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2.
Waste Manag Res ; 37(5): 461-468, 2019 May.
Article in English | MEDLINE | ID: mdl-30726169

ABSTRACT

Household food waste management and treatment has been recognised as a significant issue worldwide and at a European Union level. Source-separation of household food waste following drying at source presents a viable solution to this problem. The present research aims at investigating the effect of drying of model household food waste at different temperatures (i.e. 63 ±3 °C and 83 ±3 °C) on its biochemical methane potential. The drying process was carried out using a prototype household waste dryer. The model sample consisted of 77%w/w vegetables and fruits (48%w/w and 29%w/w, respectively), 12%w/w pasta/rice, 6%w/w meat and fish, 3%w/w bread and bakery and 2%w/w dairy. Moreover, drying at the same temperatures was applied for two household food wastes samples with different composition, in order to assess the influence of the samples' composition on both the drying process and the methane generation. For all temperatures used, the higher %w/w mass reduction was observed for model waste (MD) (67.39%w/w and 75.79%w/w for 63 °C and 83 °C, respectively), then for rich-in-protein content (PRO) (66.18%w/w and 69.73%w/w for 63 °C and 83 °C, respectively) and finally for rich-in-fat content (FAT) samples (54.35%w/w and 66.31%w/w for 63 °C and 83 °C, respectively), which confirmed the effectiveness of the drying process. The biochemical methane potential experiments have confirmed that the substrate produced the highest methane yields was the FAT, producing 524.25 ±2.86 L CH4 kg-1 volatile solids.


Subject(s)
Methane , Waste Management , Anaerobiosis , Animals , Bioreactors , Desiccation , Food , Temperature
3.
Clin Genet ; 91(4): 611-615, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27882536

ABSTRACT

This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Ovarian Neoplasms/genetics , Triple Negative Breast Neoplasms/genetics , Adult , Aged , Cyprus/epidemiology , Female , Genetic Predisposition to Disease , Genetic Testing , Genetics, Population , Humans , Middle Aged , Molecular Epidemiology , Mutation , Ovarian Neoplasms/epidemiology , Triple Negative Breast Neoplasms/epidemiology
4.
J Environ Manage ; 203(Pt 2): 664-669, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-27784578

ABSTRACT

This work aims to assess the operation of the first large scale segregated biowaste composting scheme in Greece to divert Household Food Waste (HFW) from landfill and produce a material which can be recovered and used as compost. The source separation and collection of HFW was deployed in selected areas in Attica Region serving about 3700 households. Sorted HFW is collected & transported to the Mechanical and Biological Treatment (MBT) plant in Attica Region that has been designed to produce Compost Like Output (CLO) from mixed MSW. The MBT facility has been adjusted in order to receive and treat aerobically HFW mixed with shredded green waste in a dedicated composting tunnel. The composting process was monitored against temperature, moisture and oxygen content indicating that the biological conditions are sufficiently developed. The product quality was examined and assessed against the quality specifications of EU End of Waste Criteria for biowaste subjected to composting aiming to specify whether the HFW that has undergone recovery ceases to be waste and can be classified as compost. More specifically, the heavy metals concentrations (Cr, Cu, Ni, Cd, Pb, Zn and Hg) are within the set limits and much lower compared to the CLO material that currently is being produced at the MBT plant. In regard to the hygienic requirements of the product it has been found that the process conditions result in a pathogen free material (i.e. E. Coli and Salmonella) which does not favor the growth of viable weeds and plant propagules, while it acquires sufficient organic matter content for soil fertilization. Noticeable physical impurities (mainly fractions of glass) have been detected exceeding the quality control threshold limit of 0.5% w/w (plastics, metals and glass). The latter is related to the missorted materials and to the limited pre-treatment configurations prior to composting. The above findings indicate that effective source separation of biowaste is prerequisite for good quality production and marketing of compost and special consideration should be made to minimize glass impurities prior composting (i.e. awareness raising and pretreatment stage). Therefore, it is feasible to gradually replace the production of questionable quality CLO in MBTs with biowaste compost which is in line with the required quality control standards especially when heavy metals concentrations is concerned.


Subject(s)
Escherichia coli , Refuse Disposal , Cities , Greece , Soil , Soil Microbiology
5.
Org Biomol Chem ; 14(48): 11488-11501, 2016 Dec 07.
Article in English | MEDLINE | ID: mdl-27886311

ABSTRACT

Efficient syntheses of cell-penetrating peptide-porphyrin conjugates are described using a variety of bioconjugation chemistries. This provides a flexible means to convert essentially hydrophobic tetrapyrolle photosensitisers into amphiphilic derivatives which are well-suited for use in light-triggered drug delivery by photochemical internalisation (PCI) and targeted photodynamic therapy (PDT).


Subject(s)
Antimicrobial Cationic Peptides/chemical synthesis , Drug Delivery Systems , Light , Phenothiazines/chemical synthesis , Photochemotherapy , Porphyrins/chemical synthesis , Antimicrobial Cationic Peptides/chemistry , Molecular Structure , Phenothiazines/chemistry , Porphyrins/chemistry
6.
Eur Arch Paediatr Dent ; 17(1): 3-12, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26732946

ABSTRACT

BACKGROUND: The European Academy of Paediatric Dentistry (EAPD) encourages prevention and arrest of active dental caries. Therefore, the present guidance provides evidence- and clinically-based recommendations for detecting and diagnosing early/non-cavitated caries lesions, risk assessment and disease management. METHODS: A search of different databases was conducted using all terms related to the subject. Relevant papers were identified after a review of their titles, abstracts or full texts. Three workshops were held during the corresponding EAPD interim seminar in Brussels in 2015. Several statements were agreed upon and, furthermore, gaps in our knowledge were identified. RESULTS: Following the systematic reviews and outcomes of the seminars, it was concluded that visual and radiographic caries detection should be utilised as a basic diagnostic approach to locate, assess and monitor non-cavitated caries lesions in primary and permanent teeth. As another important evaluation step, a caries risk assessment should be performed at a child's first dental visit, and reassessments should be performed on a regular basis. It is widely accepted that non-cavitated caries lesions can be managed non-invasively in the majority of cases. The spectrum of measures includes a low cariogenicity tooth-friendly diet, daily and appropriate management of the biofilm, home and within the dental office/surgery usage of fluorides as well as sealing techniques. CONCLUSION: The detection and management of non-cavitated caries is an essential aspect of preventive dentistry. Therefore, the EAPD encourages oral health care providers and caregivers to implement preventive practices that can arrest early caries and improve individual and public dental health.


Subject(s)
Dental Caries/therapy , Pediatric Dentistry , Preventive Dentistry , Adult , Child , Dental Care , Dental Caries/diagnosis , Dentition, Permanent , Humans , Risk Assessment
7.
Environ Technol ; 37(8): 929-39, 2016.
Article in English | MEDLINE | ID: mdl-26507489

ABSTRACT

Domestic food waste drying foresees the significant reduction of household food waste mass through the hygienic removal of its moisture content at source. In this manuscript, a new approach for the development and optimization of an innovative household waste dryer for the effective dehydration of food waste at source is presented. Food waste samples were dehydrated with the use of the heated air-drying technique under different air-drying conditions, namely air temperature and air velocity, in order to investigate their drying kinetics. Different thin-layer drying models have been applied, in which the drying constant is a function of the process variables. The Midilli model demonstrated the best performance in fitting the experimental data in all tested samples, whereas it was found that food waste drying is greatly affected by temperature and to a smaller scale by air velocity. Due to the increased moisture content of food waste, an appropriate configuration of the drying process variables can lead to a total reduction of its mass by 87% w/w, thus achieving a sustainable residence time and energy consumption level. Thus, the development of a domestic waste dryer can be proved to be economically and environmentally viable in the future.


Subject(s)
Desiccation , Food , Models, Theoretical , Refuse Disposal/methods , Kinetics , Temperature , Waste Products
8.
Waste Manag Res ; 33(5): 439-52, 2015 May.
Article in English | MEDLINE | ID: mdl-25819929

ABSTRACT

Waste management in Greece relies heavily on unsustainable waste practices (mainly landfills and in certain cases uncontrolled dumping of untreated waste). Even though major improvements have been achieved in the recycling of municipal solid waste during recent years, there are some barriers that hinder the achievement of high recycling rates. Source separation of municipal solid waste has been recognised as a promising solution to produce high-quality recycled materials that can be easily directed to secondary materials markets. This article presents an innovative miniature waste separator/compressor that has been designed and developed for the source separation of municipal solid waste at a household level. The design of the system is in line with the Waste Framework Directive (2008/98/EC), since it allows for the separate collection (and compression) of municipal solid waste, namely: plastic (polyethylene terephthalate and high-density polyethylene), paper (cardboard and Tetrapak) and metal (aluminium and tin cans). It has been designed through the use of suitable software tools (LS-DYNA, INVENTROR and COMSOL). The results from the simulations, as well as the whole design process and philosophy, are discussed in this article.


Subject(s)
Product Packaging , Recycling/methods , Solid Waste/analysis , Waste Management/methods , Greece , Metals/analysis , Paper , Plastics , Polyethylene Terephthalates/analysis , Polyethylenes/analysis , Waste Management/instrumentation
9.
J Hazard Mater ; 207-208: 44-50, 2012 Mar 15.
Article in English | MEDLINE | ID: mdl-21983167

ABSTRACT

The environmental impact from the operation of thermal waste treatment facilities mainly originates from the air emissions, as well as the generated solid residues. The objective of this paper is to examine the slag residue generated by a demonstration plasma gasification/vitrification unit and investigate the composition, the leaching properties of the slag under different conditions, as well as the role of the cooling method used. The influence of pH, particle size and contact time on the leachability of heavy metals are discussed. The main outcome is that the vitrified slag is characterized as inert and stable and can be safely disposed at landfills or used in the construction sector. Finally, the water-cooled slag showed better resistance in relation to heavy metal leachability compared to the air-cooled slag.


Subject(s)
Gases/chemistry , Hydrogen-Ion Concentration , Particle Size , Waste Management
10.
Br J Pharmacol ; 163(2): 220-33, 2011 May.
Article in English | MEDLINE | ID: mdl-21232046

ABSTRACT

The endothelins (ET) are a group of proteins that act through G-protein coupled receptors. Endothelin-1 (ET-1) was initially identified as a potent vasoconstrictor and dysregulation of the ET axis contributes to pathological processes responsible for cardiovascular disease states. More recently, the ET axis, in particular ET-1 acting through the endothelin A receptor (ET(A) ), has been implicated in the development of several cancers through activation of pathways involved in cell proliferation, migration, invasion, epithelial-mesenchymal transition, osteogenesis and angiogenesis. The endothelin B receptor (ET(B) ) may counter tumour progression by promoting apoptosis and clearing ET-1; however, it has recently been implicated in the development of some tumour types including melanomas and oligodendrogliomas. Here, we review emerging preclinical and clinical data outlining the role of the ET axis in cancer, and its antagonism as an attractive and challenging approach to improve clinical cancer management. Clinical data of ET(A) antagonists in patients with prostate cancer are encouraging and provide promise for new ET(A) antagonist-based treatment strategies. Given the unexpected opportunities to affect pleiotrophic tumorigenic signals by targeting ET(A)-mediated pathways in a number of cancers, the evaluation of ET-targeted therapy in cancer warrants further investigation.


Subject(s)
Endothelin A Receptor Antagonists , Endothelin B Receptor Antagonists , Endothelins/physiology , Neoplasms/therapy , Animals , Endothelin-1/physiology , Endothelin-2/physiology , Endothelin-3/physiology , Humans , Molecular Targeted Therapy , Neoplasms/metabolism , Neoplasms/pathology , Receptor, Endothelin A/physiology , Receptor, Endothelin B/physiology
11.
Biometals ; 24(1): 143-51, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20957409

ABSTRACT

Trace elements are involved in many key pathways involving cell cycle control. The influence of zinc and zinc chelator (TPEN) on transcription levels of the main zinc transporters (ZnT1 and ZIP1) in the HT-29 colorectal cell line has not been reported. Proliferation of HT-29 cells was measured using the methylene blue assay after exposure to zinc (two concentrations), TPEN (two concentrations), or a combination of zinc and TPEN (simultaneously and sequentially) for 4 h, 8 h, and 24 h. The transcription levels of ZnT1, ZIP1, vascular endothelial growth factor (VEGF), and caspase-3 were determined using reverse transcriptase real-time polymerase chain reaction (RT-PCR) after exposure of cells to zinc and TPEN. The zinc content in the substrate (medium used for culture) was determined using atomic absorption spectrometry. TPEN decreased cellular proliferation causing complete cell death by 8 h. Zinc had a protective effect against short periods of exposure to TPEN. There was no correlation between the transcripts of main zinc transporters and the zinc content in the substrate. The zinc content in the substrate remained constant after varying periods of cell culture. TPEN decreased the transcript levels of caspase-3 and VEGF, which are surrogate markers for apoptosis and angiogenesis. Zinc chelation of HT-29 cells causes cell death. Zinc appears to be protective for short periods of exposure to TPEN but has no protective effect on prolonged exposure. HT-29 cells are not able to counteract the effect of intracellular chelation of zinc by altering zinc transport. Further research into the mechanisms of these findings is necessary and may lead to novel therapeutic options.


Subject(s)
Chelating Agents/pharmacology , Ethylenediamines/pharmacology , Zinc/pharmacology , Caspase 3/genetics , Caspase 3/metabolism , Cell Proliferation/drug effects , Chelating Agents/chemistry , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Ethylenediamines/chemistry , HT29 Cells , Humans , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Zinc/chemistry
12.
Br J Surg ; 97(4): 463-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20205212
13.
Water Sci Technol ; 61(3): 581-9, 2010.
Article in English | MEDLINE | ID: mdl-20150693

ABSTRACT

The aim of this work is to examine copper removal from sludge permeate with the use of low-cost minerals of Mediterranean origin combined with ultrafiltration membranes. The minerals used were zeolite (clinoptilolite), bentonite and vermiculite. Activated sludge was enriched with 0.01 N (317.7 ppm) of Cu(II). Fixed concentrations of minerals were added to sludge and the pH value was adjusted at 5.5. The mixture was agitated for 2 hours at 800 rpm at room temperature and was then filtered through a batch ultrafiltration system for 1 hour. This experiment was repeated, for comparison purposes, with sludge enriched with 0.01 N of Cu(II) with no mineral addition. The results showed that ultrafiltration membranes with no mineral addition were able to remove a significant amount of copper with removal efficiencies ranging from 59.4-78.3%. The addition of 10 g/l and 20 g/l of bentonite combined with ultrafiltration membranes resulted in removal efficiencies of 94.9% and 99.4% respectively and that of 10 g/l and 20 g/l of vermiculite in removal efficiencies of 93.8% and 96.8%, respectively. The ion exchange capacity of minerals followed the order bentonite > vermiculite > zeolite. Furthermore, membrane fouling was investigated. The addition of zeolite and bentonite reduced membrane fouling, while the addition of vermiculite did not impact on fouling. The use of low-cost minerals in combination with ultrafiltration membranes can be employed to treat industrial wastewater, resulting in a final effluent with very low copper concentrations.


Subject(s)
Copper/isolation & purification , Sewage/analysis , Adsorption , Air , Aluminum Silicates , Bentonite , Hydrogen-Ion Concentration , Industrial Waste , Ultrafiltration/instrumentation , Ultrafiltration/methods , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/isolation & purification , Zeolites
14.
Br J Cancer ; 101(4): 658-65, 2009 Aug 18.
Article in English | MEDLINE | ID: mdl-19638975

ABSTRACT

BACKGROUND: The effect of photodynamic therapy (PDT) on neural cells is important when tumours are within or adjacent to the nervous system. The purpose of this study was to investigate PDT using the photosensitiser, meta-tetrahydroxyphenyl chlorin (mTHPC), on rat neurons and satellite glia, compared with human adenocarcinoma cells (MCF-7). METHODS: Fluorescence microscopy confirmed that mTHPC was incorporated into all three cell types. Sensitivity of cells exposed to mTHPC-PDT (0-10 microg ml(-1)) was determined in a novel 3-dimensional collagen gel culture system. Cell death was quantified using propidium iodide and cell types were distinguished using immunocytochemistry. In some cases, neuron survival was confirmed by measuring subsequent neurite growth in monolayer culture. RESULTS: MCF-7s and satellite glia were significantly more sensitive to PDT than neurons. Importantly, 4 microg ml(-1) mTHPC-PDT caused no significant neuron death compared with untreated controls but was sufficient to elicit substantial cell death in the other cell types. Initially, treatment reduced neurite length; neurons then extended neurites equivalent to those of untreated controls. The protocol was validated using hypericin (0-3 microg ml(-1)), which caused neuron death equivalent to other cell types. CONCLUSION: Neurons in culture can survive mTHPC-PDT under conditions sufficient to kill tumour cells and other nervous system cells.


Subject(s)
Mesoporphyrins/adverse effects , Neurons/drug effects , Photochemotherapy/adverse effects , Photosensitizing Agents/pharmacology , Animals , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Immunohistochemistry , In Vitro Techniques , Microscopy, Fluorescence , Neuroglia/drug effects , Radiation Tolerance , Rats , Rats, Sprague-Dawley
15.
Eur J Clin Invest ; 39 Suppl 2: 74-7, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19335749

ABSTRACT

The endothelin peptides have an important role in the cancer-stromal interactions that promote tumour growth. Endothelin-1 (ET-1), clinically the most investigated endothelin, is a vital agent in the growth and progression of several tumours including prostate, ovarian, colorectal, bladder, breast and lung carcinomas. ET-1 exerts its effects through the activation of two distinct receptors, ET(A) and ET(B). Once activated, these receptors transmit signals via numerous intracellular signalling pathways. The effects of ET receptor stimulation in cancer cells or cancer-associated cells include proliferation, resistance to apoptosis, angiogenesis, migration and subsequent invasion. At present, the manipulation of the endothelin axis within the pre-clinical setting is the subject of intense investigation. Recent studies into ET receptor antagonism have produced interesting results highlighting the fact that these receptors may provide novel targets for a new generation of chemotherapeutic agents in a variety of cancers.


Subject(s)
Antineoplastic Agents/pharmacology , Endothelin Receptor Antagonists , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Endothelin-1/physiology , Female , Humans , Male , Neoplasm Proteins/physiology , Neoplasms/physiopathology , Receptors, Endothelin/physiology , Signal Transduction/physiology
16.
Waste Manag ; 29(1): 204-13, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18558483

ABSTRACT

This article presents the methodology and the results of the performance testing of a prototype system for the production of high quality compost from biodegradable household waste separated at the source. Selected households in three municipalities of the Attica Region in Greece constituted the users of the home composter. The results indicated the effective operational performance of the prototype household composter in practice (use of the system by the householders on a daily basis), as well as the high level of response of the householders in adopting the composting practice in their daily activities as common practice. The compost that was produced in the households was characterized by high quality, which is in accordance with the quality standards that are set for its use. In only a few cases (in the first cycle of the pilot implementation) the quality of the compost was not high due to the fact that some householders were not yet familiar with the use of the composter, but these operational problems were solved and the compost that was later produced was considered high quality.


Subject(s)
Family Characteristics , Refuse Disposal/methods , Soil , Carbon , Conservation of Natural Resources/methods , Data Collection , Hydrogen-Ion Concentration , Nitrogen , Pilot Projects , Surveys and Questionnaires , Water
17.
Waste Manag Res ; 26(3): 267-75, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18649575

ABSTRACT

This paper refers to the management of the construction and demolition (C&D) waste since, according to the EU Waste Strategy, C&D waste is considered to be one of the priority waste streams and appropriate actions need to be taken with respect to its effective management. Initially, the paper presents the state-of-the-art of the problem of C&D waste, including the amount and composition of C&D waste in EU countries, differences in the characteristics of this waste stream depending on its origin, as well as collection and management practices that are applied. A methodology is described for the estimation of the quantities of the waste stream under examination, since in most cases quantitative primary data is not available. Next, the fundamentals for the development of an integrated scheme for the management of C&D waste are presented and discussed, such as appropriate demolition procedures and location of waste management (off-site waste management, on-site waste management, direct on-site recovery, centralized on-site recovery). Finally, taking into consideration all relevant parameters, alternative systems that could be applied for the management of the C&D waste are suggested.


Subject(s)
Construction Materials , Explosions , Waste Management/methods , European Union
18.
Waste Manag ; 28(10): 1941-54, 2008.
Article in English | MEDLINE | ID: mdl-18262405

ABSTRACT

Waste from electrical and electronic equipment (WEEE) constitutes one of the most complicated solid waste streams in terms of its composition, and, as a result, it is difficult to be effectively managed. In view of the environmental problems derived from WEEE management, many countries have established national legislation to improve the reuse, recycling and other forms of recovery of this waste stream so as to apply suitable management schemes. In this work, alternative systems are examined for the WEEE management in Cyprus. These systems are evaluated by developing and applying the Multi-Criteria Decision Making (MCDM) method PROMETHEE. In particular, through this MCDM method, 12 alternative management systems were compared and ranked according to their performance and efficiency. The obtained results show that the management schemes/systems based on partial disassembly are the most suitable for implementation in Cyprus. More specifically, the optimum scenario/system that can be implemented in Cyprus is that of partial disassembly and forwarding of recyclable materials to the native existing market and disposal of the residues at landfill sites.


Subject(s)
Decision Making, Computer-Assisted , Electrical Equipment and Supplies , Waste Management , Waste Products , Cyprus , Decision Support Techniques , Environment , Social Environment , Waste Management/economics
19.
J Hazard Mater ; 151(2-3): 473-80, 2008 Mar 01.
Article in English | MEDLINE | ID: mdl-17624665

ABSTRACT

Plasma gasification/vitrification is an innovative and environmentally friendly method of waste treatment. A demonstration plasma gasification/vitrification unit was developed and installed in Viotia region in order to examine the efficiency of this innovative technology in dealing with hazardous waste. The preliminary results from the trial runs of the plasma unit, as well as the study of the influence of certain parameters in the system performance are presented and analyzed in this paper, contributing to the improvement of the operation performance. Finally, data on the final air emissions and the vitrified ash toxicity characteristic leaching procedure (TCLP) results are provided in order to assess the environmental performance of the system. The produced slag was found to be characterized by extremely low leaching properties and can be utilized as construction material, while the values of the polluting parameters of the air emissions were satisfactory.


Subject(s)
Refuse Disposal/methods , Air Pollutants/analysis , Construction Materials , Electrochemistry/methods , Electrodes , Environmental Monitoring/methods , Environmental Pollution , Equipment Design , Gases , Graphite , Incineration , Metals, Heavy , Oxygen/analysis , Pilot Projects , Water/analysis
20.
Br J Cancer ; 97(4): 502-12, 2007 Aug 20.
Article in English | MEDLINE | ID: mdl-17667930

ABSTRACT

Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; upon light activation the latter induces intracellular release of organelle-bound drug. We investigated whether co-administration of hypericin (photosensitiser) with mitoxantrone (MTZ, chemotherapeutic) plus illumination potentiates cytotoxicity in MDR cancer cells. We mapped the extent of intracellular co-localisation of drug/photosensitiser. We determined whether PCI altered drug-excreting efflux pump P-glycoprotein (Pgp) expression or function in MDR cells. Bladder and breast cancer cells and their Pgp-overexpressing MDR subclones (MGHU1, MGHU1/R, MCF-7, MCF-7/R) were given hypericin/MTZ combinations, with/without blue-light illumination. Pilot experiments determined appropriate sublethal doses for each. Viability was determined by the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay. Intracellular localisation was mapped by confocal microscopy. Pgp expression was detected by immunofluorescence and Pgp function investigated by Rhodamine123 efflux on confocal microscopy. MTZ alone (0.1-0.2 microg ml(-1)) killed up to 89% of drug-sensitive cells; MDR cells exhibited less cytotoxicity (6-28%). Hypericin (0.1-0.2 microM) effects were similar for all cells; light illumination caused none or minimal toxicity. In combination, MTZ /hypericin plus illumination, potentiated MDR cell killing, vs hypericin or MTZ alone. (MGHU1/R: 38.65 and 36.63% increase, P<0.05; MCF-7/R: 80.2 and 46.1% increase, P<0.001). Illumination of combined MTZ/hypericin increased killing by 28.15% (P<0.05 MGHU1/R) compared to dark controls. Intracytoplasmic vesicular co-localisation of MTZ/hypericin was evident before illumination and at serial times post-illumination. MTZ was always found in sensitive cell nuclei, but not in dark resistant cell nuclei. In illuminated resistant cells there was some mobilisation of MTZ into the nucleus. Pgp expression remained unchanged, regardless of drug exposure. Pgp efflux was blocked by the Pgp inhibitor verapamil (positive control) but not impeded by hypericin. The increased killing of MDR cancer cells demonstrated is consistent with PCI. PCI is a promising technique for enhancing treatment efficacy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Breast Neoplasms/drug therapy , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Mitoxantrone/pharmacokinetics , Perylene/analogs & derivatives , Photochemotherapy , Urinary Bladder Neoplasms/drug therapy , Absorption/radiation effects , Anthracenes , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Death/drug effects , Cell Survival , Dose-Response Relationship, Drug , Drug Resistance, Multiple/drug effects , Drug Resistance, Multiple/radiation effects , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/radiation effects , Humans , Mitoxantrone/administration & dosage , Models, Biological , Perylene/administration & dosage , Perylene/pharmacokinetics , Tissue Distribution , Tumor Cells, Cultured , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
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