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Fulltext An algorithmic framework for multiobjective optimization

Ganesan T, Elamvazuthi I, Shaari KZ, Vasant P

ScientificWorldJournal, 2013;2013:859701.
PMID: 24470795 DOI: 10.1155/2013/859701

Multiobjective (MO) optimization is an emerging field which is increasingly being encountered in many fields globally. Various metaheuristic techniques such as differential evolution (DE), genetic algorithm (GA), gravitational search algorithm (GSA), and particle swarm optimization (PSO) have been used in conjunction with scalarization techniques such as weighted sum approach and the normal-boundary intersection (NBI) method to solve MO problems. Nevertheless, many challenges still arise especially when dealing with problems with multiple objectives (especially in cases more than two). In addition, problems with extensive computational overhead emerge when dealing with hybrid algorithms. This paper discusses these issues by proposing an alternative framework that utilizes algorithmic concepts related to the problem structure for generating efficient and effective algorithms. This paper proposes a framework to generate new high-performance algorithms with minimal computational overhead for MO optimization.
Fulltext Oral verrucous carcinoma in peninsular Malaysia

Ramanathan K, Chelvanayagam PI, Ganesan TJ

Med J Malaysia, 1981 Dec;36(4):234-8.
PMID: 7334960
Carcinoma of the tongue in Malaysians

Ramanathan K, Ganesan TJ, Raghavan KV

Mod Med Asia, 1978 Jul;14(7):56-8.
PMID: 683170
Salivary mucoceles--racial and histological variations

Ramanathan K, Ganesan TJ, Raghavan KV

Med J Malaysia, 1977 Jun;31(4):302-8.
PMID: 927237
Fulltext Annexin A1: A Bane or a Boon in Cancer? A Systematic Review

Ganesan T, Sinniah A, Ibrahim ZA, Chik Z, Alshawsh MA

Molecules, 2020 Aug 14;25(16).
PMID: 32823805 DOI: 10.3390/molecules25163700

Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic review to date. Thus, the aim of this paper is to systematically review and critically analyse 18 studies (in-vivo and in-vitro) to consolidate, in a concerted manner, all the information on differential expression of Annexin A1 in different types of cancer and the role this protein plays in tumorigenesis. Pubmed, Scopus, Web of Science, and ScienceDirect were used for the literature search and the keywords used are "annexin A1," "lipocortin 1," "cancer," "malignancy," "neoplasm," "neoplasia," and "tumor." A total of 1128 articles were retrieved by implementing a standard search strategy subjected to meticulous screening processes and 442 articles were selected for full article screening. A total of 18 articles that adhered to the inclusion criteria were included in the systematic review and these articles possessed low to moderate bias. These studies showed a strong correlation between Annexin A1 expression and cancer progression via modulation of various cancer-associated pathways. Differential expression of Annexin A1 is shown to play a role in cellular proliferation, metastasis, lymphatic invasion, and development of resistance to anti-cancer treatment. Meta-analysis in the future may provide a statistically driven association between Annexin A1 expression and malignancy progression.
Fulltext Punicalagin Regulates Apoptosis-Autophagy Switch via Modulation of Annexin A1 in Colorectal Cancer

Ganesan T, Sinniah A, Chik Z, Alshawsh MA

Nutrients, 2020 Aug 13;12(8).
PMID: 32823596 DOI: 10.3390/nu12082430

Punicalagin (PU), a polyphenol extracted from pomegranate (Punica granatum) husk is proven to have anti-cancer effects on different types of cancer including colorectal cancer (CRC). Its role in modulating endogenous protein as a means of eliciting its anti-cancer effects, however, has not been explored to date. Hence, this study aimed to investigate the role of PU in modulating the interplay between apoptosis and autophagy by regulating Annexin A1 (Anx-A1) expression in HCT 116 colorectal adenocarcinoma cells. In the study, selective cytotoxicity, pro-apoptotic, autophagic and Anx-A1 downregulating properties of PU were shown which indicate therapeutic potential that this polyphenol has against CRC. Autophagy flux analysis via flow cytometry showed significant autophagosomes degradation in treated cells, proving the involvement of autophagy. Proteome profiling of 35 different proteins in the presence and absence of Anx-A1 antagonists in PU-treated cells demonstrated a complex interplay that happens between apoptosis and autophagy that suggests the possible simultaneous induction and inhibition of these two cell death mechanisms by PU. Overall, this study suggests that PU induces autophagy while maintaining basal level of apoptosis as the main mechanisms of cytotoxicity via the modulation of Anx-A1 expression in HCT 116 cells, and thus has a promising translational potential.
Cracking the code of Annexin A1-mediated chemoresistance

Ganesan T, Sinniah A, Ramasamy TS, Alshawsh MA

Biochem Biophys Res Commun, 2024 Sep 17;725:150202.
PMID: 38885563 DOI: 10.1016/j.bbrc.2024.150202

The annexin superfamily protein, Annexin A1, initially recognized for its glucocorticoid-induced phospholipase A2-inhibitory activities, has emerged as a crucial player in diverse cellular processes, including cancer. This review explores the multifaceted roles of Anx-A1 in cancer chemoresistance, an area largely unexplored. Anx-A1's involvement in anti-inflammatory processes, its complex phosphorylation patterns, and its context-dependent switch from anti-to pro-inflammatory in cancer highlights its intricate regulatory mechanisms. Recent studies highlight Anx-A1's paradoxical roles in different cancers, exhibiting both up- and down-regulation in a tissue-specific manner, impacting different hallmark features of cancer. Mechanistically, Anx-A1 modulates drug efflux transporters, influences cancer stem cell populations, DNA damages and participates in epithelial-mesenchymal transition. This review aims to explore Anx-A1's role in chemoresistance-associated pathways across various cancers, elucidating its impact on survival signaling cascades including PI3K/AKT, MAPK/ERK, PKC/JNK/P-gp pathways and NFκ-B signalling. This review also reveals the clinical implications of Anx-A1 dysregulation in treatment response, its potential as a prognostic biomarker, and therapeutic targeting strategies, including the promising Anx-A1 N-terminal mimetic peptide Ac2-26. Understanding Anx-A1's intricate involvement in chemoresistance offers exciting prospects for refining cancer therapies and improving treatment outcomes.
A new Febuxostat-Telmisartan Drug-Drug Cocrystal for Gout-Hypertension Combination Therapy

Ganesan T, Muthudoss P, Voguri RS, Ghosal S, Ann EYC, Kwok J, et al.

J Pharm Sci, 2022 Dec;111(12):3318-3326.
PMID: 36028135 DOI: 10.1016/j.xphs.2022.08.022

Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisartan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 1:1 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. ΔpKa of the heterosynthon is ∼1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N---H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when compared with plain drugs.
Fulltext Local Trends of Antibiotic Prescriptions for Necrotizing Fasciitis Patients in Two Tertiary Care Hospitals in Central Malaysia

Rampal S, Ganesan T, Sisubalasingam N, Neela VK, Tokgöz MA, Arunasalam A, et al.

Antibiotics (Basel), 2021 Sep 17;10(9).
PMID: 34572702 DOI: 10.3390/antibiotics10091120

BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the soft tissue (also known as the fascia) with a secondary necrosis of the subcutaneous tissues, leading to a systemic inflammatory response syndrome (SIRS), shock and eventually death despite the availability of current medical interventions. The clinical management of this condition is associated with a significant amount of morbidity with a high rate of mortality. The prognosis of the disease is affected by multiple factors, which include the virulence of the causative pathogen, local host immunity, local wound factors and empirical antibiotics used. The local trends in the prescription of empirical antibiotics are often based on clinical practice guidelines (CPG), the distribution of the causative microorganism and the cost-effectiveness of the drug. However, there appears to be a paucity of literature on the empirical antibiotic of choice when dealing with necrotizing fasciitis in the clinical setting. This paper will outline common causative microorganisms and current trends of prescription in two tertiary centres in Central Malaysia.
METHODS: This was a cross-sectional study using retrospective data of patients treated for NF collected from two tertiary care hospitals (Hospital Seremban and Hospital Ampang) in Central Malaysia. A total of 420 NF patients were identified from the five years of retrospective data obtained from the two hospitals.
RESULTS: The top three empirical antibiotics prescribed are ampicillin + sulbactam (n = 258; 61.4%), clindamycin (n = 55; 13.1%) and ceftazidime (n = 41; 9.8%). The selection of the antibiotic significantly impacts the outcome of NF. The top three causative pathogens for NF are Streptococcus spp. (n = 79; 18.8%), Pseudomonas aeruginosa (n = 61; 14.5%) and Staphylococcus spp. (n = 49; 11.7%). The patients who received antibiotics had 0.779 times lower chances of being amputated. Patients with a lower laboratory risk indicator for necrotizing fasciitis (LRINEC) score had 0.934 times lower chances of being amputated.
CONCLUSIONS: In this study, the most common empirical antibiotic prescribed was ampicillin + sulbactam followed by clindamycin and ceftazidime. The antibiotics prescribed lower the risk of having an amputation and, hence, a better prognosis of the disease. Broad-spectrum empirical antibiotics following surgical debridement reduce the mortality rate of NF.