Publications by authors named "Ahmed M Mansour"

79 Publications

Sulfonate improves water solubility and cell selective toxicity and alters the lysozyme binding activity of half sandwich Rh(iii) complexes.

Dalton Trans 2021 Aug 2;50(31):10701-10706. Epub 2021 Aug 2.

Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, Cairo 12613, Egypt.

Introduction of the propyl-sulfonic acid group at N1 of the coordinated 2-(2-pyridyl)benzimidazole ligand (L) in [RhCl(η-CMe)L](CFSO) gives rise to a water-soluble complex, which can bind to the model protein lysozyme via non-covalent interactions. The complex shows selective moderate toxicity against Cryptococcus neoformans (MIC = 21.6-43.3 μM) and exhibits no cytotoxicity to healthy HEK293 cells.
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http://dx.doi.org/10.1039/d1dt00979fDOI Listing
August 2021

The association between sarcopenia and bladder cancer-specific mortality and all-cause mortality after radical cystectomy: A systematic review and meta-analysis.

Arab J Urol 2021 Jan 16;19(1):98-103. Epub 2021 Jan 16.

Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

: To compare cancer-specific mortality (CSM) and all-cause mortality (ACM) between patients with and without sarcopenia who underwent radical cystectomy for bladder cancer. : We performed a systematic review and meta-analysis of original articles published from October 2010 to March 2019 evaluating the effect of sarcopenia on CSM and ACM. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for CSM and ACM from the included studies. Heterogeneity amongst studies was measured using the -statistic and the index. Meta-analysis was performed using a random-effects model if heterogeneity was high and fixed-effects models if heterogeneity was low. : We identified 145 publications, of which five were included in the meta-analysis. These five studies represented 1447 patients of which 453 were classified as sarcopenic and 534 were non-sarcopenic. CSM and ACM were increased in sarcopenic vs non-sarcopenic patients (HR 1.64, 95% CI 1.30-2.08, < 0.01 and HR 1.41, 95% CI 1.22-1.62, < 0.01, respectively). : Sarcopenia is significantly associated with increased CSM and ACM in bladder cancer. Identifying patients with sarcopenia will augment preoperative counselling and planning. Further studies are required to evaluate targeted interventions in patients with sarcopenia to improve clinical outcomes. ACM: all-cause mortality; ASA: American Association of Anesthesiologists; BMI: body mass index; CCI: Charlson Comorbidity Index; CSM: cancer-specific mortality; CSS: cancer-specific survival; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; NAC: neoadjuvant chemotherapy; NIH: National Institutes of Health; OS: overall survival; RC: radical cystectomy; RCT: randomised controlled trial; SMI: Skeletal Muscle Index.
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http://dx.doi.org/10.1080/2090598X.2021.1876289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954502PMC
January 2021

Phototriggered cytotoxic properties of tricarbonyl manganese(I) complexes bearing α-diimine ligands towards HepG2.

J Biol Inorg Chem 2021 02 27;26(1):135-147. Epub 2021 Feb 27.

Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, 12613, Cairo, Egypt.

Reaction between bromo tricarbonyl manganese(I) and N,N'-bis(phenyl)-1,4-diaza-1,3-butadiene ligands, bearing different electron-donating and electron-withdrawing groups R = OCH, Cl, and NO in the ortho- and para-positions on the phenyl substituent, afforded [MnBr(CO)(N-N)] complexes. The influence of the character and position of the substituent on the dark stability and carbon monoxide releasing kinetics was systematically investigated and correlated with the data of the time-dependent density functional theory calculations. The combined UV/Vis and IR data clearly revealed that the aerated solutions of [MnBr(CO)(N-N)] in either coordinating or noncoordinating solvents are dark stable and the fluctuations observed during the incubation period especially in the case of the nitro derivatives may be attributed to the exchange of the axial bromo ligand with the coordinating solvent molecules. The free ligands and nitro complexes were non-cytotoxic to HepG2 cells under both the dark and illumination conditions. In the dark, Mn(I) compounds, incorporating o-OCH and o-Cl, exhibited excellent cytotoxicity with IC values of 18.1 and 11.8 μM, while their para-substituted analogues were inactive in the dark and active upon the irradiation at 365 nm with IC values of 5.7 and 6.7 μM, respectively.
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http://dx.doi.org/10.1007/s00775-020-01843-7DOI Listing
February 2021

Role of the ancillary ligand in controlling the lysozyme affinity and electronic properties of terpyridine -Re(CO) complexes.

Dalton Trans 2021 Feb;50(4):1197-1201

Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, Cairo 12613, Egypt.

The lysozyme binding affinity and the electronic properties of [ReX(CO)3(terpy-κ2N1,N2)] (X = Br- and triazolateCOOCH2CH3,CF3) were reported. The triazolate complex was prepared in a [3 + 2] cycloaddition click reaction. The bromo compound reacted with lysozyme affording adducts with Re(CO)3+ fragments, while the triazolate compound persisted. A red shift of the MLCT band of the triazolate compound in progressively less polar solvents may be due to the negative solvatochromism.
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http://dx.doi.org/10.1039/d0dt04140hDOI Listing
February 2021

Correlates of refusal of radical cystectomy in patients with muscle-invasive bladder cancer.

Urol Oncol 2021 04 8;39(4):236.e9-236.e20. Epub 2021 Jan 8.

Department of Urology, UT Health San Antonio, San Antonio, TX; UT Health San Antonio/MD Anderson Mays Cancer Center, San Antonio, TX; Urology and Nephrology Center, Mansoura University, Egypt. Electronic address:

Purpose: To evaluate factors associated with radical cystectomy (RC) refusal, subsequent treatment decisions, and their influence on overall survival (OS).

Materials And Methods: We queried the National Cancer Database for patients with non-metastatic muscle-invasive bladder cancer (MIBC), cT2-T4M0. Patients who refused recommended RC were further stratified by treatment into chemotherapy, radiation therapy, chemoradiotherapy, and no treatment groups. Patients were excluded from the analysis if surgery was not planned, not recommended; or if survival data were unknown. Multivariate logistic regression modeling was utilized to identify independent predictors of refusing RC. Cox proportional hazards model with propensity score overlap weighting was utilized to identify survival predictors. Kaplan-Meier analysis was utilized to evaluate survival according to treatment.

Results: A total of 74,159 MIBC patients were identified. Among patients with documented reasons for no surgery, 5.4% refused RC despite physician recommendation. Predictors of refusal on multivariate analysis included female gender (P = 0.016), advancing age ≥80 (vs. <60, P < 0.001), African American race (vs. white, P < 0.001) Medicaid (vs. private insurance, P < 0.001) and advancing T stage (T4 vs. T2, P < 0.001). Patients treated at academic centers were less likely to decline RC (vs. community centers, P < 0.001). Median survival after RC was 40.44 months vs. 12.52 months in refusal group. Undergoing chemoradiation had significantly improved survival in those patients compared to monotherapy or no treatment (hazard ratio 0.25, P < 0.001). Overlap weighted model Identified RC refusal as an independent predictor of poor OS (P < 0.001).

Conclusions: Several sociodemographic and clinical factors are associated with refusing radical cystectomy. Such refusal is associated with poor survival outcomes.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.023DOI Listing
April 2021

Development and implementation of competency-based assessment for urological ultrasound training using SonoSim: A preliminary evaluation.

Indian J Urol 2020 Oct-Dec;36(4):270-275. Epub 2020 Oct 1.

Department of Urology, University of Texas Health San Antonio, San Antonio, TX, USA.

Introduction: Urology residents are encouraged to learn ultrasound (U/S) imaging, yet there are few tools available for teaching and assessing a resident`s competence. The aim of this study was to test the new SonoSim LiveScan and to propose a competency-based assessment model for the urology graduate medical education.

Materials And Methods: Urology residents attended an interactive training session covering the urological U/S techniques guided by the assessment model developed by the authors. Faculty members evaluated the residents using defined objectives, and the residents were surveyed on their comfort level for performing each of the model tasks. A subset of the residents then underwent a structured testing using the SonoSim LiveScan device 6 months following the training. The model developed assessed: general U/S setup, structure identification, and pathologic clinical scenarios.

Results: The residents felt most comfortable in identifying the bladder (4.73/5) and the kidneys (4.53/5) during the training sessions. They felt least comfortable while testing for total ureteric obstruction (3.13/5). All the residents were confident that additional U/S training sessions would improve their comfort level in performing the assessed objectives. Resident`s assessment performed at 6 months had a median test score of 15.5/20 and the assessment scores increased with resident seniority. Self-reported comfort, however, did not seem to correlate with seniority. In general, the residents felt that the SonoSim device was highly functional (4.4/5) and the pathologic assessments in particular were very helpful (4.4/5).

Conclusions: Through pilot testing, we propose that a competency-based assessment used with the SonoSim LiveScan could guide the resident`s education through the acquisition of U/S skills and warrants testing in a larger cohort.
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http://dx.doi.org/10.4103/iju.IJU_22_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759178PMC
October 2020

Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes.

Pharmaceuticals (Basel) 2020 Jul 29;13(8). Epub 2020 Jul 29.

Department of Pharmacy, University of Naples Federico II, 80134 Napoli, Italy.

Three Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1), a model amyloidogenic system, before and after irradiation at 365 nm. Thioflavin T (ThT) binding assays and UV/Vis absorption spectra indicate that binding of the compounds to the peptide inhibits its aggregation and that the inhibitory effect increases upon irradiation (half maximal effective concentration (EC) values in the high micromolar range). Electrospray ionization mass spectrometry data of the peptide in the presence of one of these compounds confirm that the modulation of amyloid aggregation relies on the formation of adducts obtained when the Ru compounds react with the peptide upon releasing of labile ligands, like chloride and carbon monoxide. This mechanism of action explains the subtle different behavior of the three compounds observed in ThT experiments. Overall, data support the hypothesis that metal-based CO releasing molecules can be used to develop metal-based drugs with potential application as anti-amyloidogenic agents.
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http://dx.doi.org/10.3390/ph13080171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464691PMC
July 2020

National Trends and Impact of Regionalization of Radical Cystectomy on Survival Outcomes in Patients with Muscle Invasive Bladder Cancer.

Clin Genitourin Cancer 2020 12 22;18(6):e762-e770. Epub 2020 May 22.

Department of Urology, University of Texas Health, San Antonio, TX; Mays Cancer Center at UT Health San Antonio/MD Anderson, San Antonio, TX; Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. Electronic address:

Objective: To evaluate national trends and the effect of surgical volume on perioperative mortality and overall survival (OS)in patients undergoing radical cystectomy (RC) for muscle invasive bladder cancer (MIBC).

Methods: We investigated the National Cancer Database to identify patients with localized MIBC (cT2a-T4, M0) who underwent RC from 2004 to 2014. Demographics, 30- and 90-day mortality rates, as well as OS were analyzed. Hospitals were stratified into low-, medium-, and high-volume centers according to median number of RCs performed per year. Multivariate logistic regression models were fitted to identify independent predictors of perioperative mortality. Kaplan-Meier survival curves were generated to evaluate OS. Cox proportional hazard modeling was performed to identify independent predictors of OS.

Results: A total of 24,763 patients with localized MIBC who underwent RC from 2004 to 2014 were included in the study. Overall, most (70.85%) RCs occurred at low-volume hospitals, whereas only 15.83% were performed at high-volume hospitals. Thirty-day mortality rates were 2.87%, 2.19%, and 1.83% (P < .01); and 90-day mortality rates were 8.25%, 6.9%, and 5.9% (P < .01) at low-, medium-, and high-volume hospitals, respectively. Multivariate analyses identified RC volume as an independent predictor of 30- and 90-day mortality. RC in high-volume hospitals was associated with a 35% risk reduction in 30-day mortality (odds ratio 0.65, 95% confidence interval [CI] 0.49-0.85; P < .01), and a 26% risk reduction in 90-day mortality (0.74, 95% CI, 0.63-0.87; P < .01).

Conclusions: Treatment at high-volume centers offers improved outcomes and OS benefit. However, in the United States, only 16% of RCs are performed in high-volume hospitals.
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http://dx.doi.org/10.1016/j.clgc.2020.05.012DOI Listing
December 2020

Cytotoxicity of photoactivatable bromo tricarbonyl manganese(i) compounds against human liver carcinoma cells.

Dalton Trans 2020 Jul;49(27):9294-9305

Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, Cairo 12613, Egypt.

Two series of photoinduced tricarbonyl manganese(i) compounds were prepared from the reaction of [MnBr(CO)3(2-C(H)[double bond, length as m-dash]O)] (2-C(H)[double bond, length as m-dash]O: quinoline-2-carboxaldehyde and pyridine-2-carboxaldehyde) and para-substituted aniline derivatives (X = OH, OCH3, Cl and NO2). Different electron-donating and electron-withdrawing substituents were introduced in the para-position of the phenyl ring to investigate their influence on the stability of the compounds in the dark and the photophysical properties upon illumination at 525 nm. When kept in the dark, the aerated solutions of the complexes in dimethyl sulfoxide (DMSO) and CH2Cl2 were stable. In the solution, the complexes bearing electron-withdrawing substituents, exchange their bromo ligands with DMSO solvent molecules, as evidenced from infrared and UV/Vis studies as well as time-dependent density functional theory (TDDFT) calculations. The complexes were assessed for their cytotoxicity, both in the dark and upon exposure to a 525 nm LED, against the human hepatocarcinoma cell line (HepG2). A marked reduction in the viability of HepG2 cells treated with the complex functionalized with quinoline and methoxy substituent was observed after illumination in a dose-dependent manner, with an IC50 value of 7.1 μM, making it the most phototoxic compound in our study.
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http://dx.doi.org/10.1039/d0dt01539cDOI Listing
July 2020

Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.

Transl Res 2020 09 31;223:1-14. Epub 2020 May 31.

Department of Urology, University of Texas Health, San Antonio, Texas.

Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.
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http://dx.doi.org/10.1016/j.trsl.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111697PMC
September 2020

Analyzing National Incidences and Predictors of Open Conversion During Minimally Invasive Partial Nephrectomy for cT1 Renal Masses.

J Endourol 2021 01 22;35(1):30-38. Epub 2020 Jun 22.

Department of Urology and UT Health San Antonio, San Antonio, Texas, USA.

To analyze predictors of open conversion during minimally invasive partial nephrectomy (MIPN) for cT1 renal masses. The National Cancer Database (NCDB) was investigated for kidney cancer patients who underwent partial nephrectomy (PN) between 2010 and 2015. Patients who underwent MIPN were stratified into converted and nonconverted groups. Sociodemographics, facility characteristics, and surgical outcomes were compared between the two groups, and multivariate logistic regression model was fitted to identify independent predictors of open conversion. In total, 54,246 patients underwent PN for kidney cancer during the 6-year period. Of those, 18,994 (35%) were open partial nephrectomies (OPNs) and 35,252 (64%) were MIPN. Overall, 1010 (2.87%) of MIPNs were converted to OPN. There was an increasing utilization of MIPN from 50.35% in 2010 to 74.73% in 2015. Patients who had open conversion had more 30-day readmissions (5.95% 3.31%,  < 0.01). On multivariate analysis; high-volume facility (>30 MIPNs/year), year of surgery (2015 2010), and robotic approach predicted a lower likelihood of conversion (odds ratio [OR] 0.52, confidence interval [CI] 0.44-0.62; OR 0.59, CI 0.47-0.73; and OR 0.31, CI 0.27-0.35; respectively,  < 0.001 for all). Conversely, Medicaid ( private insurance; OR 1.75, CI 1.39-2.19,  < 0.001) and male sex (OR 1.26, CI 1.11-1.44,  < 0.001) were independent predictors of conversion. Open conversion in MIPN occurred in 2.87% of cases. There was an increasing utilization of MIPN associated with decreased conversion rates. Higher volume hospitals and progressing year of surgery were associated with less likelihood of conversion.
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http://dx.doi.org/10.1089/end.2020.0161DOI Listing
January 2021

Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury.

Life Sci 2020 Aug 1;255:117743. Epub 2020 May 1.

Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt. Electronic address:

Aims: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms.

Main Methods: BALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-β; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot.

Key Findings: The results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-β with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined.

Significance: 2ME2 is a promising radioprotectant with fewer anticipated side effects.
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http://dx.doi.org/10.1016/j.lfs.2020.117743DOI Listing
August 2020

The potential chemotherapeutic effect of β-ionone and/or sorafenib against hepatocellular carcinoma via its antioxidant effect, PPAR-γ, FOXO-1, Ki-67, Bax, and Bcl-2 signaling pathways.

Naunyn Schmiedebergs Arch Pharmacol 2020 09 8;393(9):1611-1624. Epub 2020 Apr 8.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Beni-Suef University, P.O. Box 62514, Beni-Suef, Egypt.

Proliferation and apoptosis are two primary driving forces behind the pathogenesis of hepatocellular carcinoma (HCC). HCC is associated with Ki-67 and Bcl-2 overexpression, reduced Bax expression inducing disturbance of equilibrium between cellular proliferation and apoptosis, and exacerbated by reduced expression of PPAR-γ and FOXO-1. Our objective was to examine the mechanism by which the cyclic isoprenoid, β-ionone (βI), attenuated hepatocarcinogenesis and compare its possible anticancer activity with sorafenib (SF) as standard HCC treatment. HCC induction was achieved by supplying Wistar rats with 0.01% diethylnitrosamine (DENA) for 8 consecutive weeks by free access of drinking water. The effects of βI (160 mg/kg/day) administered orally were evaluated by biochemical, oxidative stress, macroscopical, and histopathological analysis. In addition, immunohistochemical assay for localization and expression of Bax and Bcl-2 and RT-PCR for expression levels of PPAR-γ, FOXO-1, and Ki-67 mRNA were performed. βI treatment significantly reduced the incidence, total number, and multiplicity of visible hepatocyte nodules, attenuated LPO, near-normal restoration of all cancer biomarkers, and antioxidant activities, indicating the chemotherapeutic impact of βI. Histopathological analysis of the liver confirmed that further. βI also induced pro-apoptotic protein Bax expression and reduced anti-apoptotic expression of Bcl-2 protein. Moreover, βI induced mRNA expression of tumor suppressor genes (PPAR-γ and FOXO-1) and decreased proliferative marker Ki-67 mRNA expression. For the first time, the present study provides evidence that βI exerts a major anticancer effect on DENA-induced HCC, at least in part, through inhibition of cell proliferation, oxidative stress, and apoptogenic signal induction mediated by downregulation of Bcl-2 and upregulation of Bax, PPAR-γ, and FOXO-1 expressions.
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http://dx.doi.org/10.1007/s00210-020-01863-9DOI Listing
September 2020

Metal complexes as a promising source for new antibiotics.

Chem Sci 2020 Mar 12;11(10):2627-2639. Epub 2020 Feb 12.

Centre for Superbug Solutions , Institute for Molecular Bioscience , The University of Queensland , St. Lucia , Queensland 4072 , Australia . Email: ; Email:

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.
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http://dx.doi.org/10.1039/c9sc06460eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069370PMC
March 2020

Antimicrobial properties of half-sandwich Ir(iii) cyclopentadienyl complexes with pyridylbenzimidazole ligands.

Dalton Trans 2020 Apr;49(14):4491-4501

Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.

Reaction between 2-(2'-pyridyl)benzimidazole derivatives and [{IrCl(η5-C5Me5)}2(μ-Cl)2] afforded mono- and binuclear "piano-stool" Ir(iii) compounds of type [IrnCln(η5-C5Me5)n(L)]Cln (n = 1, L = LET (1) and LSO3H (2); n = 2, L = LBN (3)), which were fully characterized, including the X-ray crystallographic analysis of 1. While the free ligands and compound 3 exhibited no toxicity to the tested microbes, compound 1 was highly potent against bacteria (MIC = 12.9-25.8 nM) and fungi (MIC < 0.40 nM). However, complex 1 induced damage to non-malignant cell lines (human embryonic kidney (HEK293), CC50 = 0.995 μg mL-1) and human RBCs (HC10 = 10.9 μg mL-1 and HC50 > 32 μg mL-1). Interestingly, complex 2, bearing the benzimidazole ligand with an alkylated sulfonate side chain (LSO3H), was selectively potent against C. neoformans with MIC value of 11.2 nM and was non-toxic to HEK293. According to DNA binding studies, compounds 1-3 could be considered as moderate metallo intercalators with a binding constant of 5.0 × 104-1.0 × 105 M-1. Alternatively, evidence was obtained, from ESI-MS measurements, for the non-covalent mode of binding of 2 to hen egg white lysozyme, while compounds 1 and 3 decomposed during the interaction with that protein. This may be attributed to the electrostatic and H-bonding interactions between the polar sulfonate group and charged protein side-chains.
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http://dx.doi.org/10.1039/d0dt00451kDOI Listing
April 2020

Pathological downstaging following radical cystectomy for muscle-invasive bladder cancer: Survival outcomes in the setting of neoadjuvant chemotherapy versus transurethral resection only.

Urol Oncol 2020 04 16;38(4):231-239. Epub 2020 Jan 16.

Department of Urology, UT Health San Antonio, San Antonio, TX; Mays Cancer Center at UT Health San Antonio/MD Anderson, San Antonio, TX; Department of Urology, Urology and Nephrology Center, Mansoura University, Egypt. Electronic address:

Introduction: Neoadjuvant chemotherapy (NAC) improves survival for patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). The overall survival (OS) advantage with NAC is primarily seen in patients who achieve pathological downstaging. However, a substantial number of patients achieve pathological downstaging following transurethral resection (TUR) without NAC.

Objectives: To analyze the OS outcomes in patients who achieve pathological downstaging in the setting of NAC vs. TUR only.

Materials And Methods: We reviewed the National Cancer Database (NCDB) for patients diagnosed with MIBC who underwent radical cystectomy between 2004 and 2014. Patients who achieved complete downstaging (CD) (pT0N0) or noninvasive downstaging (NID) (pT0/Tis/TaN0) were further analyzed. OS was evaluated by comparing those who underwent NAC to those who underwent TUR only.

Results: A total of 24,763 patients with MIBC were identified. 1,781 (7.2%) patients had NID and 1,015 (4.1%) had CD. Of all patients, 3,838 (15.5%) underwent NAC. In patients with NID, 757 (42.5%) underwent NAC and 1024 (57.5%) had cystectomy after TUR only. In patients with CD, 465 (45.8%) had NAC, while 550 (54.2%) had TUR only. In both NID and CD, cT2 patients were more likely to have TUR only (P = 0.019, P < 0.001), cT3 patients were more likely to receive NAC (P = 0.008, P < 0.001). Compared to the TUR only group, NAC was associated with improved 5-year OS in those with NID, 77% compared to 68% (HR 0.68, 95% CI [0.52-0.90]), as well as those with CD, 80% vs. 70% (HR 0.59, 95% CI [0.39-0.89]).

Conclusions: NAC was associated with significant overall survival benefit in the subset of patients who achieved CD and NID at radical cystectomy. Overall, NAC was underutilized in patients with MIBC.
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http://dx.doi.org/10.1016/j.urolonc.2019.12.019DOI Listing
April 2020

Urinary Diversion Disparity Following Radical Cystectomy for Bladder Cancer in the Hispanic Population.

Urology 2020 Mar 27;137:66-71. Epub 2019 Dec 27.

Department of Urology, University of Texas Health San Antonio (UTHSA), San Antonio, TX; Experimental Development Therapeutics Program/Urology, MD Anderson Cancer Center/UT Health Science Center, Houston, TX. Electronic address:

Objective: To determine if disparities in quality of surgical care exist between Hispanics and non-Hispanics undergoing radical cystectomy for bladder cancer.

Materials And Methods: An observational cohort study was conducted retrospectively on patients who underwent radical cystectomy for urothelial carcinoma of the bladder at our institution between January 2005 and July 2018. Data was collected on demographic, clinical, and pathological characteristics of patients, including self-reported ethnicity. Univariable and multivariable logistic or linear regression analyses were used to evaluate the association of ethnicity with receipt of neoadjuvant chemotherapy, utilization of laparoscopic surgery, number of lymph nodes removed, and continent urinary diversion.

Results: We identified 507 patients in our database out of which, 136 (27%) were Hispanic and 371 (73%) were non-Hispanic. Compared to non-Hispanics, Hispanics had a higher body mass index (26.9 kg/m vs 28.2 kg/m, P = .006) and lived further away from site of surgery (34 vs 96 miles, P = .02). No significant differences were observed in receipt of neoadjuvant chemotherapy, laparoscopic surgery, or number of lymph nodes removed during cystectomy between ethnicity groups. However, Hispanics were less likely than non-Hispanics to receive a continent urinary diversion on multivariable analysis (odds ratio 0.30, 95% confidence interval 0.10 - 0.92, P = .03).

Conclusion: Disparity exists in the delivery of continent urinary diversions for Hispanic patients undergoing radical cystectomy for bladder cancer. Further investigation is needed to determine the potential causes for this disparity in care delivered.
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http://dx.doi.org/10.1016/j.urology.2019.12.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063861PMC
March 2020

Carotenoid Intake and Circulating Carotenoids Are Inversely Associated with the Risk of Bladder Cancer: A Dose-Response Meta-analysis.

Adv Nutr 2020 05;11(3):630-643

Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, USA.

Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary β-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 μmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 μmol/L increase in circulating concentration of β-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 μmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary β-cryptoxanthin intake and circulating concentrations of α-carotene, β-carotene, and lutein and zeaxanthin were inversely associated with BC risk. The protocol was registered at PROSPERO as CRD42019133240.
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http://dx.doi.org/10.1093/advances/nmz120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231589PMC
May 2020

Spectroscopic investigation of π-acceptors in the determination and photoinduced degradation of Sulfacetamide.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 22;228:117821. Epub 2019 Nov 22.

Chemistry Department, Faculty of Science, Cairo University, Cairo University street, Giza 12613, Egypt. Electronic address:

The presence of expired and unused Sulfacetamide (SA) drug in water led to a global need for the development of effective advanced method for the quantitative analysis and for minimizing its occurrence in the nature. To find new effective photochemical decomposition method close to that obtained by the well-known Fenton reaction, the photodegradation of SA was investigated in presence of dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and/or other common additives at two different wavelengths (365 and 256 nm). The role of DDQ in the degradation process of SA was evaluated in comparison to the other investigated π-acceptor systems (Chloranilic acid (CHL) and Picric acid (PA)). While the photodegradation process of SA was hardly to proceed in the absence of a catalyst and/or additive, addition of DDQ and NaNO to the solution of SA induced decomposition of about 94% of SA within 25 min upon the exposure to light source at 256 nm. On the other hand, SA was quantitatively analyzed by recording the absorbance of its charge transfer (CT) products with DDQ, CHL and PA at a certain wavelength. CHL is preferred with concentrated samples of SA, while PA is recommended for diluted samples of SA. SA → DDQ has a widely range of stability over the pH range of 4.5-12.0. While SA → CHL is stable only in the acidic medium (pH = 4.8-5.6), SA → PA is steady in the basic medium (pH = 7.5-11.0). The nature of the DDQ CT complex was investigated in the solid state. The electronic structures of the complexes were studied by calculating the time dependent density functional theory (TDDFT) spectra.
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http://dx.doi.org/10.1016/j.saa.2019.117821DOI Listing
March 2020

The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats.

Life Sci 2019 Dec 19;239:117082. Epub 2019 Nov 19.

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

Aim: Investigating the impact of 17β-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity.

Main Methods: Three weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty-eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule -1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers.

Key Findings: Estrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury.

Significance: Estrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.
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http://dx.doi.org/10.1016/j.lfs.2019.117082DOI Listing
December 2019

Author Reply.

Urology 2019 11;133:172-173

Department of Urology, University of Texas Health, San Antonio, TX.

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http://dx.doi.org/10.1016/j.urology.2019.05.064DOI Listing
November 2019

Screening logs from a pilot randomized controlled trial of radical cystectomy versus chemoradiation therapy for muscle-invasive bladder cancer.

Urol Oncol 2020 01 29;38(1):4.e1-4.e6. Epub 2019 Oct 29.

Department of Urology, University of Texas Health, San Antonio, TX.

Introduction And Objectives: There is growing interest in a bladder preservation approach using chemoradiation therapy with transurethral resection of bladder tumor (TURBT), i.e., combined modality treatment (CMT), for muscle-invasive bladder cancer (MIBC). We have initiated a pilot study to determine feasibility of conducting a larger-scale clinical trial comparing CMT to radical cystectomy (RC) in patients with MIBC. Here we present the screening logs from the recruitment phase of this trial.

Methods: Patients who were diagnosed to have MIBC after TURBT between April 2016 and August 2017 and considered to be candidates for surgery were enrolled in this prospective, single center, randomized controlled pilot feasibility trial and scheduled to undergo RC (with neoadjuvant chemotherapy if appropriate) or CMT.

Results: Of 62 patients screened during the recruitment phase, only 5 were found to be suitable candidates for either treatment modality hence eligible for randomization. The reasons for exclusion were as follows: multifocal disease (n = 24, 40%), variant histology (n = 15, 25%), previous pelvic radiation (n = 6, 10%), severe lower urinary tract symptoms (n = 5, 8.3%), unwillingness to be enrolled (n = 8, 13.3%), and receipt of neoadjuvant chemotherapy (n = 2, 3.3%). One of the 5 eligible patients was randomized to CMT but was subsequently switched to RC because of a high tumor burden, 1 was randomized to RC, 2 were randomized to CMT but subsequently underwent TURBT and were considered ineligible because of extensive bladder disease, and 1 elected to undergo RC.

Conclusions: We identified many patients with MIBC over a period of 16 months. However, the number of patients eligible to receive chemotherapy and in whom cystectomy and radiation therapy were both valid options was not as high as previously reported in retrospective CMT series. Many patients were excluded after TURBT. Our preliminary data indicate that only a very small subset of patients with MIBC are ideal candidates for CMT. Further research is required to identify patients who are suitable for CMT.
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http://dx.doi.org/10.1016/j.urolonc.2019.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003712PMC
January 2020

Role of the Metal Center in the Modulation of the Aggregation Process of Amyloid Model Systems by Square Planar Complexes Bearing 2-(2'-pyridyl)benzimidazole Ligands.

Pharmaceuticals (Basel) 2019 Oct 12;12(4). Epub 2019 Oct 12.

Department of Pharmacy, University of Naples Federico II, Napoli 80134, Italy.

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2'-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.
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http://dx.doi.org/10.3390/ph12040154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958441PMC
October 2019

Protein-mediated disproportionation of Au(i): insights from the structures of adducts of Au(iii) compounds bearing N,N-pyridylbenzimidazole derivatives with lysozyme.

Dalton Trans 2019 Oct 6;48(37):14027-14035. Epub 2019 Sep 6.

Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, via Cinthia, 21, 80126, Naples, Italy.

Au(iii) compounds bearing N,N-pyridylbenzimidazole derivatives with the ethyl (1) or propyl sulfonate (2) appendage react with the model protein hen egg white lysozyme (HEWL), forming adducts with different gold-containing fragments. The conformation of the enzyme, the exact gold binding sites and the oxidation state of Au in the adducts are unknown. Here we report a structural study on the reaction of 1 and 2 with HEWL in solution and solid state. In agreement with previously reported electrospray ionization mass spectra, the compounds degrade in their interaction with the protein. In the structure derived from HEWL crystals exposed to 1 for less than one day, three Au binding sites were identified: Au(i) ions are bound to the side chain of His15 and to the side chains of His15 and Asn93. The third gold centre is buried in the hydrophobic pocket of the protein via the binding to the side chain of Met105 and the trapping between the side chains of Trp28, Trp108 and Trp111. In a second crystal fished three hours later from the same drop, only one Au ion, probably in the +1 oxidation state, is observed; it binds the protein close to the side chains of Asn93 and His15. After three days of soaking, the colour of HEWL crystals obtained in the presence of 1 turned violet. In these crystals, anomalous signals attributable to Au are found on the protein surface; gold atoms are not directly coordinated to residue side chains. Longer exposure of HEWL crystals to 1 produces gold-free crystals. In the adduct of HEWL exposed to 2 for one day, three Au(i) ions are detected close to the side chains of both Asn93 and His15, the side chain of His15 and that of Met105. Longer exposure of HEWL crystals to 2 affords gold-free crystals. These structural data and those of the other protein/gold adducts available at the Protein Data Bank suggest that the reduction of Au(iii) into Au(i) is the basis of the mechanism of action of the biologically active gold(iii) compounds. Besides, Au(i) ions can undergo disproportionation into Au(iii) and Au(0) that can diffuse away from the protein crystals.
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http://dx.doi.org/10.1039/c9dt02729gDOI Listing
October 2019

Chemoradiation Vs Radical Cystectomy for Muscle-invasive Bladder Cancer: A Propensity Score-weighted Comparative Analysis Using the National Cancer Database.

Urology 2019 11 8;133:164-174. Epub 2019 Aug 8.

Department of Urology, University of Texas Health, San Antonio, TX.

Objective: To address the overarching question whether chemoradiation therapy (CMT) offers overall survival (OS) similar to that of radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC), we performed analyses using the National Cancer Database.

Materials And Methods: Patients diagnosed with MIBC in 2004-2014 who underwent RC or received primary CMT were identified in the National Cancer Database. Survival was estimated using the weighted Kaplan-Meier method, and propensity score-weighted Cox proportional hazards model were used to evaluate association of clinicopathologic features with outcome.

Results: Of 484,367 patients with a diagnosis of bladder cancer, 35,856 underwent RC and 4050 received CMT. After applying the exclusion/inclusion criteria, data for 15,854 patients who underwent RC and 2083 who received CMT were available for analysis. Five-year OS was 40.4% in the RC group and 29.4% in the CMT group (P <.001). OS was significantly shorter in the CMT group than in the RC group in both multivariate analysis (hazards ratio [HR] 1.15, 95% CI 1.08-1.22; P <.001) and propensity score-weighted analysis (HR 1.18, 95% CI 1.07-1.30; P <.001). Interaction terms indicated better survival after RC in patients younger than 70 years (HR 1.61, 95% CI 1.34-1.93; P <.001); subgroup analyses identified a survival benefit in patients with N0/N1 disease who underwent RC (HR 1.21, 95% CI 1.09-1.33; P <.001).

Conclusion And Relevance: OS after 1 year of treatment was increased in RC group compared to CMT group in patient with MIBC. Further studies are required to identify optimal treatment for specific patients.
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http://dx.doi.org/10.1016/j.urology.2019.05.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842694PMC
November 2019

Initial Evaluation of Computer-Assisted Radiologic Assessment for Renal Mass Edge Detection as an Indication of Tumor Roughness to Predict Renal Cancer Subtypes.

Adv Urol 2019 23;2019:3590623. Epub 2019 Apr 23.

University of Texas Health San Antonio, Department of Urology, San Antonio, TX, USA.

Objective: To develop software to assess the potential aggressiveness of an incidentally detected renal mass using images.

Methods: Thirty randomly selected patients who underwent nephrectomy for renal cell carcinoma (RCC) had their images independently reviewed by engineers. Tumor "Roughness" was based on image algorithm of tumor topographic features visualized on computed tomography (CT) scans. Univariant and multivariant statistical analyses are utilized for analysis.

Results: We investigated 30 subjects that underwent partial or radical nephrectomy. After excluding poor image-rendered images, 27 patients remained (benign cyst = 1, oncocytoma = 2, clear cell RCC = 15, papillary RCC = 7, and chromophobe RCC = 2). The mean roughness score for each mass is 1.18, 1.16, 1.27, 1.52, and 1.56 units, respectively ( < 0.004). Renal masses were correlated with tumor roughness (Pearson's, =0.02). However, tumor size itself was larger in benign tumors (=0.1). Linear regression analysis noted that the roughness score is the most influential on the model with all other demographics being equal including tumor size (=0.003).

Conclusion: Using basic CT imaging software, tumor topography ("roughness") can be quantified and correlated with histologies such as RCC subtype and could lead to determining aggressiveness of small renal masses.
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http://dx.doi.org/10.1155/2019/3590623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507235PMC
April 2019

Epidermal growth factor expression as a predictor of chemotherapeutic resistance in muscle-invasive bladder cancer.

BMC Urol 2018 Nov 9;18(1):100. Epub 2018 Nov 9.

University of California Los Angeles, Los Angeles, CA, USA.

Background: Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC.

Methods: The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse.

Results: The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin.

Conclusions: Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.
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http://dx.doi.org/10.1186/s12894-018-0413-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234794PMC
November 2018

Rectal vs. sublingual misoprostol before cesarean section: double-blind, three-arm, randomized clinical trial.

Arch Gynecol Obstet 2018 12 5;298(6):1115-1122. Epub 2018 Oct 5.

Obstetrics and Gynecology Department, Ain Shams University, Cairo, 16646, Egypt.

Purpose: The commonest surgical procedure for women is cesarean delivery. Postpartum hemorrhage and intra-operative blood during cesarean delivery is a major concern to all obstetricians. This study was conducted to assess the efficacy of the adjuvant use of misoprostol and oxytocin in decreasing intra-operative blood loss in cesarean delivery.

Methods: This was a double-blinded randomized clinical trial including 636 term pregnant woman scheduled for cesarean section at Ain Shams University Maternity Hospital, Cairo, Egypt, between February 2013 and February 2014. Participants received either 400-μg misoprostol rectally or sublingually or placebo before cesarean section together with 5-IU oxytocin IV. The main outcome measure was intra-operative blood loss. Difference between the three groups was analyzed using one-way ANOVA test (for numeric variables) and Chi-square test (for categorical variables). P < 0.05 was considered statistically significant.

Results: Intra-operative blood loss was higher in patients who did not receive misoprostol (Placebo Group) (295-1075 ml, 641.7 ± 135.7) than those who received it, regardless the route of administration, rectal (135-830 ml, 457.5 ± 140.7; P < 0.001), and sublingual (135-680 ml, 357.8 ± 129.7; P < 0.001). In addition, sublingual route was associated with significantly lower estimated intra-operative blood loss compared to rectal administration (P < 0.001).

Conclusions: Misoprostol with oxytocin is an effective drug-combination for decreasing intra-operative blood loss during cesarian section with clinical superiority to sublingual over rectal route.
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http://dx.doi.org/10.1007/s00404-018-4894-2DOI Listing
December 2018

Ovarian Reserve Following Laparoscopic Ovarian Cystectomy vs Cyst Deroofing for Endometriomas.

J Minim Invasive Gynecol 2019 Jul - Aug;26(5):877-882. Epub 2018 Sep 5.

Department of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt (Drs. Sweed, Makled, El-Sayed, Shawky, Abd-Elhady, Mansour, Mohamed, Hemeda, Attia, Eltaieb, Allam, and Husseein).

Study Objective: Because laparoscopic ovarian cystectomy of endometriomas is known to adversely impact patient ovarian reserve, the search for other techniques of surgical management is ongoing. The present study was undertaken to evaluate laparoscopic cyst deroofing as a feasible alternative.

Study Design: Prospective, randomized clinical trial (Canadian Task Force classification I).

Setting: University maternity hospital.

Patients: Women diagnosed with unilateral or bilateral ovarian endometriomas.

Interventions: Patients were managed with either laparoscopic ovarian cystectomy or cyst deroofing.

Measurements And Main Results: A total of 122 women with endometriomas were randomized to either laparoscopic cystectomy (group 1) or laparoscopic cyst deroofing (group 2). The primary endpoint was the effect on ovarian reserve based on changes in anti-Müllerian hormone (AMH) values. At 1 month postsurgery, anti-Müllerian hormone values were significantly decreased (p < .001) from preoperative values, from 4.25 ± 0.87 ng/mL to 1.66 ± 1.02 ng/mL in group 1 and from 4.2 ± 1.69 ng/mL to 2.15 ± 1.48 ng/mL in group 2. In addition, antral follicle count and ovarian volume decreased significantly (p < .001) in both groups by 1 month postsurgery. The decreases in these 3 parameters were more significant (p < .001) in group 1 than in group 2.

Conclusion: Laparoscopic cyst deroofing of endometriomas appears to be a promising alternative to laparoscopic cystectomy, with less postoperative decrease in ovarian reserve; however, the higher rate of endometrioma recurrence warrants future clinical research to determine the optimal surgical management of endometriomas.
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http://dx.doi.org/10.1016/j.jmig.2018.06.022DOI Listing
January 2020
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