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1.
Transpl Immunol ; 79: 101859, 2023 08.
Article in English | MEDLINE | ID: mdl-37230393

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accountable for the coronavirus disease 2019 (Covid-19) prompted a catastrophic pandemic striking millions of people with diverse presentations, from asymptomatic to severe, potentially lethal disease requiring unprecedented levels of specialized care and extraordinary resources that have overwhelmed healthcare systems around the world. In this detailed communication we postulating a novel hypothesis, based on the viral replication and transplantation immunology. This based on reviewing published journal articles and text book chapters to account for variable mortality and degrees of morbidity among various race and origins. Homo sapiens evolution over millions of years, for that the matter the origin of any biologic form of life form initiated by microorganisms. The entire body of a human has several millions of bacterial and viral genomes incorporated over millions of years. Perhaps the answer or a clue lies how compatible a foreign genomic sequence fits into three billion copies of human genome.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Virus Replication
2.
Mar Pollut Bull ; 174: 113264, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34959101

ABSTRACT

The current study identifies groundwater quality issues and investigates the most important geochemical processes that control seawater intrusion using various ionic ratios, hydrochemical facies evolution, and geochemical modelling. Cl-/Br ratio is an important indicator to identify the origin of groundwater salinity in coastal aquifers. Nineteen percent of the groundwater samples with Cl-/Br- ratio similar to that of Standard Mean Ocean Water (SMOW) are affected by seawater intrusion in the study area. Particularly, nine groundwater samples have high chloride values and are similar to SMOW, and it may derived salinity from seawater sources from the Bay of Bengal due to the over-pumping of production wells in the Uvari zone. Five samples are similar to SMOW, which is due to the presence of salt pan activities. The bivariate plots such as Ca2+ + Mg2+ vs Cl-, EC vs Cl-, and Na+/Cl- ratio indicate that seawater intrusion is the primary source for groundwater salinisation. Evaporation is the dominant process controlling groundwater chemistry, rather than rock-water interaction and precipitation, according to mechanisms controlling groundwater chemistry. Direct ion exchange and converse ion exchange are the critical controlling factors for groundwater salinisation, according to the hydrochemical facies evolution diagram (HFED). The water quality index (WQI) shows that most groundwater belongs to the poor to the marginal category. The saturation indices show that the groundwater samples are saturated with minerals such as dolomite, calcite, aragonite and magnesite. Therefore, these minerals are susceptible to precipitation due to the effective leaching of calcareous minerals from the bedrocks. Compiled hydrogeochemical analysis and multivariate statistical analysis revealed that the Tiruchendur and Uvari zone was affected by the seawater intrusion and led to an increase in the salinity of the groundwater.


Subject(s)
Groundwater , Water Pollutants, Chemical , Chlorides , Environmental Monitoring , India , Salinity , Seawater , Water Pollutants, Chemical/analysis
3.
Mar Pollut Bull ; 126: 381-388, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29421115

ABSTRACT

Forty two surface sediment samples were collected in order to document baseline elemental concentration along the Southwest coast of Tamil Nadu, India. The elements detected were Manganese (Mn), Zinc (Zn), Iron (Fe), Copper (Cu), Nickel (Ni) and Lead (Pb). The concentration of Fe and Mn was primarily controlled by the riverine input. The source of Pb and Zn is attributed to leaded petrol and anti-biofouling paints. The calculated index (EF, Igeo and CF) suggests that the sediments of the study area are significantly enriched with all elements except Pb. The contamination factor showed the order of Mn>Zn>Fe>Cu>Ni>Pb. The sediment pollution index (SPI) revealed that the sediments belonged to low polluted to dangerous category. The correlation matrix and dendrogram showed that the elemental distribution was chiefly controlled by riverine input as well as anthropogenic activity in the coast.


Subject(s)
Geologic Sediments/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring , India
4.
Mar Pollut Bull ; 125(1-2): 522-529, 2017 Dec 15.
Article in English | MEDLINE | ID: mdl-28838599

ABSTRACT

Fifty two surface sediments were collected from the northern part of the Gulf of Mannar biosphere reserve to assess the geospatial risk of sediments. We found that distribution of organic matter and CaCO3 distributions were locally controlled by the mangrove litters and fragmented coral debris. In addition, Fe and Mn concentrations in the marine sediments were probably supplied through the riverine input and natural processes. The Geo-accumulation of elements fall under the uncontaminated category except Pb. Lead show a wide range of contamination from uncontaminated-moderately contaminated to extremely contaminated category. The sediment toxicity level of the elements revealed that the majority of the sediments fall under moderately to highly polluted sediments (23.07-28.84%). The grades of potential ecological risk suggest that predominant sediments fall under low to moderate risk category (55.7-32.7%). The accumulation level of trace elements clearly suggests that the coral reef ecosystem is under low to moderate risk.


Subject(s)
Coral Reefs , Geologic Sediments/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Animals , Anthozoa , Calcium Carbonate/analysis , Environmental Monitoring , India , Rhizophoraceae , Risk Assessment
5.
Data Brief ; 13: 575-581, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28706967

ABSTRACT

Spatial dataset representing the nutrient distribution in Karayar reservoir during pre and post-monsoon season is presented. Random sampling method was used for data collection and the sample location were fixed using a handheld global positioning system (Garmin GPSMAP-76). The nutrients were estimated using the standard techniques as described in the American Public Health Association (APHA) manual. Physical parameters were estimated using a Hanna portable multi water quality probe (HI-9828, USA). The spatial distribution of physical and nutrient content in surface water is carried out using an inverse distance weighted technique.

6.
Chemosphere ; 185: 468-479, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28715757

ABSTRACT

This study investigates the concentration of trace elements in the groundwater of Tamiraparani river basin, South India. 124 groundwater samples were collected representing diverse landuse condition over the study area. The results reveal that the mean concentrations of Fe, Mn, Cu, Cr, Pb, Zn and Ni were 0.269, 0.02, 0.007, 0.007, 0.003, 0.066, and 0.004 ppm respectively. The decreasing trend of trace element content shows the following order: Fe > Zn > Mn > Cu > Cr > Ni > Pb. Significant positive correlation (p < 0.05) is found between most of the variables such as water level and Fe, Pb; EC and Ni; Fe and Pb; Mn and Pb; Cu and Zn, Ni; Cr and Pb; Zn and Ni. The studied trace elements are found below the international drinking water guidelines except Fe, Mn, and Pb. The Empirical Bayesian Kriging (EBK) model is used to interpolate the studied metal concentrations in the groundwater of the study area. A health risk assessment was carried out using exposure dose index (CDI) and hazard quotient (HQ). The CDI values of trace elements for oral and dermal pathways shows the following order of Fe > Zn > Mn > Cu > Cr > Ni > Pb and Fe > Zn > Mn > Cr > Cu > Ni > Pb respectively. The Hazard quotients suggest that the risk of contamination through oral and dermal pathways is feeble as all the elements show values less than one. The multivariate statistical analysis reveals that the source of trace elements in the groundwater is through natural origin except copper, chromium and lead as these contaminants are derived from anthropogenic activities.


Subject(s)
Environmental Monitoring/methods , Groundwater/chemistry , Multivariate Analysis , Trace Elements/analysis , Bayes Theorem , Drinking Water , Environmental Monitoring/standards , Humans , India , Metals/analysis , Risk Assessment , Rivers , Skin Absorption , Water Pollutants, Chemical/analysis
7.
Data Brief ; 13: 306-311, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28649591

ABSTRACT

The chronicles of nearshore morphology and surficial beach deposits provide valuable information about the nature of the beach condition and the depositional environment. It imparts an understanding about the spatial and temporal relationship of nearshore waves and its influence over the distribution of beach sediments. This article contains data about wave and sediment dynamics of the ten sandy beaches along the central Tamil Nadu coast, India. This present dataset comprises nearshore wave parameters, breaker wave type, beach morphodynamic state, grain size distribution and weight percentage of heavy and light mineral distribution. The dataset will figure out the beach morphology and hydrodynamic condition with respect to the different monsoonal season. This will act as a field reference to realize the coastal dynamics in an open sea condition. The nearshore entities were obtained from the intensive field survey between January 2011 and December 2011, while characteristics of beach sediments are examined by the chemical process in the laboratory environment.

8.
Mar Pollut Bull ; 119(1): 416-422, 2017 Jun 15.
Article in English | MEDLINE | ID: mdl-28343631

ABSTRACT

Trace element concentration in the beach placer mining areas of Kanyakumari coast, South India was assessed. Sewage and contaminated sediments from mining sites has contaminated the surface sediments. Enrichment factor indicates moderately severe enrichment for Pb, minor enrichment for Mn, Zn, Ni, Fe and no enrichment for Cr and Cu. The Igeo values show higher concentration of Pb ranging in the scale of 3-4, which shows strong contamination due to high anthropogenic activity such as mining and terrestrial influences into the coastal regions. Correlation coefficient shows that most of the elements are associated with each other except Ni and Pb. Factor analysis reveals that Mn, Zn, Fe, Cr, Pb and Cu are having a significant loading and it indicates that these elements are mainly derived from similar origin. The cluster analysis clearly indicated that the mining areas are grouped under cluster 2 and non-mining areas are clustered under group 1.


Subject(s)
Mining , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring , Geologic Sediments , India , Metals, Heavy
9.
Mar Pollut Bull ; 117(1-2): 515-522, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28196651

ABSTRACT

Extensive field work was conducted in order to assess the sediment pollution level and potential ecological risk on coral reef ecosystem. Thirty three surface sample was collected using grid sampling technique. The calcium carbonate and organic matter were primarily controlled by the distribution of coral rubbles and seagrass meadows. The concentration of trace elements is higher than the crustal average in few locations and the same result was derived from index calculations. However, the significant concentration of lead was observed throughout the study area. The elevated level of lead is probably due to coal incinerating power plants, and confluence of urban runoff from the nearby coastal areas. Based on the sediment pollution index, the majority of the sediments belongs to highly polluted to dangerously polluted category. The ecological risk indicates that the sediments are under low risk to moderate risk category and this result was proved by correlation analysis.


Subject(s)
Coral Reefs , Environmental Monitoring , Geologic Sediments/analysis , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Animals , India , Islands
10.
Mar Pollut Bull ; 116(1-2): 508-516, 2017 Mar 15.
Article in English | MEDLINE | ID: mdl-28065553

ABSTRACT

The present study focused on the elemental distribution of nearshore environment and to understand the interrelationship between different parameters such as trace elements, organic matter, calcium carbonate and sediment texture. For this purpose, 24 surface samples were collected from the nearshore environment using a stainless steel Van Veen grab sampler. The above said parameters indicate that nearshore sediment transport, contaminants from estuarine source and anthropogenic activities deteriorates the sediment quality in the nearshore area. The enrichment factor reveals that the sediments are enriched with Pb, Co, Ni and Cr, whereas the geoaccumulation index highlights that the sediments are polluted with Pb, Ni and Co. The elevated concentration of Pb in the nearshore sediments are possibly from the port activities and thermal power plants situated in the north of the study area. Proper management of industrial effluents is needed to curb further metal pollution in the nearshore environment off Tamiraparani estuary.


Subject(s)
Environmental Monitoring , Estuaries , Geologic Sediments/analysis , Trace Elements/analysis , Water Pollutants, Chemical/analysis , India
11.
Mar Pollut Bull ; 115(1-2): 444-450, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-27817885

ABSTRACT

Forty eight surface sediment samples were collected from the vicinity of Van Island in order to assess the sediment pollution level and potential ecological risk on coral reef ecosystem. The analytical and correlation results indicate a distribution of elements is chiefly controlled by the CaCO3 and OM. The enrichment factor and geoaccumulation index show the elevated level of Pb in the surface sediments is due to application of lead petrol and coal incinerating power plants. The sediment pollution index reveals that majority of the sediments falling under highly polluted sediment category (35.4%) followed by moderately polluted (25%) and dangerous sediment category (14.58%). The potential ecological risk suggests that nearly 66.6% of the samples falling under the low risk category, moderate risk category (20.8%) followed by considerable risk category (8.33%) and very high risk category (4.1%). The accumulation level of trace elements clearly suggests that the coral reef ecosystem is under low risk.


Subject(s)
Coral Reefs , Geologic Sediments , Trace Elements , Environmental Monitoring , India , Islands , Lead , Metals, Heavy , Risk Assessment , Water Pollutants, Chemical
12.
Mar Pollut Bull ; 101(1): 409-416, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26490406

ABSTRACT

The present study was carried out on the Porites coral growth bands (1979 to 2014) to measure the metal accumulation for assessing the environmental pollution status. The concentrations of studied metals are compared with similar global studies, which indicate that the metals are probably derived from natural sources. The identical peaks of Fe and Mn are perfectly matched with Cu, Cr and Ni concentrations. However, the metal profile trend is slightly depressed from a regular trend in Zn, Cd and Pb peaks. The metal accumulation affinity of the reef skeleton is ranked in the following order Cr>Cd>Pb>Fe>Mn>Cu>Ni>Zn. The distribution of metal constituents in coral growth bands is primarily controlled by Fe and Mn in the reef skeleton. Other reef associated metals such as Pb and Cd are derived from other sources like coastal developments and anthropogenic sources.


Subject(s)
Anthozoa/growth & development , Metals/analysis , Water Pollutants, Chemical/analysis , Water Pollution/analysis , Animals , Anthozoa/chemistry , Anthozoa/metabolism , Coral Reefs , Environmental Monitoring/methods , India , Metals/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics
13.
Environ Monit Assess ; 187(1): 4073, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25407988

ABSTRACT

The south west coast of Kanyakumari district in Tamil Nadu, India, is significantly affected by seawater intrusion and diffusion of pollutants into the aquifers due to unregulated beach placer mining and other anthropogenic activities. The present study investigates the vulnerability of the coastal aquifers using Geographic Information System (GIS)-based DRASTIC model. The seven DRASTIC parameters have been analyzed using the statistical equation of this model to demarcate the vulnerable zones for aquifer contamination. The vulnerability index map is prepared from the weighted spatial parameters, and an accounting of total index value ranged from 85 to 213. Based on the categorization of vulnerability classes, the high vulnerable zones are found near the beach placer mining areas between Manavalakurichi and Kodimanal coastal stretches. The aquifers associated with settlements and agricultural lands in the middle-eastern part have experienced high vulnerability due to contaminated water bodies. Similarly, the coastal areas of Thengapattinam and Manakudi estuary and around the South Tamaraikulam have also been falling under high vulnerability condition due to backwater and saltpan. In general, the nearshore region except the placer mining zone and the backwater has a moderately vulnerable condition, and the vulnerability index values range from 149 to180. Significantly, the northern and northeastern uplands and some parts of deposition zones in the middle-south coast have been identified as low to no vulnerable conditions. They are structurally controlled by various geological features such as charnockite, garnet biotite gneiss and granites, and sand dunes, respectively. The aquifer vulnerability assessment has been cross-verified by geochemical indicators such as total dissolved solids (TDS), Cl(-), HCO3(-), and Cl(-)/HCO3(-) ratio. The high ranges of TDS (1,842--3,736 mg/l) and Cl(-) (1,412--2,112 mg/l) values are well correlated with the observed high vulnerable zones in the study area. The Cl(-)/HCO3(-) ratio (7.13 to 12.18) of the high vulnerable zone obviously indicates deterioration of the aquifer contamination. Sensitivity analysis has also been performed to evaluate sensitivity of the individual DRASTIC parameters to aquifer vulnerability. This reveals the net recharge rate and groundwater table depth are becoming more sensitive to aquifer contamination. It is realized that the GIS is an effective platform for aquifer vulnerability mapping with reliable accuracy, and hence, the study is more useful for sustainable water resource management and the aquifer conservation.


Subject(s)
Environmental Monitoring/methods , Groundwater/analysis , Models, Theoretical , Water Resources/analysis , Water Supply/analysis , Estuaries , Geographic Information Systems , Groundwater/chemistry , India , Seawater/analysis , Water Pollution/analysis
14.
Mar Pollut Bull ; 73(1): 355-61, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23790446

ABSTRACT

Sediment samples were collected from Kallar, Korampallam creek and Punnakayal estuaries of Tuticorin coast for assessing the level of contamination by trace elements in these estuarine sediments. The trace element concentration, calcium carbonate, organic carbon and mercury level were analyzed by Inductively Coupled Plasma Atomic Emission Spectrophotometer, Titrimetric method and SnCl2 reduction method. The results reveals that the enrichment factor, metal pollution index and geo-accumulation index of these estuarine sediments were predominantly polluted by Cd, As, Zn, Hg and Pb. The factor analysis revealed the source of trace element accumulation in the estuarine sediments particularly Mn and Fe are from riverine inputs and As and Hg from untreated industrial effluents. Among the selected estuaries, Korampallam creek was found to be highly contaminated by trace elements due to the discharge of effluents from thermal power plant, Tuticorin alkali chemicals, copper smelting, Petrochemical industries and shipping activities.


Subject(s)
Estuaries , Geologic Sediments/chemistry , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring , India , Metals/analysis
15.
Bull Environ Contam Toxicol ; 88(6): 876-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22481209

ABSTRACT

The aim of the present study is to investigate the pollution vulnerability of groundwater aquifers in the coastal regions of Tuticorin city, Tamil Nadu, India. Fourteen samples were analyzed to determine the concentration of trace elements (Pb, Zn, Cd, Hg, Cr and Cu) in the groundwater. Among the total samples six were collected from industrial areas and eight from non-industrial areas of Tuticorin city. The concentration of trace element ranges from 0.01 to 0.19 mg/kg(-1) for Pb, from 0.01 to 0.16 mg/kg(-1) for Zn, from BDL to 0.21 mg/kg(-1) for Cd, from BDL (Below Detection Limit) to 0.023 mg/kg(-1) for Hg, from 0.02 to 0.18 mg/kg(-1) for Cr and from 0.01 to 0.16 mg/kg(-1) for Cu. The trace element concentration in groundwater is higher than the WHO suggested maximum permissible limit except Zn and Cu.


Subject(s)
Groundwater/chemistry , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Cities , Environmental Monitoring , India , Water Pollution, Chemical/statistics & numerical data
16.
Environ Monit Assess ; 184(7): 4127-38, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21842165

ABSTRACT

Groundwater quality assessment has been carried out based on physicochemical parameters (pH, EC, TDS, CO(3), HCO(3), Cl, SO(4), PO(4), NO(2), Ca(+2), Mg(+2), Na(+) and K(+)) and metal concentration in the Rameswaram Island from 25 bore wells. The Langelier Saturation Index of the groundwater shows positive values (63% samples) with a tendency to deposit the CaCO(3) in the majority of water samples. Scatter plot (Ca + Mg/HCO(3)) suggests carbonate weathering process, which is the main contributor of Ca(2+), Mg(2+) and HCO(3) ions to the water. Gibbs diagram suggests rock-water interaction dominance and evaporation dominance which are responsible for the change in the quality of water in the study area. NaCl and mixed CaNaHCO(3) facies are two main hydrogeochemical facies of groundwater. Mathematical calculations and graphical plots of geochemical data reveal that the groundwater of Rameswaram Island is influenced by natural weathering of rocks, anthropogenic activities and seawater intrusion due to over exploitation. Weathering and dissolution of carbonate and gypsum minerals also control the concentration of major ions (Ca(+2), Mg(+2), Na(+) and K(+)) in the groundwater. The nutrient concentration of groundwater is controlled to a large extent by the fertilizers used in agricultural lands and aquaforms. Comparison of geochemical data shows that majority of the groundwater samples are suitable for drinking water and irrigation purposes.


Subject(s)
Carbonates/analysis , Groundwater/chemistry , Minerals/analysis , Water Pollutants, Chemical/analysis , Water Quality/standards , Environmental Monitoring , India , Metals/analysis , Seawater/analysis , Seawater/chemistry , Water Supply/statistics & numerical data
17.
Bull Environ Contam Toxicol ; 84(1): 141-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19943034

ABSTRACT

Coral samples were collected from Kurusadi, Shingle and Appa islands of Gulf of Mannar for analyzing the trace elements. The mean concentrations in the coral reef skeleton ranges from 0.19 to 0.62 microg g(-1) for Fe, from 6.71 to 15.6 microg g(-1) for As, from 0.28 to 1.31 microg g(-1) for Cd, from 0.56 to 5.29 microg g(-1) for Co, from 7.25 to 22.34 microg g(-1) for Cr, from 0.63 to 5.08 microg g(-1) for Cu, from 98.38 to 138 microg g(-1) for Mn, from 0.18 to 2.53 microg g(-1) for Ni, from 0.18 to 4.56 microg g(-1) for Pb and from 44 to 135.25 microg g(-1) for Zn. The factor analysis revealed the source of trace elements accumulation in the coral skeleton particularly Mn from detrital inputs and Cd from anthropogenic sources. This paper also highlights the nature of trace elements available in coral skeleton.


Subject(s)
Anthozoa/chemistry , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Animals , Environmental Monitoring , India
18.
Oncogene ; 20(47): 6938-45, 2001 Oct 18.
Article in English | MEDLINE | ID: mdl-11687973

ABSTRACT

Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase-type plasminogen activator, tissue plasminogen activator, or thrombin. Preliminary findings in our laboratory suggested that the expression of TFPI-2 is downregulated or lost during tumor progression in human gliomas. To investigate the role of TFPI-2 in the invasiveness of brain tumors, we stably transfected the human high-grade glioma cell line SNB19 and the human low-grade glioma cell line Hs683 with a vector capable of expressing a transcript complementary to the full-length TFPI-2 mRNA in either sense (0.7 kb) or antisense (1 kb) orientations. Parental cells and stably transfected cell lines were analysed for TFPI-2 protein by Western blotting and for TFPI-2 mRNA by Northern blotting. The levels of TFPI-2 protein and mRNA were higher in the sense clones (SNB19) and decreased in the antisense (Hs683) clones than in the corresponding parental and vector controls. In spheroid and matrigel invasion assays, the SNB19 parental cells were highly invasive, but the sense-transfected SNB-19 clones were much less invasive; the antisense-transfected Hs683 clones were more invasive than their parental and vector controls. After intracerebral injection in mice, the sense-transfected SNB19 clones were less able to form tumors than were their parental and vector controls, and the antisense-Hs683 clones but not the parental or vector controls formed small tumors. This is the first study to demonstrate that down- or upregulation of TFPI-2 plays a significant role in the invasive behavior of human gliomas.


Subject(s)
Brain Neoplasms/pathology , Glioma/pathology , Glycoproteins/physiology , Neoplasm Invasiveness , Animals , Cell Movement , Collagen/physiology , Drug Combinations , Glycoproteins/genetics , Humans , Laminin/physiology , Mice , Mice, Nude , Proteoglycans/physiology , RNA, Messenger/biosynthesis , Rats , Transfection , Tumor Cells, Cultured
19.
J Biol Chem ; 276(50): 47171-7, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11572856

ABSTRACT

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.


Subject(s)
Adenoviridae/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Down-Regulation , Glioma/metabolism , Integrins/metabolism , Oligonucleotides, Antisense/pharmacology , Receptors, Cell Surface/genetics , Receptors, Vitronectin/biosynthesis , Signal Transduction , Apoptosis , Blotting, Western , Cell Division , Cell Movement , Cell Separation , DNA, Complementary/metabolism , Enzyme Inhibitors/pharmacology , Flow Cytometry , Gene Transfer Techniques , Humans , Immunoblotting , Immunohistochemistry , Models, Biological , Mutagenesis, Insertional , Phenotype , Phosphatidylinositol 3-Kinases/metabolism , Protein Binding , Receptors, Urokinase Plasminogen Activator , Spheroids, Cellular/metabolism , Time Factors , Tumor Cells, Cultured , Vitronectin/metabolism
20.
Clin Cancer Res ; 7(8): 2519-26, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11489835

ABSTRACT

The diffuse and extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modifications of the proteolysis of extracellular matrix components. A key molecule in regulating plasminogen-mediated extracellular proteolysis is the urokinase-type plasminogen activator (uPA). To investigate the role of uPA in the invasive process of brain tumors, we stably transfected a human glioblastoma cell line SNB19 with a vector capable of expressing an antisense transcript complementary to the 1020 bases at the 3' end of the uPA cDNA. Parental, vector-, and antisense construct-stably transfected cell lines were analyzed for uPA mRNA transcript by Northern blot analysis, for uPA enzyme activity by zymography, and for uPA protein levels by Western blotting. The levels of uPA mRNA, protein, and enzyme activities were significantly lower in antisense clones than in parental and vector controls. Radioreceptor binding studies demonstrated that uPA receptor levels remained the same in parental, vector-, and antisense-transfected cells. The antisense-transfected cells showed a markedly lower level of invasion in the Matrigel invasion assays, and their spheroids failed to invade the fetal rat brain aggregates in the coculture system. Green fluorescent protein (GFP) expressing parental and antisense transfectants was generated for detection in mouse brain tissue without any posttreatment. Intracerebral injection of antisense stable transfectants significantly reduced tumor formation compared with that in controls. Our results suggested that down-regulation of uPA expression may be a feasible approach to reducing the malignancy and invasiveness of glial tumors.


Subject(s)
DNA, Antisense/genetics , Glioblastoma/therapy , Urokinase-Type Plasminogen Activator/genetics , Animals , Blotting, Northern , Blotting, Western , Brain/embryology , Brain/pathology , Fibrin/metabolism , Genetic Therapy/methods , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Mice , Mice, Nude , Microscopy, Confocal , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/prevention & control , Protein Binding , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Transfection , Tumor Cells, Cultured , Urokinase-Type Plasminogen Activator/metabolism , Xenograft Model Antitumor Assays
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