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Biomedical subjects

M Loizidou

Publications and source records attributed to M Loizidou.

At least 19 recordsLinked to original sources

Mechanisms of endothelin 1-stimulated proliferation in colorectal cancer cell lines.

BACKGROUND: The peptide endothelin (ET) 1 promotes proliferation in a number of epithelial cancers. The aim of this study was to identify the mechanism of ET-1-stimulated proliferation in colorectal cancer cells in vitro. METHODS: The effects of ET-1 on colorectal cancer cell lines HT29, LIM1215 and SW620 were studied. Cells were cultured with ET-1 plus antagonists/inhibitors to ET(A) or ET(B) receptors, G protein subtypes, phosphoinositide 3-kinase (PI3K) or protein kinase C (PKC). DNA replication and apoptosis were investigated by 5-bromo-2'-deoxyuridine incorporation and Annexin V staining. Transactivation of the epidermal growth factor (EGF) receptor was investigated by blockade of the receptor in the presence of ET-1, measurement of levels of phosphorylated EGF receptor in the presence of ET-1, and comparing the effects of ET-1 and EGF on cell proliferation. RESULTS: ET-1 significantly stimulated growth of all cell lines via ET(A) receptors. ET-1 stimulated DNA replication, not apoptosis. ET-1-stimulated growth was inhibited by antagonism of pertussis toxin-sensitive G proteins, PI3K and PKC. Inhibition of the EGF receptor reduced the effect of ET-1. ET-1 increased levels of phosphorylated EGF receptor via the ET(A) receptor. CONCLUSION: ET-1 increased DNA replication in colorectal cancer cells via the ET(A) receptor. This mitogenic action was mediated via pertussis toxin-sensitive G proteins, PI3K, PKC and transactivation of the EGF receptor.

Analysis of Variance↗

Novel germline mutations in the APC gene of Cypriot patients with familial and sporadic adenomatous polyposis.

Familial adenomatous polyposis (FAP) is one of the two commonest familial syndromes that predispose to colorectal cancer. FAP is caused by mutations in the adenomatous polyposis coli (APC) tumour suppressor gene that has a high penetrance. The disease is characterized by the occurrence of hundreds to thousands of colorectal polyps, which if left untreated give rise to colorectal cancer. In Cyprus, there are no molecular data available as yet on families with FAP. This work presents the results of APC analysis in our population for the first time. The APC gene was analyzed in 33 DNA samples from 20 individuals belonging to four FAP families and 13 patients with sporadic polyposis. We identified three truncating mutations, four missense mutations and 11 polymorphisms. It is of interest that two of the three truncating mutations, 2307delA and Q1242X, are novel, which supports the existence of a unique genetic pool in the Cypriot population. This ethnic molecular study in addition to highlighting population heterogeneity also contributes to phenotype-genotype associations that are essential for the clinical management of FAP families in Cyprus.

Adenomatous Polyposis Coli↗

Changes in vasoconstrictor and vasodilator neurotransmitters in nerves supplying arterioles in developing colorectal polyps.

OBJECTIVE: To examine the changes that occur in the immunohistochemistry of vasoconstrictor and vasodilator transmitters in nerves supplying early and advanced colorectal polyps. SUBJECTS AND METHODS: We studied the perivascular innervation of submucosal arterioles of colorectal polyps (n = 18) and the innervation of the epithelial layer of polyps compared to normal controls (n=8), using immunohistochemical markers for the neurotransmitters; noradrenaline (NA) (marker used; tyrosine hydroxylase (TH)), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related polypeptide (CGRP). (Advanced polyps; villous adenomas>1.5 cm, polyps with severe dysplasia or partial carcinoma). RESULTS: In submucosal arterioles there was a progressive decrease from controls through early polyps to advanced polyps in TH and NPY perivascular immunoreactivity (P<0.015 for both). VIP and SP immunoreactivity was higher in early polyps compared to controls, but markedly reduced in advanced polyps (P<0.05 for VIP). Sparse CGRP immunoreactivity was present in polyps only. Neural VIP and SP immunoreactivity in the lamina propria of polyp mucosa was more intense than in controls. CONCLUSION: There is a decrease in vasoconstrictor neurotransmitters NPY and NA (shown by TH) around submucosal arterioles of both early and advanced polyps, but an increase in the vasodilator neurotransmitters, particularly VIP, in early colorectal polyps. These results suggest a predominantly vasodilatory neural influence in early polyps, perhaps indicating a mechanism that maintains polyp growth.

Aged↗

Demonstration plasma gasification/vitrification system for effective hazardous waste treatment.

Plasma gasification/vitrification is a technologically advanced and environmentally friendly method of disposing of waste, converting it to commercially usable by-products. This process is a drastic non-incineration thermal process, which uses extremely high temperatures in an oxygen-starved environment to completely decompose input waste material into very simple molecules. The intense and versatile heat generation capabilities of plasma technology enable a plasma gasification/vitrification facility to treat a large number of waste streams in a safe and reliable manner. The by-products of the process are a combustible gas and an inert slag. Plasma gasification consistently exhibits much lower environmental levels for both air emissions and slag leachate toxicity than other thermal technologies. In the framework of a LIFE-Environment project, financed by Directorate General Environment and Viotia Prefecture in Greece, a pilot plasma gasification/vitrification system was designed, constructed and installed in Viotia Region in order to examine the efficiency of this innovative technology in treating industrial hazardous waste. The pilot plant, which was designed to treat up to 50kg waste/h, has two main sections: (i) the furnace and its related equipment and (ii) the off-gas treatment system, including the secondary combustion chamber, quench and scrubber.

Equipment Design↗

Endothelin-1: a multifunctional molecule in cancer.

Endothelin-1 is a small vasoconstrictor peptide that was first identified in 1988. Here we review the evidence implicating ET-1 in tumorigenesis. In particular, we concentrate on the role of ET-1 in mitogenesis, apoptosis, angiogenesis, tumour invasion and metastasis, and discuss the potential for endothelin-system modulation as an adjuvant therapeutic strategy.

Apoptosis↗

Development of guidelines on best practices for the slaughter of animals in Cyprus.

Cyprus is one of the candidate countries to become a full member of the European Union. In order to access formally to the EU, Cyprus has to follow an implementation process and take into account all the obligations that the fifteen Member States have to respect. A large number of obligations derive from the European Integrated Pollution Prevention and Control (IPPC) Directive 96/61/EC, which intends to result in the protection of the environment as a whole and the public health as well. This will be the outcome of determining ways of pollution prevention and control for several industrial sectors, which are covered by the IPPC Directive and then taking action so that all operators act according to the Directive's demands. In this framework, the National Technical University of Athens, after thorough examination of a large number of documents relevant to the Best Available Techniques (BATs), developed guidelines for the application of BATs for 14 categories of the industry of Cyprus. This paper concerns the developed guidelines for slaughterhouses.

Abattoirs↗

Integrated environmental monitoring and simulation system for use as a management decision support tool in urban areas.

Leachates are generated as a result of water or other liquid passing through waste at a landfill site. These contaminated liquids originate from a number of sources, including the water produced during the decomposition of the waste as well as rain-fall which penetrates the waste and dissolves the material with which it comes into contact. The penetration of the rain-water depends on the nature of the landfill (e.g. surface characteristics, type and quantity of vegetation, gradient of layers, etc). The uncontrolled infiltration of leachate into the vadose (unsaturated) zone and finally into the saturated zone (groundwater) is considered to be the most serious environmental impact of a landfill. In the present paper the water flow and the pollutant transport characteristics of the Ano Liosia Landfill site in Athens (Greece) were simulated by creating a model of groundwater flows and contaminant transport. A methodology for the model is presented. The model was then integrated into the Ecosim system which is a prototype funded by the EU, (Directorate General XIII: Telematics and Environment). This is an integrated environmental monitoring and modeling system, which supports the management of environmental planning in urban areas.

Cities↗

Increased expression of NOS and ET-1 immunoreactivity in human colorectal metastatic liver tumours is associated with selective depression of constitutive NOS immunoreactivity in vessel endothelium.

The absence of perivascular nerves in tumour vessels suggests that endothelium derived vasoactive substances [nitric oxide (NO) and endothelin-1 (ET-1)] may be key factors in controlling tumour blood flow during tumour growth and metastasis. We have studied the ultrastructural distribution and immunoreactivity of different NO synthase (NOS) isoforms and ET-1 in human colorectal metastatic liver tumour tissues using pre-embedding peroxidase-anti-peroxidase and post-embedding immunoelectron microscopic triple gold labelling techniques. Dramatically lower NOS 1 immunoreactivity was observed in tumour vascular endothelium (1-3% and 15-20% in tumour and normal groups, respectively). As compared to control groups there were significantly less NOS3 immunopositive EC in metastatic tumour vessels (45-50% and 1-3% in normal and tumour groups, respectively). A striking rise in NOS2 was observed in tumour vessel endothelium (< 1% in normal and 65-70% in tumour vessel endothelium). ET-1 immunoreactivity levels were also significantly higher in tumour vessel endothelium (85-90% in tumour, 15-20% in normal group). This increased expression of NOS2 and ET-1 immunoreactivity was accompanied by the increased expression of three NOS isoforms and ET-1 immunoreactivity in liver parenchymal cells. These data suggest that metastatic tumour vessel endothelium is characterized by increased expression of NOS2 and ET-1 and by decreases in NOS1 and NOS3. These characteristics are associated with the overexpression of all three NOS isoforms and ET-1 immunoreactivity in non-vascular cells.

Aged↗

Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.

Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET(A) and ET(B), on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 +/- 1.4, 4.5 +/- 1.5, vs. 2.75 +/- 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET(A) antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET(A) receptors. ET(A) antagonists are indicated as potential anti-cancer agents.

Adult↗

Design of an inventory system for the volatile organic compounds emitted by various activities.

In this study an inventory system was designed which fulfills the reporting requirements of the current European Union legislation for air emissions. Given the reporting requirements deriving from the EU Directives, International Conventions, and Inventory Methodologies developed at the EU level, there are significant differences in the required data in terms of industrial categories, definitions of point and area sources, whether TVOC or individual species must be determined, and expression of VOCs emissions. On the basis of this concept, an inventory system was structured that aims to comply with the framework set by the European Union for the evaluation of VOCs emissions from industrial activities and other facilities in Greece. This inventory can be very helpful to all the EU members states, as well as the Eastern European countries that are in pre-accession phase, who must implement the European legislation concerning VOCs emissions.

Air Pollutants↗

Positron emission tomography and colorectal cancer.

BACKGROUND: The oncological applications of positron emission tomography (PET) have gained widespread acceptance. This rapidly evolving technology has been applied successfully to colorectal cancer, but has not yet become part of routine clinical practice. This review considers (1) the biological basis for the use of PET in colorectal cancer, (2) the technical aspects of PET relevant to the referring clinician and (3) the application of PET to the management of primary and recurrent disease. METHODS: A Medline database search was performed for the period 1980-2000. Experience was also drawn from the first 40 patients with colorectal cancer investigated at this institution. RESULTS AND CONCLUSION: PET has a proven role, and is cost effective in the management of recurrent cancer and the monitoring of therapy. However, further evaluation is still required to justify its routine use for other indications in colorectal cancer. Development of new positron-labelled radio- pharmaceuticals, in parallel with advances in detector technology and innovative models for tracer production and distribution, means that the availability of PET and its applications in the management of colorectal cancer will expand over the coming years.

Colorectal Neoplasms↗

Treatment of leachate from a domestic solid waste sanitary landfill by an electrolysis system.

This study deals with the characteristisation and the treatability of leachates from the new municipal domestic waste (DW) landfill site in Athens, Greece, using an electrolysis system. This site has been in operation since July 1998. The leachate from this site has mean COD and BOD5 values of 53300 and 30300 mg l(-1), respectively, and constitutes a major environmental problem that must be taken into serious consideration. An electrolysis system, using Ti/Pt electrode in alkaline conditions was used to treat the leachate. The study showed, that the COD was reduced by 84%, and that VSS, N-NH4 and Total Phosphorus were reduced by 100% within one hour of electolysis and at pH 9. The efficiency of electrolysis went up to 32 g COD removed (CODr)/h-A-m2 and the energy consumption was 12.6 kWh kg(-1)CODr.

Chloramines↗

Removal of heavy metals from sewage sludge by acid treatment.

Sludge samples were found to contain significant amounts of heavy metals (Cr, Cu, Ni, Pb and Zn) and were subjected to acid treatment using either hydrochloric, sulfuric, nitric or phosphoric acid. The optimum combination, in terms of metal removal efficiency and environmental impacts was sought through a variety of tests by applying a ratio of 1:5 of sludge quantity (g) per volume of acid (ml). The concentrations of the different acids used, were in the range of 5%-20% and the contact times ranged between 15 and 60 minutes. The optimum combination was achieved when the sludge samples were in contact with H2SO4 20% v/v for 60 minutes. In order to estimate the metal leachability, the heavy metal content as well as the metal distribution in the residue were investigated and it was found that most of the heavy metal content was extracted while the remaining was removed from the initial mobile phases to the more stable ones.

Acids↗

Cement-based stabilization/solidification of metal plating industry sludge.

This study examines the cement-based Stabilization/Solidification (S/S) technique of sludge produced from a metal plating industry. The sludge samples were characterized in terms of pH and heavy metal content (Cr, Cu, Fe, Ni, Pb and Zn). The leachability of the sludge was estimated using the Toxicity Characteristic Leaching Procedure (TCLP). Two binder mixtures were used for the S/S process, fly ash/cement and zeolite/cement. The weight ratio of the binder mixtures was optimized to achieve the highest strength. The optimum ratio binder mixtures was mixed with sludge samples of different weight ratios and cured for 28 days in order to find the S/S products with the highest strength and the lowest leachability.

Environmental Pollution↗

Compost produced from organic fraction of municipal solid waste, primary stabilized sewage sludge and natural zeolite.

The aim of this work is to present the physicochemical characteristics of the compost produced from dewatered anaerobically stabilized primary sewage sludge (DASPSS), organic fraction of municipal solid waste (OFMSW) and the metal uptaken by zeolite (clinoptilolite). The final results indicated that the composted material produced from clinoptilolite 20% w/w and 80% w/w DASPSS and OFMSW (60% and 40%, respectively) provided better soil conditioning compared to the compost produced from DASPSS. The co-composting products had a higher concentration of total humic and organic matter (O.M.) than the sewage sludge compost. Also, the heavy metals concentration in the final products was in lower concentration than in the sewage sludge compost. The zeolite appeared to uptake a significant (p<0.05) amount of metals. Specifically, the use of 20-25% w/w of clinoptilolite appears to uptake 100% of Cd, 10-15% of Cr, 28-45% of Cu, 41-47% of Fe, Mn 9-24% of Mn, 50-55% of Ni and Pb, and 40-46% of Zn. Although by the application of the composting process, the reduction in dry mass is between 30% and 40% for all samples.

Metals, Heavy↗

Progressive loss of perivascular nerves adjacent to colorectal cancer.

AIMS: The perivascular innervation of arterioles in colorectal cancer and adjacent submucosa was investigated. METHODS: Neurotransmitter markers, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), were studied and immunoreactivity was compared with that of control normal tissue. RESULTS: There was absence of perivascular nerves within tumours and loss of perivascular innervation in the submucosa adjacent to the tumour. The pattern of loss varied for different transmitters. The loss was progressively greater with advancing tumour stage for NPY (controls 95%, Dukes' A 68%, Dukes>> B 13%, Dukes' C 6%) and VIP (50%, 23%, 20%, 17%). For TH there was extensive loss of innervation around tumours of all stages (69%, 5%, 7%, 0%). SP immunoreactive peri-arteriolar nerves were similar in control tissue (39%) and tissue adjacent to Dukes' A tumours (40%) but diminished to 19% and 0% in tissue adjacent to Dukes' B and C tumours, respectively. In none of the tissues was CGRP immunoreactivity above 4%. The mean distance over which there was reduced NPY immunoreactivity from the tumour edge was 2.43 mm for Dukes' A/B tumours compared with 7.20 mm for Dukes' C tumours; for VIP immunoreactivity this distance was 5.22 mm for Dukes' A/B tumours and 5.52 mm for Dukes' C tumours. CONCLUSIONS: The progressive loss, both in terms of vascular nerve immunoreactivity and distance from the tumour edge with tumour grade, suggests that the tumour itself may influence neural integrity in perivascular plexuses, perhaps via the secretion of an inhibitory factor.

Aged↗

Endothelin receptor expression in colorectal cancer.

The distribution of endothelin-A- and B- (ET(A), ET(B)) receptor subtypes was compared in colorectal cancer to that in normal colon and their expression in the colorectal cancer cell lines LIM1215. HT29, SKCO1, SKCO17 and LoVo was determined, using gross and high resolution autoradiography and quantified by densitometry. ET(A) and ET(B) binding sites were expressed by all the cell lines. There was significantly (p = 0.008) higher expression of ET(A)-receptors by cancers (205.95 dpm x 1000/mm2) compared normal colon (129.19 dpm x 1000/mm2). However, for ET(B)-receptors, this was reversed, with significantly (p = 0.008) higher expression of ET(B) binding in normal colon (207.00 dpm x 1000/mm2) than in tumours (122.35 dpm x 1000/mm2).

Autoradiography↗

Stimulation of colorectal cancer cell line growth by ET-1 and its inhibition by ET(A) antagonists.

BACKGROUND: The vasoactive peptide endothelin 1 (ET-1) acts via two receptors, endothelin receptors A (ET(A)) and B (ET(B)). ET-1 is overexpressed by human cancers in vivo and in vitro and may be mitogenic for cancer cells. METHOD: To elucidate if ET-1 is a growth regulator the following were investigated in human colorectal cancer cell lines (LIM1215 and HT29): ET-1 production by ELISA; ET receptor expression using radioligand autoradiographic techniques; and responsiveness to ET-1, and to ET(A) and ET(B) antagonism by growth measurements. RESULTS: ET-1 was produced by LIM1215 and HT29 cells (21.3 and 41.7 fmol/ml/10(6) cells (24 hours); 22.6 and 71.7 fmol/ml/10(6) cells (48 hours), respectively). ET(A) and ET(B) receptors were expressed by both cell lines. Addition of ET-1 resulted in a dose dependent increase in cell numbers which was significant at 10(-8)-10(-9) M for LIM1215, with the greatest increase at 10(-8) M (32.7% and 28.4% increase above controls at 48 hours and 72 hours; p<0.05) and at 10(-8)-10(-9) M for HT29, with the greatest increase at 10(-9) M (13.4% and 15.7% increase above controls at 48 hours and 72 hours; p<0.05). ET(A) antagonists BQ123 and BQ610, but not the ET(B) antagonist BQ788, inhibited ET-1 induced proliferation of both LIM1215 and HT29 (p<0.05). CONCLUSION: ET-1 can stimulate the proliferation of colorectal cancer cell lines via the ET(A), but not the ET(B), receptor.

Cell Division↗