| 1. |
- Paramita, Pragyan, et al.
(författare)
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Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells
- 2018
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Ingår i: IET Nanobiotechnology. - : INST ENGINEERING TECHNOLOGY-IET. - 1751-8741 .- 1751-875X. ; 12:6, s. 727-732
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Tidskriftsartikel (refereegranskat)abstract
- Research dealing with early diagnosis and efficient treatment in colon cancer to improve patients survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.
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| 2. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 3. |
- Gopinath, Madhumala, et al.
(författare)
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Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC)
- 2018
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Ingår i: International Journal of Hematology-Oncology and Stem Cell Research. - : Tehran University of Medical Sciences. - 2008-3009 .- 2008-2207. ; 12:2, s. 153-165
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Forskningsöversikt (refereegranskat)abstract
- Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.
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| 4. |
- Pathak, Surajit, et al.
(författare)
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Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:7, s. 7739-7748
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Forskningsöversikt (refereegranskat)abstract
- Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.
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| 5. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India - a cohort study
- 2023
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Ingår i: The Lancet Regional Health - Southeast Asia. - : ELSEVIER. - 2772-3682. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Methods Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Findings Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Interpretation Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants.Funding National Health Mission (India), SIDA SARC, VINNMER (Sweden), ORIP/NIH (USA).Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 6. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Evolution of the Omicron B.1.1.529 Sars-Cov-2 and its Variants in Tamil Nadu, India – a State-Wide Prospective Longitudinal Genomic Surveillance
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The emergence of the omicron SARS-CoV-2 variant beholding many mutations, especially in the spike (S) protein severely threatens global health. With an aim to understand the mutational pattern of the variant and its genetic interrelationship in the Indian population, here we prospectively followed the viral evolution and transmission between December 2021 and March 2023 in Tamil Nadu.Methods: A total of 11526 nasopharyngeal and oropharyngeal swabs (6431 males, 5095 females including 603 children) collected from across the 38 districts of Tamil Nadu were subjected to WGS. Of the 10663 samples (92.5%) positive for omicron variants, 1688 were sequenced at the State Public Health Laboratory. We longitudinally studied the evolutionary dynamics of the different omicron variants, starting from the first detected case (B.1.1.529) to the recently reported recombinant XBB variants by sequencing the S gene and by performing phylo-geographic and molecular modeling analyses.Findings: Administration of a booster dose was associated with reduced risk of hospitalization and death. BA.1 sub-variants and BA.2.75 were associated with increased risk of severe disease, whereas BA.1 and BA.2 were associated with increased risk of death. High quality WGS data from 150 samples revealed six major omicron clusters and several other sub-clusters. Seven variants in the same BA lineages with different divergences in the S protein were noticed. Of the 5009 mutations detected, the highest was seen in the receptor-binding domain (RBD) followed by the N-terminal domain (NTD) in varying proportions among the different omicron lineages. Importantly, the mutations were observed in the sub-domain (SD1/2) furin cleavage site, fusion peptide (FP), and the heptapeptide repeat sequence (HR1) regions. Notably, unique mutations Y473I, P479F, C480F, V483T, E484C, G485T, P491G, L492K, S494M, Y495C, and G496Q were detected in BA.2.43 whereas A475Q and T478S occurred in the RBD domain of the BA.2.43 variant. The XBB variant showed 41 different mutations between the HR1 and HR2 domains of the S2 subunit. Molecular modeling using BA.2 lineage as a template for seven divergent proteins showed that BA.2.12.1, BA.4 and BA.5 exhibited strong binding affinity towards ACE2.Interpretation: The high frequency of mutations in the RBD highlights the wider distribution of vaccine escape-variants that would impact the structural and functional attributes of the omicron variant in the population. Further, our work provides key insights on the evolutionary pattern leading to the identification of seven divergent variants of omicron in Tamil Nadu, India.
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| 7. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Genomic surveillance of omicron B.1.1.529 SARS‐CoV‐2 and its variants between December 2021 and March 2023 in Tamil Nadu, India—A state‐wide prospective longitudinal study
- 2024
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
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| 8. |
- Selvavinayagam, Sivaprakasam T, et al.
(författare)
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Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundEarly detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy.Methods We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay.ResultsIncreased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold.ConclusionsWe postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.
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| 9. |
- Selvavinayagam, Sivaprakasam T, et al.
(författare)
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Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study
- 2023
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Ingår i: PLOS Global Public Health. - : Public Library of Science (PLoS). - 2767-3375. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-a, and IFN-? were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.
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| 10. |
- Sriramulu, Sushmitha, et al.
(författare)
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Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types : A Concise Review
- 2021
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:6
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Forskningsöversikt (refereegranskat)abstract
- Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-kappa B; (iii) the ERK or mitogen-activated protein kinase and Wnt or beta-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.
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