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D Dinsdale

Publications and source records attributed to D Dinsdale.

At least 19 recordsLinked to original sources
PubMed2006

FLASH is an essential component of Cajal bodies.

Cajal bodies are small nuclear organelles with a number of nuclear functions. Here we show that FLICE-associated huge protein (FLASH), originally described as a component of the apoptosis signaling pathway, is mainly localized in Cajal bodies and is essential for their structure. Reduction in FLASH expression by short hairpin RNA results in disruption of the normal architecture of the Cajal body and relocalization of its components. Because the function of FLASH in the apoptosis receptor signaling pathway has been strongly questioned, we have now identified a clear function for this protein.

Animals↗
PubMed2006

Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice.

Epidermal development requires the transcription factor p63, as p63-/- mice are born dead, without skin. The gene expresses two proteins, one with an amino-terminal transactivation domain (TAp63) and one without (deltaNp63), although their relative contribution to epidermal development is unknown. To address this issue, we reintroduced TAp63alpha and/or deltaNp63alpha under the K5 promoter into p63-/- mice by in vivo genetic complementation. Whereas p63-/- and p63-/-;TA mice showed extremely rare patches of poorly differentiated keratinocytes, p63-/-;deltaN mice showed significant epidermal basal layer formation. Double TAp63alpha/deltaNp63alpha complementation showed greater patches of differentiated skin; at the ultrastructural level, there was clear reformation of a distinct basal membrane and hemidesmosomes. At the molecular level, deltaNp63 regulated expression of genes characteristic of the basal layer (K14), interacting (by Chip, luc assay) with the third p53 consensus site. Conversely, TAp63 transcribed the upper layer's genes (Ets-1, K1, transglutaminases, involucrin). Therefore, the two p63 isoforms appear to play distinct cooperative roles in epidermal formation.

Animals↗
PubMed2003

Kinetics of an intratracheally administered chromium catalyst in rats.

Chromium-based catalysts are used for the synthesis of polyethylene, but little is known about the hazard and biomonitoring possibilities of this type of chromium for workers who may be occupationally exposed to such compounds. Therefore, the bioavailability and toxicokinetics of chromium were studied in male Wistar rats after a single intratracheal instillation (2 ml/kg body weight) of various doses (1, 5, or 25 mg/kg body weight) of the catalyst (approximately 1% chromium bound to an amorphous silica matrix), either before (CAT-Cr[III]) or after (CAT-Cr[VI]) heat treatment. The results were compared with those of equivalent amounts of two chromium salts (CrCl(3) and K(2) Cr(2) O (7). Each dose group was composed of three rats. The concentration of chromium was determined by atomic absorption spectrometry in urine (collected daily for 7 d) and in plasma, erythrocytes, lung, and liver tissue obtained 2 d (only highest concentration) and 7 d after dosing. On d 2, a significant increase in lung weight was found in the animals treated with the highest dose of the hexavalent Cr products. On d 7, on the basis of body weights, lung weights, and lung histology, there was no overt toxicity, except after the highest dose of CAT-Cr(VI). The elimination of all forms of chromium was apparently monoexponential, with calculated half-life elimination times in urine of 4-11 h for Cr(III) (CAT-Cr[III] and CrCl3 ) and 8-21 h for Cr(VI) (CAT-Cr[VI] and K(2) Cr(2) O(7). On d 2, the erythro-cytes Cr concentrations were significantly higher for the hexavalent Cr products than for the trivalent Cr products. After 7 d, the erythrocytes Cr concentrations were significantly increased above control values (3 microg/L) only in rats treated with the 2 highest doses of Cr( VI) compounds (12 and 64 microg/L for K(2) Cr(2) O(7), and 14 and 79 microg/L for CAT-Cr[VI]). The present study shows that intratracheally instilled Cr(VI) and Cr(III) have different toxicokinetic profiles and that the Cr(VI) catalyst has the same bioavailability and excretion kinetics as a water-soluble Cr(VI) salt. Exposure to chromium compounds could be monitored by measuring Cr concen-trations in urine (shortly after exposure) and in erythrocytes (also at later time points after high Cr[VI] exposure).

Animals↗
PubMed2002

Passage of inhaled particles into the blood circulation in humans.

BACKGROUND: Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. METHODS AND RESULTS: To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine (99m)Technetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized (99m)Tc, ie, pertechnetate, there was also a species corresponding to particle-bound (99m)Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. CONCLUSIONS: We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

Adult↗
PubMed2001

Cell-specific loss of cytochrome P450 2B1 in rat lung following treatment with pneumotoxic and non-pneumotoxic trialkylphosphorothioates.

This study was designed to test the hypothesis that the reduction in cytochrome P450 (CYP) 2B1 content and activity of rat lung microsomes, following dosing with pneumotoxic trimethylphosphorothioates, results from damage to specific cell types. Of the lung cells exhibiting immunolabelling for CYP2B1, only type I cells showed signs of susceptibility to the pneumotoxins O,O.S-trimethylphosphorothioate and O,S,S-trimethylphosphorodithioate. While most type I cells became necrotic, type II and Clara cells showed no signs of injury, despite their gradual loss of CYP2B1, as detected by immunogold labelling. This loss of labelling was accompanied by a 75% reduction in the immunoreactive CYP2B1 content and an 85% reduction in pentoxyresorufin O-dealkylase activity in lung microsomes. In contrast, the non-pneumotoxic analogue O,O,S-trimethylphosphorodithioate, differing from O,O,S-trimethylphosphorothioate by only the presence of a P = S rather than a P = O moiety, caused an even more rapid fall in pulmonary pentoxyresorufin O-dealkylase activity, but only a slight reduction in the microsomal content of CYP2B1. The recovery of this activity began within 12 hr of dosing. O,O,S-Trimethylphosphorodithioate, which acts as a suicidal inhibitor of pulmonary CYP2B1, did not cause any detectable lung injury or increase in cell division. These results are consistent with the initial reduction in both enzyme content and activity caused by the P = O - containing pneumotoxins resulting, almost entirely, from death of type I cells. Subsequent reductions that occur long after clearance of the toxin may be exacerbated by the onset of mitosis in Clara and type II cells.

Animals↗
PubMed2001

A novel synthetic erionite fibre radiolabelled with (57)Co.

The aim was to produce a radiolabelled fibre suitable for long-term carcinogenesis studies. To this end, we have successfully synthesised erionite fibres by a method adapted to incorporate (57)Co into the crystal framework. Morphologically the fibres are straight, of median length 2.5 microm, with 11% of fibres > 8 microm long, and median width 0.32 microm. These values are comparable to natural Oregon erionite. Autoradiography confirmed that the (57)Co was associated with the fibres themselves. The stability of the radiolabel in vivo was examined by instilling 1 mg of synthetic erionite into the lungs of F-344 rats. About half of the thoracic content of (57)Co was cleared in the first week, and over the following 5 weeks the remainder was cleared slowly with a half-time of 120 days. After 6 weeks the urinary excretion of (57)Co was only 0.054% of the initial lung content per day. This represented fibre dissolution plus any leaching of (57)Co from the fibres. It can be concluded that the (57)Co is bound into the erionite fibres with sufficient stability in vivo for studying their effects in relation to translocation to the pleura.

Animals↗
PubMed2001

Proteasome inhibitor-induced apoptosis of B-chronic lymphocytic leukaemia cells involves cytochrome c release and caspase activation, accompanied by formation of an approximately 700 kDa Apaf-1 containing apoptosome complex.

Proteasome inhibitors, including lactacystin and MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal), potently induce apoptosis in leukaemic B cells from patients with B cell chronic lymphocytic leukaemia (B-CLL). This pro-apoptotic effect occurs in cells from patients at all stages of the disease, including those resistant to conventional chemotherapy, suggesting that proteasome inhibitors may be useful for treatment of B-CLL. Following initial inhibition of proteasomal activity, these agents induce mitochondrial cytochrome c release and caspase-dependent apoptosis, involving cleavage/activation of caspases -2, -3, -7, -8 and -9. Pre-treatment with the cell permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe)fluoromethyl ketone (Z-VAD.fmk), did not prevent the release of cytochrome c or partial processing of caspase-9 but prevented activation of effector caspases and the induction of apoptosis. These results suggest that the release of cytochrome c is caspase independent and that caspase-9 is the initiator caspase in proteasome inhibitor-induced apoptosis of B-CLL cells. Activation of B-CLL lysates with dATP results in the formation of an approximately 700 kDa caspase-activating apoptosome complex containing Apaf-1. We describe for the first time the formation of a similar approximately 700 kDa caspase-activating apoptosome complex in B-CLL cells induced to undergo apoptosis by proteasome inhibitors.

Acetylcysteine↗
PubMed2001

Ultrafine particles in alveolar macrophages from normal children.

BACKGROUND: Increased ambient levels of particulate matter <10 microm (PM(10)) from fossil fuel combustion are associated with an increased prevalence of respiratory symptoms in children. However, it is unknown whether, and to what extent, pollutant particles penetrate the paediatric lower airway. The capacity of alveolar macrophages (AM) to phagocytose inhaled material was used to directly assess exposure of normal children to particles. METHODS: AM from 22 children aged 3 months to 16 years with no respiratory symptoms were obtained by non-bronchoscopic bronchoalveolar lavage prior to elective surgery. In each child the size and composition of environmental particles within single sections from 100 separate AM was determined by electron microscopy and microanalysis. RESULTS: Single and clusters of particles were seen in AM from all children. The percentage of particle-containing AM ranged from 1% to 16% per child. Particles consisted of a carbonaceous core and all were ultrafine (<0.1 microm). Other elements such as metals and silicon were not detected. The percentage of particle-containing AM did not change with age, but was increased in children whose parents lived on a main road compared with those living on a quiet residential road (median 10% v 3%, p = 0.014). CONCLUSIONS: All children had AM containing ultrafine carbonaceous particles. The predominant source of these particles is most likely to be from the combustion of fossil fuels.

Adolescent↗
PubMed2000

Active caspases and cleaved cytokeratins are sequestered into cytoplasmic inclusions in TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) -induced apoptosis, in transformed human breast epithelial MCF-7 cells, resulted in a time-dependent activation of the initiator caspases-8 and -9 and the effector caspase-7. Cleavage of caspase-8 and its preferred substrate, Bid, preceded processing of caspases-7 and -9, indicating that caspase-8 is the apical initiator caspase in TRAIL-induced apoptosis. Using transient transfection of COOH-terminal-tagged green fluorescent protein fusion constructs, caspases-3, -7, and -8 were localized throughout the cytoplasm of MCF-7 cells. TRAIL-induced apoptosis resulted in activation of caspases-3 and -7, and the redistribution of most of their detectable catalytically active small subunits into large spheroidal cytoplasmic inclusions, which lacked a limiting membrane. These inclusions, which were also induced in untransfected cells, contained cytokeratins 8, 18, and 19, together with both a phosphorylated form and a caspase-cleavage fragment of cytokeratin 18. Similarly, in untransfected breast HBL100 and lung A549 epithelial cells, TRAIL induced the formation of cytoplasmic inclusions that contained cleaved cytokeratin 18 and colocalized with active endogenous caspase-3. We propose that effector caspase-mediated cleavage of cytokeratins, resulting in disassembly of the cytoskeleton and formation of cytoplasmic inclusions, may be a characteristic feature of epithelial cell apoptosis.

Apoptosis↗
PubMed2000

In vitro cytotoxicity of various forms of cobalt for rat alveolar macrophages and type II pneumocytes.

It has been shown that cobalt (Co) and the mixture cobalt-tungsten carbide (CoWC) are cytotoxic for alveolar macrophages (AM) and alveolar type II cells (AT-II), but the exact mechanisms of toxicity are not entirely elucidated. In this study, we exposed primary cultures of AT-II and AM, in vitro, to different forms of Co (Co particles, CoWC particles, CoCl(2)) and assessed cell damage using the dimethylthiazol diphenyl tetrazolium bromide test. In some experiments, inserts were used to separate the particles from the cells. The results show that AT-II are twice as sensitive to the effects of 100 microg Co particles/well (1.88 cm(2)) than AM. For this latter cell type, the presence of WC almost doubled (at 25 microg Co/well) the toxic effects compared to pure Co, but this synergy between Co and WC only occurred if the particles were in close contact with the cells. Lactalbumin and, to a lesser degree, EDTA were able to reduce the toxicity of Co, CoWC, and CoCl(2) for AT-II and AM. CoCl(2) showed a similar toxicity for AT-II and AM. The use of Co-conditioned medium revealed that Co particles are "aged" after having been incubated for 24 h in an aqueous medium and are then no longer able to cause the same degree of cell damage as fresh Co particles (71 versus 15% viability for 100 microg Co/well). The time course of the toxicity of the different forms of Co for AT-II and AM showed different patterns in causing cell damage, suggesting different action mechanisms. Evaluation of cell damage by electron microscopy was consistent with biochemical indices. Overall, our results indicate that the Co ion does play a role in the toxicity of both Co particles and CoWC particles.

Animals↗
PubMed2000

Release of hydrogen peroxide by rat type II pneumocytes in the prolonged culture.

Type II pneumocytes (T II pneumocytes) produce hydrogen peroxide (H(2)O(2)), which may be potentially dangerous for the lung. These cells in culture differentiate to type I-like pneumocytes and it may reflect the differentiation which follows the injury of alveolar epithelium. This work was undertaken to estimate the H(2)O(2) release by T II pneumocytes, freshly isolated and cultured up to 8 days. The light and electron microscopy evaluation confirmed the differentiation of T II pneumocytes to type I-like cells. The release of H(2)O(2), estimated spectrofluorimetrically as homovanillic acid oxidation product obtained in the presence of horseradish peroxidase, was significantly higher at day 4 (0.63+/-0. 68nmol/mg protein/min, P</=0.02) and 6 (0.46+/-0.31, P</=0.001) compared to fresh cells (0.15+/-0.08). Phorbol esters increased H(2)O(2) release at day 2 (0.39+/-0.22 vs 0.16+/-0.08, P</=0.02) and the inhibition of protein kinase C resulted in the decrease at day 2 (0.14+/-0.06 vs 0.07+/-0.02, P</=0.025), day 6, (0.49+/-0.25 vs 0. 15+/-0.08, P</=0.005) and 8 (0.76+/-0.63 vs 0.23+/-0.29, P</=0.02). Inhibition of intracellular catalase resulted in a significant increase only at day 2 (0.23+/-0.1 vs 0.15+/-0.09, P</=0.05). Inhibition of mitochondrial respiratory chain decreased H(2)O(2) release at day 2 (0.13+/-0.11 vs 0.07+/-0.07, P</=0.002) and 4 (0. 75+/-0.88 vs 0.61+/-0.85, P</=0.002). These results indicate that alveolar epithelium may be a source of potentially dangerous ROS and that the cell differentiation is accompanied by the increase of H(2)O(2) production. Both mitochondrial respiratory chain and membrane-bound NADPH-oxidase may be responsible for the production of H(2)O(2) by T II pneumocytes.

Animals↗
PubMed2000

Pulmonary availability of isotretinoin in rats after inhalation of a powder aerosol.

Repeated oral administration of chemopreventive retinoids such as isotretinoin over extended periods of time is associated with intolerable systemic toxicity. Here isotretinoin was formulated as a powder aerosol, and its delivery to the lungs of rats was studied with the aim to explore the possibility of minimizing adverse effects associated with its oral administration. Rats received isotretinoin orally (0.5, 1 or 10 mg kg(-1)) or by inhalation (theoretical dose approximately 1 or approximately 10 mg kg(-1)) in a nose-only inhalation chamber. Isotretinoin was quantitated by high-pressure liquid chromatography in plasma and lung tissue. The ratios of mean area of concentration-vs-time curve (AUC) values in the lungs over mean AUCs in the plasma for isotretinoin following single or repeated aerosol exposure surpassed those determined for the oral route by factors of between two (single low-dose) and five (single high-dose). Similarly, the equivalent ratios for the maximal peak concentrations in lungs and plasma obtained after aerosol exposure consistently exceeded those seen after oral administration, suggesting that lungs were exposed to higher isotretinoin concentrations after aerosol inhalation than after oral administration of similar doses. Repeated high doses of isotretinoin by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. The results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lungs.

Administration, Inhalation↗
PubMed1999

Redistribution of cytochrome c precedes the caspase-dependent formation of ultracondensed mitochondria, with a reduced inner membrane potential, in apoptotic monocytes.

Apoptosis was induced in human monocytic THP.1 cells by the use of chemicals with disparate mechanisms of action. Apoptotic cells were characterized by a reduced inner mitochondrial membrane potential, increased cytosolic cytochrome c, ultracondensed mitochondria, condensed chromatin, cytoplasmic inclusions of beta-actin, and fragmentation of the Golgi apparatus. All of these changes, except the release of cytochrome c, were prevented by caspase inhibition. Cells were separated into two populations, with either normal or low inner mitochondrial membrane potential, using fluorescence-activated cell sorting. Ultracondensed mitochondria were observed only in the cells with low inner mitochondrial membrane potential, whereas noncondensed mitochondria were found in the cells with a normal inner mitochondrial membrane potential. We have demonstrated a sequence of related biochemical and ultrastructural changes, commencing with the release of mitochondrial cytochrome c, followed by activation of caspases and a reduction of inner mitochondrial membrane potential. These changes involved the formation of ultracondensed but not swollen mitochondria. Thus the release of mitochondrial cytochrome c was not the result of the mitochondrial permeability transition, reduction of inner mitochondrial membrane potential, or rupture of the outer mitochondrial membrane. Discontinuities in the outer membrane of ultracondensed mitochondria may, however, facilitate the further release of caspase-activating proteins, thereby amplifying the apoptotic process.

Actins↗
PubMed1999

A comparative study of the isolation of type II epithelial cells from rat, hamster, pig and human lung tissue.

Data is reported on the reproducibility and purity of alveolar type II cell isolations from 4 species. Human and pig type II cells were isolated using a tissue slice method to remove blood and contaminating cells, whilst rat and hamster cells were isolated using the method of protease instillation. All cells were purified on Percoll gradients and by differential attachment. Cell type purity was assessed by phase contrast microscopy, electron microscopy (EM), percentage of cells alkaline phosphatase (AP) positive and percentage of cells staining strongly for NADPH dependent nitro blue tetrazolium reductase (NBT). These enzymes are considered as markers for type II and Clara cells respectively. The purity of all cell preparations was enhanced following 24 h culture on a biomatrix and whilst plating efficiency was similar for all species, the human tissue consistently yielded the highest purity of type II cells. All cells with lamellar bodies did not contain AP, and activity was variable between species. Further studies are needed to determine if NBT is equally nonspecific as a cell marker enzyme. In summary, sufficient type II cells of high purity can be isolated thus permitting interspecies comparative studies to investigate the effects of selective and non-specific pulmonary toxins, but more specific marker enzymes are required to identify Type II and Clara cells.

Alkaline Phosphatase↗
PubMed1998

Selective induction of apoptosis in mouse and human lung epithelial cell lines by the tert-butyl hydroxylated metabolite of butylated hydroxytoluene: a proposed role in tumor promotion.

Butylated hydroxytoluene (BHT) causes lung injury in mice and promotes tumor formation. Hydroxylation of a tert-butyl group on BHT to yield the metabolite, 6-tert-butyl-2-[2'-(2'-hydroxymethyl)-propyl]-4-methylphenol (BHTOH), may be required. BHTOH is more potent than BHT on an equimolar basis in causing lung damage, enhancing lung tumor development, killing isolated bronchiolar non-ciliated Clara cells, and inhibiting lung epithelial gap junctional intercellular communication. One mechanism proposed for tumor promoting agents is selective cytotoxicity; killing normal cells allows uninhibited clonal expansion of neighboring initiated cells. We compared the abilities of BHT, BHTOH, and other BHT metabolites to kill non-tumorigenic and tumorigenic mouse and human lung cell lines, and examined the contribution of apoptosis to this cytotoxicity. These cells lack the cytochrome P450 2B isozyme necessary for converting BHT to BHTOH. BHTOH and 4-hydroperoxy-4-methyl-2,6-di-tert-butyl-2,5-cyclohex-adienone+ ++ (BHTOOH) were most toxic, BHT and 2,6-di-tert-butyl-1,4-benzoquinone (BHTQu) were less potent, and 4-methyl BHT metabolites that are not pneumotoxic were ineffective. BHTOH most strongly induced apoptosis, based on nuclear condensation and transmission electron microscopy. Non-tumorigenic cells were as susceptible to cell death as the neoplastic cell lines when apoptosis and necrosis are not distinguished, but more sensitive to BHTOH-induced apoptosis. An apoptotic mechanism may underlie the lung tumor promoting actions of BHTOH.

Animals↗
PubMed1998

Apoptosis, in human monocytic THP.1 cells, results in the release of cytochrome c from mitochondria prior to their ultracondensation, formation of outer membrane discontinuities and reduction in inner membrane potential.

Induction of apoptosis in human monocytic THP.1 cells by etoposide or N-tosyl-L-phenylalanyl chloromethyl ketone resulted in release of mitochondrial cytochrome c, formation of ultracondensed mitochondria, development of outer mitochondrial membrane discontinuities and a reduction in mitochondrial membrane potential (delta psi m), as well as externalisation of phosphatidylserine, caspase-3 and -7 activation, proteolysis of poly(ADP-ribose) polymerase and lamin B1. The caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone inhibited all these ultrastructural and biochemical characteristics of apoptosis except for the release of cytochrome c. Release of mitochondrial cytochrome c was a late event in non-apoptotic cell death occurring after commitment to cell death and without caspase activation. Thus apoptosis is characterised by release of mitochondrial cytochrome c prior to formation of ultracondensed mitochondria and a reduction in delta psi m and by a mechanism independent of rupture of the outer mitochondrial membrane.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Human lung carcinoma cell line DLKP contains 3 distinct subpopulations with different growth and attachment properties.

Many human solid tumours, particularly lung tumours, contain different subpopulations, the presence of which can complicate diagnosis and treatment, yet few models exist for in vitro studies. We have found that DLKP, a human lung cell line established from a tumour histologically diagnosed as a 'poorly differentiated squamous carcinoma', contains 3 morphologically distinct populations. Three clones corresponding to these populations were established from the parental DLKP cells. Confirmation that the clones were derived from the parental population was obtained by DNA fingerprinting. The clones were designated M (mesenchymallike), I (intermediate) and SQ (squamous). On prolonged subculture, SQ and M can each interconvert with I, but SQ and M do not interconvert. We investigated the growth patterns of these isolated populations in monolayer culture, soft agar, spinner flasks and serum-free medium. In all but the latter assay, the parental DLKP cells grew faster than each of the clones, indicating some form of physiological co-operation between the clones. The growth of the clones themselves varied under the different assay conditions (DLKP-I showing greatest growth in monolayer, in serum-containing and serum-free media but, surprisingly, being unable to grow in soft agar, unlike the SQ and M clones). Addition of fibronectin permitted growth of DLKP-M and DLKP-SQ in serum-free medium at equivalent rates to those of DLKP and DLKP-I. In some cases, morphological adaptation to specific growth conditions was observed. Variation between the clones was also evident in their respective chromosome numbers (with the M clone being predominantly hyperdiploid and the other clones predominantly hypertetraploid) and in their ability to adhere to extracellular matrix proteins, with DLKP-M showing most rapid attachment. Electrical resistance studies revealed the absence of tight junctions from the parental line and clonal subpopulations. Extensive immunohistological studies showed that neither DLKP nor the clones express cytokeratin or any other epithelial marker examined, but neuroendocrine markers were present. Further analysis of these different clonal populations may help to reveal some of the mechanisms involved in lung tumour development and progression.

Biomarkers↗