King Institute of Preventive Medicine and Research

Chennai, India

King Institute of Preventive Medicine and Research

Chennai, India
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Bedford T.,Fred Hutchinson Cancer Research Center | Riley S.,Imperial College London | Riley S.,U.S. National Institutes of Health | Barr I.G.,World Health Organization | And 26 more authors.
Nature | Year: 2015

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour. © 2015 Macmillan Publishers Limited. All rights reserved.


Vivek R.,Bharathiar University | Nipun Babu V.,Bharathiar University | Thangam R.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | And 2 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2013

Tamoxifen (Tam) has a broad spectrum of anticancer activity, but is limited in clinical application. The aim of this study was to explore the smart pH-responsive drug delivery system (DDS) based on chitosan (CH) nanoparticles (NPs) for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic efficiency of Tamoxifen. Tamoxifen was loaded onto CH-nanoparticles by forming complexes and Tamoxifen was released from the DDS much more rapidly at pH 4.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Tamoxifen-loaded CH nanoparticles induced remarkable improvement in anticancer activity, as demonstrated by MTT-assay, AO/EtBr and Hoechst nuclear staining. Furthermore, the possible signaling pathway was explored by RT-PCR. For instance, in human breast cancer MCF-7 cells, it was demonstrated that Tamoxifen-loaded CH nanoparticles increase intracellular concentration of Tamoxifen and enhance its anticancer efficiency by inducing apoptosis in a caspase-dependent manner, indicating that drug loaded nanoparticles could act as an efficient DDS importing Tamoxifen into target cancer cells. © 2013 Elsevier B.V.


Thangam R.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | Suresh V.,Annamalai University | Suresh V.,Plant Cell Technology Laboratory | And 2 more authors.
International Journal of Biological Macromolecules | Year: 2014

In this study the extraction of hot water soluble polysaccharides (HWSPs) from Cymbopogon citratus using hot water decoction was discussed. Response surface methodology (RSM) based on a three level, three variable central composite rotatable design (CCRD), was employed to obtain best possible combination of extraction time (X1: 30-180min), extraction temperature (X2: 70-100°C) and water to the raw material ratio (X3: 10-60) for maximum HWSPs extraction. The optimum extraction conditions were as follows: extraction time was around 113.81min, extraction temperature at 99.66°C and the ratio of water to raw material was 33.11g/mL. Under these conditions, the experimental yield was 13.24±0.23%, which is well in close agreement with the value predicted by RSM model yield (13.19%). The basic characterization of HWSPs was determined by using the FTIR. These preliminary in vitro biological studies indicated that lemongrass polysaccharides were useful for anticancer therapy. © 2014 Elsevier B.V.


Sukirtha R.,Bharathidasan University | Priyanka K.M.,Bharathidasan University | Antony J.J.,Bharathidasan University | Kamalakkannan S.,Bharathidasan University | And 4 more authors.
Process Biochemistry | Year: 2012

This communication explains the biosynthesis of stable silver nanoparticles (AgNPs) from Melia azedarach and its cytotoxicity against in vitro HeLa cells and in vivo Dalton's ascites lymphoma (DAL) mice model. The AgNPs synthesis was determined by UV-visible spectrum and it was further characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. Zeta potential analysis revealed stable AgNPs at -24.9 mV. UV visible spectrum indicated an absorption peak at 436 nm which reflects its specific Surface Plasmon Resonance (SPR). Biosynthesized AgNPs were predominantly cubical and spherical with an average particle size of 78 nm approximately as observed through SEM and DLS analysis, respectively. Cytotoxicity of biosynthesized AgNPs against in vitro Human epithelial carcinoma cell line (HeLa) showed a dose-response activity. Lethal dose (LD 50) value was found to be 300 μg/mL of AgNPs against HeLa cell line. Cytotoxicity against normal continuous cell line human breast lactating, donor 100 (HBL 100) was found only in increased concentration of both AgNPs and 5-FU. In addition, in vivo DAL mice model showed significant increase in life span, induction of apoptosis was evidenced by acridine orange and ethidium bromide (AO and EB) staining. © 2011 Elsevier Ltd. All rights reserved.


Sundarraj S.,Bharathiar University | Kannan S.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | Gunasekaran P.,King Institute of Preventive Medicine and Research
Journal of Cancer Research and Clinical Oncology | Year: 2012

Purpose: The aim of this study was to investigate the expression of cPLA 2α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA 2α sensitivity in three different non-small lung cancer cell lines. Methods: The expression of cPLA 2α was determined in lung cancer cells by Western blot. Cytotoxicity, cell growth and inhibition of cPLA 2α activity were determined in relation to the concentration of pyrrolidine-2. Finally, this study investigated immunohistochemical expressions of cPLA 2α in 23 species of human non-small lung cancer and 5 species of human normal lung to assess their clinicopathological relevance. Results: cPLA 2α is expressed in A549 and H460, however, no expression in H661 cells. Pyrrolidine-2 demonstrated a dose-dependent inhibitory effect on cell growth and its significantly inhibited BrdU incorporation of human non-small lung cancer cells. Inhibition with pyrrolidine-2 results in reduction in cPLA 2α activity in A549 and H460 lung cancer cells by 50% when present at IC 50 concentration in arachidonoyl thio-PC assay. Immunohistochemistry of human lung tissue revealed that cPLA 2α is increased in lung cancer tissues. Conclusions: Pyrrolidine-2 is a more potent and specific cPLA 2α inhibitor than MAFP and AACOCF3 and represents an excellent pharmacological tool to investigate the biosynthesis and the biological roles of cancer. The present study suggests that pyrrolidine-2 could be a potential therapeutic agent for cancer therapy. © Springer-Verlag 2012.


Prasanna R.,Presidency College at Chennai | Harish C.C.,King Institute of Preventive Medicine and Research
Oncology Research | Year: 2010

A novel compound 2-arylidene-4,7-dimethyl indan-1-one synthesized was screened for anticancer effect against the human breast adenocarcinoma cell line, MCF-7. An IC50 value of ≥ 80 μM, nontoxic to the normal breast cell line HBL-100, showed complete inhibition of the MCF-7 cells. Analysis of mechanisms showed nuclear fragmentation and DNA laddering in gel electrophoresis. GSH and GR levels were found to be reduced after the compound treatment. Cell cycle analysis using fluorescent cytometry revealed G 2/M phase arrest, which indicates the compound deserves consideration for further studies against cancer. Copyright © 2010 Cognizant Comm. Corp.


Vivek R.,Bharathiar University | Thangam R.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | Muthuchelian K.,Madurai Kamaraj University | And 3 more authors.
Process Biochemistry | Year: 2012

The biological method for the synthesis of silver nanoparticles (AgNPs) using Annona squamosa leaf extract and its cytotoxicity against MCF-7 cells are reported. The synthesized AgNPs using A. squamosa leaf extract was determined by UV-visible spectroscopy and it was further characterized by FT-IR, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Zeta potential and energy dispersive spectrometric (EDS) analysis. The UV-visible spectrum showed an absorption peak at 444 nm which reflects surface plasmon resonance (SPR) of AgNPs. TEM photography showed biosynthesized AgNPs were predominantly spherical in shape with an average size ranging from 20 to 100 nm. The Zeta potential value of -37 mV revealed the stability of biosynthesized AgNPs. Furthermore, the green synthesized AgNPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and normal breast epithelial cells (HBL-100) and the inhibitory concentration (IC50) were found to be 50 μg/mL, 30 μg/mL, and 80 μg/mL, 60 μg/ml for AgNPs against MCF-7 and normal HBL-100 cells at 24 h and 48 h incubation respectively. An induction of apoptosis was evidenced by (AO/EtBr) and DAPI staining. Application of such eco-friendly nanoparticles makes this method potentially exciting for the large scale synthesis of nanoparticles. © 2012 Elsevier Ltd.


Thangam R.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | Gunasekaran P.,King Institute of Preventive Medicine and Research | Kaveri K.,King Institute of Preventive Medicine and Research | And 4 more authors.
Process Biochemistry | Year: 2012

Animal venoms and toxins are potential bioresources that have been known to mankind as a therapeutic tool for more than a century through folk and traditional medicine. The purified "disintegrin protein" (64 kDa) from the venom of the Indian cobra snake (Naja naja) exhibited cytotoxic effects of various types of human cancer cell lines such as breast cancer (MCF-7), lung cancer (A549) and liver cancer (HepG2). In vitro cytotoxicity, DNA fragmentation, an apoptotic assay and a cell cycle analysis were performed to evaluate the anticancer activity of disintegrin against the above cell lines. The IC 50 value of disintegrin was determined to be 2.5 ± 0.5 μg/mL, 3.5 ± 0.5 μg/mL, and 3 ± 0.5 μg/mL for the MCF-7, A549 and HepG2 cell lines respectively. Moreover, the increased distribution of G0/G1 and S phase led to decreased populations of cells in the G2/M phase of MCF-7, HepG2 and A549 cells. © 2012 Elsevier Ltd. All rights reserved.


Vivek R.,Bharathiar University | Thangam R.,Bharathiar University | Thangam R.,King Institute of Preventive Medicine and Research | Nipunbabu V.,Bharathiar University | And 3 more authors.
International Journal of Biological Macromolecules | Year: 2014

This study was to investigate "smart" pH-responsive drug delivery system (DDS) based on chitosan nano-carrier for its potential intelligent controlled release and enhancing chemotherapeutic efficiency of Oxalipaltin. Oxaliplatin was loaded onto chitosan by forming complexes with degradable to construct nano-carrier as a DDS. Oxaliplatin was released from the DDS much more rapidly at pH 4.5 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Furthermore, the possible intrinsic apoptotic signaling pathway was explored by Western blot. It was found that expression of Bax, Bik, cytochrome C, caspase-9 and -3 was significantly up-regulated while the Bcl-2 and Survivin were inhibited in breast cancer MCF-7 cells. For instance, nanoparticles inducing apoptosis in caspase-dependent manner indicate that chitosan nanoparticles could act as an efficient DDS importing Oxalipaltin to target cancer cells. These approaches suggest that "smart" Oxaliplatin delivery strategy is a promising approach to cancer therapy. © 2014 Elsevier B.V.


Basavaraj V.H.,Vydehi Institute of Medical science and Research Center | Sampath G.,King Institute of Preventive Medicine and Research | Hegde N.R.,Ella Foundation | Mohan V.K.,Bharat Biotech International Ltd | Ella K.M.,Bharat Biotech International Ltd
Vaccine | Year: 2014

The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n= 60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 μg of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of ≥40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years. © 2014 Elsevier Ltd.

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