journal of Clinical Nutrition (2006) 60, 41–47. doi:10.1038/sj.ejcn.1602265; published online 31 August 2005
- Published
- 2005
12. Dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in pediatric patients: a case series.
- Author
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Garbo V, Condemi A, Albano C, Polara VF, Parrino R, Macaluso A, Venuti L, and Colomba C
- Abstract
Acute bacterial skin and skin-structure infections (ABSSSI) are a significant cause of morbidity in pediatric patients, requiring timely and effective treatment. Dalbavancin, a long-acting lipoglycopeptide antibiotic recently approved for pediatric use, offers advantages such as excellent bactericidal activity against Gram-positive bacteria (including multidrug-resistant pathogens) and high tissue penetration. We present a case series of pediatric patients with ABSSSI treated with dalbavancin. Five cases were described demonstrating the efficacy of dalbavancin in different clinical scenarios. Patients with complex skin conditions, including cellulitis and deep abscesses, benefited from dalbavancin therapy, achieving significant clinical improvement. Notably, dalbavancin facilitated early discharge, improving quality of life and reducing healthcare costs. These cases highlight the potential of dalbavancin as a valuable treatment option for ABSSSI in pediatric patients, particularly in settings where conventional therapies fail to achieve optimal clinical outcomes or prolonged hospitalization is not feasible. Further research is needed to clarify its role and optimize its use in pediatric patients with ABSSSI., Competing Interests: Conflict of interest: The authors declare no conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
13. Tuberculous Pericarditis in Childhood: A Case Report and a Systematic Literature Review.
- Author
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Venuti L, Condemi A, Albano C, Boncori G, Garbo V, Bagarello S, Cascio A, and Colomba C
- Abstract
Tuberculous pericarditis (TBP) is an important cause of pericarditis worldwide while being infrequent in childhood, especially in low-TB-incidence countries. We report a case of TBP and provide a systematic review of the literature, conducted by searching PubMed, Scopus, and Cochrane to find cases of TBP in pediatric age published in the English language between the year 1990 and the time of the search. Of the 587 search results obtained, after screening and a backward citation search, 45 studies were selected to be included in this review, accounting for a total of 125 patients. The main signs and symptoms were fever, cough, weight loss, hepatomegaly, dyspnea, and increased jugular venous pressure or jugular vein turgor. A definitive diagnosis of TBP was made in 36 patients, either thanks to microbiological investigations, histological analysis, or both. First-line antitubercular treatment (ATT) was administered in nearly all cases, and 69 children underwent surgical procedures. Only six patients died, and only two died of TBP. TBP in childhood is relatively uncommon, even in high-TB-prevalence countries. Clinical manifestations, often suggestive of right-sided cardiac failure, are subtle, and diagnosis is challenging. TBP has an excellent prognosis in childhood; however, in a significant proportion of cases, invasive surgical procedures are necessary.
- Published
- 2024
- Full Text
- View/download PDF
14. Imported cutaneous myiasis in a child and her father.
- Author
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Albano C, Linares G, Garbo V, Stancampiano S, Giordano S, and Colomba C
- Subjects
- Humans, Animals, Female, Child, Male, Fathers, Larva, Myiasis diagnosis, Diptera
- Abstract
Competing Interests: Declaration of competing interest Nothing to declare.
- Published
- 2023
- Full Text
- View/download PDF
15. Mucosal Relapse of Visceral Leishmaniasis in a Child with SARS-CoV-2 Infection.
- Author
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Colomba C, Boncori G, Albano C, Garbo V, Bagarello S, Condemi A, Giordano S, and Cascio A
- Abstract
Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse.
- Published
- 2023
- Full Text
- View/download PDF
16. Streptococcus mitis as a New Emerging Pathogen in Pediatric Age: Case Report and Systematic Review.
- Author
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Colomba C, Garbo V, Boncori G, Albano C, Bagarello S, Condemi A, Giordano S, Canduscio LA, Gallo C, Parrinello G, and Cascio A
- Abstract
Streptococcus mitis , a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We present a rare case of sinusitis complicated by meningitis and cerebral sino-venous thrombosis (CSVT) caused by S. mitis in a previously healthy 12-year-old boy with poor oral health status. With the aim of understanding the real pathogenic role of this microorganism, an extensive review of the literature about invasive diseases due to S. mitis in pediatric patients was performed. Our data define the critical role of this microorganism in invasive infections, especially in immunocompetent children and in the presence of apparently harmful conditions such as sinusitis and caries. Attention should be paid to the choice of therapy because of VGS's emerging antimicrobial resistance patterns.
- Published
- 2023
- Full Text
- View/download PDF
17. Granulicatella spp., a Causative Agent of Infective Endocarditis in Children
- Author
-
Albano C, Bagarello S, Giordano S, Sanfilippo MF, Comparato C, Scardino G, Garbo V, Boncori G, Condemi A, Cascio A, and Colomba C
- Abstract
Granulicatella spp. are non-motile, non-sporulating, facultatively anaerobic Gram-positive cocci. Throughout the literature, these organisms have been referred to by several names, such as “nutritionally deficient streptococci”, “vitamin-B dependent streptococci” and “pyridoxal-dependent streptococci”, because of their fastidious nutritional requirements, which can often make culture isolation challenging. Known to be a member of the normal microbiota of the human oral cavity and urogenital and intestinal tracts, similar to other streptococci, Granulicatella spp. can cause bacteremia, sepsis and infective endocarditis. Considering the difficulty in growing this organism on culture medium, the fact that it is now included among the bacteria known to be responsible for culture-negative infective endocarditis suggests that its pathogenic role could be highly underestimated. Moreover, being considered such a rare causative agent, it is not a target of standard antibiotic empiric treatment. We present a rare case of G. elegans endocarditis in a young child and review the medical literature on Granulicatella endocarditis in the pediatric population, with the aim of sharing knowledge about this microorganism, which can be challenging for a clinician who is not familiar with it.
- Published
- 2022
- Full Text
- View/download PDF
18. Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.
- Author
-
Guerra E, Trerotola M, Relli V, Lattanzio R, Tripaldi R, Vacca G, Ceci M, Boujnah K, Garbo V, Moschella A, Zappacosta R, Simeone P, de Lange R, Weidle UH, Rotelli MT, Picciariello A, Depalo R, Querzoli P, Pedriali M, Bianchini E, Angelucci D, Pizzicannella G, Di Loreto C, Piantelli M, Antolini L, Sun XF, Altomare DF, and Alberti S
- Subjects
- ADAM10 Protein genetics, Amyloid Precursor Protein Secretases genetics, Animals, Antigens, CD genetics, Antigens, Neoplasm genetics, Cadherins genetics, Cell Adhesion Molecules genetics, Colonic Neoplasms genetics, Female, HCT116 Cells, HT29 Cells, Humans, Membrane Proteins genetics, Mice, Mice, Nude, Mice, Transgenic, Survival Rate trends, Xenograft Model Antitumor Assays methods, ADAM10 Protein metabolism, Amyloid Precursor Protein Secretases metabolism, Antigens, CD metabolism, Antigens, Neoplasm metabolism, Cadherins metabolism, Cell Adhesion Molecules metabolism, Colonic Neoplasms metabolism, Epithelial-Mesenchymal Transition physiology, Gene Expression Profiling methods, Membrane Proteins metabolism
- Abstract
We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from β-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of β-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/β-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
19. Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.
- Author
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Trerotola M, Guerra E, Ali Z, Aloisi AL, Ceci M, Simeone P, Acciarito A, Zanna P, Vacca G, D'Amore A, Boujnah K, Garbo V, Moschella A, Lattanzio R, and Alberti S
- Subjects
- ADAM10 Protein antagonists & inhibitors, ADAM10 Protein genetics, Amino Acid Sequence genetics, Amyloid Precursor Protein Secretases antagonists & inhibitors, Amyloid Precursor Protein Secretases genetics, Animals, Cell Line, Tumor, Cell Membrane metabolism, Epithelial Cells metabolism, HCT116 Cells, HT29 Cells, Humans, MCF-7 Cells, Membrane Proteins antagonists & inhibitors, Membrane Proteins genetics, Mice, Mice, Inbred BALB C, Models, Molecular, Neoplasm Metastasis pathology, Neoplasm Transplantation, Proteolysis, Signal Transduction, Transplantation, Heterologous, ADAM10 Protein metabolism, Amyloid Precursor Protein Secretases metabolism, Antigens, Neoplasm metabolism, Cell Adhesion Molecules metabolism, Cell Proliferation physiology, Membrane Proteins metabolism, Neoplasms pathology
- Abstract
Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. No Trop-2 cleavage was detected in normal human tissues, whereas most tumors showed Trop-2 cleavage, including skin, ovary, colon, and breast cancers. Coimmunoprecipitation and mass spectrometry analysis revealed that ADAM10 physically interacts with Trop-2. Immunofluorescence/confocal time-lapse microscopy revealed that the two molecules broadly colocalize at the cell membrane. We show that ADAM10 inhibitors, siRNAs and shRNAs abolish the processing of Trop-2, which indicates that ADAM10 is an effector protease. Proteolysis of Trop-2 at R87-T88 triggered cancer cell growth both in vitro and in vivo. A corresponding role was shown for metastatic spreading of colon cancer, as the R87A-T88A Trop-2 mutant abolished xenotransplant metastatic dissemination. Activatory proteolysis of Trop-2 was recapitulated in primary human breast cancers. Together with the prognostic impact of Trop-2 and ADAM10 on cancers of the skin, ovary, colon, lung, and pancreas, these data indicate a driving role of this activatory cleavage of Trop-2 on malignant progression of tumors., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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