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6. Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines.

Author

Ferrario, Nicole, Marras, Emanuela, Vivona, Veronica, Randisi, Federica, Fallica, Antonino Nicolò, Marrazzo, Agostino, Perletti, Gianpaolo, and Gariboldi, Marzia Bruna

Subjects
BLADDER tumors, DIAGNOSTIC imaging, ANTINEOPLASTIC agents, BREAST tumors, DESCRIPTIVE statistics, DNA, QUINOLONE antibacterial agents, CELL lines, MOLECULAR structure, WESTERN immunoblotting, CELL death, PHARMACODYNAMICS
Abstract

Simple Summary: Besides their antibacterial effects, fluoroquinolones possess other valuable properties such as immunomodulatory and anticancer activities. These features make fluoroquinolones ideal compounds for 'drug repositioning'. In the last decades, fluoroquinolone derivatives with improved anticancer effects have been synthesized. We have previously shown that certain ciprofloxacin and norfloxacin derivatives were more potent anticancer agents than their precursors. For this study, the mechanisms of action of the most active among these derivatives were evaluated in a panel of tumor cell lines, including particularly untreatable cancer forms (e.g., triple-negative breast cancer). The tested compounds exerted several well-known fluoroquinolone effects, like cell cycle arrest, apoptosis induction, migration, and topoisomerase II inhibition, along with rather unexplored mechanisms for fluoroquinolones, namely, alternative cell death and histone deacetylase inhibition. Our results delve deeper into the anticancer mechanisms of fluoroquinolone derivatives that, given their known tolerability, could represent a valid therapeutic option, even in poorly treatable tumors. Antibacterial fluoroquinolones have emerged as potential anticancer drugs, thus prompting the synthesis of novel molecules with improved cytotoxic characteristics. Ciprofloxacin and norfloxacin derivatives, previously synthesized by our group, showed higher anticancer potency than their progenitors. However, no information about their mechanisms of action was reported. In this study, we selected the most active among these promising molecules and evaluated, on a panel of breast (including those triple-negative) and bladder cancer cell lines, their ability to induce cell cycle alterations and apoptotic and necrotic cell death through cytofluorimetric studies. Furthermore, inhibitory effects on cellular migration, metalloproteinase, and/or acetylated histone protein levels were also evaluated by the scratch/wound healing assay and Western blot analyses, respectively. Finally, the DNA relaxation assay was performed to confirm topoisomerase inhibition. Our results indicate that the highest potency previously observed for the derivatives could be related to their ability to induce G2/M cell cycle arrest and apoptotic and/or necrotic cell death. Moreover, they inhibited cellular migration, probably by reducing metalloproteinase levels and histone deacetylases. Finally, topoisomerase inhibition, previously observed in silico, was confirmed. In conclusion, structural modifications of progenitor fluoroquinolones resulted in potent anticancer derivatives possessing multiple mechanisms of action, potentially exploitable for the treatment of aggressive/resistant cancers. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Treatment of urge incontinence in postmenopausal women: A systematic review

Author

Bapir, Rawa, primary, Bhatti, Kamran Hassan, additional, Eliwa, Ahmed, additional, García-Perdomo, Herney Andrés, additional, Gherabi, Nazim, additional, Hennessey, Derek, additional, Magri, Vittorio, additional, Mourmouris, Panagiotis, additional, Ouattara, Adama, additional, Perletti, Gianpaolo, additional, Philipraj, Joseph, additional, Stamatiou, Konstantinos, additional, Tolani, Musliu Adetola, additional, Tzelves, Lazaros, additional, Trinchieri, Alberto, additional, and Buchholz, Noor, additional

Published
2023
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12. Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis

Author

Bapir, Rawa, primary, Bhatti, Kamran Hassan, additional, Eliwa, Ahmed, additional, García-Perdomo, Herney Andrés, additional, Gherabi, Nazim, additional, Hennessey, Derek, additional, Magri, Vittorio, additional, Mourmouris, Panagiotis, additional, Ouattara, Adama, additional, Perletti, Gianpaolo, additional, Philipraj, Joseph, additional, Stamatiou, Konstantinos, additional, Adetola Tolani, Musliu, additional, Tzelves, Lazaros, additional, Trinchieri, Alberto, additional, and Buchholz, Noor, additional

Published
2022
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13. Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials

Author

Bapir, Rawa, primary, Bhatti, Kamran Hassan, additional, Eliwa, Ahmed, additional, García-Perdomo, Herney Andrés, additional, Gherabi, Nazim, additional, Hennessey, Derek, additional, Magri, Vittorio, additional, Mourmouris, Panagiotis, additional, Ouattara, Adama, additional, Perletti, Gianpaolo, additional, Philipraj, Joseph, additional, Stamatiou, Konstantinos, additional, Trinchieri, Alberto, additional, and Buchholz, Noor, additional

Published
2022
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16. Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis

Author

Bapir, Rawa, primary, Bhatti, Kamran Hassan, additional, Eliwa, Ahmed, additional, García-Perdomo, Herney Andrés, additional, Gherabi, Nazim, additional, Hennessey, Derek, additional, Magri, Vittorio, additional, Mourmouris, Panagiotis, additional, Ouattara, Adama, additional, Perletti, Gianpaolo, additional, Philipraj, Joseph, additional, Trinchieri, Alberto, additional, and Buchholz, Noor, additional

Published
2022
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17. Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

Author

Bapir, Rawa, Bhatti, Kamran Hassan, Eliwa, Ahmed, Andrés García-Perdomo, Herney, Gherabi, Nazim, Hennessey, Derek, Magri, Vittorio, Mourmouris, Panagiotis, Ouattara, Adama, Perletti, Gianpaolo, Philipraj, Joseph, Stamatiou, Konstantinos, Tolani, Musliu Adetola, Tzelves, Lazaros, Anker, Stefan D., Trinchieri, Alberto, and Buchholz, Noor

Subjects
GLUCOSE transporters, URINARY tract infections, SODIUM-glucose cotransporter 2 inhibitors, SODIUM-glucose cotransporters, TYPE 2 diabetes, CHRONIC kidney failure
Abstract

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. Materials and methods: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. Results: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93-4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. Conclusions: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Infectious complications of endourological treatment of kidney stones: A meta-analysis of randomized clinical trials

Author

Bapir, Rawa, primary, Bhatti, Kamran Hassan, additional, Eliwa, Ahmed, additional, García-Perdomo, Herney Andrés, additional, Gherabi, Nazim, additional, Hennessey, Derek, additional, Mourmouris, Panagiotis, additional, Ouattara, Adama, additional, Perletti, Gianpaolo, additional, Philipraj, Joseph, additional, Trinchieri, Alberto, additional, and Buchholz, Noor, additional

Published
2022
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27. Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis

Author

Trinchieri, Alberto, primary, Abdelrahman, Khalid Mohammed, additional, Bhatti, Kamran Hassan, additional, Bello, Jibril O., additional, Das, Krishanu, additional, Gatsev, Ognyan, additional, Gergova, Ivanka, additional, Magri, Vittorio, additional, Mourmouras, Nikos, additional, Mourmouris, Panagiotis, additional, Murdeshwar, Soni, additional, Perletti, Gianpaolo, additional, Saltirov, Iliya, additional, Sissoko, Idrissa, additional, Stamatiou, Konstantinos, additional, and Buchholz, Noor, additional

Published
2021
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30. Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis

Author

Trinchieri, Alberto Abdelrahman, Khalid Mohammed Bhatti, Kamran Hassan Bello, Jibril O. Das, Krishanu Gatsev, Ognyan and Gergova, Ivanka Magri, Vittorio Mourmouras, Nikos and Mourmouris, Panagiotis Murdeshwar, Soni Perletti, Gianpaolo and Saltirov, Iliya Sissoko, Idrissa Stamatiou, Konstantinos and Buchholz, Noor

Abstract

Objective: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. Materials: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. Results: Escherichia colt (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was

Published
2021

42. Decreased DNA double‑strand break repair and enhanced chromosomal radiosensitivity in irradiated non‑tumorigenic human breast epithelial cells with a partial BRCA1 or BRCA2 knockdown

Author

Baert, Annelot, primary, Palermo, Maria, additional, Van Heetvelde, Mattias, additional, Verstraete, Bram, additional, Depuydt, Julie, additional, Vierstraete, Jeroen, additional, Philippe, Jan, additional, Sablina, Anna, additional, Perletti, Gianpaolo, additional, Claes, Kathleen, additional, and Vral, Anne, additional

Published
2020
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47. Current assessment of Ηemospermia

Author

Konstantinos, Stamatiou, Perletti, Gianpaolo, Vittorio, Magri, Hippocrates, Moschouris, Raffi, Avakian, Nectaria, Rekleiti, and Alberto, Trinchieri

Published
2019

48. Serenoa repens and Pygeum Africanum in the treatment of BPH

Author

Stamatiou, Konstantinos, Magri, Vittorio, Samara, Evangelia, and Perletti, Gianpaolo

Subjects
Pygeum africanum, Benign Prostatic Hypertrophy, Serenoa repens, Pygeum africanum, Benign Prostatic Hypertrophy, Serenoa repens
Published
2019

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