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Fulltext Combination therapy of a novel ruthenium polypyridyl complex and cisplatin for the treatment of cancer

Haslina Ahmad, Yusoh N. A., Harun S. N., Chia, S. L.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):25-25.
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Introduction: Combination therapy to treat cancer have been demanded due to the complexity of the disease and to prevent resistance mechanisms commonly found in classic chemotherapeutic methods. Recently, we have reported that [Ru(dppz)2(PIP)]2+ (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) (RuPIP) immediately stalls replication fork progression in HeLa human cervical cancer cells. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells. These discoveries indicate that this class of compounds merit further investigation as anticancer drugs, especially within combinational therapy roles. However, information pertaining to the effects of combining ruthenium compounds with existing chemotherapeutic drugs remain scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using RuPIP in combination with cisplatin on different cancer cell lines. Methods: A549, MCF7, Hela and T24 cells were treated with different concentrations of RuPIP or cisplatin alone, as well as different combinations of these two agents at a fixed ratio 1:1 over the course of 72 hr to assess their individual and combination effects. Cell viability was analysed using MTT assay. The combination index (CI) was calculated based on the Chou Talalay Method. Results: Single-agent treatment at 72 hr with RuPIP or cisplatin led to dose-dependent decreases in the viability of the A549, MCF7, Hela and T24 cells at 72 hr. Furthermore, increasing the concentrations of the combinations up to four folds of half maximal inhibitory concentration (IC50) statistically decrease the cell survival rates of A549 and MCF7 cells thus, displayed synergistic effects. Conclusion: Treatment of MCF7 and A549 cells with a combination of RuPIP and cisplatin showed a synergistic effect and thus are promising as a combination therapy for cancer treatment.
Fulltext Improved in vitro toxicity of ruthenium complex by mesoporous silica nanoparticles encapsulation

Harun S. N., Haslina Ahmad, Chia, S. L., Leong, S. W.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):27-27.
MyJurnal

Introduction: Ruthenium compounds are widely studied for its biological activity. However, potent ruthenium drugs often have limited bioavailability due to its poor aqueous solubility. In order to assist the preparation of these hydrophobic compounds, a carrier or drug delivery agent is often introduced. Herein, we encapsulated a hydrophobic ruthenium polypyridyl complex [Ru(dppz)PIP]2+, (dppz = dipyrido-[3,2-a:20,30-c]phenazine, PIP = 2-phenylimidazo[4,5-f][1,10] phenanthroline) in mesoporous silica nanoparticles (MSN). Methods: The MSN was synthesized by using ionic liquid 1-hexadecylphenanthrolinium as a novel template and have 833.99 m2/g in surface area. The cytotoxicity of the synthesized ruthenium complex, MSN and MSN-loaded ruthenium was studied on Hela and A549 cancer cell lines. Results: MSN was non-toxic at lower dosage (
Healthcare-associated infections among neonates and children in Pakistan: findings and the implications from a point prevalence survey

Mustafa ZU, Khan AH, Salman M, Harun SN, Meyer JC, Godman B, et al.

J Hosp Infect, 2023 Nov;141:142-151.
PMID: 37774930 DOI: 10.1016/j.jhin.2023.09.011

BACKGROUND: Healthcare-associated infections (HAIs) increase morbidity, mortality and costs. The overall prevalence of HAIs is greater in low- and middle-income countries due to poor resources and infrastructure, with the incidence of HAIs greater among neonates and children. There is a need to understand the current situation in Pakistan including key drivers to improve future care.
METHODS: Point prevalence survey (PPS) of HAIs in the children's wards of 19 public sector secondary- and tertiary-care hospitals of Pakistan and associated key drivers.
RESULTS: A total of 1147 children were included in the PPS. 35.7% were neonates with 32.8% aged >1-5 years. 35.2% were admitted to the intensive care units (ICUs). Peripheral, central venous and urinary catheters were present in 48%, 2.9% and 5.6% of the patients, respectively. A total of 161 HAIs from various pathogens were observed in 153 cases, giving a prevalence of 13.3%. The majority of HAIs were caused by Staphylococcus aureus (31.7%) followed by Klebsiella pneumoniae (22.9%) and Escherichia coli (17.4%). Bloodstream infections were identified in 42 cases followed by lower-respiratory-tract infections in 35. Increased length of hospital stays and being admitted to the ICU, 'rapidly fatal' patients under the McCabe and Jackson criteria, central and peripheral catheterization, and invasive mechanical ventilation were, associated with higher HAIs (P<0.001). 99.7% of HAI patients fully recovered and were discharged from the hospital.
CONCLUSION: There is a high prevalence of HAIs among neonates and children admitted to health facilities in Pakistan. Infection prevention and control measures should be implemented to help prevent future HAIs.

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