24 results on '"Ingenito C"'
Search Results
2. Erratum: miR-194-5p/BCLAF1 deregulation in AML tumorigenesis
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Dell'Aversana, C, Giorgio, C, D'Amato, L, Lania, G, Matarese, F, Saeed, S, Di Costanzo, A, Belsito Petrizzi, V, Ingenito, C, Martens, J H A, Pallavicini, I, Minucci, S, Carissimo, A, Stunnenberg, H G, and Altucci, L
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- 2018
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3. Erratum: miR-194-5p/BCLAF1 deregulation in AML tumorigenesis
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Dell'Aversana, C, primary, Giorgio, C, additional, D'Amato, L, additional, Lania, G, additional, Matarese, F, additional, Saeed, S, additional, Di Costanzo, A, additional, Belsito Petrizzi, V, additional, Ingenito, C, additional, Martens, J H A, additional, Pallavicini, I, additional, Minucci, S, additional, Carissimo, A, additional, Stunnenberg, H G, additional, and Altucci, L, additional
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- 2017
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4. miR-194-5p/BCLAF1 deregulation in AML tumorigenesis
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Dell'Aversana, C, primary, Giorgio, C, additional, D'Amato, L, additional, Lania, G, additional, Matarese, F, additional, Saeed, S, additional, Di Costanzo, A, additional, Belsito Petrizzi, V, additional, Ingenito, C, additional, Martens, J H A, additional, Pallavicini, I, additional, Minucci, S, additional, Carissimo, A, additional, Stunnenberg, H G, additional, and Altucci, L, additional
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- 2017
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5. Mir-194-5p/BCLAF1 deregulation in AML tumorigenesis
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Dell'aversana, C., Giorgio, C., D'Amato, L., Lania, G., Matarese, F., Saeed, S., Di Costanzo, A., Belsito Petrizzi, V., Ingenito, C., Martens, J.H.A., Pallavicini, I., Minucci, S., Carissimo, A., Stunnenberg, H., Altucci, L., Dell'aversana, C., Giorgio, C., D'Amato, L., Lania, G., Matarese, F., Saeed, S., Di Costanzo, A., Belsito Petrizzi, V., Ingenito, C., Martens, J.H.A., Pallavicini, I., Minucci, S., Carissimo, A., Stunnenberg, H., and Altucci, L.
- Abstract
Contains fulltext : 168891.pdf (publisher's version ) (Open Access), Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially /`immortal/' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.
- Published
- 2017
6. c-Myc modulation & acetylation is a key HDAC inhibitor target in cancer
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Nebbioso, A., Carafa, V., Conte, M., Tambaro, F.P., Abbondanza, C., Martens, J.H.A., Nees, M., Benedetti, R., Pallavicini, I., Minucci, S., Garcia-Manero, G., Iovino, F., Lania, G., Ingenito, C., Belsito Petrizzi, V., Stunnenberg, H.G., Altucci, L., Nebbioso, A., Carafa, V., Conte, M., Tambaro, F.P., Abbondanza, C., Martens, J.H.A., Nees, M., Benedetti, R., Pallavicini, I., Minucci, S., Garcia-Manero, G., Iovino, F., Lania, G., Ingenito, C., Belsito Petrizzi, V., Stunnenberg, H.G., and Altucci, L.
- Abstract
Contains fulltext : 165880.pdf (Publisher’s version ) (Closed access), PURPOSE: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, the mechanism(s) underlying their tumor selectivity are poorly understood. Experimental Design/Results: Using gene expression analysis, we define a core set of 6 genes commonly regulated in acute myeloid leukemia (AML) blasts and cell lines. c-Myc, the most prominently modulated, is preferentially altered in leukemia. Upon HDACi treatment, c-Myc is acetylated at lysine 323 and its expression decreases, leading to TRAIL activation and apoptosis. c-Myc binds to the TRAIL promoter on the proximal GC box through Sp1 or Miz1, impairing TRAIL activation. HDACi exposure triggers TRAIL expression, altering c-Myc-TRAIL binding. These events do not occur in normal cells. Excitingly, this inverse correlation between TRAIL and c-Myc is supported by HDACi treatment ex vivo of AML blasts and primary human breast cancer cells. The predictive value of c-Myc to HDACi responsiveness is confirmed in vivo in AML patients undergoing HDACi-based clinical trials. CONCLUSIONS: Collectively, our findings identify a key role for c-Myc in TRAIL deregulation and as a biomarker of the anticancer action of HDACi in AML. The potential improved patient stratification could pave the way towards personalized therapies.
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- 2017
7. Erratum: miR-194-5p/BCLAF1deregulation in AML tumorigenesis
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Dell'Aversana, C, Giorgio, C, D'Amato, L, Lania, G, Matarese, F, Saeed, S, Di Costanzo, A, Belsito Petrizzi, V, Ingenito, C, Martens, J H A, Pallavicini, I, Minucci, S, Carissimo, A, Stunnenberg, H G, and Altucci, L
- Abstract
Correction to: Leukemia (2017) 31, 2315–2325; doi:10.1038/leu.2017.64; published online 10 March 2017 Following the publication of this article, the authors noted a mistake in the author affiliations. 4. Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan Should be replaced with:
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- 2018
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8. Clinical Characteristics of Metastatic Prostate Cancer Patients Infected with COVID-19 in South Italy
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Gianluca Ragone, Carlo Buonerba, Ciro Imbimbo, Antonella Sciarra, Giuseppe Di Lorenzo, Roberto Sanseverino, Concetta Ingenito, Emilio Leo, Sabino De Placido, Annamaria Libroia, Felice Crocetto, Simona Iaccarino, Giorgio Napodano, Luciana Buonerba, Zisis Kozlakidis, Di Lorenzo, G, Buonerba, L, Ingenito, C, Crocetto, F, Buonerba, C, Libroia, A, Sciarra, A, Ragone, G, Sanseverino, R, Iaccarino, S, Napodano, G, Imbimbo, C, Leo, E, Kozlakidis, Z, De Placido, S, Di Lorenzo, G., Buonerba, L., Ingenito, C., Crocetto, F., Buonerba, C., Libroia, A., Sciarra, A., Ragone, G., Sanseverino, R., Iaccarino, S., Napodano, G., Imbimbo, C., Leo, E., Kozlakidis, Z., and De Placido, S.
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Oncology ,Male ,Cancer Research ,medicine.medical_treatment ,Disease ,Comorbidities ,Prostate cancer ,0302 clinical medicine ,030212 general & internal medicine ,Androgen Antagonist ,Aged, 80 and over ,General Medicine ,Middle Aged ,Hospitalization ,Prostatic Neoplasms, Castration-Resistant ,Italy ,030220 oncology & carcinogenesis ,Urologic cancer ,Disease Progression ,Hormonal therapy ,Drug Therapy, Combination ,Comorbiditie ,Human ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Prognosi ,Drug interaction ,Coronavirus disease SARS-CoV-2 ,Pneumonia, Viral ,Protective factor ,Clinical Trial Note ,03 medical and health sciences ,Internal medicine ,medicine ,Risk factor ,Aged ,Antiviral Agent ,Chemotherapy ,Betacoronaviru ,Pandemic ,business.industry ,Coronavirus Infection ,Heparin ,SARS-CoV-2 ,Risk Factor ,COVID-19 ,medicine.disease ,business - Abstract
Background: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. Methods: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. Results: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. Conclusions: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.
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- 2020
9. Mir-194-5p/BCLAF1 deregulation in AML tumorigenesis
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Lucia Altucci, S. Minucci, Concetta Ingenito, Isabella Pallavicini, Loredana D’Amato, V Belsito Petrizzi, A. Di Costanzo, Carmela Dell'Aversana, Sadia Saeed, Filomena Matarese, Annamaria Carissimo, G Lania, Hendrik G. Stunnenberg, Joost H.A. Martens, Cristina Giorgio, Dell'Aversana, C., Giorgio, C, D'Amato, L., Lania, G., Matarese, F., Saeed, S., Di Costanzo, A., Belsito Petrizzi, V., Ingenito, C., Martens, J. H. A., Pallavicini, I., Minucci, S., Carissimo, A., Stunnenberg, H. G., and Altucci, Lucia
- Subjects
0301 basic medicine ,Cancer Research ,Myeloid ,medicine.drug_class ,Cellular differentiation ,Down-Regulation ,Apoptosis ,Biology ,medicine.disease_cause ,Acute myeloid leukaemia ,03 medical and health sciences ,Cancer epigenetics ,Cell Line, Tumor ,miR-194-5p/BCLAF1 ,microRNA ,medicine ,Humans ,Molecular Biology ,Oncogenesis ,Regulation of gene expression ,Tumor Suppressor Proteins ,Cell Cycle ,Histone deacetylase inhibitor ,Myeloid leukemia ,Cell Differentiation ,Hematology ,3. Good health ,Repressor Proteins ,Leukemia, Myeloid, Acute ,MicroRNAs ,Haematopoiesis ,Anesthesiology and Pain Medicine ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Oncology ,miRNAs ,Immunology ,Cancer research ,Original Article ,Erratum ,Carcinogenesis - Abstract
Contains fulltext : 168891.pdf (Publisher’s version ) (Open Access) Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially /`immortal/' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance. 11 p.
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- 2017
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10. Correction: Study on the Impact of Hormone Therapy for Prostate Cancer on the Quality of Life and the Psycho-Relational Sphere of Patients: ProQoL.
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Cappuccio F, Buonerba C, Scafuri L, Di Trolio R, Dolce P, Trabucco SO, Erbetta F, Tulimieri E, Sciscio A, Ingenito C, Verde A, and Di Lorenzo G
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- 2024
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11. Study on the Impact of Hormone Therapy for Prostate Cancer on the Quality of Life and the Psycho-Relational Sphere of Patients: ProQoL.
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Cappuccio F, Buonerba C, Scafuri L, Di Trolio R, Dolce P, Trabucco SO, Erbetta F, Tulimieri E, Sciscio A, Ingenito C, Verde A, and Di Lorenzo G
- Abstract
Introduction: Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients' quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy., Methods: Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T
0 ) and after 3 months (T1 ) and 6 months (T2 ) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews., Results: Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T0 to 76.7 at T2 ; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres., Conclusions: ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care., Competing Interests: Declarations. Conflict of Interest: Francesca Cappuccio, Carlo Buonerba, Luca Scafuri, Rossella Di Trolio, Pasquale Dolce, Serena Orsola Trabucco, Filomena Erbetta, Elvira Tulimieri, Antonella Sciscio, Concetta Ingenito and Antonio Verde have nothing to disclose. Giuseppe Di Lorenzo is an Editorial Board member of Oncology and Therapy. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: The study was approved by the Ethics Committee (“Comitato Etico Campania Centro”; approval/ protocol number 1945). The research was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent. Permission was received by the EORTC Quality of Life Group to use the questionnaires., (© 2024. The Author(s).)- Published
- 2024
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12. Unraveling the Dietary Puzzle: Exploring the Influence of Diet, Nutraceuticals, and Supplements on Bladder Cancer Risk, Outcomes, and Immunotherapy Efficacy: Insights from the BLOSSOM Study and Beyond.
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Buonerba C, Ingenito C, Di Trolio R, Cappuccio F, Rubino R, Piscosquito A, Verde A, Costabile F, Iuliucci M, Crocetto F, Chiancone F, Nacchia A, Campitelli A, Scafuri L, Sanseverino R, and Di Lorenzo G
- Abstract
Bladder cancer is considered a global health concern characterized by significant morbidity and mortality rates. The complex relationship between diet and bladder cancer is examined, with a specific focus on the role of diet in risk, outcomes, and treatment efficacy. Attention is drawn to the burgeoning field of immunotherapy in bladder cancer treatment, and the possible influence of diet on its outcomes is explored. While evidence remains limited, prior studies in other cancer types have suggested a potential connection between diet and immunotherapy response. To address this knowledge gap, the ongoing BLOSSOM study is presented, which aims to investigate the link between dietary factors, lifestyle, and the effectiveness of immunotherapy in patients with non-muscle-invasive bladder cancer. Ongoing efforts to decipher the intricate relationship between diet and bladder cancer care are highlighted, emphasizing the quest to unravel the dietary puzzle for the improvement of bladder cancer management., (© 2024. The Author(s).)
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- 2024
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13. A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.
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Di Lorenzo G, Michele A, Silvana L, Bilancia D, Di Trolio R, Iuliucci MR, Ingenito C, Rubino R, Piscosquito A, Caraglia M, Donnarumma M, Costabile F, Conca R, Pisino M, Vaia A, Scafuri L, Verde A, and Buonerba C
- Abstract
Introduction: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin., Methods: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes., Results: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1)., Conclusion: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management., (© 2023. The Author(s).)
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- 2024
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14. Effective Management of Nasal Vestibule Squamous Cell Carcinoma with Cemiplimab: A Case Report.
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Costabile F, Donnarumma M, Piscosquito A, Ingenito C, Iuliucci MR, Buonerba C, Di Lorenzo G, and Di Trolio R
- Abstract
Nasal vestibule squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options. This case report presents an 83-year-old female with SCC of the nasal vestibule who was ineligible for surgery or radiotherapy due to various factors. The patient was successfully treated with cemiplimab, a systemic anti-PD-1 antibody, resulting in a remarkable tumor reduction without any observed side effects. This is the first reported case of nasal vestibule SCC treated with cemiplimab, highlighting its potential as a promising therapeutic option., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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15. PREVES: A Population-Based Survey Focused on Cancer and Nutrition.
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Di Lorenzo G, Ingenito C, Iervolino M, Sosto G, Sergianni P, Primiano F, Piscosquito A, Iuliucci MR, Rubino R, Gatani S, Ugliano F, Scafuri L, Costabile F, D'Ambrosio B, D'Antonio A, Crescenzo A, Cappuccio F, and Buonerba C
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- Humans, Cross-Sectional Studies, Vegetables, Surveys and Questionnaires, Diet adverse effects, Neoplasms epidemiology
- Abstract
Introduction: Approximately a third of cancer-related deaths are attributable to modifiable factors., Methods: As a pilot experience, a cross-sectional survey was conducted in 8,000 citizens residing in four different municipalities of the Salerno province (Sarno, Pagani, San Valentino Torio, and San Marzano sul Sarno) to investigate key lifestyle and dietary habits., Results: A total of 703 of participants (8.7%) reported a history of malignancy. Alarmingly, 30.5% declared to be a current smoker, while 78.8% did not report any kind of physical activity. Encouragingly, 64.5% declared to be abstemious, and 83.0% declared to consume fruit and vegetables every day, while 4.7% and 31.9% declared not to consume meat and fried food, respectively, at any time. Never-consumers of fruit and vegetables had higher odds of having a history of colorectal cancer (OR = 5.01; 95% CI = 1.46-17.15; p = 0.01)., Conclusions: The PREVES study has served to prove the validity of an operational model allowing to integrate hospital and territorial healthcare services, which we expect to be applied at a larger scale. Key information regarding dietary and lifestyle habits of the investigated population was obtained. Larger studies conducted using more accurate approaches to investigate diet, such as 24-h recalls and food frequency questionnaires, are warranted., (© 2023 S. Karger AG, Basel.)
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- 2023
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16. Mediterranean Diet as a Supportive Intervention in Cancer Patients: Current Evidence and Future Directions.
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Rubino R, Iuliucci MR, Gatani S, Piscosquito A, D'Ambrosio B, Ingenito C, Scafuri L, Buonerba C, and Di Lorenzo G
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- Humans, Diet, Mediterranean, Neoplasms therapy
- Abstract
Cancer currently represents a leading cause of morbidity and mortality, and it can be held responsible for about one in six deaths worldwide [...]., Competing Interests: The authors declare no conflicts of interest.
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- 2022
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17. The Effect of Vaccination against COVID-19 in Cancer Patients: Final Results of the COICA Trial.
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Di Lorenzo G, Ingenito C, D'Ambrosio B, Ranieri C, Iuliucci MR, Iervolino M, Primiano F, Buonerba L, Busto G, Ferrara C, Libroia A, Ragone G, De Falco F, Costabile F, Fimiani P, Ugliano F, Leo E, Roviello G, Scafuri L, and Buonerba C
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- Case-Control Studies, Clinical Trials as Topic, Female, Humans, Male, Observational Studies as Topic, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Neoplasms complications
- Abstract
Background: The COICA study is an ambispective, observational trial that was conceived to assess the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients. A recently published, population-based, case-control study reported a reduced vaccine efficacy at 3-6 months in cancer patients compared to individuals without cancer. Objectives: The aim of the study was to describe coronavirus disease 19 (COVID-19) outcomes in cancer patients and analyze differences in SARS-CoV-2 outcomes between vaccinated and unvaccinated patients. Methods: Descriptive statistics and frequency counts were used to summarize characteristics of the study population. χ
2 test and the log-rank test were used to compare outcomes between vaccinated and unvaccinated patients. Results: A total of 141 cancer patients (80 males, 61 females) were recruited at two participating Institutions from March 2020 until April 2022 and observed from the time of positive SARS-CoV-2 test to the time of negativization or death. Approximately 35% of patients had been vaccinated at the time of infection with 2 (16 patients) or 3 (33 patients) vaccine doses. Vaccinated patients consistently and significantly showed improved COVID-19 outcomes compared to unvaccinated patients, with CT-diagnosed pneumonia, hospitalization, O2 therapy, and death reported in 0% versus 48.6%, 2.0% versus 15.2%, 0% versus 14.1%, and 0% versus 7.6%, respectively, of assessable patients ( p < 0.05). Vaccinated versus unvaccinated patients showed a significantly shorter time to negativization, with a median (95% confidence interval) time of 12 (10-14) versus 20 (17-23) days, respectively ( p < 0.001). Conclusions: Vaccination consistently improved all COVID-19 outcomes. No death was recorded among vaccinated patients. Additional research is especially warranted to establish optimal timing and patient selection for administration of the fourth vaccination dose., (© 2022 S. Karger AG, Basel.)- Published
- 2022
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18. The Impact of Routine Molecular Screening for SARS-CoV-2 in Patients Receiving Anticancer Therapy: An Interim Analysis of the Observational COICA Study.
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Di Lorenzo G, Iervolino M, Primiano F, D'Ambrosio M, Ingenito C, Buonerba L, Busto G, Ferrara C, Libroia A, Ragone G, De Falco F, Costabile F, Fimiani P, Ugliano F, Ranieri C, Leo E, Roviello G, Scafuri L, Guerra G, and Buonerba C
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- Hospitalization, Humans, SARS-CoV-2, COVID-19 diagnosis, COVID-19 epidemiology, Neoplasms drug therapy, COVID-19 Drug Treatment
- Abstract
Introduction: Cancer aggravates COVID-19 prognosis. Nosocomial transmission of SARS-CoV-2 is particularly frequent in cancer patients, who need to attend hospitals regularly. Since March 2020, all cancer patients having access to the Oncology Unit at the "Andrea Tortora" Hospital (Pagani, Salerno - referred to as "the Hospital") as inpatients or outpatients receiving intravenous therapy have been screened for SARS-CoV-2 using RT-PCR nasal swab. The ongoing COICA (COVID-19 infection in cancer patients) study is an ambispective, multicenter, observational study designed to assess the prognosis of SARS-CoV-2 infection in cancer patients. The aim of the study presented here was to explore potential differences in COVID-19-related outcomes among screening-detected versus nonscreening-detected SARS-CoV-2-infected patients. Methods: The COICA study enrolled cancer patients who had received any anticancer systemic therapy within 3 months since the day they tested positive for SARS-CoV-2 on RT-PCR. The target accrual is 128 patients, and the study was approved by the competent Ethics Committee. Only the subgroup of patients enrolled at the Hospital was considered in this unplanned interim analysis. Logistic regression analysis was used to evaluate the association of screening-based versus nonscreening-based diagnosis. Results: Since March 15, 2020, until August 15, 2021, a total of 931 outpatients and 230 inpatients were repeatedly screened for SARS-CoV-2 using RT-PCR nasal swab at the Hospital. Among these, 71 asymptomatic patients were positive on routine screening and 5 patients were positive for SARS-CoV-2 outside the institutional screening. Seven patients died because of COVID-19. At univariate analysis, nonscreening- versus screening-detected SARS-CoV-2 infection was associated with significantly higher odds of O
2 therapy (OR = 16.2; 95% CI = 2.2-117.1; p = 0.006), hospital admission (OR = 31.5; 95% CI = 3.1-317.8; p = 0.003), admission to ICU (OR = 23.0; 95% CI = 2.4-223.8; p = 0.007), and death (OR = 8.8; 95% CI = 1.2-65.5; p = 0.034). Conclusion: Routine screening with RT-PCR may represent a feasible and effective strategy in reducing viral circulation and possibly COVID-19 mortality in patients with active cancer having repeated access to hospital facilities., (© 2021 S. Karger AG, Basel.)- Published
- 2022
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19. Hematological Toxicity During Concomitant Treatment With Ruxolitinib and Avelumab for Merkel Cell Carcinoma.
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Buonerba L, Di Trolio R, Grimaldi A, Tucci A, Leo E, Ingenito C, Costabile F, Ragone G, Savastano B, Uzzauto MT, Belsito Petrizzi V, and Di Lorenzo G
- Abstract
Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. It frequently emerges in the presence of immunosuppression states such as myeloproliferative syndrome (MS). MS is treated with ruxolitinib, a selective JAK1 and JAK2 inhibitor. Avelumab, an anti PDL-1 inhibitor, is the standard treatment for MCC. To date it is unknown if avelumab and ruxolitinib have a synergistic or antagonistic effect when used together. Methods: We have identified all patients diagnosed with MCC, treated with avelumab, concomitant ruxolitinib, belonging to Tortora Hospital, Pagani and Santa Maria La Pietà Hospital, Nola, Italy between June 1 2019 and April 1 2020. Results: Among six MCC patients, we have found two patients in treatment with concomitant drugs. Both patients were being treated with ruxolitinib for MS as a standard regimen without suffering any hematological side effects. After starting doses of avelumab, we found thrombocytopenia, leukopenia, and anemia after cycle 1 and cycle 4, respectively, and decided to suspend both treatments. Following the suspension, the hematological values improved allowing us to restart treatment with avelumab without the need to resume ruxolitinib treatment. Conclusions: The combined treatment of ruxolitinib and avelumab demonstrated severe toxicity. Modifying the schedule or reducing the dose of both drugs needs to be studied in order to be able to treat both pathologies., (Copyright © 2020 Buonerba, Di Trolio, Grimaldi, Tucci, Leo, Ingenito, Costabile, Ragone, Savastano, Uzzauto, Belsito Petrizzi and Di Lorenzo.)
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- 2020
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20. COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature.
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Di Lorenzo G, Di Trolio R, Kozlakidis Z, Busto G, Ingenito C, Buonerba L, Ferrara C, Libroia A, Ragone G, Ioio CD, Savastano B, Polverino M, De Falco F, Iaccarino S, and Leo E
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- Betacoronavirus, COVID-19, Humans, SARS-CoV-2, COVID-19 Drug Treatment, Antineoplastic Agents therapeutic use, Coronavirus Infections drug therapy, Pandemics, Pneumonia, Viral drug therapy
- Abstract
Background: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID- 19)., Methods: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. A total of 205 articles were identified and 53 were included in this review., Results: We describe the ongoing COVID-19 therapies that should be known by oncologists and highlight the potential interactions with antineoplastic drugs, commonly used in clinical practice. The main drug interactions were found with tocilizumab, ruxolitinib and colchicine., Conclusions: The literature provides an inconclusive picture on potential preferred treatments for COVID-19 and their interactions with antineoplastic agents. Future clinical trials are needed to better understand the interactions between different drugs in the context of COVID-19 pandemic., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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21. Coronavirus Disease 2019 Emergency and Cancer in the South of Italy: What's New for the Oncologist?
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Ingenito C, Buonerba L, Ferrara C, Busto G, Libroia A, Ragone G, Leo E, Savastano B, Ioio CD, De Falco F, Iaccarino S, Tarantino L, Polverino M, and Di Lorenzo G
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- 2020
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22. Clinical Characteristics of Metastatic Prostate Cancer Patients Infected with COVID-19 in South Italy.
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Di Lorenzo G, Buonerba L, Ingenito C, Crocetto F, Buonerba C, Libroia A, Sciarra A, Ragone G, Sanseverino R, Iaccarino S, Napodano G, Imbimbo C, Leo E, Kozlakidis Z, and De Placido S
- Subjects
- Aged, Aged, 80 and over, COVID-19, Coronavirus Infections transmission, Coronavirus Infections virology, Disease Progression, Drug Therapy, Combination, Hospitalization, Humans, Italy, Male, Middle Aged, Pandemics, Pneumonia, Viral transmission, Pneumonia, Viral virology, Prognosis, Prostatic Neoplasms, Castration-Resistant secondary, Prostatic Neoplasms, Castration-Resistant virology, Risk Factors, SARS-CoV-2, Androgen Antagonists therapeutic use, Antiviral Agents therapeutic use, Betacoronavirus isolation & purification, Coronavirus Infections complications, Heparin therapeutic use, Pneumonia, Viral complications, Prostatic Neoplasms, Castration-Resistant drug therapy
- Abstract
Background: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown., Methods: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy., Results: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities., Conclusions: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful., (© 2020 S. Karger AG, Basel.)
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- 2020
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23. Combined HAT/EZH2 modulation leads to cancer-selective cell death.
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Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-Megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, and Altucci L
- Abstract
Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro , ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2. Even aggressive models of cancer, such as p53
-/- or TET2-/- cells, responded to MC2884, suggesting MC2884 therapeutic potential also for the therapy of TP53 or TET2-deficient human cancers. MC2884 induced massive apoptosis in ex vivo human primary leukemia blasts with poor prognosis in vivo , by targeting BCL2 expression. MC2884-treatment reduced acetylation of the BCL2 promoter at higher level than combined p300 and EZH2 inhibition. This suggests a key role for BCL-2 reduction in potentiating responsiveness, also in combination therapy with BCL2 inhibitors. Finally, we identified both the mechanism of MC2884 action as well as a potential therapeutic scheme of its use. Altogether, this provides proof of concept for the use of epi-drugs coupled with epigenome analyses to 'personalize' precision medicine., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflict of interest. A patent application that includes some results is being filled with n° WO2017/198870 A1.- Published
- 2018
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24. c-Myc Modulation and Acetylation Is a Key HDAC Inhibitor Target in Cancer.
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Nebbioso A, Carafa V, Conte M, Tambaro FP, Abbondanza C, Martens J, Nees M, Benedetti R, Pallavicini I, Minucci S, Garcia-Manero G, Iovino F, Lania G, Ingenito C, Belsito Petrizzi V, Stunnenberg HG, and Altucci L
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- Acetylation, Cell Line, Tumor, Clinical Trials as Topic, Gene Expression Regulation, Leukemic drug effects, Histone Deacetylase 1 antagonists & inhibitors, Histone Deacetylase Inhibitors administration & dosage, Humans, Kruppel-Like Transcription Factors genetics, Neoplasms pathology, Protein Binding, Signal Transduction drug effects, Sp1 Transcription Factor genetics, Histone Deacetylase 1 genetics, Neoplasms drug therapy, Proto-Oncogene Proteins c-myc genetics, TNF-Related Apoptosis-Inducing Ligand genetics
- Abstract
Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, the mechanism(s) underlying their tumor selectivity are poorly understood. Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts and cell lines. MYC , the most prominently modulated, is preferentially altered in leukemia. Upon HDACi treatment, c-Myc is acetylated at lysine 323 and its expression decreases, leading to TRAIL activation and apoptosis. c-Myc binds to the TRAIL promoter on the proximal GC box through SP1 or MIZ1, impairing TRAIL activation. HDACi exposure triggers TRAIL expression, altering c-Myc- TRAIL binding. These events do not occur in normal cells. Excitingly, this inverse correlation between TRAIL and c-Myc is supported by HDACi treatment ex vivo of AML blasts and primary human breast cancer cells. The predictive value of c-Myc to HDACi responsiveness is confirmed in vivo in AML patients undergoing HDACi-based clinical trials. Conclusions: Collectively, our findings identify a key role for c-Myc in TRAIL deregulation and as a biomarker of the anticancer action of HDACi in AML. The potential improved patient stratification could pave the way toward personalized therapies. Clin Cancer Res; 23(10); 2542-55. ©2016 AACR ., (©2016 American Association for Cancer Research.)
- Published
- 2017
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