21 results on '"Cirincione R"'
Search Results
2. Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma
- Author
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Borasi, G, Nahum, A, Paulides, M, Powathil, G, Russo, G, Fariselli, L, Lamia, D, Cirincione, R, Forte, G, Borrazzo, C, Caccia, B, di Castro, E, Pozzi, S, Gilardi, M, Borasi G., Nahum A., Paulides M. M., Powathil G., Russo G., Fariselli L., Lamia D., Cirincione R., Forte G. I., Borrazzo C., Caccia B., di Castro E., Pozzi S., Gilardi M. C., Borasi, G, Nahum, A, Paulides, M, Powathil, G, Russo, G, Fariselli, L, Lamia, D, Cirincione, R, Forte, G, Borrazzo, C, Caccia, B, di Castro, E, Pozzi, S, Gilardi, M, Borasi G., Nahum A., Paulides M. M., Powathil G., Russo G., Fariselli L., Lamia D., Cirincione R., Forte G. I., Borrazzo C., Caccia B., di Castro E., Pozzi S., and Gilardi M. C.
- Abstract
Background: A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy. Methods/Design: To investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction-diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction-diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario. Our results show that patient survival could be significantly improved by this combined treatment modality. Discussion: High priority should be given to experiments to validate the therapeutic benefit predicted by our model.
- Published
- 2016
3. High-Intensity Focused Ultrasound– and Radiation Therapy–Induced Immuno-Modulation: Comparison and Potential Opportunities
- Author
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Cirincione, R, Di Maggio, F, Forte, G, Minafra, L, Bravatà, V, Castiglia, L, Cavalieri, V, Borasi, G, Russo, G, Lio, D, Messa, M, Gilardi, M, Cammarata, F, Cammarata, F., MESSA, MARIA CRISTINA, GILARDI, MARIA CARLA, Cirincione, R, Di Maggio, F, Forte, G, Minafra, L, Bravatà, V, Castiglia, L, Cavalieri, V, Borasi, G, Russo, G, Lio, D, Messa, M, Gilardi, M, Cammarata, F, Cammarata, F., MESSA, MARIA CRISTINA, and GILARDI, MARIA CARLA
- Abstract
In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity. Radiation therapy (RT) is the main treatment modality used for many types of tumors and about 50% of all cancer patients receive RT, often used in combination with surgery and chemotherapy. It is well known that RT can modulate anti-tumor immune responses, modifying micro-environment and stimulating inflammatory factors that can greatly affect cell invasion, bystander effects, radiation tissue complications (such as fibrosis), genomic instability and thus, intrinsic cellular radio-sensitivity. To date, various combined therapeutic strategies (such as immuno-therapy) have been performed in order to enhance RT success in treating locally advanced and recurrent tumors. Recent works suggested the combined use of HIFU and RT treatments to increase the tumor cell radio-sensitivity, in order to synergize the effects reaching the maximum results with minimal doses of ionizing radiation (IR). Here, we highlight the opposite immuno-modulation roles of RT and HIFU, providing scientific reasons to test, by experimental approaches, the use of HIFU immune-stimulatory capacity to improve tumor radio-sensitivity, to reduce the RT induced inflammatory response and to decrease the dose-correlated side effects in normal tissues.
- Published
- 2017
4. PD-028 Malignant molecular features of spiral CT scan-detected lungtumors: Methylation and K-Ras mutation profiles
- Author
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Sozzi, G., primary, Cirincione, R., additional, Thunnissen, F., additional, Prinsen, C., additional, Roz, L., additional, Pelosi, G., additional, and Pastorino, U., additional
- Published
- 2005
- Full Text
- View/download PDF
5. Extracellular matrix regulation of PTHrP and PTH/PTHrP receptor in a human breast cancer cell line
- Author
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Luparello, C., Schilling, T., Cirincione, R., and Pucci-Minafra, I.
- Published
- 1999
- Full Text
- View/download PDF
6. High-Intensity Focused Ultrasound- and Radiation Therapy-Induced Immuno-modulation: Comparison and Potential Opportunities
- Author
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Roberta Cirincione 1, Federica Maria Di Maggio 1, 2, Giusi Irma Forte 1, Luigi Minafra 1, Valentina Bravatà 1, Laura Castiglia 1, Vincenzo Cavalieri 4, Giovanni Borasi 1, Giorgio Russo 1, Domenico Lio 2, Cristina Messa 1, 4, 5, Maria Carla Gilardi 1, Francesco Paolo Cammarata 1, Cirincione, R, Di Maggio, F, Forte, G, Minafra, L, Bravatà, V, Castiglia, L, Cavalieri, V, Borasi, G, Russo, G, Lio, D, Messa, C, Gilardi, M, Cammarata, F, and Messa, M
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Radiology, Nuclear Medicine and Imaging ,Acoustics and Ultrasonics ,medicine.medical_treatment ,Biophysics ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,medicine ,Bystander effect ,Humans ,Cancer ,Chemotherapy ,Radiological and Ultrasound Technology ,business.industry ,medicine.disease ,Primary tumor ,Thermal ablation ,High-intensity focused ultrasound ,Radiation therapy ,Immuno-therapy ,Tumor vaccine ,030104 developmental biology ,Biophysic ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,High-Intensity Focused Ultrasound Ablation ,Anti-tumor immunity ,business - Abstract
In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity. Radiation therapy (RT) is the main treatment modality used for many types of tumors and about 50% of all cancer patients receive RT, often used in combination with surgery and chemotherapy. It is well known that RT can modulate anti-tumor immune responses, modifying micro-environment and stimulating inflammatory factors that can greatly affect cell invasion, bystander effects, radiation tissue complications (such as fibrosis), genomic instability and thus, intrinsic cellular radio-sensitivity. To date, various combined therapeutic strategies (such as immuno-therapy) have been performed in order to enhance RT success in treating locally advanced and recurrent tumors. Recent works suggested the combined use of HIFU and RT treatments to increase the tumor cell radio-sensitivity, in order to synergize the effects reaching the maximum results with minimal doses of ionizing radiation (IR). Here, we highlight the opposite immuno-modulation roles of RT and HIFU, providing scientific reasons to test, by experimental approaches, the use of HIFU immune-stimulatory capacity to improve tumor radio-sensitivity, to reduce the RT induced inflammatory response and to decrease the dose-correlated side effects in normal tissues.
- Published
- 2017
- Full Text
- View/download PDF
7. Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma
- Author
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Debora Lamia, Giorgio Ivan Russo, Elisabetta Di Castro, Gibin G. Powathil, Cristian Borrazzo, Barbara Caccia, Giovanni Borasi, Alan E. Nahum, Roberta Cirincione, Giusi Irma Forte, S. Pozzi, Laura Fariselli, Margarethus M. Paulides, Maria Carla Gilardi, Radiotherapy, Borasi, G, Nahum, A, Paulides, M, Powathil, G, Russo, G, Fariselli, L, Lamia, D, Cirincione, R, Forte, G, Borrazzo, C, Caccia, B, di Castro, E, Pozzi, S, and Gilardi, M
- Subjects
Hyperthermia ,medicine.medical_specialty ,medicine.medical_treatment ,Context (language use) ,Glioblastoma, Hyperthermia, Magnetic resonance-guided focused ultrasound, Oncology ,030218 nuclear medicine & medical imaging ,Study Protocol ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,Tumor growth ,External beam radiotherapy ,Magnetic resonance-guided focused ultrasound ,business.industry ,Ultrasound ,medicine.disease ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,Glioblastoma ,business ,Tissue volume - Abstract
Background A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy. Methods/Design To investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction–diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction–diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario. Our results show that patient survival could be significantly improved by this combined treatment modality. Discussion High priority should be given to experiments to validate the therapeutic benefit predicted by our model. Electronic supplementary material The online version of this article (doi:10.1186/s40349-016-0078-3) contains supplementary material, which is available to authorized users.
- Published
- 2016
- Full Text
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8. Antibiotic Resistance Genes Carried by Commensal Escherichia coli from Shelter Cats in Italy.
- Author
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Gambino D, Galluzzo FG, Cicero L, Cirincione R, Mannino E, Fiore V, Proverbio D, Spada E, Cassata G, and Gargano V
- Abstract
Antimicrobial resistance is a widespread global health problem. The presence of resistant bacteria and antibiotic resistance genes has been demonstrated not only in humans but also in animals, including pets. Stray cats share the urban environment with people and pets. This may facilitate transmission of resistant bacteria and resistance genes between stray animals, people and domestic animals. Several studies have investigated the role of stray cats as a fecal carrier of ESBL-producing bacteria. However, there are many genes and resistance mechanisms that can be detected in commensal E. coli , which, because of its genetic plasticity, is considered an indicator for monitoring antibiotic resistance. In this study, rectal swabs were collected from stray cats from colonies and shelters in the city of Monza (Monza Brianza, Italy) to isolate commensal E. coli . Phenotypic tests, such as the minimum inhibitory concentration (MIC) and the double disc test (DDST), and molecular analyses to detect antimicrobial resistance genes (ARGs) were used to study the resistance of these isolates. The results obtained confirm that stray cats can carry ESBL-producing E. coli (6.7%) and genes conferring resistance to other important antibiotic classes such as tetracyclines and sulfonamides.
- Published
- 2023
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9. Peripheral Nerve Regeneration at 1 Year: Biodegradable Polybutylene Succinate Artificial Scaffold vs. Conventional Epineurial Sutures.
- Author
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Cicero L, Puleio R, Cassata G, Cirincione R, Camarda L, Caracappa D, D'Itri L, Licciardi M, and Vigni GE
- Abstract
The utilization of a planar poly(1,4-butylene succinate) (PBS) scaffold has been demonstrated as an effective approach for preserving nerve continuity and facilitating nerve regeneration. In this study, we assessed the characteristics of a microfibrous tubular scaffold specifically designed and fabricated through electrospinning, utilizing PBS as a biocompatible and biodegradable material. These scaffolds were evaluated as nerve guide conduits in a rat model of sciatic nerve neurotmesis, demonstrating both their biodegradability and efficacy in enhancing the reconstruction process over a long-term period (1-year follow-up). Histological assay and electrophysiological evaluation were performed to compare the long-term outcomes following sutureless repair with the microfibrillar wrap to outcomes obtained using traditional suture repair.
- Published
- 2023
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10. Inflammatory-like status and acute stress response in horses after road transport.
- Author
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Arfuso F, Rizzo M, Giannetto C, Giudice E, Piccione G, Fazio F, Cirincione R, Cassata G, and Cicero L
- Subjects
- Horses, Animals, C-Reactive Protein, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Albumins, Hydrocortisone, Globulins
- Abstract
This study aimed to evaluate the change of white blood cell count, serum concentration of cortisol, C-reactive protein, albumin and globulin fractions in horse after road transport, and to assess the linkage among hypothalamic-pituitary-adrenal axis (HPA) and inflammatory reaction. From 10 horses blood samples were collected at rest, before road transport (218 km) (BT); after unloaded (AT), 30 and 60 min after unloaded (AT30 and AT60) in order to assess white blood cell count (WBC), serum cortisol, C-reactive protein (CRP), total proteins, albumin, α1-, α-2, β1-, β2- and γ-globulins. WBC, cortisol, CRP, α1-, α-2 and β2-globulins values increased after road transport than rest condition (p < 0.001). Albumin and A/G ratio showed lower values after road transport than rest (p < 0.001). Pearson's test showed a negative correlation between cortisol and the values of WBC, CRP, α1-, α2-, β1-, β2- globulins, and a positive correlation between WBC and serum concentration of CRP, α1- and α2-, β1-, β2-globulins at AT and AT30. The results showed that road transport evokes an inflammatory like-status in horses. Moreover, the activation of HPA and the onset of acute phase reaction in response to road transport seem to be interconnected with effects on horse's immune status., (© 2023. The Author(s).)
- Published
- 2023
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11. Improved Bone Regeneration Using Biodegradable Polybutylene Succinate Artificial Scaffold in a Rabbit Model.
- Author
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Vigni GE, Cassata G, Caldarella G, Cirincione R, Licciardi M, Miceli GC, Puleio R, D'Itri L, Lo Coco R, Camarda L, and Cicero L
- Abstract
The treatment of extensive bone loss represents a great challenge for orthopaedic and reconstructive surgery. Most of the time, those treatments consist of multiple-stage surgeries over a prolonged period, pose significant infectious risks and carry the possibility of rejection. In this study, we investigated if the use of a polybutylene succinate (PBS) micro-fibrillar scaffold may improve bone regeneration in these procedures. In an in vivo rabbit model, the healing of two calvarial bone defects was studied. One defect was left to heal spontaneously while the other was treated with a PBS scaffold. Computed tomography (CT) scans, histological and immunohistochemical analyses were performed at 4, 12 and 24 weeks. CT examination showed a significantly larger area of mineralised tissue in the treated defect. Histological examination confirmed a greater presence of active osteoblasts and mineralised tissue in the scaffold-treated defect, with no evidence of inflammatory infiltrates around it. Immunohistochemical analysis was positive for CD56 at the transition point between healthy bone and the fracture zone. This study demonstrates that the use of a PBS microfibrillar scaffold in critical bone defects on a rabbit model is a potentially effective technique to improve bone regeneration., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.
- Published
- 2022
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12. Can Stray Cats Be Reservoirs of Antimicrobial Resistance?
- Author
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Gargano V, Gambino D, Orefice T, Cirincione R, Castelli G, Bruno F, Interrante P, Pizzo M, Spada E, Proverbio D, Vicari D, Salgado-Caxito M, Benavides JA, and Cassata G
- Abstract
The emergence and spread of antimicrobial resistance (AMR) is a global problem that requires a One Health approach. Despite several studies have reported the role of companion animals as reservoirs of AMR, limited information is available regarding the role of cats in the circulation of AMR. In this study, we evaluated the phenotypic and genotypic profile of 75 Escherichia coli isolated from rectal swabs and fecal samples of 75 stray cats (living in solitary or in a colony) sampled in Palermo (Sicily, Italy), to determine whether these animals may participate in the spread of AMR. Susceptibility to 8 antibiotics was tested using Minimum Inhibitory Concentration assays, while the presence of the common antibiotic resistance genes bla
TEM , blaCTX-M , tet (A), and tet (B) was investigated by PCR. From the 75 E. coli isolates analyzed, 43% were resistant to at least one of the eight antibiotics tested, with 31% of the isolates resistant to ampicillin, 23% to cefotaxime, 21% to tetracycline, 20% to cefazolin, and 17% to amoxicillin/clavulanic acid. Most isolates harbored the blaTEM gene (29%), followed by blaCTX-M (23%), tet (A) (21%), and tet (B) (20%). Our results confirm the fecal carriage of antibiotic-resistant E. coli and clinically relevant resistance genes in stray cats. This study highlights the potential role of stray cats in the spread of AMR in urban environments, emphasising the need to better understand their role in AMR circulation when planning strategies to combat it.- Published
- 2022
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13. Oxidant and Antioxidant Parameters' Assessment Together with Homocysteine and Muscle Enzymes in Racehorses: Evaluation of Positive Effects of Exercise.
- Author
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Arfuso F, Rizzo M, Giannetto C, Giudice E, Cirincione R, Cassata G, Cicero L, and Piccione G
- Abstract
This study aimed to evaluate the changes in serum oxidant and antioxidant parameters together with the serum values of homocysteine (Hcy) and muscle enzymes including creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in regularly trained athletic horses during official races of 1200, 1600 and 2000 m. Thirty Thoroughbred horses were divided into three groups of 10 subjects each according to the race distance: Group 1, 1200 m race; Group 2, 1600 m race; Group 3, 2000 m race. Blood samples were collected from horses 1 week prior to the race (1WB), on the day of the race at rest (TREST), immediately after the race (TPOST), and after 30 (TPOST30) and 120 (TPOST120) minutes. Serum total proteins, reactive oxygen metabolites (dROMs), thiol antioxidant barrier (SHp), antioxidant barrier (Oxy-ads), Hcy, CK, AST and LDH values were assessed. A two-way repeated measures ANOVA did not show differences referable to the race distance (Group effect) on all investigated parameters (p > 0.05). An exercise effect on oxidative stress markers, Hcy and muscle enzymes herein investigated was found in all groups (p < 0.001). A Pearson’s test showed dROMs positively correlated with SHp, Oxy-ads and Hcy after exercise (p < 0.05). This study suggests that, though well-trained racing horses are subjected to oxidative stress during a race, a proper antioxidant capacity may improve their ability to cope with exercise-induced oxidative stress.
- Published
- 2022
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14. Polybutylene succinate artificial scaffold for peripheral nerve regeneration.
- Author
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Cicero L, Licciardi M, Cirincione R, Puleio R, Giammona G, Giglia G, Sardo P, Edoardo Vigni G, Cioffi A, Sanfilippo A, and Cassata G
- Subjects
- Animals, Butylene Glycols, Humans, Nerve Regeneration, Polymers, Rats, Rats, Sprague-Dawley, Sciatic Nerve, X-Ray Microtomography, Quality of Life, Tissue Scaffolds chemistry
- Abstract
Regeneration and recovery of nerve tissues are a great challenge for medicine, and positively affect the quality of life of patients. The development of tissue engineering offers a new approach to the problem with the creation of multifunctional artificial scaffolds that act on various levels in the damaged tissue, providing physical and biochemical support for the growth of nerve cells. In this study, the effects of the use of a tubular scaffold made of polybutylene succinate (PBS), surgically positioned at the level of a sciatic nerve injured in rat, between the proximal stump and the distal one, was investigated. Scaffolds characterization was carried out by scanning electron microscopy and X-ray microcomputed tomography and magnetic resonance imaging, in vivo. The demonstration of the nerve regeneration was based on the evaluation of electroneurography, measuring the weight of gastrocnemius and tibialis anterior muscles, histological examination of regenerated nerves and observing the recovery of the locomotor activity of animals. The PBS tubular scaffold minimized iatrogenic trauma on the nerve, acting as a directional guide for the regenerating fibers by conveying them toward the distal stump. In this context, neurotrophic and neurotropic factors may accumulate and perform their functions, while invasion by macrophages and scar tissue is hampered., (© 2021 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)
- Published
- 2022
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15. Residue analysis of a synthetic glucocorticoid in liver samples by a 1HMR spectroscopy approach: An exploratory study on animal model.
- Author
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Cicero L, Cirincione R, Comelli A, Coronnello C, and Cassata G
- Subjects
- Animals, Male, Proton Magnetic Resonance Spectroscopy instrumentation, Rats, Rats, Wistar, Betamethasone analysis, Drug Residues analysis, Liver chemistry
- Abstract
Betamethasone is a glucocorticoid authorised in cattle for the treatment of metabolic and inflammatory diseases, but, in Europe, it is illegally employed to improve productive performances. LC-MS/MS is the official control method of veterinary drugs residues in food of animal origin. An experimental study was developed to evaluate the feasibility of proton magnetic resonance spectroscopy (1H-MRS) as a potential alternative approach to detect the presence of betamethasone residues. Eight rat liver samples were collected 24 h post-betamethasone-treatment from experimental and control animals and were analysed by 1H-MRS using a 7-Tesla MRI scanner. 1H-MR reference spectra both of the Bentelan formulation used for treatment, and of three solutions of betamethasone in dimethyl sulphoxide (DMSO) at 5, 10 and 100 mM, respectively, were acquired to fit analyte-peaks in the liver samples spectra. Betamethasone-peaks were found only in the 100 mM betamethasone in DMSO solution spectrum. Betamethasone residues were not detected in any of the tissue samples analysed, probably related to the low concentration of injected drug. These findings allow us to establish, for the first time in the literature, the detection limit (in the range 10-100 mM) of betamethasone for the 7-Tesla MRI scanner used here. Given this very-low sensitivity, we conclude that the evaluated 1H-MR spectroscopy approach is not suitable for the detection of betamethasone residues in edible tissues, since the maximum residue limit imposed by Commission Regulation (EC) 37/2010 for betamethasone in the liver, and metabolic concentrations required to be detected in animal samples from livestock, are far below the detection limit we found.
- Published
- 2020
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16. Implementing a Process to Systematically Identify and Address Poor Medication Adherence in Pediatric Liver Transplant Recipients.
- Author
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Wadhwani SI, Nichols M, Klosterkemper J, Cirincione R, Whitesell K, Owen D, Rengering R, Walz B, Heubi J, and Hooper DK
- Abstract
Objectives: Poor adherence to medication following pediatric liver transplantation remains a major challenge, with some estimates suggesting that 50% of adolescent liver transplant recipients exhibit reduced medication adherence. To date, no gold standard has emerged to address this challenge; however, system interventions are most likely to be successful. We sought to implement a system to identify and address adherence barriers in a liver transplant clinic., Methods: Using structured quality improvement methods, including multiple plan-do-study-act cycles, we developed a system to screen for patients at risk of poor adherence, identify patient- and/or parent-reported barriers to adherence, and partner with patients to overcome identified barriers. We developed a process to track key outcomes, including the variability in tacrolimus trough levels and episodes of late acute cellular rejection., Results: The practice saw a total of 85 patients over 6 months, and about half were females. Over this period, the improvement team implemented this system-level process with high reliability (>90% of patients received the bundle of interventions). The most commonly identified adherence barrier by patients and caregivers was "forgetting." The second most commonly identified adherence barrier by patients was that the medication "gets in the way of their activities," whereas by caregivers, it was "difficulty swallowing pills.", Discussion: We identified challenges and opportunities to screen for poor adherence and identify patient- and/or caregiver-reported barriers to immunosuppression adherence. Identifying such barriers and partnering with patients to overcome those barriers using patient-centered, barrier-specific interventions could improve long-term graft survival through improved medication adherence., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2020
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17. Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case-control study.
- Author
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Cirincione R, Lintas C, Conte D, Mariani L, Roz L, Vignola AM, Pastorino U, and Sozzi G
- Subjects
- Aged, Case-Control Studies, Cyclin-Dependent Kinase Inhibitor p16 genetics, DNA, Neoplasm genetics, Female, Humans, Lung Neoplasms pathology, Male, Middle Aged, Promoter Regions, Genetic genetics, Receptors, Retinoic Acid genetics, Smoking, Tomography, Spiral Computed, Tumor Suppressor Proteins genetics, DNA Methylation, DNA, Neoplasm metabolism, Lung Neoplasms genetics, Sputum metabolism
- Abstract
We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARbeta2, p16(INK4A) and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARbeta2, 12/29 (41.4%) for p16(INK4A) and 15/29 (51.7%) for RASSF1A. Twenty-three of twenty-nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RARbeta2 and 1/18 (5%) for both RASSF1A and p16(INK4A). At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer-free smokers was observed in 58/112 (51.7%) for RARbeta2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RARbeta2, p16(INK4A) and RASSF1A promoters is present in spiral CT-detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection., ((c) 2005 Wiley-Liss, Inc.)
- Published
- 2006
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18. Lack of telomerase activity in lung carcinoids is dependent on human telomerase reverse transcriptase transcription and alternative splicing and is associated with long telomeres.
- Author
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Zaffaroni N, Villa R, Pastorino U, Cirincione R, Incarbone M, Alloisio M, Curto M, Pilotti S, and Daidone MG
- Subjects
- Carcinoid Tumor enzymology, Carcinoid Tumor genetics, DNA-Binding Proteins, Humans, Lung Neoplasms enzymology, Lung Neoplasms genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Telomerase metabolism, Telomere enzymology, Transcription, Genetic, Alternative Splicing, Carcinoid Tumor pathology, Lung Neoplasms pathology, Telomerase genetics, Telomere genetics
- Abstract
Purpose: Preliminary evidence indicates that telomerase activity is significantly less expressed in typical carcinoids than in large cell neuroendocrine carcinomas or in small cell lung cancers. Knowledge of the mechanisms by which telomerase is differentially regulated in neuroendocrine lung tumors is important for a better understanding of the pathogenesis of these malignancies., Experimental Design: We investigated telomerase activity in 86 neuroendocrine lung tumors and correlated the enzyme activity with the expression of the enzyme subunits [human RNA component (hTR), human telomerase reverse transcriptase (hTERT), and alternatively spliced hTERT variants], with the telomere-associated protein human protection of telomere-1, and with the telomere length pattern., Results: A significantly (P = 0.0001) lower frequency of telomerase-positive cases was found in typical carcinoids (14%) than in large cell neuroendocrine carcinomas (87%) and small cell lung cancers (92%). hTR was constitutively expressed in all carcinoids. Telomerase-negative carcinoids were characterized by the absence of any hTERT transcript, only displayed the beta(-) alternatively spliced variant, or concomitantly expressed the alpha(+)beta(+) full-length message with different combinations of alternatively spliced variants. However, in these tumors, a more abundant level of alternatively spliced transcripts than that of the alpha(+)beta(+) full-length transcript was generally found. No significant difference was observed in human protection of telomere-1 expression between telomerase-negative and telomerase-positive carcinoids. Telomeres were significantly (P < 0.05) longer in telomerase-negative carcinoids than in telomerase-positive carcinoids (median value, 9.15 versus 4.47 kb). However, alternative lengthening of telomeres, as shown by associated promyelocytic leukemia bodies, was not observed in these tumors., Conclusions: Our results indicate that telomerase is repressed in most lung carcinoids and that hTERT transcription and alternative splicing play a role in such a negative regulation. Moreover, the absence of any telomerase maintenance mechanism may contribute to the favorable prognosis of this malignancy.
- Published
- 2005
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19. Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.
- Author
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Bianchi F, Hu J, Pelosi G, Cirincione R, Ferguson M, Ratcliffe C, Di Fiore PP, Gatter K, Pezzella F, and Pastorino U
- Subjects
- Aged, Calcium-Binding Proteins biosynthesis, Caveolin 2, Caveolins biosynthesis, Cystatins biosynthesis, Disease Progression, Extracellular Matrix Proteins biosynthesis, Female, Humans, Immunohistochemistry, Lung Neoplasms metabolism, Male, Middle Aged, Phenotype, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Statistics as Topic, Tomography, X-Ray Computed, Matrix Gla Protein, DNA, Complementary metabolism, Gene Expression Regulation, Neoplastic, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Oligonucleotide Array Sequence Analysis methods, Tomography, Spiral Computed methods
- Abstract
Purpose: Spiral computed tomography (CT) can detect lung cancer at an early stage, but the malignant potential is unknown. The question is, as follows: do these small lesions have the same lethal potential as do symptomatic tumors?, Experimental Design: We used a cDNA microarray platform and compared the gene expression profile of spiral CT-detected lung carcinomas with a matched case-control population of patients presenting with symptomatic lung cancer., Results: CT-detected and symptomatic tumors have shown a comparable gene expression profile. Correspondence analysis has demonstrated that nine genes were differentially expressed, although with a high variability across the samples that prevented distinguishing the two groups of tumors. Analysis of these nine genes has suggested that early-detected tumors have higher levels of retinoic acid production and higher expression levels of caveolin 2, matrix Gla, and cystatin A, which are already known to be lost during tumor progression., Conclusions: All of the tumors observed are histologically malignant according to the WHO Classification. Early lung cancers that are detected by screening have a gene expression pattern similar to, but not identical to, that of symptomatic lung carcinomas.
- Published
- 2004
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20. Sports after total joint replacement.
- Author
-
Cirincione RJ
- Subjects
- Hip Prosthesis rehabilitation, Humans, Knee Prosthesis rehabilitation, Prosthesis Failure, Joint Prosthesis rehabilitation, Postoperative Complications rehabilitation, Sports
- Abstract
Functional return after total joint replacement is the goal of the patient and orthopedic surgeon. Return to sports is possible and encouraged following replacement surgery. However, appropriate guidelines need to be followed to prevent complications. Overuse or a too rapid return to strenuous activity has been shown to result in an increased tendency for loosening of the prosthetic components. Recommendations for a safe return to sport activity are outlined.
- Published
- 1996
21. Tendon ruptures with secondary hyperparathyroidism. A case report.
- Author
-
Cirincione RJ and Baker BE
- Subjects
- Adult, Humans, Male, Rupture, Tendons surgery, Hyperparathyroidism, Secondary complications, Tendon Injuries
- Published
- 1975
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