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Sample records for ascites tumour cells

  1. Stability of artemisinin in aqueous environments : Impact on its cytotoxic action to Ehrlich ascites tumour cells

    NARCIS (Netherlands)

    Beekman, AC; Woerdenbag, HJ; Van Uden, W; Pras, N; Konings, AWT; Wikstrom, HV

    1997-01-01

    We have recently shown artemisinin to be cytotoxic against Ehrlich ascites tumour cells. The aim of this study was to investigate the stability of this compound in the aqueous environment of the in-vitro Ehrlich ascites tumour cell system (RPMI 1640 cell culture medium supplemented with 10% foetal b

  2. L-lactate transport in Ehrlich ascites-tumour cells.

    Science.gov (United States)

    Spencer, T L; Lehninger, A L

    1976-02-15

    Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an "inhibitor stop" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids. PMID:7237

  3. Transport of calcium ions by Ehrlich ascites-tumour cells.

    Science.gov (United States)

    Landry, Y; Lehninger, A L

    1976-08-15

    Ehrlich ascites-tumour cells accumulate Ca2+ when incubated aerobically with succinate, phosphate and rotenone, as revealed by isotopic and atomic-absorption measurements. Ca2+ does not stimulate oxygen consumption by carefully prepared Ehrlich cells, but des so when the cells are placed in a hypo-osmotic medium. Neither glutamate nor malate support Ca2+ uptake in 'intact' Ehrlich cells, nor does the endogenous NAD-linked respiration. Ca2+ uptake is completely dependent on mitochondrial energy-coupling mechansims. It was an unexpected finding that maximal Ca2+ uptake supported by succinate requires rotenone, which blocks oxidation of enogenous NAD-linked substrates. Phosphate functions as co-anion for entry of Ca2+. Ca2+ uptake is also supported by extra-cellular ATP; no other nucleoside 5'-di- or tri-phosphate was active. The accumulation of Ca2+ apparently takes place in the mitochondria, since oligomycin and atractyloside inhibit ATP-supported Ca2+ uptake. Glycolysis does not support Ca2+ uptake. Neither free mitochondria released from disrupted cells nor permeability-damaged cells capable of absorbing Trypan Blue were responsible for any large fraction of the total observed energy-coupled Ca2+ uptake. The observations reported also indicate that electron flow through energy-conserving site 1 promotes Ca2+ release from Ehrlich cells and that extra-cellular ATP increase permeability of the cell membrane, allowing both ATP and Ca2+ to enter the cells more readily. PMID:988829

  4. The evaluation of in vitro effect of daunorubicin and tamoxifen in ehrlich ascites tumour (EAT) cells

    International Nuclear Information System (INIS)

    In the most countries, breast cancer is still the most important cancer among women. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of Ehrlich Ascites Tumour (EAT) cells, initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is estrogen receptor positive was used. An anthracycline-derived antibiotic, Daunorubicin (DNR, Cerubidine) is one of the clinically used anticancer drugs. DNR has been used alone or in combination with other cytotoxic agents against a variety of animal and human tumours. In vitro cell culture studies show that DNR enters the cell nuclei, inhibits nucleic acid synthesis, and arrest cell division. Tamoxifen (TAM, Nolvadex) is a semi-synthetical estrogen antagonist, used in the management of pre and post menopausal breast cancer. This drug bind to intracellular estrogen receptors, and prevents endogenous estrogens from binding to their own receptors. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of EAT cells initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is Estrogen Receptor (+) was used. Estrogen Receptor levels were studied by the methods of Lippman and Huff and Raynaud et al. with minor modifications. Estrogen Receptor activity as demonstrated by dextran-coated charcoal technique is closely correlated with the clinical ability of Tamoxifen to inhibit tumour growth

  5. DNA double strand breaks in Ehrlich ascites tumour cells at low doses of X-rays

    International Nuclear Information System (INIS)

    DNA double strand breaks (dsb) were determined in Ehrlich ascites tumour cells at doses down to 5 Gy. Sedimentation profiles were analysed using a computer program and the number of dsb was determined by simulation of random breaks in the mass distribution of the control sample and by comparison of this simulated profile with that of the irradiated one. The number of dsb formed was proportional to X-ray dose in the range of 5 to 2000 Gy. The induction per dose was found to be nmsub(r)-1 D-1=(11.7+-2) x 10-12 Gy-1. (author)

  6. Energy metabolism and ATP turnover time during the cell cycle in roentgen irradiated Ehrlich ascites tumour cells

    International Nuclear Information System (INIS)

    The cell-cycle related energy metabolism after roentgen irradiation of in vivo growing Ehrlich ascites tumour cells was investigated in cell fractions obtained by elutriator centrifuging. The oxygen consumption and the lactate and pyruvate production, measured in vitro after 4.5, 5 and 9 Gy up to 24 h, were undisturbed, while the decrease in the in vivo ATP content was dose-independent in all parts of the cell cycle. On the basis of these data the ATP turnover time was found to be decreased. The decrease in the ATP content is considered to be less likely to be due to membrane leakage or increased ATP consumption than to reduced ATP production. Since in vitro incubation normalizes the ATP content, it is suggested that environmental factors in the ascites liquid after irradiation cause a decrease in the ATP production. Low ATP contents of the cells do not appear to influence the irradiation-induced changes in the cell flow through the cell cycle. (Auth.)

  7. Protective effect of pantothenic acid and related compounds against permeabilization of Ehrlich ascites tumour cells by digitonin.

    Science.gov (United States)

    Slyshenkov, V S; Rakowska, M; Wojtczak, L

    1996-01-01

    Preincubation of Ehrlich ascites tumour cells with millimolar concentrations of pantothenic acid, pantothenol or pantethine, but not with homopantothenic acid, at 22 degrees C or 32 degrees C, but not at 0 degrees C, makes the plasma membrane more resistant to the damaging effect of submillimolar concentrations of digitonin. It is proposed that this increased resistance is due to the increased rate of cholesterol biosynthesis. In fact, incorporation of [14C]acetate into cholesterol is by 45% increased in the cells preincubated with pantothenic acid; this probably reflects elevation of the content of CoA in such cells [Slyshenkov, V.S., Rakowska, M., Moiseenok, A.G. & Wojtczak, L. (1995) Free Radical Biol. Med. 19, 767-772]. PMID:8862188

  8. Photodynamic therapy of ascites tumours within the peritoneal cavity.

    OpenAIRE

    Tochner, Z.; Mitchell, J B; SMITH, P.; Harrington, F.; Glatstein, E.; Russo, D; Russo, A.

    1986-01-01

    A murine ascites tumour was treated with intraperitoneal haematoporphyrin derivative (HPD) and laser light (10mW, 514nm, Argon laser). HPD was given intraperitoneally 2 hours before 16 minute laser treatment. Uptake studies 2 hours after HPD injection showed 5-12 fold greater concentration of HPD in tumour cells than in 4 different normal tissues. A total of four HPD/laser treatments, given at 2 day intervals, resulted in 100% complete response; the cure rate was 85%. This study illustrates t...

  9. On the action of radioprotective agents on the endogenous serotonin content and radiosensitivity of isolated Ehrlich ascites tumour and E. coli B. cells

    International Nuclear Information System (INIS)

    At a higher radioresistance level attained by incubation of isolated Ehrlich ascites tumour and E. coli B. cells with MEA or noradrenaline, the endogenous serotonin content of these cells was found to increase. The extent of radioresistance increase and the serotonin content of the cells were interrelated, i.e. washing the protector off cells decreased both the radioresistance and the content of endogenous serotonin. It is concluded that radioresistance of cells is connected with the content of biologically active substances (serotonin) that possess radioprotective action

  10. Changes in energy metabolism following roentgen irradiation of in vivo growing Ehrlich ascites tumour cells studied by 31P magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    The energy metabolism in Ehrlich ascites tumour cells following in vivo irradiation of a dose of 5.0 Gy was studied in vitro in their ascites fluid up to 48 hours using 31P magnetic resonance spectroscopy measuring ATP, ADP and inorganic phosphate (Psub(i)). The results are also related to radiation induced changes in cell cycle composition. ATP was reduced by more than 50 per cent 20 to 24 hours after irradiation but normalized at 48 hours. ADP was reduced to about half the normal level 24 to 48 hours after irradiation. When the ATP and ADP had reduced levels, the inorganic phosphate increased correspondingly. Addition of glucose to the ascites cell suspension at the time of minimum ATP level immediately raised the ATP:Psub(i) ratio. Since the glucose concentrations in blood and in ascites fluid following irradiation were also reduced, lack of glucose for energy production might have been a major contributing factor for the reduced ATP production. (orig.)

  11. A cell shrinkage-induced non-selective cation conductance with a novel pharmacology in Ehrlich-Lettre-ascites tumour cells

    DEFF Research Database (Denmark)

    Lawonn, Peter; Hoffmann, Else K; Hougaard, Charlotte;

    2003-01-01

    In whole-cell recordings on Ehrlich-Lettre-ascites tumour (ELA) cells, the shrinkage-induced activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(choline):P(NMDG) of 1.00:0.97:0.88:0.03:0.01 was observed. In order of potency, this conductance was blocked by Gd(3+)=benzamil......>amiloride>ethyl-isopropyl-amiloride (EIPA). In patch-clamp studies using the cell-attached configuration, a 14 pS channel became detectable that was reversibly activated upon hypertonic cell shrinkage. It is concluded that ELA cells express a shrinkage-induced cation channel that may reflect a molecular link between amiloride...

  12. Cytokinetic Control Mechanisms in Ehrlich Ascites Tumour Growth

    International Nuclear Information System (INIS)

    Ehrlich ascites tumour in mice was studied as a model system to elucidate the cytokinetic mechanisms controlling growth of cell populations. The basis for a retardation in growth rate during tumour development was determined with the aid of 3H-thymidine labelling and autoradiography. Three possible cytokinetic variables in growth regulation, namely, duration of the mitotic cell cycle, fraction of the cycling cells in the population (growth fraction) and rate of cell loss, were measured at different stages of growth. It was concluded that a deceleration in growth was a result of (1) a gradual prolongation of the cell cycle and its components and (2) a progressive decline in the growth fraction. Rate of cell loss did not appreciably change during most of the growth. It was also found that the total cell mass rather than the tumour age dictated the growth rate at any instant over a considerable range of growth. Non-cycling cells were found to resume cycle when a fraction of an old tumour was transplanted in new hosts, 3H-thymidine labelling combined with microspectrophotometric estimates of cellular DNA was utilized to locate the stages at which a cell cycle could be suspended or resumed. It was found that decycling or recycling could occur only after mitosis and before DNA synthesis; non-cycling (G0) state resembled G1, which was absent in the proliferating tumour cells. These findings are relevant to a further understanding of the molecular events leading to the initiation or suspension of a cell cycle. They are also pertinent to formulating a rationale for tumour therapy — for example with radiation — when coupled with the existing knowledge of the relative sensitivity of cells at different stages of cycle. (author)

  13. Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide

    DEFF Research Database (Denmark)

    Nielsen, D; Maare, C; Eriksen, J;

    2000-01-01

    -extractable immunoreactive topoisomerase IIalpha and beta in EHR2/VP16 was reduced by 30-40% relative to that in EHR2. The multidrug resistance-associated protein (MRP) mRNA was increased 20-fold in EHR2/VP16 as compared with EHR2, whereas the expression of P-glycoprotein was unchanged. In EHR2/VP16, the steady......M. ATPase activity was slightly stimulated by daunorubicin, whereas vinblastine, verapamil, and cyclosporin A had no effect. In conclusion, development of resistance to VP16 in EHR2 is accompanied by a significant reduction in topoisomerase II (alpha and beta) and by increased expression of MRP mRNA (20......-fold). MRP displays several points of resemblance to P-glycoprotein in its mode of action: 1) like P-glycoprotein, MRP causes resistance to a range of hydrophobic drugs; 2) MRP decreases drug accumulation in the cells and this decrease is abolished by omission of energy; and 3) MRP increases efflux of...

  14. Effect of 2-deoxy-D-glucose on DNA double strand break repair, cell survival and energy metabolism in euoxic Ehrlich ascites tumour cells

    International Nuclear Information System (INIS)

    Effects of 2-deoxy-D-glucose (2-DG) on DNA double strand break (dsb) repair, cell survival and on the energy metabolism were investigated in exponentially growing Ehrlich ascites tumour (EAT) cells. Cells in suspension were exposed to 40 Gy of X-rays and allowed to repair (up to 4h) with or without 2-DG at 37oC. DNA dsb rejoining was measured by means of clamped homogeneous electric field (CHEF), a pulsed field gel electrophoresis technique. The fraction of activity released (FAR) during electrophoresis (DNA associated 14C-thymidine) was used as a parameter to determine the number of dsb present in the DNA. Biphasic kinetics for dsb repair were observed. The presence of 2-DG significantly inhibited the slow component of dsb repair. The presence of 2-DG also enhanced radiation-induced cell killing. ATP content of cells was measured by a bioluminescence method. ATP content in exponentially growing cells was about 4 pg per cell. The level of ATP was reduced by 50% in presence of 2-DG (C2-DG/CG = 1.0). (author)

  15. Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

    Science.gov (United States)

    Smina, T P; Mathew, J; Janardhanan, K K

    2016-01-01

    G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities. PMID:27188870

  16. Some novel aspects of the relationship between the amino acid gradient and the sodium electrochemical gradient in mouse ascites tumour cells.

    Science.gov (United States)

    Eddy, A A; Hopkins, P; Johnson, E

    1988-02-01

    Accumulation of 2-aminoisobutyrate by mouse ascites tumour cells was studied in circumstances where nigericin reversed the normal direction of the Na+ concentration gradient. The membrane potential (delta psi) was assayed using oxonol V as a voltage-sensitive probe. The amino acid gradient (delta mu A) that formed did not significantly exceed the likely magnitude of the Na+ electrochemical gradient when this was in the range 2-6 kJ mol-1. When delta-Na mu increased up to 11 kJ mol-1, delta mu A was almost constant at 7-8 kJ mol-1. The observations indicate that when delta psi is large changes in cellular [Na+] in the range 16-80 mM scarcely affect delta mu A. PMID:3358997

  17. Radiation-induced DNA double strand breaks in Ehrlich ascites tumour cells and their possible effects on cell survival

    International Nuclear Information System (INIS)

    A method to prepare high-molecular, pure DNA with the aid of enzymes, detergents, and heat treatment is presented. A sedimentation technique with neutral density gradients has been introduced which permits mass separation and molecular mass analysis of high-molecular DNA (msub(r) 10). Using this method, the induction of DNA double strand breaks (DSB) in the dose range between 10 Gy <= D <= 100 Gy has been measured. Further, the induction of DSB in dependence of the radiation quality has been studied. A correlation between DSB induction and cell survival was not found for any type of radiation investigated. DNA repair was measured in a multitude of repair conditions. The repair kinetics shows that the ''apparent'' DNA fraction is negligible. A large number of DSB was found to be repaired. The effects of some repair inhibitors have been investigated. DSB repair after cell plating on agar was proved. This factor has been underestimated in all former estimates of DSB influence on cell survival. It has been shown that DSB in living cells cannot be tolerated. There was no indication of biologically irrelevant DSB. (orig./AJ)

  18. Renal cell carcinoma presenting with malignant ascites

    OpenAIRE

    Jennison, Erica; Wathuge, Gayathri W; Gorard, David A

    2015-01-01

    Lesson It is rare for renal cell carcinoma to involve the peritoneum and cause malignant ascites. Furthermore, it is uncommon for malignant ascites to be a presenting feature of this cancer. An unusual case of renal cell carcinoma presenting with malignant ascites is reported, and its response to sunitinib described.

  19. Characterisation of non-P-glycoprotein multidrug-resistant Ehrlich ascites tumour cells selected for resistance to mitoxantrone

    DEFF Research Database (Denmark)

    Nielsen, D; Eriksen, J; Maare, C;

    2000-01-01

    (i) value for P-glycoprotein-positive cells. However, whereas verapamil (50 microM) inhibited the ATPase activity of EHR2/MITOX microsomes, it stimulated the ATPase activity of microsomes derived from P-glycoprotein-positive cells. In conclusion, the resistance in EHR2/MITOX was multifactorial and appeared...

  20. Surface markers of small lymphocytes appearing in the mouse Ehrlich ascites tumour, host spleen and blood

    International Nuclear Information System (INIS)

    Small lymphocytes sampled from intraperitoneally growing Ehrlich ascites tumour in CBA/H-T6 mice as well as host spleen and blood at different days of tumour development were characterized radioautographically on the basis of two surface markers, IgM for B cells and theta antigen for T cells. A direct binding of 125I-labelled anti-IgM detected natural surface IgM, while an indirect binding following a prior exposure to anti-theta antibody detected theta antigen. Cells remaining unlabelled with the latter procedure were considered to lack both markers (double negative). Changes in the proportions and absolute numbers of the different cells were related to tumour growth and development. (author)

  1. Phosphorylation in vivo of non-ribosomal proteins from native 40 S ribosomal particles of Krebs II mouse ascites-tumour cells

    DEFF Research Database (Denmark)

    Schuck, J; Reichert, G; Issinger, O G

    1981-01-01

    Four non-ribosomal proteins from native 40 S ribosomal subunits with mol.wts. of 110 000, 84 000, 68 000 and 26 000 were phosphorylated in vivo when ascites cells were incubated in the presence of [32P]Pi. The 110 000-, 84 000- and 26 000-dalton proteins are identical with phosphorylated products...... from native 40 S subunits after phosphorylation in vitro by a cyclic nucleotide-independent protein kinase. Phosphoserine was the major phosphorylated amino acid of the proteins phosphorylated in vivo and in vitro....

  2. Surface markers of small lymphocytes appearing in the mouse Ehrlich ascites tumour, host spleen and blood

    Science.gov (United States)

    Garnis, Sylvia; Lala, P. K.

    1978-01-01

    Small lymphocytes sampled from intraperitoneally growing Ehrlich ascites tumour in CBA/H-T6 mice as well as host spleen and blood at different days of tumour development were characterized radioautographically on the basis of two surface markers, IgM for B cells and θ antigen for T cells. A direct binding of 125I-labelled anti-IgM detected natural surface IgM, while an indirect binding following a prior exposure to anti-θ antibody detected θ antigen. Cells remaining unlabelled with the latter procedure were considered to lack both markers (double negative). While the incidence of IgM+ve small lymphocytes within the tumour declined, their absolute numbers increased with tumour growth. Low levels of antiglobulin binding shown by these cells were considered to reflect low levels of maturation, because (1) our previous studies indicated that they were newly formed, and (2) the extent of antiglobulin binding by B lymphocytes in the marrow is known to increase with increasing post-mitotic age. The proportions and the absolute numbers of θ+ve as well as the double negative small lymphocytes increased within the growing tumours. Within the host spleen, the incidence of IgM+ve small lymphocytes remained unchanged but their absolute numbers increased because of splenomegaly. The degree of antiglobulin binding by these cells was comparable to that of the normal splenic population. The incidence of θ+ve cells dropped but their absolute numbers remained unchanged in the spleen during tumour growth. In contrast, the incidence as well as the absolute numbers of double negative cells increased markedly. This cell category increased also in the blood, possibly in transit to the tumour site and other lymphoid organs from the bone marrow, where they were most prevalent. Their bone marrow origin was further suggested by a preponderance of marrow derived small lymphocytes at the tumour site as well as in the host spleens found in our earlier studies. Double negative population in

  3. Percutaneous radiofrequency ablation of hepatic tumours: Factors affecting technical failure of artificial ascites formation using an angiosheath

    International Nuclear Information System (INIS)

    Aim: To evaluate the technical feasibility of artificial ascites formation using an angiosheath before percutaneous radiofrequency ablation (RFA) for hepatic tumours and to determine predictive factors affecting the technical failure of artificial ascites formation. Materials and methods: This retrospective study was approved by the institutional review board. One hundred and thirteen patients underwent percutaneous RFA of hepatic tumours after trying to make artificial ascites using an angiosheath to avoid collateral thermal damage. The technical success rate of making artificial ascites using an angiosheath and conversion rate to other techniques after initial failure of making artificial ascites were evaluated. The technical success rate for RFA was assessed. In addition, potential factors associated with technical failure including previous history of transcatheter arterial chemoembolization (TACE) or RFA, type of abdominal surgery, and adjacent perihepatic structures were reviewed. Predictive factors for the technical failure of artificial ascites formation were analysed using multivariate analysis. Results: The technical success rates of artificial ascites formation by angiosheath and that of RFA were 84.1% (95/113) and 97.3% (110/113), respectively. The conversion rate to other techniques after the failure of artificial ascites formation using an angiosheath was 15.9% (18/113). Previous hepatic resection was the sole independent predictive factor affecting the technical failure of artificial ascites formation (p<0.001, odds ratio = 29.03, 95% confidence interval: 4.56–184.69). Conclusion: Making artificial ascites for RFA of hepatic tumours using an angiosheath was technically feasible in most cases. However, history of hepatic resection was a significant predictive factor affecting the technical failure of artificial ascites formation. - Highlights: • Making artificial ascites (AA) using an angiosheath is feasible (84.1%, 95/113). • However

  4. Bacterial-mediated DNA delivery to tumour associated phagocytic cells.

    Science.gov (United States)

    Byrne, W L; Murphy, C T; Cronin, M; Wirth, T; Tangney, M

    2014-12-28

    Phagocytic cells including macrophages, dendritic cells and neutrophils are now recognised as playing a negative role in many disease settings including cancer. In particular, macrophages are known to play a pathophysiological role in multiple diseases and present a valid and ubiquitous therapeutic target. The technology to target these phagocytic cells in situ, both selectively and efficiently, is required in order to translate novel therapeutic modalities into clinical reality. We present a novel delivery strategy using non-pathogenic bacteria to effect gene delivery specifically to tumour-associated phagocytic cells. Non-invasive bacteria lack the ability to actively enter host cells, except for phagocytic cells. We exploit this natural property to effect 'passive transfection' of tumour-associated phagocytic cells following direct administration of transgene-loaded bacteria to tumour regions. Using an in vitro-differentiated human monocyte cell line and two in vivo mouse models (an ovarian cancer ascites and a solid colon tumour model) proof of delivery is demonstrated with bacteria carrying reporter constructs. The results confirm that the delivery strategy is specific for phagocytic cells and that the bacterial vector itself recruits more phagocytic cells to the tumour. While proof of delivery to phagocytic cells is demonstrated in vivo for solid and ascites tumour models, this strategy may be applied to other settings, including non-cancer related disease. PMID:25466954

  5. An Ovarian Steroid Cell Tumor Causing Virilization and Massive Ascites

    OpenAIRE

    Kim, Young Tae; Kim, Sang Wun; Yoon, Bo Sung; Kim, Sung Hoon; Kim, Jae Hoon; Kim, Jae Wook; Cho, Nam Hoon

    2007-01-01

    Steroid cell tumors, not otherwise specified (NOS), are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce several steroids, particularly testosterone. Various virilizing symptoms such as hirsutism, temporal balding, and amenorrhea are common in these patients; however massive ascites is an infrequent symptom. A 52-year-old woman with the sudden onset of virilization and massive ascites presented for treatment at Severance Hospital. After clini...

  6. Anticancer activity of Jasminum angustifolium Linn against Ehrlich ascites carcinoma cells bearing mice

    Directory of Open Access Journals (Sweden)

    Pradeep Rajkumar

    2012-06-01

    Full Text Available Objective: Present investigations were carried out for evaluation of antitumor and in vitro antioxidant activity of ethanol and aqueous extracts of Jasminum angustifolium Linn. Methods: For its antitumor activity, Ehrlich ascites carcinoma (EAC induced swiss albino mice were used and were divided into five group with 6 animal each.The antitumor effect was assessed using viable tumour cell count, packed cell volume, body weight, mean survival time and percentage increase in life span. Apart from that, hematological and liver enzyme studies were noticed upon the ethanol and aqueous extracts of Jasminum angustifolium Linn administered at 500 mg/kg per day for 14 days, after 24 hours of tumor inoculation. Results: Treatment with extracts significantly restored the altered parameters to normal when compared to cancer control group. Conclusion: The results suggest that ethanol extract of Jasminum angustifolium Linn possess significant antitumor effects in EAC tumour bearing mice. [J Exp Integr Med 2012; 2(3.000: 271-275

  7. Leydig cell tumours in childhood.

    Science.gov (United States)

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  8. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba

    2009-01-01

    Full Text Available Granular cell tumour (GCT affecting the larynx is not common, especially in children. Most cases are apt to be confused with respiratory papilloma and may even be mistaken for a malignant neoplasia. We present a case of laryngeal GCT in a 12-year-old child to emphasize that the tumour should be regarded in the differential of growths affecting the larynx in children.

  9. Role of malignant ascites on human mesothelial cells and their gene expression profiles

    International Nuclear Information System (INIS)

    Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role

  10. Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

    International Nuclear Information System (INIS)

    Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

  11. PROTEN TYROSINE PHOSPHATASE ACTIVITY IN RAT ASCITES HEPATOMA CELLS

    Directory of Open Access Journals (Sweden)

    M.Saadat

    1998-10-01

    Full Text Available Protein tyrosine phosphatases (PTPases regulate tyrosine phosphorylation of target proteins involved in several aspects of cellular functions. Enzyme activities of the PTPases in cytosolic and particulate fractions of rat ascites hepatoma cell lines were determined and compared with those of normal rat liver. Our present data revealed that although there was no neoplatic-specific alteration of the PTPase activity in examined hepatomas, the activity in particulate fractions of island type of hepatomas was remarkably decreased compared with either rat liver or free type hepatomas.

  12. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

    Directory of Open Access Journals (Sweden)

    R A Lawal

    2012-12-01

    Full Text Available Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assay by incubating Ehrlich ascites carcinoma cells with various concentrations of Securidaca longepedunculata aqueous extract. In vivo study was carried out by intraperitoneal administration of varied doses of Securidaca longepedunculata to tumour-bearing mice. Isolated DNA from Ehrlich ascites carcinoma cells in treated and untreated animals was used for DNA fragmentation assay on agarose gel. Securidaca longepedunculata Aqueous extract, Securidaca longepedunculata was cytotoxic to Ehrlich ascites both in vivo and in vitro. The IC50 of Securidaca longepedunculata was 67 µg/ml. Securidaca longepedunculata caused a decrease in angiogenesis as observed in the reduction in weight of treated animals and a reduction in volume of ascitic fluid in treated mice.  DNA fragmentation assay of Ehrlich ascites carcinoma cells from treated animals depicted a possible pro-apoptotic effect of the Securidaca longepedunculata extract due to the ladder forming pattern which was comparable to that of the standard drug (fluorouracil. Securidaca longepedunculata aqueous extract had a cytotoxic and pro-apoptotic effect on Ehrlich ascites carcinoma cells. Industrial relevance: The use of Securidaca longepedunculata in traditional medicine in the treatment and management of cancer has been brought to the fore. Development of herbal drugs from the crude extracts could be achieved due to findings suggesting the plant could increase life span in patients with advanced stages of cancer

  13. Monovalent ions control proliferation of Ehrlich Lettre ascites cells

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Preisler, Sarah; Pedersen, Stine Helene Falsig;

    2010-01-01

    little effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G(1). Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl(-) may regulate proliferation by......Channels and transporters of monovalent ions are increasingly suggested as putative anticarcinogenic targets. However, the mechanisms involved in modulation of proliferation by monovalent ions are poorly understood. Here, we investigated the role of K+, Na+, and Cl(-) ions for the proliferation of...... Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G(0), G(1), and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na+ and Cl(-) were reduced in the G(0)-G(1) phase...

  14. Effects of D2O on biochemical parameters of normal cells and tumour cells

    International Nuclear Information System (INIS)

    The influence of high temperatures (Hyperthermia) on normal tissue and Ehrlich-Ascites tumour cells ('ATZ') was examined under several conditions with regard to the application of deuterium oxide as a stabilising factor. It was proven that the DNA-synthesis of normal tissue (liver, mouse) is not sensitive to temperature. This effect of hyperthermia only occurs when the tissue is damaged, e.g. by trypsinising. The influence of hyperthermia on several biochemical parameters and on morphological changes of the Ascites cells was examined. The findings show that deuterium oxide (D2O) is able to reduce both the thermal and the ureal denaturation of enzymes. Thus tests were carried out to find out if D2O also reduces toxic influence in complicated biological systems. The assumption of high D2O concentrations to prevent several reactions was confirmed. When the Ascites tumour cells in the H2O-buffer were exposed to the damaging influence of hyperthermia, the high degree of damage was seen with the decreasing DNA synthesis, reduced aerobic glycose capacity, a drop in the ATP values and breakdown of the permeability of the membrane. Deuterium oxide was able under high temperature (from appr. 440C on) to reduce the degree of damage to DNA synthesis, while auto-effects (inhibition of synthesis) of D2O predominate in the lower region. Aerobic glycolysis was damaged in both cases to the same degree, however. In D2O after hyperthermia the ATP-level dropped faster than in H2O. D2O not only reduces the thermal denaturation of the Ascites tumour cells, but it also eliminates the toxic influence of the zytostaticum TRENIMONsup(R) (under 380 or 460C incubation). (orig./AJ)

  15. Sialomucin and lytic susceptibility of rat mammary tumor ascites cells.

    Science.gov (United States)

    Moriarty, J; Skelly, C M; Bharathan, S; Moody, C E; Sherblom, A P

    1990-11-01

    The potential role of cell surface sialomucin in preventing natural killer (NK)-mediated lysis of tumor cell targets has been addressed by comparing the properties of 2 NK-resistant [ascites (ASC) and short-term cultured (STC)] and 2 NK-susceptible [tunicamycin-treated (TUN) and long-term cultured (LTC)] preparations of 13762 MAT-B1 rat mammary tumor cells. Both the ASC and STC cell preparations contain elevated levels of the sialomucin ASGP-1 relative to TUN and LTC preparations as determined by [3H]glucosamine labeling and by binding of peanut agglutinin. The major difference in the susceptibility to NK-mediated lysis appeared to be due to the differences in the susceptibility to lysis by lytic granules, rather than to differences in the ability to bind or trigger effector cells, since TUN and LTC cells were approximately 10-fold more sensitive to lysis by lytic granules than were ASC and STC cells. All preparations inhibited the lysis of the susceptible target YAC-1 by normal rat splenocytes, indicating an ability to bind these effector cells. Triggering of effectors, as monitored either by incorporation of 32P into phosphatidylinositol or by transmethylation of phosphatidylcholine, was similar for the positive control YAC-1, STC, TUN, and LTC, whereas ASC appeared to be defective in triggering effectors. These results suggest that tumor sialomucin blocks the final phase of lysis, but not the initial recognition of tumor cells by NK effectors. PMID:2208144

  16. Targeting hypoxic tumour cells to overcome metastasis

    International Nuclear Information System (INIS)

    The microenvironment within solid tumours can influence the metastatic dissemination of tumour cells, and recent evidence suggests that poorly oxygenated (hypoxic) cells in primary tumours can also affect the survival and proliferation of metastatic tumour cells in distant organs. Hypoxic tumour cells have been historically targeted during radiation therapy in attempts to improve loco-regional control rates of primary tumours since hypoxic cells are known to be resistant to ionizing radiation-induced DNA damage. There are, therefore, a number of therapeutic strategies to directly target hypoxic cells in primary (and metastatic) tumours, and several compounds are becoming available to functionally inhibit hypoxia-induced proteins that are known to promote metastasis. This mini-review summarizes several established and emerging experimental strategies to target hypoxic cells in primary tumours with potential clinical application to the treatment of patients with tumour metastases or patients at high risk of developing metastatic disease. Targeting hypoxic tumour cells to reduce metastatic disease represents an important advance in the way scientists and clinicians view the influence of tumour hypoxia on therapeutic outcome

  17. The impact of inflammatory cells in malignant ascites on small intestinal ICCs’ morphology and function

    OpenAIRE

    Li, Jing; Kong, Dan; He, Yan; Wang, Xiuli; Gao, Lei; Li, Jiade; Yan, Meisi; Liu, Duanyang; Wang, Yufu; Zhang, Lei; Jin, Xiaoming

    2015-01-01

    Malignant ascites is one of the common complication at the late stage of abdominal cancers, which may deteriorate the environment of abdominal cavity and lead to potential damage of functional cells. Interstitial cells of Cajal (ICCs) are mesoderm-derived mesenchymal cells that function normal gastrointestinal motility. The pathological changes of ICCs or the reduced number may lead to the motility disorders of gastrointestinal tract. In this study, through analysis of malignant ascites which...

  18. Radiosensitivity of Ehrlich ascites tumor clonogenic cells forming colonies in agar cultures in diffuse chambers

    International Nuclear Information System (INIS)

    A study was made of the dependence of survival of Ehrlich ascites tumor clonogenic cells on the 3d and 7th days following inoculation upon radiation dose (60Co-γ-rays) delivered under well oxygenated in vitro conditions. No differences were detected in radiosensitivity of 3- and 7-day Ehrlich ascites tumor cells: in both cases, the ''dose - effect'' curves were S-shaped with a small shoulder and close D0 values

  19. Myoepithelial cells in canine mammary tumours.

    Science.gov (United States)

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  20. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    Science.gov (United States)

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  1. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    Science.gov (United States)

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  2. pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Litman, Thomas; Pedersen, S F; Kramhøft, B;

    1998-01-01

    Maintenance and regulation of intracellular pH (pHi) was studied in wild-type Ehrlich ascites tumor cells (EHR2) and five progressively daunorubicin-resistant, P-glycoprotein (P-gp)-expressing strains, the maximally resistant of which is EHR2/1.3. Steady-state pHi was similar in cells expressing ...

  3. Ovarian stimulation and granulosa-cell tumour.

    Science.gov (United States)

    Willemsen, W; Kruitwagen, R; Bastiaans, B; Hanselaar, T; Rolland, R

    1993-04-17

    Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation--ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present. PMID:8096944

  4. 43. Inhibition effect of Solanum nigrum. L juice on S180 ascites cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To study the action and application of Solanum nigrum.L Juice (abbreviate: S.J) on inhibiting tumors of S180 ascites cancer. Methods: Build mice tumor model through injecting S180 ascites cancer into mice's right armbet .48 male mice from KunMing of four to six weeks were randomly divided into 4 groups: Solanum Nigrum L Juice—high dosage (3mg/ml), middle dosage (1.5mg/ml), low dosage (0.75mg/ml); control group. After taking medicine for 15 days, kill the mice and measure the weight of tumor、spleen and thymus. Result: ①Tumor weights in middle and high dosage group are lighter than control group(P<0.05). ②Spleen index of test groups are different from control group(P<0.05). Conclusion: Solanum. nigrum.L Juice has inhibitory roles to S180 ascites cells.

  5. Role of Th9 cells and Th17 cells in the pathogenesis of malignant ascites

    Institute of Scientific and Technical Information of China (English)

    Xian-Wen Yang; Hai-Xing Jiang; Xiao-Li Huang; Shi-Jia Ma; Shan-Yu Qin

    2015-01-01

    Objective:To assess the role of Th9 and Th17 cells in malignant ascites (MA). Methods: MA from 30 hepatic carcinoma patients and benign ascites from 30 cirrhotic patients were collected. Corresponding peripheral blood samples from these hepatic carcinoma and cirrhotic patients as well as 30 healthy subjects were collected. The frequency of Th9 and Th17 cells was tested by flow cytometry. Serum levels of interleukin (IL)-9 and IL-17 were examined byELISA. Results: The observed frequency of Th9 and Th17 cells, and the IL-9 and IL-17 serum levels were significantly higher in MA patients than those in cirrhotic patients and healthy control samples (P Conclusions:The increased frequency of Th9 and Th17 cells in MA patients suggests that these two T cell subsets play a synergistic role in MA pathogenesis. This study also demonstrated that Th9 and Th17 cells may perform their biological functions in conjunction with IL-9 production.

  6. In vitro effect of X radiation on respiration and glycolysis of Ehrlich ascites carcinoma cells of the mouse - an experimental comparison with the mouse tumortetanus assay

    International Nuclear Information System (INIS)

    Depending on the dose of X-rays, in vitro irradiation of Ehrlich ascites carcinoma cells of the mouse affected both respiration and glycolysis. 38.7 C/kg irradiation suppressed the aerobic and anaerobic energy metabolism rather strongly followed by a reduction of the 'take' and growth of the subcutaneously injected tumour cells, as opposed to the growth behavior of non-irradiated cells. In analogy, tetanus mortality rates were reduced in the mouse tumor-tetanus assay with 38.7 C/kg irradiated cells. On the other hand, irradiation with 5.16 C/kg of Ehrlich carcinoma cells resulted in unchanged rates of respiration and glycolysis, in spite of the strongly limited growth capacity of the tumor cells. The tumor-tetanus assay of the mouse showed good correlation with subcutaneous tumor growth; no such correlation was found in the tetanus assay and the manometric values of respiration and glycolysis with 5.16 C/kg irradiated tumor cells. After subcutaneous injection of mixed cell suspensions consisting of 1 x 105 viable and 1 x 106 38.7 C/kg irradiated Ehrlich ascites carcinoma cells as well as of 3 x 102 tetanus spores per single dose, we observed similar rates of tumor growth and tetanus mortality, respectively, if 1 x 105 viable tumor cells alone were administered together with 3 x 102 tetanus spores, without addition of irradiated tumor cells. (author)

  7. Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Ardian Latifi

    Full Text Available Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD and non-adherent (NAD cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN and 14 chemoresistant (CR. AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125, epithelial cell adhesion molecule (EpCAM and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p. injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.

  8. Cell swelling activates separate taurine and chloride channels in Ehrlich mouse ascites tumor cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hoffmann, Else Kay

    1994-01-01

    The taurine efflux from Ehrlich ascites tumor cells is stimulated by hypotonic cell swelling. The swelling-activated taurine efflux is unaffected by substitution of gluconate for extracellular Cl– but inhibited by addition of MK196 (anion channel blocker) and 4,4 -diisothiocyanostilbene-2......,2 -disulfonic acid (DIDS; anion channel and anion exchange blocker) and by depolarization of the cell membrane. This is taken to indicate that taurine does not leave the osmotically swollen Ehrlich cells in exchange for extracellular Cl–, i.e., via the anion exchanger but via a MK196- and DIDS-sensitive channel...... that is potential dependent. An additional stimulation of the swelling-activated taurine efflux is seen after addition of arachidonic acid and oleic acid. Cell swelling also activates a Mini Cl– channel. The Cl– efflux via this Cl– channel, in contrast to the swelling-activated taurine efflux, is...

  9. Cell Swelling Activates Phospholipase A2 in Ehrlich Ascites Tumor Cells

    DEFF Research Database (Denmark)

    Thoroed, S.M.; Lauritzen, L.; Lambert, I.H.;

    1997-01-01

    Ehrlich ascites tumor cells! loaded with H-labeled arachidonic acid and C-labeled stearic acid for two hours, were washed and transferred to either isotonic or hypotonic media containing BSA to scavenge the labeled fatty acids released from the cells. During the first two minutes of hypo......-osmotic exposure the rate of H-labeled arachidonic acid release is 3.3 times higher than that observed at normal osmolality. Cell swelling also causes an increase in the production of C-stearic acid-labeled lysophosphatidylcholine. This indicates that a phospholipase A is activated by cell swelling in the Ehrlich...... cells. Within the same time frame there is no swelling-induced increase in C-labeled stearic acid release nor in the synthesis of phosphatidyl C-butanol in the presence of C-butanol. Furthermore, U7312, an inhibitor of phospholipase C, does not affect the swelling induced release of C...

  10. Granular cell tumour of the neurohypophysis: a rare sellar tumour with specific radiological and operative features.

    LENUS (Irish Health Repository)

    Aquilina, K

    2012-02-03

    Symptomatic granular cell tumours of the neurohypophysis are rare sellar lesions. Preoperative prediction of the diagnosis on the basis of radiological appearance is useful as these tumours carry specific surgical difficulties. This is possible when the tumour arises from the pituitary stalk, rostral to a normal pituitary gland. This has not been emphasized previously.

  11. Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.

    Science.gov (United States)

    Slyshenkov, V S; Rakowska, M; Moiseenok, A G; Wojtczak, L

    1995-12-01

    Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids. PMID:8582649

  12. MRI of intracranial germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, M. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Uozumi, T. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kiya, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Mukada, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Arita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kurisu, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Sugiyama, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Onda, J. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Satoh, H. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Ikawa, F. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Migita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan)

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  13. Effect of tunicamycin on sialomucin and natural killer susceptibility of rat mammary tumor ascites cells.

    Science.gov (United States)

    Bharathan, S; Moriarty, J; Moody, C E; Sherblom, A P

    1990-09-01

    The MAT-B1 and MAT-C1 ascites sublines of the 13762 rat mammary adenocarcinoma contain a dominant cell surface "complex" consisting of two glycoproteins: ascites sialoglycoprotein (ASGP)-1, a Mr 600,000-700,000 peanut agglutinin-binding sialomucin, and ASGP-2, a Mr 120,000 concancavalin A-binding glycoprotein (Sherblom et al., J. Biol. Chem., 255: 783-790, 1980; Sherblom and Carraway, J. Biol. Chem., 255: 12051-12059, 1980). Although both cell lines are resistant to lysis by natural killer cells, treatments which result in loss of cell surface ASGP-1 render the cells susceptible to natural killer cell lysis (Sherblom and Moody, Cancer Res., 46:4543-4546, 1986). Treatment of the ascites cells with 5 micrograms/ml tunicamycin for 24 h effectively inhibits glycosylation of ASGP-2 without affecting cell viability or total protein synthesis. Under these conditions, expression of ASGP-1 is depressed by at least 50% in both cell lines, as monitored by [3H]glucosamine incorporation and by binding of peanut agglutinin to intact cells. The size distribution of O-linked oligosaccharides in ASGP-1 from tunicamycin-treated versus control MAT-B1 cells is indistinguishable, as determined by Bio-Gel P-4 chromatography following alkaline-borohydride treatment. Complex isolated from either treated or control cells bands at the same density in a CsCl gradient containing Triton X-100 and contains a diffuse band corresponding to ASGP-2 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tunicamycin-treated cells, consistent with the reduced expression of ASGP-1, are significantly more susceptible to natural killer cell-mediated lysis, when compared to untreated controls. The results suggest that N-linked glycosylation is a prerequisite for sialomucin synthesis and/or complex formation. PMID:2386935

  14. Detection of SMARCB1 loss in ascites cells in the diagnosis of an abdominal rhabdoid tumor.

    Science.gov (United States)

    Kerl, Kornelius; Oyen, Florian; Leuschner, Ivo; Schneppenheim, Reinhard; Nagel, Inga; Siebert, Reiner; Groll, Andreas H; Hartmann, Wolfgang; Barth, Peter Josef; Bartelheim, Kerstin; Seringer, Angela; Wardelmann, Eva; Frühwald, Michael C

    2015-05-01

    We report on how MLPA and Sequencing of SMARCB1/INI1/SNF5 might be applied for initial diagnosis of rhabdoid tumor patients. These techniques were successfully used to detect loss of SMARCB1 in tumor cells of the ascites in a 3-month-old patient in which tumor biopsy could not initially be made due to life threatening intraabdominal bleedings. PMID:25663425

  15. In vivo Anticancer Activities of Benzophenone Semicarbazone against Ehrlich Ascites Carcinoma Cells in Swiss Albino Mice

    International Nuclear Information System (INIS)

    Benzophenone semicarbazone (BSC) was synthesized and characterized to identify compounds with anticancer activities. Anticancer activities were studied against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice by monitoring parameters such as tumor weight measurement, survival time of tumor bearing mice, tumor cell growth inhibition, and so on. Some hematological parameters, such as red blood cells, white blood cells, and hemoglobin content, were also measured. The results showed that BSC has a positive effect against EAC cells. An assessment was conducted by comparing these results with those obtained using the standard drug bleomycin. The BSC compound can be considered as a potent anticancer agent

  16. Cell metabolism, tumour diagnosis and multispectral FLIM

    Science.gov (United States)

    Rück, A.; Hauser, C.; Lorenz, S.; Mosch, S.; Rotte, S.; Kessler, M.; Kalinina, S.

    2013-02-01

    Fluorescence guided diagnosis of tumour tissue is in many cases insufficient, because false positive results are interfering with the outcome. Discrimination between tumour and inflammation could be therefore difficult. Improvement of fluorescence diagnosis through observation of cell metabolism could be the solution, which needs a detailed understanding of the origin of autofluorescence. However, a complex combination of fluorophores give rise to the emission signal. Also in PDD (photodynamic diagnosis) different photosensitizer metabolites contribute to the fluorescence signal. Therefore, the fluorescence decay in many cases does not show a simple monoexponential profile. In those cases a considerable improvement could be achieved when time-resolved and spectral-resolved techniques are simultaneously incorporated. The discussion will focus on the detection of NADH, FAD and 5-ALA induced porphyrins. With respect to NADH and FAD the discrimination between protein bound and free coenzyme was investigated with multispectral FLIM in normal oral keratinocytes and squamous carcinoma cells from different origin. The redox ratio, which can be correlated with the fluorescence lifetimes of NADH and FAD changed depending on the state of the cells. Most of the investigations were done in monolayer cell cultures. However, in order to get information from a more realistic in vivo situation additionally the chorioallantoismembrane (CAM) of fertilized eggs was used where tumour cells or biopsies were allowed to grow. The results of theses measurements will be discussed as well.

  17. Effect of cytochalasins on F-actin and morphology of Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Mills, J W; Falsig Pedersen, S; Walmod, P S;

    2000-01-01

    that, in intact cells, different cytochalasins can have varying effects on cell morphology and F-actin content and organization. To examine this problem in more detail, we analyzed the effects of cytochalasins on the cell morphology of and F-actin content and organization in Ehrlich ascites tumor (EAT...... appearance of numerous blebs. At 10 microM, blebbing was present in all conditions and the organization of cortical F-actin was disrupted. F-actin content, however, was not further reduced by this higher concentration and in CD it was identical to control levels. Exposure of EAT cells to similar...

  18. Influence of femtosecond laser radiation on cells of the transplantable tumour Krebs-2

    Energy Technology Data Exchange (ETDEWEB)

    Meshalkin, Yu P; Popova, N A; Nikolin, V P; Kaledin, V I; Kirpichnikov, A V; Pestryakov, Efim V

    2012-06-30

    The influence of femtosecond radiation of a titaniumsapphire laser on cells of the transplantable ascitic tumour Krebs-2 was studied. After in vitro irradiation by the pulsed fundamentalharmonic radiation with the wavelength 800 nm, pulse duration 30 fs, repetition rate 1 kHz, mean power 100 and 300 mW and exposure time 3 min, as well as by the second-harmonic radiation (40 nm, 50 fs, 120 mW), all cells were diffusely stained by the vital stain trypan blue, which may be an evidence of their death or abnormalities of membrane permeability. However, implantation of such cells to experimental animals led to formation of tumours at the transplantation site with the kinetics slightly different from the control one. In the group of mice to which the cells were inoculated after irradiation with second harmonic pulses of titanium-sapphire laser the inhibition of tumour growth was observed due to partial death of cells under the action of UV spectral components. To explain the mechanism of the observed phenomenon the possibility of pore formation (photoporation) in the cell membrane, described earlier in the papers on foreign DNA transfection into cells, is considered.

  19. Influence of femtosecond laser radiation on cells of the transplantable tumour Krebs-2

    International Nuclear Information System (INIS)

    The influence of femtosecond radiation of a titaniumsapphire laser on cells of the transplantable ascitic tumour Krebs-2 was studied. After in vitro irradiation by the pulsed fundamentalharmonic radiation with the wavelength 800 nm, pulse duration 30 fs, repetition rate 1 kHz, mean power 100 and 300 mW and exposure time 3 min, as well as by the second-harmonic radiation (40 nm, 50 fs, 120 mW), all cells were diffusely stained by the vital stain trypan blue, which may be an evidence of their death or abnormalities of membrane permeability. However, implantation of such cells to experimental animals led to formation of tumours at the transplantation site with the kinetics slightly different from the control one. In the group of mice to which the cells were inoculated after irradiation with second harmonic pulses of titanium-sapphire laser the inhibition of tumour growth was observed due to partial death of cells under the action of UV spectral components. To explain the mechanism of the observed phenomenon the possibility of pore formation (photoporation) in the cell membrane, described earlier in the papers on foreign DNA transfection into cells, is considered.

  20. Pedunculated islet-cell tumour of the duodenum.

    Science.gov (United States)

    Britt, R P

    1966-05-01

    An unusual islet-cell tumour found at necropsy in a patient who had died from a myocardial infarction is described. Of particular interest were the pedunculated nature and large size of the tumour. The clinical features of the case are considered. Four islet-cell tumours in the duodenum have previously been reported and it seems probable that such tumours arise in heterotopic pancreas. PMID:4287114

  1. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

    2009-02-15

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  2. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

    International Nuclear Information System (INIS)

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  3. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects

    OpenAIRE

    Taylor, D D; Gerçel-Taylor, C

    2005-01-01

    Dendritic and lymphoid ‘exosomes' regulate immune activation. Tumours release membranous material mimicking these ‘exosomes,' resulting in deletion of reactive lymphocytes. Tumour-derived ‘exosomes' have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour-derived ‘exosomes' and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients (n=6) and Western imm...

  4. Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by Abrin

    Directory of Open Access Journals (Sweden)

    V. Ramnath

    2009-01-01

    Full Text Available The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.

  5. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    Directory of Open Access Journals (Sweden)

    Neha Garg

    2015-01-01

    Full Text Available CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs, are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools.

  6. Incidence of spontaneous bacterial peritonitis in patients with ascites. Diagnostic value of white blood cell count and pH measurement in ascitic fluid

    DEFF Research Database (Denmark)

    Storgaard, J S; Svendsen, Jesper Hastrup; Hegnhøj, J;

    1991-01-01

    During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured...... patients with SBP. In contrast to several previous studies, neither ascites pH nor ascites leucocyte counts were any help in obtaining a rapid diagnosis. Survival time of patients with SBP was significantly shorter than of patients without SBP....

  7. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.

    Science.gov (United States)

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M; Chen, Maoshan; Findlay, Jock K; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  8. Inhibition of oxidative phosphorylation in ascites tumor mitochondria and cells by intramitochondrial Ca2+.

    Science.gov (United States)

    Villalobo, A; Lehninger, A L

    1980-03-25

    Accumulation of Ca2+ (+ phosphate) by respiring mitochondria from Ehrlich ascites or AS30-D hepatoma tumor cells inhibits subsequent phosphorylating respiration in response to ADP. The respiratory chain is still functional since a proton-conducting uncoupler produces a normal stimulation of electron transport. The inhibition of phosphorylating respiration is caused by intramitochondrial Ca2+ (+ phosphate). ATP + Mg2+ together, but not singly, prevents the inhibitory action of Ca2+. Neither AMP, GTP, GDP, nor any other nucleoside 5'-triphosphate or 5'-diphosphate could replace ATP in this effect. Phosphorylating respiration on NAD(NADP)-linked substrates was much more susceptible to the inhibitory effect of intramitochondrial Ca2+ than succinate-linked respiration. Significant inhibition of oxidative phosphorylation is given by the endogenous Ca2+ present in freshly isolated tumor mitochondria. The phosphorylating respiration of permeabilized Ehrlich ascites tumor cells is also inhibited by Ca2+ accumulated by the mitochondria in situ. Possible causes of the Ca2+-induced inhibition of oxidative phosphorylation are considered. PMID:6766937

  9. MicroRNA Expression Profiles Associated with Development of Drug Resistance in Ehrlich Ascites Tumor Cells

    DEFF Research Database (Denmark)

    Husted, Susanne; Søkilde, Rolf; Rask, Lene;

    2011-01-01

    in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines...... clusters miR-30d∼miR-30b and miR-23b∼miR-27b∼miR-24-1 were downregulated in most of the resistant EAT cells. Several of the target genes for these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could contribute to the drug-resistant phenotype, although we did not find that the degree of...

  10. MRI of intracranial germ-cell tumours

    International Nuclear Information System (INIS)

    Abstract. Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes. (orig.)

  11. MRI of intracranial germ-cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Liang, L.; Korogi, Y.; Sugahara, T.; Ikushima, I.; Shigematsu, Y.; Okuda, T.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine (Japan); Kochi, M.; Ushio, Y. [Department of Neurosurgery, Kumamoto University School of Medicine (Japan)

    2002-05-01

    Abstract. Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes. (orig.)

  12. Chylous Ascites

    Directory of Open Access Journals (Sweden)

    Siva K Talluri

    2011-01-01

    Full Text Available Context: Chylous ascites is the accumulation of milky chyle in the peritoneal cavity. Chylous ascites has been reported after surgeries like abdominal aortic aneurysm repair, radical gastrectomy, duodenectomy, nephrectomy and Wilm′s tumor resection. Our literature search did not reveal any reports of chylous ascites after a gastric ulcer resection. We report about an elderly woman with a rare complication of chylous ascites after an emergent surgery for a perforated gastric ulcer. Case Report : A 70-year-old woman developed sudden respiratory distress on 5 th post-operative day after an elective C3-C7 cervical discectomy and fusion. Her past medical history was significant for cervical spondylosis. The Computed Tomography (CT scan of the chest revealed air under the diaphragm suspicious for hollow viscus perforation. She underwent an emergent surgery for drainage of hematoma in the neck along with an emergent laparotomy to repair a large perforated gastric ulcer distal to the gastro-esophageal junction. The patient had worsening of abdominal distention on 4 th post-operative day. The CT scan of abdomen showed fluid collection in the abdomen. The abdominal drain revealed large amount of serous milky fluid at the rate of 1500 ml per day. The fluid analysis showed that the triglyceride level was 170 mg/dl and cholesterol level was 15 mg/dl. The fluid cultures did not grow any organism. She responded to treatment with octreotide and a diet of medium chain triglyceride oil. Conclusion: Any obstruction or damage to the lymphatic channels results in chylous ascites. Lymphomas, metastatic malignancies, and abdominal surgeries commonly cause chylous ascites. Ascitic fluid triglyceride level greater than 110 mg/dl is diagnostic of chylous ascites. Chylous ascites is a rare complication of a peptic ulcer resection which can be managed effectively with octreotide.

  13. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O; Fenger, C; Jensenius, Jens Christian; Zeuthen, J; Kristensen, T; Christensen, P B

    1998-01-01

    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression of...... immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled the...... criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80. There...

  14. Shrinkage insensitivity of NKCC1 in myosin II-depleted cytoplasts from Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Hoffmann, Else K; Pedersen, Stine F

    2007-01-01

    Protein phosphorylation/dephosphorylation and cytoskeletal reorganization regulate the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) during osmotic shrinkage; however, the mechanisms involved are unclear. We show that in cytoplasts, plasma membrane vesicles detached from Ehrlich ascites tumor cells (EATC......) by cytochalasin treatment, NKCC1 activity evaluated as bumetanide-sensitive (86)Rb influx was increased compared with the basal level in intact cells yet could not be further increased by osmotic shrinkage. Accordingly, cytoplasts exhibited no regulatory volume increase after shrinkage. In cytoplasts......, cortical F-actin organization was disrupted, and myosin II, which in shrunken EATC translocates to the cortical region, was absent. Moreover, NKCC1 activity was essentially insensitive to the myosin light chain kinase (MLCK) inhibitor ML-7, a potent blocker of shrinkage-induced NKCC1 activity in intact...

  15. Magnetic resonance imaging of ganglion cell tumours

    International Nuclear Information System (INIS)

    The MRI and CT studies of four patients with ganglion cell tumours, one with a cerebellar gangliocytoma (Lhermitte-Duclos disease), and three with gangliogliomas are reported. MRI in Lhermitte-Duclos disease clearly demonstrated a mass of low signal intensity in the left cerebellum on T1-weighted spin-echo (SE) images and an area of high signal intensity with a blurred margin on T2-weighted SE images. These MRI studies were useful for delineating the lesion, which was verified at surgery. In the ganglioglioma, MRI demonstrated two isointense solid masses on T1-weighted SE images, which enhanced clearly with Gd-DTPA. The enhancement study was advantageous in planning surgery. (orig.)

  16. Inhibition of lactate transport in Ehrlich ascites tumor cells and human erythrocytes by a synthetic anhydride of lactic acid.

    Science.gov (United States)

    Johnson, J H; Belt, J A; Dubinsky, W P; Zimniak, A; Racker, E

    1980-08-01

    The synthesis and some of the physical and biological characteristics of a new inhibitor of lactate transport are described. The inhibitor is isobutylcarbonyl lactayl anhydride (iBCLA). It is formed by the condensation of lactic acid and isobutylchloroformate. It inhibits lactate transport 50% at 0.5 microgram/mg of protein in both Ehrlich ascites tumor cells and human erythrocytes. In contrast, 15 microgram of iBCLA/mg of protein is required for 50% inhibition of phosphate transport in erythrocytes, and phosphate transport in Ehrlich ascites tumor cells is unaffected at levels as high as 50 microgram of iBCLA/mg of protein. A time-dependent and concentration-dependent reversal of lactate transport inhibition took place on exposure of iBCLA-treated Ehrlich ascites cells to hydroxylamine or dithiothreitol. These data, along with the observed sensitivity of the lactate transporter to sulfhydryl reagents [Spencer, T. L., & Lehninger, A. L. (1976) Biochem. J. 154, 405-414], suggest that iBCLA acylates an essential sulfhydryl group on the transporter. When glycolyzing Ehrlich ascites tumor cells were treated with concentrations of iBCLA sufficient for complete inhibition of lactate transport, intracellular lactate levels increased, intracellular pH and extra-cellular lactate levels decreased, and overall lactate production was inhibited. PMID:7407072

  17. Cellular uptake of {sup 212}BiOCl by Ehrlich ascites cells: A dosimetric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Roeske, J.C.; Whitlock, J.L.; Harper, P.V.; Rotmensch, J. [Univ. of Chicago, IL (United States); Stinchcomb, T.G. [DePaul Univ., Chicago, IL (United States). Dept. of Physics; Schwartz, J.L. [Univ. of Washington, Seattle, WA (United States). Dept. of Radiation Oncology; Hines, J.J. [Argonne National Lab., IL (United States). Chemistry Div.

    1999-01-01

    Bi-212 is an alpha-emitting radionuclide being investigated as a therapeutic agent in the intraperitoneal treatment of micrometastatic ovarian carcinoma. In evaluating a new therapeutic modality, cell-survival studies are often used as a means of quantifying the biological effects of radiation. In this analysis, Ehrlich ascites cells were irradiated under conditions similar to therapy in various concentrations of Bi-212. Immediately following irradiation, a cell survival assay was performed in which cells were plated and colonies were counted after 10--14 days. Both a macrodosimetric and a microdosimetric approach were used in analyzing these data. These models used as input the fraction of activity within the cell and in solution, the distribution of cell sizes, and the variation of LET along individual alpha-particle tracks. The results indicate that the energy deposited within the nucleus varies significantly among individual cells. There is a small fraction of cell nuclei which receive no hits, while the remaining cells receive energy depositions which can differ significantly from the mean value. These dosimetric parameters are correlated with measured cell survival and will be a useful predictor of outcome for therapeutic doses.

  18. Ovarian small cell carcinoma of pulmonary type appearing in ante-mortem ascites: An autopsy case and review of the literature

    Directory of Open Access Journals (Sweden)

    Hirotsugu Hashimoto, MD

    2015-09-01

    Full Text Available Ovarian small cell carcinoma of pulmonary type (OSCCPT is an extremely rare and aggressive disease. The diagnostic significance of cytology of ascites for OSCCPT, however, has not been shown so far. Here, we report the diagnosis of this carcinoma in an autopsy case with ante-mortem cytology of ascites. A 75 year-old woman was detected with bilateral ovarian cancer by radiological imaging. Although operation was planned, massive ascites was discovered a few weeks later. Ascites was removed with abdominocentesis, which cytologically diagnosed presence of carcinoma, suspicious of adenocarcinoma. A few days later, she died. From autopsy samples, we diagnosed this case as bilateral OSCCPT, showing neuroendocrine differentiation by immunohistochemistry. We reviewed ante-mortem cytology of ascites and found scattered small atypical cells. Immunocytochemical study of the cell block of the ascites showed neuroendocrine differentiation of the atypical cells in an identical manner as the autopsy specimens. Since small atypical cells of OSCCPT often exist with other histological tumor components, careful screening of all cells on the preparation is advisable to accurately diagnose OSCCPT by cytology of ascites.

  19. Single-cell Raman spectroscopy of irradiated tumour cells

    Science.gov (United States)

    Matthews, Quinn

    This work describes the development and application of a novel combination of single-cell Raman spectroscopy (RS), automated data processing, and principal component analysis (PCA) for investigating radiation induced biochemical responses in human tumour cells. The developed techniques are first validated for the analysis of large data sets (˜200 spectra) obtained from single cells. The effectiveness and robustness of the automated data processing methods is demonstrated, and potential pitfalls that may arise during the implementation of such methods are identified. The techniques are first applied to investigate the inherent sources of spectral variability between single cells of a human prostate tumour cell line (DU145) cultured in vitro. PCA is used to identify spectral differences that correlate with cell cycle progression and the changing confluency of a cell culture during the first 3-4 days after sub-culturing. Spectral variability arising from cell cycle progression is (i) expressed as varying intensities of protein and nucleic acid features relative to lipid features, (ii) well correlated with known biochemical changes in cells as they progress through the cell cycle, and (iii) shown to be the most significant source of inherent spectral variability between cells. This characterization provides a foundation for interpreting spectral variability in subsequent studies. The techniques are then applied to study the effects of ionizing radiation on human tumour cells. DU145 cells are cultured in vitro and irradiated to doses between 15 and 50 Gy with single fractions of 6 MV photons from a medical linear accelerator. Raman spectra are acquired from irradiated and unirradiated cells, up to 5 days post-irradiation. PCA is used to distinguish radiation induced spectral changes from inherent sources of spectral variability, such as those arising from cell cycle. Radiation induced spectral changes are found to correlate with both the irradiated dose and the

  20. An investigation of the shedding of macromolecules from the Ehrlich mouse ascites tumor cell

    International Nuclear Information System (INIS)

    The spontaneous release, or shedding, of cell surface components into the extracellular medium may be important in the determination of several features of the cancer cell phenotype. The release of macromolecules from the Erhlich mouse ascites tumor cell was studied under a variety of experimental conditions to elucidate the origin and the underlying mechanisms of release. The extrinsic macromolecules are a diverse group with apparent molecular weights ranging from 13,500 to 400,000 daltons. External labeling of the cell surface with tritiated 4,4'-diisothiocyano-1,2-diphenylethane-2,2-disulfonic acid ([3H]H2DIDS) reveals a slow loss of labeled components at 4 degrees C, while at 21 degrees C and 37 degrees C an initial rapid loss is followed by a slower release. In vitro metabolic labeling with [1-14C]-D-glucosamine hydrochloride, D-[2-3H]-mannose and various [3H]-L-amino acids results in the appearance of labeled macromolecules in the medium suggesting tumor, not mouse, origin. These data suggest that the extrinsic macromolecules originate from the cell surface. Macromolecules are shed by a temperature and pH sensitive process. These results suggest that a limited proteolytic digestion, or sublethal autolysis, of the cell surface may occur in this system. The macromolecules shed by the Ehrlich cell originate from the surface and are probably released by sublethal autolysis, direct secretion and a passive process

  1. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    Directory of Open Access Journals (Sweden)

    Wintzell My

    2012-08-01

    Full Text Available Abstract Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells and cells showing epithelial-mesenchymal-transition (EMT are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9 and monolayer-forming single-cell suspensions (M-type, n=18. Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs. Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

  2. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    International Nuclear Information System (INIS)

    In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies

  3. Breast spindle cell tumours: about eight cases

    Directory of Open Access Journals (Sweden)

    Abd El All Howayda S

    2006-07-01

    Full Text Available Abstract Background Breast spindle cell tumours (BSCTs, although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC, histopathology and immunohistochemistry (IHC in differentiating BSCTs. Methods FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results FNAC defined the tumors as benign (n = 4, suspicious (n = 2 and malignant (n = 3, based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5 and malignant (n = 3. In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma. For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma. In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

  4. Interaction between three subpopulations of Ehrlich carcinoma in mixed solid tumours in nude mice: evidence of contact domination

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Spang-Thomsen, M

    1994-01-01

    Clonal interaction between three subpopulations of Ehrlich carcinoma were studied during growth as mixed solid tumours and as ascites tumours in immune-incompetent nude NMRI mice. The tumour cell lines differed in DNA content as determined by DNA flow cytometry (FCM). Tumour growth was evaluated ...... line had no dominating effect on the E1.15 or E1.95. It is concluded that non-immunologically mediated cellular dominance in heterogeneous tumours may contribute to the evolution of these tumours and may be involved in fundamental tumour biological phenomena....

  5. Application of a low-angle light scattering technique to cell volume and cell signaling studies on Ehrlich ascite tumor cells

    OpenAIRE

    Zinchenko, Valeriy P.; Lee, Vyacheslav V.; Berezhnov, Alexey V.; Mindukshev, Igor V.; Jenkins, Richard O; Goncharov, Nikolay V.

    2006-01-01

    A method for studying cells based on low-angle light scattering was applied to cell volume and cell signaling studies on Ehrlich ascite tumor cells (EATC). Changes in the volume of EATC were measured in hypotonic medium, as well as after activation with exogenous ATP, ionomycin and thimerosal. Increase of [Ca2+]i under ATP and ionomycin action induced reversible changes of cell volume: fast shrinking was followed by swelling. Thimerosal caused a reversible change in EATC volume with high ampl...

  6. Effect of paclitaxel, epirubicin and tamoxifen on labelling index in cultured ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    The effect of Paclitaxel (PAC), Epirubicin (EPR) and Tamoxifen (TAM) on ''3H-thymidine labelling index (''3H-TdR LI) of Ehrlich ascites tumor cells (EAT) was investigated in cultured. In the present study, an estrogen receptor positive ER(+) hyper diploid cell lines were studied. We used optimum doses of PAC, EPR and TAM (12 mg/ml, 12 mg/ml and 2 mg/ml, respectively). Cells were treated with these doses for 0, 4, 8, 16 and 32 hours. At the end of these periods, both control and treated cells were labelled for 5 mCi/ml 3H-thymidine for 30 minutes. The results showed that inhibition of DNA synthesis in cultured EAT cells were increased in the combined treatment of two drugs when compared to the treatment of a single drug (p<0.01). In the treatment of three drugs, however, this effect reached a maximum (p<0.001). As a result, PAC+EPR+TAM treatment's had a maximum synergistic effect at 4 hours treatment

  7. Enzyme-controlled scavenging of ascorbyl and 2,6-dimethoxy-semiquinone free radicals in Ehrlich ascites tumor cells.

    OpenAIRE

    Pethig, R; Gascoyne, P R; McLaughlin, J. A.; Szent-Györgyi, A

    1985-01-01

    The rate of scavenging by Ehrlich ascites cells of anionic ascorbyl and 2,6-dimethoxy-p-semiquinone free radicals has been investigated by electron spin resonance spectroscopy both for viable cells and for subcellular fractions obtained by differential centrifugation. The scavenging activity is concluded to be associated with an NAD(P)H enzyme containing an active sulfhydryl group. Attempts to identify the enzyme with the reported properties of either semi-dehydro-ascorbate reductase or DT-di...

  8. Increased cell membrane arachidonic acid in experimental colorectal tumours.

    OpenAIRE

    Nicholson, M. L.; Neoptolemos, J P; Clayton, H A; Talbot, I C; Bell, P R

    1991-01-01

    Tumour cell membrane fatty acid composition was investigated using an animal model of colorectal carcinogenesis. Eighty six male Wistar rats were fed experimental diets containing either 5% saturated fat or 20% saturated fat. Colorectal tumours were induced by intraperitoneal injection of azoxymethane, and control rats received saline. Animals were killed at intervals up to 26 weeks after the last injection of carcinogen for histology and lipid analysis. Cell membrane fatty acids in colonic m...

  9. Innate Lymphoid Cells: Roles In Tumour Genesis And Progression

    OpenAIRE

    Jovanovic Ivan; Gajovic Nevena; Radosavljevic Gordana; Pantic Jelena; Pejnovic Nada; Arsenijevic Nebojsa; Lukic Miodrag L.

    2015-01-01

    Innate lymphoid cells (ILCs) represent the most recently identified members of the innate immune system. These cells play important roles in inflammation, tissue remodelling and metabolic disease. ILCs can be subdivided into three major groups according to their cytokine production. The role of ILCs in tumourigenesis and tumour progression is not completely clarified. In this review, we discuss whether and how ILCs are involved in tumour genesis, growth and metastasis.

  10. Innate Lymphoid Cells: Roles In Tumour Genesis And Progression

    Directory of Open Access Journals (Sweden)

    Jovanovic Ivan

    2015-06-01

    Full Text Available Innate lymphoid cells (ILCs represent the most recently identified members of the innate immune system. These cells play important roles in inflammation, tissue remodelling and metabolic disease. ILCs can be subdivided into three major groups according to their cytokine production. The role of ILCs in tumourigenesis and tumour progression is not completely clarified. In this review, we discuss whether and how ILCs are involved in tumour genesis, growth and metastasis.

  11. Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis

    International Nuclear Information System (INIS)

    Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro. In the present study, effects of combinations of WX-UK1 with matrix metalloprotease inhibitors (MMP, galardin®) and cyclooxygenase-2 (COX-2, celecoxib®) inhibitors on tumour cell proliferation, invasion, and angiogenesis induction were evaluated. Matrigel invasion chambers and a spheroid co-cultivation model with human fibroblast served to determine the invasive potential of both FaDu (SCCHN) and HeLa (cervical carcinoma) cells, each treated with combinations of Celecoxib®, Galardin®, and WX-UK1. Blocking of single protease systems resulted in a significant 50% reduction of tumour cell invasion using WX-UK1, while the triple combination was even more effective with 80% reduction of invasion. Additionally, a sprouting assay with HUVEC was used to test the anti-angiogenetic potential of the triple combination, resulting in a 40% decrease in the sprouting rate. A combined approach targeting different families of proteases and cyclooxygenases represents a promising adjuvant therapy

  12. Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma

    International Nuclear Information System (INIS)

    The effects of immunotherapy with irradiated tumour cells and BCG were studied in a non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 x 106 irradiated tumour cells each 1 to 3 weeks before administration of 1 x 106 living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P<0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-weeks intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast o the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere. (author)

  13. Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

    OpenAIRE

    Dirks, Peter B.

    2007-01-01

    Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence poin...

  14. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yijun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Lu, Hongjuan [Productivity Center of Jiangsu Province, Nanjing 210042, Jiangsu (China); Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Taylor, Ethan Will [Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC 27402 (United States); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

    2012-12-15

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  15. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

    OpenAIRE

    R A Lawal; M D Ozaslan; O S Odesanmi; I D Karagoz; I H Kilic; O AT Ebuehi

    2012-01-01

    Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assa...

  16. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...... and in established cell lines was reduced to about the same basic level after treatment with heparin, a highly specific inhibitor of CKII activity. The activity of the cAMP-dependent protein kinase was virtually the same in fibroblasts and various human tumour cell lines investigated....

  17. TH17 cells in tumour immunity and immunotherapy

    OpenAIRE

    Zou, Weiping; Restifo, Nicholas P

    2010-01-01

    T helper 17 (TH17) cells have well-described roles in autoimmune disease. Recent evidence suggests that this effector T cell subset is also involved in tumour immunology and may be a target for cancer therapy. In this Review, we summarize recent findings regarding the nature and relevance of TH17 cells in mouse models of cancer and human disease. We describe the interplay between TH17 cells and other immune cells in the tumour microenvironment, and we assess both the potential antitumorigenic...

  18. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)], e-mail: consuelo@pq.cnpq.br; Cassali, Geovanni D. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada], e-mail: cassalig@icb.ufmg.br

    2009-07-01

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  19. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  20. Effect of chloro- and bromo-derivatives of isocrotonic acid on bioenergetic processes in Ehrlich ascites cells and isolated mitochondria

    International Nuclear Information System (INIS)

    The effect of nine chloro- and bromoderivatives of isocrotonic acid on some bioenergetic processes in both Ehrlich ascites cells and isolated rat liver mitochondria has been investigated. Substances studied in the concentration range 25 to 200 μM significantly inhibited incorporation of both 14C-adenine and 14C-valine into acid-insoluble material of Ehrlich ascites cells. The rate of 14C-precursors incorporation being directly related to the concentration of the inhibitor. γ,γ-bis-4-ethylphenyl-α,β-dichloroisocrotonic acid fully inhibits both aerobic glucose utilization and lactic acid formation at 200 μM concentration. At lower concentrations, however, glycolysis is stimulated. Maximal stimulation of rat liver mitochondrial respiration in state 4 with succinate as substrate was reached at concentrations as low as 10 μM. On the other hand, these substances were able to release the oligomycin-inhibited respiration of rat liver mitochondria. Our data suggest that cytotoxic and cancerostatic action of isocrotonic acid derivatives lies primarily in the exclusion of key processes in the energy metabolism of Ehrlich ascites cells and isolated mitochondria. (author)

  1. Mediastinal germ cell tumour with massive pulmonary involvement

    OpenAIRE

    Kawamukai, Kenji; Di Saverio, Salomone; Antonacci, Filippo; Lacava, Nicola; Boaron, Maurizio

    2011-01-01

    Multimodality treatment, with chemotherapy and surgery, is potentially curative in case of non-seminomatous germ cell tumours. The authors present the case of a primitive mediastinal GTC with bilateral lung metastases. The patient was treated with five cycles of chemotherapy. Restaging showed reduction of the extent and of 18 FDG intake and β-HCG serum levels. The patient underwent two-step surgical excision of the tumours: mediastinal lesion and 35 lung metastases were resected by a right th...

  2. Turnover of phosphocholine and phosphoethanolamine in ether-phospholipids of Krebs II ascite cells

    International Nuclear Information System (INIS)

    Krebs II ascite cells suspended in Eagle medium were incubated at 37 C for up to 6 hr in the presence of [3H] glycerol or [32P] orthophosphate. After extraction, their lipids were treated with guinea pig phospholipase A1 under conditions where all diacyl-phospholipids (diacyl-PL) became hydrolyzed with 55% recovery of lyso-PL. Using a bidimensional thin layer chromatography (TLC) involving exposure to HCl fumes between the two runs, it then became possible to determine at once the specific radioactivity of the three subclasses present in choline glycerophospholipids (CGP) and ethanolamineglycerophospholipids (EGP). Compared to diacyl-PL, a lower de novo synthesis of ether subclasses was evidenced in both CGP and EGP by [3H] glycerol incorporation. Although the same profile was obtained for CGP with [32P] orthophosphate, the three EGP subclasses displayed in this case the same specific radioactivity. These data indicate a higher turnover rate of the polar head group of ether-EGP compared to either-CGP. The simple methodology used in the present study might thus prove helpful in developing enzymatic studies dealing with the mechanism of this accelerated renewal

  3. Properties of a purified nucleolar ribonuclease from Ehrlich ascites carcinoma cells.

    Science.gov (United States)

    Eichler, D C; Tatar, T F

    1980-06-24

    A nucleolar ribonuclease specific for single-stranded ribonucleic acid (RNA) has been isolated and extensively purified from Ehrlich ascites carcinoma cells. The enzyme is optimally active at neutral pH and degrades RNA via a 2',3'-cyclic intermediate leaving 3'- or 2',3'-cyclic terminated oligonucleotides. The ribonuclease has an apparent molecular weight of 38 500 as judged by sedimentation equilibrium and is a basic protein having an isoelectric point greater than 9.0. The enzyme preferentially cleaves poly(C) over poly (U), poly(A), or poly(C).poly(I). Limit digestion products of poly(C) degratation are on the average tri-, tetra-, and pentanucleotides. In the partial digestion of yeast 5.8S rRNA, the nucleolar ribonuclease cleaves only CpA phosphodiester bonds. Spermidine, spermine, and histone I inhibit the activity of nucleolar ribonuclease. Antibodies directed toward pancreatic RNase do not cross-react with the Ehrlich nucleolar ribonuclease. PMID:7397114

  4. Effect of fast electrons and menadione on the structural and functional status of Ehrlich ascites tumor cells at early periods following irradiation

    International Nuclear Information System (INIS)

    Irradiation of Ehrlich ascites tumor cells stimulates oxygen consumption, and menadione supresses cell respiration. The combined effect of the two factors produces an additional, in comparison with the effect of menadione alone, inhibition of the rate of oxygen consumption by cells. There is an additive effect of radiation and menadione with regard to the level of cell thiols and interphase cell death

  5. Niche appropriation by Drosophila intestinal stem cell tumours.

    Science.gov (United States)

    Patel, Parthive H; Dutta, Devanjali; Edgar, Bruce A

    2015-09-01

    Mutations that inhibit differentiation in stem cell lineages are a common early step in cancer development, but precisely how a loss of differentiation initiates tumorigenesis is unclear. We investigated Drosophila intestinal stem cell (ISC) tumours generated by suppressing Notch (N) signalling, which blocks differentiation. Notch-defective ISCs require stress-induced divisions for tumour initiation and an autocrine EGFR ligand, Spitz, during early tumour growth. On achieving a critical mass these tumours displace surrounding enterocytes, competing with them for basement membrane space and causing their detachment, extrusion and apoptosis. This loss of epithelial integrity induces JNK and Yki/YAP activity in enterocytes and, consequently, their expression of stress-dependent cytokines (Upd2, Upd3). These paracrine signals, normally used within the stem cell niche to trigger regeneration, propel tumour growth without the need for secondary mutations in growth signalling pathways. The appropriation of niche signalling by differentiation-defective stem cells may be a common mechanism of early tumorigenesis. PMID:26237646

  6. Malignant granular cell tumour of the sciatic nerve

    International Nuclear Information System (INIS)

    A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated isodensity with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis. 9 refs., 3 figs

  7. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  8. The genomic landscape of epithelioid sarcoma cell lines and tumours.

    Science.gov (United States)

    Jamshidi, Farzad; Bashashati, Ali; Shumansky, Karey; Dickson, Brendan; Gokgoz, Nalan; Wunder, Jay S; Andrulis, Irene L; Lazar, Alexander J; Shah, Sohrab P; Huntsman, David G; Nielsen, Torsten O

    2016-01-01

    We carried out whole genome and transcriptome sequencing on four tumour/normal pairs of epithelioid sarcoma. These index cases were supplemented with whole transcriptome sequencing of three additional tumours and three cell lines. Unlike rhabdoid tumour (the other major group of SMARCB1-negative cancers), epithelioid sarcoma shows a complex genome with a higher mutational rate, comparable to that of ovarian carcinoma. Despite this mutational burden, SMARCB1 mutations remain the most frequently recurring event and are probably critical drivers of tumour formation. Several cases show heterozygous SMARCB1 mutations without inactivation of the second allele, and we explore this further in vitro. Finding CDKN2A deletions in our discovery cohort, we evaluated CDKN2A protein expression in a tissue microarray. Six out of 16 cases had lost CDKN2A in greater than or equal to 90% of cells, while the remaining cases had retained the protein. Expression analysis of epithelioid sarcoma cell lines by transcriptome sequencing shows a unique profile that does not cluster with any particular tissue type or with other SWI/SNF-aberrant lines. Evaluation of the levels of members of the SWI/SNF complex other than SMARCB1 revealed that these proteins are expressed as part of a residual complex, similarly to previously studied rhabdoid tumour lines. This residual SWI/SNF is susceptible to synthetic lethality and may therefore indicate a therapeutic opportunity. PMID:26365879

  9. Anticancer Potential of Aqueous Ethanol Seed Extract of Ziziphus mauritiana against Cancer Cell Lines and Ehrlich Ascites Carcinoma

    Directory of Open Access Journals (Sweden)

    Tulika Mishra

    2011-01-01

    Full Text Available Ziziphus mauritiana (Lamk. is a fruit tree that has folkloric implications against many ailments and diseases. In the present study, anticancer potential of seed extract of Ziziphus mauritiana in vitro against different cell lines (HL-60, Molt-4, HeLa, and normal cell line HGF by MTT assay as well as in vivo against Ehrich ascites carcinoma bearing Swiss albino mice was investigated. The extract was found to markedly inhibit the proliferation of HL-60 cells. Annexin and PI binding of treated HL-60 cells indicated apoptosis induction by extract in a dose-dependent manner. The cell cycle analysis revealed a prominent increase in sub Go population at concentration of 20 μg/ml and above. Agarose gel electrophoresis confirmed DNA fragmentation in HL-60 cells after 3 h incubation with extract. The extract also exhibited potent anticancer potential in vivo. Treatment of Ehrlich ascites carcinoma bearing Swiss albino mice with varied doses (100–800 mg/kg b.wt. of plant extract significantly reduced tumor volume and viable tumor cell count and improved haemoglobin content, RBC count, mean survival time, tumor inhibition, and percentage life span. The enhanced antioxidant status in extract-treated animals was evident from decline in levels of lipid peroxidation and increased levels of glutathione, catalase, and superoxide dismutase.

  10. Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

    DEFF Research Database (Denmark)

    Bush, J M; Gardiner, D W; Palmer, J S; Rajpert-De Meyts, E; Veeramachaneni, D N R

    Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated and characte......Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated and...... characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted in...... canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model for...

  11. Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.

    Science.gov (United States)

    Navabi, H; Croston, D; Hobot, J; Clayton, A; Zitvogel, L; Jasani, B; Bailey-Wood, R; Wilson, K; Tabi, Z; Mason, M D; Adams, M

    2005-01-01

    Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial. PMID:16061407

  12. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Sehested, A; Juhler, M;

    2006-01-01

    , suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with...

  13. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    Energy Technology Data Exchange (ETDEWEB)

    Peres, Elodie A.; Valable, Samuel [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Guillamo, Jean-Sebastien [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Departement de Neurologie, CHU de Caen (France); Marteau, Lena [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Bernaudin, Jean-Francois [Service d' Histologie-Biologie Tumorale, ER2UPMC, Universite Paris 6, Hopital Tenon, Paris (France); Roussel, Simon [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Lechapt-Zalcman, Emmanuele [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Service d' Anatomie Pathologique, CHU de Caen (France); Bernaudin, Myriam [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Petit, Edwige, E-mail: epetit@cyceron.fr [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)

    2011-10-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  14. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  15. Tumour growth delay and cell survival in rat R-1 tumours after radiation and methotrexate treatment

    International Nuclear Information System (INIS)

    The rat R-1 rhabdomyosarcoma which forms colonies in vitro has been used to investigate the effectiveness of radiochemotherapy. Tumour growth delay data were compared with those on survival of cells derived from tumours treated in situ. Methotrexate (MTX) was administered i.p. in three doses of 10 mg per kg body weight at intervals of 4 h. A dose of 10 Gy of 300 kV X rays was given at different time intervals before or after the MTX treatment. The observed tumour growth delays for the combined treatment for intervals of up to 4 d were less than the sum of those following separate treatments. An excess in growth delay was observed when MTX was given 6 to 8 days after or 5 days before a dose of 10 Gy. The radiation treatment resulted in fractions of surviving cells which remained constant for up to 6 days after treatment. The effectiveness of the MTX treatment could be assessed at 3d after administration of the drug, that of the combined treatments as at least 3 days after the MTX treatment. (Auth.)

  16. Systemic therapy for selected skull base sarcomas: Chondrosarcoma, chordoma, giant cell tumour and solitary fibrous tumour/hemangiopericytoma.

    Science.gov (United States)

    Colia, Vittoria; Provenzano, Salvatore; Hindi, Nadia; Casali, Paolo G; Stacchiotti, Silvia

    2016-01-01

    This review highlights the data currently available on the activity of systemic therapy in chondrosarcoma, chordoma, giant cell tumour of the bone (GCTB) and solitary fibrous tumour, i.e., four rare sarcomas amongst mesenchymal malignancy arising from the skull base. PMID:27330421

  17. Vascular mimicry in cultured head and neck tumour cell lines

    OpenAIRE

    Upile, Tahwinder; Jerjes, Waseem; Radhi, Hani; Al-Khawalde, Mohammed; Kafas, Panagiotis; Nouraei, Seyed; Sudhoff, Holger

    2011-01-01

    Introduction Vascuologenesis is the de novo establishment of blood vessels and vascular networks from mesoderm-derived endothelial cell precursors (angioblasts). Recently a novel mechanism, by which some genetically deregulated and aggressive tumour cells generate "micro-vascular" channels without the participation of endothelial cells and independent of angiogenesis, has been proposed. This has been termed "vasculogenic mimicry" and has implications beyond angiogenesis and adds another layer...

  18. Ultrastructure of the extended ribonucleic acid molecules from purified ribosomes of Rous sarcoma virus-induced mouse ascites sarcoma cells

    Directory of Open Access Journals (Sweden)

    Yamamoto,Goki

    1974-04-01

    Full Text Available To clarify the ultrastructure of the extended ribosomal RNA molecules, electron microscopic observations were carried out on the RNA molecules extracted from purified ribosomes of mouse ascites sarcoma cells. By the treatment with ethylenediamine-tetraacetate agglomerated rRNA molecules were elongated to thread-like structure by partial unfolding. The lengths of thread-like molecules were measured as less than Iii. The strand of RNA molecules stained with uranyl acetate was observed approximately l5A in width.

  19. Retracing Circulating Tumour Cells for Biomarker Characterization after Enumeration

    DEFF Research Database (Denmark)

    Frandsen, Anders; Fabisiewicz, Anna; Jagiello-Gruszfeld, Agnieszka;

    2015-01-01

    Background: Retracing and biomarker characterization of individual circulating tumour cells (CTCs) may potentially contribute to personalized metastatic cancer therapy. This is relevant when a biopsy of the metastasis is complicated or impossible to acquire. Methods: A novel disc format was used ...

  20. Mitochondria: An intriguing target for killing tumour-initiating cells

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Dong, L.; Neužil, Jiří

    2016-01-01

    Roč. 26, JAN 2016 (2016), s. 86-93. ISSN 1567-7249 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * ALPHA-TOCOPHERYL SUCCINATE * Therapeutic resistance * Mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.249, year: 2014

  1. Future use of mitocans against tumour-initiating cells?

    Czech Academy of Sciences Publication Activity Database

    Morrison, B.J.; Anděra, Ladislav; Reynolds, B.A.; Ralph, S.J.; Neužil, Jiří

    2009-01-01

    Roč. 53, č. 1 (2009), s. 147-153. ISSN 1613-4125 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : mitocans * tumour-initiating cells * metastasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.356, year: 2009

  2. Genetic analysis of neonatal and infantile germ cell tumours

    NARCIS (Netherlands)

    Veltman, I.M.

    2006-01-01

    Human germ cell tumours (GCTs) can be classified into five distinct types, based on differences in anatomical location, histology, clinical outcome, age and genotype. The first type, the type I GCTs primarily occur in neonates and infants under the age of five years and include teratomas and yolk sa

  3. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    International Nuclear Information System (INIS)

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133+ cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well

  4. Biosensors for the Detection of Circulating Tumour Cells

    Directory of Open Access Journals (Sweden)

    Clotilde Costa

    2014-03-01

    Full Text Available Metastasis is the cause of most cancer deaths. Circulating tumour cells (CTCs are cells released from the primary tumour into the bloodstream that are considered the main promoters of metastasis. Therefore, these cells are targets for understanding tumour biology and improving clinical management of the disease. Several techniques have emerged in recent years to isolate, detect, and characterise CTCs. As CTCs are a rare event, their study requires multidisciplinary considerations of both biological and physical properties. In addition, as isolation of viable cells may give further insights into metastatic development, cell recovery must be done with minimal cell damage. The ideal system for CTCs analysis must include maximum efficiency of detection in real time. In this sense, new approaches used to enrich CTCs from clinical samples have provided an important improvement in cell recovery. However, this progress should be accompanied by more efficient strategies of cell quantification. A range of biosensor platforms are being introduced into the technology for CTCs quantification with promising results. This review provides an update on recent progress in CTCs identification using different approaches based on sensor signaling.

  5. Phyllanthus amarus inhibits cell growth and induces apoptosis in Dalton's lymphoma ascites cells through activation of caspase-3 and downregulation of Bcl-2.

    Science.gov (United States)

    Harikumar, Kuzhuvelil B; Kuttan, Girija; Kuttan, Ramadasan

    2009-06-01

    The authors found in an earlier study that Phyllanthus amarus extract could significantly inhibit the solid and ascites tumor development in mice induced by Dalton's lymphoma ascites (DLA) cells. In the present study, the apoptotic effects of P. amarus against DLA cells in culture was evaluated. P. amarus produced significant reduction in cell viability as determined by the MTT assay. It also induces the formation of apoptotic bodies with characteristic features like plasma membrane invagination, elongation, fragmentation, and chromatin condensation. P. amarus at concentrations of 100 and 200 microg/mL is shown to induce DNA fragmentation. Gene expression analysis reveals that P. amarus induces the expression of caspase-3 and inhibits the expression of Bcl-2, which is an antiapoptotic protein. So the present study provides some insights into the possible mechanism by which P. amarus brings about apoptosis and growth inhibition in DLA cells. PMID:19223368

  6. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Science.gov (United States)

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment. PMID:27509858

  7. The influence of tumour cell DNA content on survival in colorectal cancer: a detailed analysis.

    OpenAIRE

    Armitage, N C; Ballantyne, K. C.; Evans, D F; Clarke, P; Sheffield, J.; Hardcastle, J. D.

    1990-01-01

    We have investigated the influence of tumour cell DNA content (ploidy) on survival of 416 patients undergoing excisional surgery for colorectal cancer. Two hundred and eleven (51%) tumours had an abnormal DNA content (aneuploid or tetraploid). There was no correlation between ploidy status, sex, age and pathological stage, histological grade, tumour site, local tumour extension or assessment of curability. Patients with tumours with an abnormal DNA content had a poorer survival 68/211 (32%) t...

  8. Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation

    DEFF Research Database (Denmark)

    Nielsen, D; Maare, C; Eriksen, J;

    2001-01-01

    ATPase activity was neither stimulated by vinblastine nor VER. CONCLUSION: Irradiation induced a multidrug-resistant phenotype in sensitive tumor cells. This phenotype was characterized by increased expression of Mrp1 mRNA, Mrp1, and PGP but decreased expression of mdr1a + b mRNA. The influence of......PURPOSE: To characterize irradiated murine tumor cells with respect to drug resistance, drug kinetics, and ATPase activity, and to evaluate the possible role of P-glycoprotein (PGP) and murine multidrug resistance associated protein (Mrp1) in the drug-resistant phenotype of these cells. METHODS AND...... MATERIALS: Sensitive Ehrlich ascites tumor cells (EHR2) were in vitro exposed to fractionated irradiation (60 Gy). Western blot analysis was performed for determination of PGP and Mrp1, reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of mdr1a + b mRNA, and semiquantitative RT...

  9. Effect of Irradiation on the Kinetics of Cellular Proliferation in Animal and Human Tumours

    International Nuclear Information System (INIS)

    The kinetics of cellular proliferation in tumours is governed by three main factors, the average duration of the cell cycle, the 'growth fraction' and cell losses. The effect of the last-mentioned factors is the main reason for the variations in rate of growth among solid tumours and for the slackening in the rate of growth observed in a solid tumour as its volume increases. In ascitic tumours the duration of the cell cycle has been found to increase considerably during tumour growth. When a cell is transplanted in the form of an ascitic tumour the mechanisms which explain the gradual slackening of the rate of tumour growth are different from those which obtain when it is grafted in the form of a solid tumour; this shows that these mechanisms depend on extrinsic factors relating to the metabolic conditions,- the cellular micro environment and intercellular contact phenomena. The phenomena which occur in an irradiated tumour are quantitatively similar to those found in normal tissue, but they may differ from the qualitative point of, view and in respect of temporal behaviour. These differences, which doubtless depend on the type of tumour, will have to be analysed before radiotherapy can be used to the maximum advantage. (author)

  10. Proliferation of pulmonary artery smooth muscle cells in the development of ascites syndrome in broilers induced by low ambient temperature.

    Science.gov (United States)

    Wang, J; Qiao, J; Zhao, L H; Li, K; Wang, H; Xu, T; Tian, Y; Gao, M; Wang, X

    2007-12-01

    Pulmonary vascular remodelling, mainly characterized by arterial medial thickening, is an important pathological feature of broiler ascites syndrome (AS). Since vascular smooth muscle cells (VSMC) form the major cellular component of arterial medial layer, we speculate that VSMC proliferation is one of the causes of pulmonary arterial medial thickening in ascitic broilers. Hence, the present study was designed to investigate the role of VSMC proliferation in pulmonary vascular remodelling in development of AS induced by low ambient temperature. Broilers in control group (22 +/- 1.5 degrees C) and low temperature group (11 +/- 2 degrees C) were sampled every week at 15-50 days of age. Proliferative indexes of VSMC in pulmonary arteries were assessed with proliferating cell nuclear antigen, and the relative medial thickness (RMT) and relative wall area (RWA), as indexes of pulmonary vascular remodelling, were examined by computer-image analysing system. The results showed that the high incidence (18.75%) of AS was induced by low temperature, and a significantly increased VSMC proliferation was observed in pulmonary arteries in the low temperature group at 22-50 days of age (P < 0.05). In addition, RMT and RWA in pulmonary arteries were significantly elevated in the low temperature group from 36 days of age (P < 0.05), indicating that pulmonary vascular remodelling occurred following VSMC proliferation in AS. Our data suggest that proliferation of VSMC may facilitate pulmonary vascular remodelling and have a pivotal role in AS induced by low ambient temperature. PMID:18045340

  11. Selective assessment of in vitro radiosensitivity of tumour cells and fibroblasts from single tumour biopsies using immunocytochemical identification of colonies in the soft agar clonogenic assay

    International Nuclear Information System (INIS)

    The assumed selective growth of tumour cells has formed the basis for the use of the soft agar clonogenic assay to test in vitro radio- and chemosensitivity of tumours. However, recent studies have demonstrated that fibroblasts proliferate in soft agar in addition to tumour cells. The present study was initiated to quantify the contaminating growth of non-malignant cells in the modified form of the Courtenay-Mills soft agar assay, in order to establish a reliable assay for estimating tumour cell radiosensitivity in squamous cell carcinomas of the head and neck. DNA flow cytometry analysis confirmed that 'tumour fibroblasts' (fibroblasts obtained from tumour biopsies) grow in soft agar. In contrast, white blood cells did not form colonies. Different media were tested with soft agar, but a selective medium for tumour cells was not found. Therefore, a colony filter-technique combined with an immunocytochemical analysis was developed to quantify the number of tumour cell and fibroblast colonies. In 12 tumour biopsies, 2-33% of the colonies were Cytokeratin AE1-3 positive, whereas 83-100% of the colonies were 5B5 fibroblast antibody positive. The parameter normally reported, the overall SF2 (surviving cell fraction at 2 Gy) based on colonies in agar, was found to be statistically significantly correlated to the fibroblast SF2, but not to the tumour cell SF2. The overall SF2 was significantly different from the tumour cell SF2 in half of the tumours. Furthermore, the tumour cell SF2 was not correlated to fibroblast SF2. In consequence of our findings, correcting for fibroblast contamination is a necessity, when studying in vitro sensitivity of tumour cells. Combining the soft agar clonogenic assay with the new colony filter-technique and the immunocytochemical analysis appear to be useful for making this routine correction and for measuring the in vitro radiosensitivity of both tumour cells and fibroblasts from single tumour biopsies, which is of interest in future

  12. Interaction of the 2,6-dimethoxysemiquinone and ascorbyl free radicals with Ehrlich ascites cells: a probe of cell-surface charge.

    OpenAIRE

    Pethig, R; Gascoyne, P R; McLaughlin, J. A.; Szent-Györgyi, A

    1984-01-01

    The rate of quenching by Ehrlich ascites cells of anionic 2,6-dimethoxy-p-semiquinone and ascorbyl free radicals is investigated as a function of cell concentration, the blocking of cell-surface sulfhydryl groups by N-ethylmaleimide, and the reduction of cell-surface charge by neuraminidase. The rate of quenching is found to be proportional to cell viability and to the number of free cell-surface sulfhydryl groups. The enzymatic action of neuraminidase results in an increase of the free radic...

  13. The role of myeloid cells in the promotion of tumour angiogenesis.

    Science.gov (United States)

    Murdoch, Craig; Muthana, Munitta; Coffelt, Seth B; Lewis, Claire E

    2008-08-01

    The use of various transgenic mouse models and analysis of human tumour biopsies has shown that bone marrow-derived myeloid cells, such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells, have an important role in regulating the formation and maintenance of blood vessels in tumours. In this Review the evidence for each of these cell types driving tumour angiogenesis is outlined, along with the mechanisms regulating their recruitment and activation by the tumour microenvironment. We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies. PMID:18633355

  14. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

    NARCIS (Netherlands)

    Boks, Martine A.; Ambrosini, Martino; Bruijns, Sven C.; Kalay, Hakan; Van Bloois, Louis; Storm, G; Garcia-Vallejo, Juan J.; Van Kooyk, Yvette

    2015-01-01

    Abstract Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhance

  15. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses

    NARCIS (Netherlands)

    Boks, M.A.; Ambrosini, Martino; Bruijns, Sven C.M.; Kalay, Hakan; Bloois, van Louis; Storm, G.; Garcia-Vallejo, Juan J.; Kooyk, van Y.

    2015-01-01

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with st

  16. Ultrastructural changes produced in Ehrlich ascites carcinoma cells by ultraviolet-visible radiation in the presence of melanins

    Energy Technology Data Exchange (ETDEWEB)

    Lea, P.J.; Pawlowski, A.; Persad, S.D.; Menon, I.A.; Haberman, H.F.

    1988-01-01

    Irradiation of Ehrlich ascites carcinoma (EAC) cells in the presence of pheomelanin, i.e., red hair melanin (RHM), has been reported to produce extensive cell lysis. Irradiation in the presence of eumelanin, i.e., black hair melanin (BHM), or irradiation in the absence of either type of melanin did not produce this effect. We observed that RHM particles penetrated the cell membrane without apparent structural damage to the cell or the cell membrane. Irradiation of the cells in the absence of melanin did not produce any changes in the ultrastructure of the cells. Incubation of the cells in the dark in the presence of RHM produced only minor structural, mainly cytoplasmic changes. Irradiation of the cells in the presence of RHM produced extensive ultrastructural changes prior to complete cell lysis; these changes were more severe than the effects of incubation of the cells in the dark in the presence of RHM. When the cells incubated in the dark or irradiated in the presence of latex particles or either one of the eumelanins particles, viz. BHM or synthetic dopa melanin, these particles did not penetrate into the cells or produce any ultrastructural changes. These particles were in fact not even ingested by the cells.

  17. Ultrastructural changes produced in Ehrlich ascites carcinoma cells by ultraviolet-visible radiation in the presence of melanins

    International Nuclear Information System (INIS)

    Irradiation of Ehrlich ascites carcinoma (EAC) cells in the presence of pheomelanin, i.e., red hair melanin (RHM), has been reported to produce extensive cell lysis. Irradiation in the presence of eumelanin, i.e., black hair melanin (BHM), or irradiation in the absence of either type of melanin did not produce this effect. We observed that RHM particles penetrated the cell membrane without apparent structural damage to the cell or the cell membrane. Irradiation of the cells in the absence of melanin did not produce any changes in the ultrastructure of the cells. Incubation of the cells in the dark in the presence of RHM produced only minor structural, mainly cytoplasmic changes. Irradiation of the cells in the presence of RHM produced extensive ultrastructural changes prior to complete cell lysis; these changes were more severe than the effects of incubation of the cells in the dark in the presence of RHM. When the cells incubated in the dark or irradiated in the presence of latex particles or either one of the eumelanins particles, viz. BHM or synthetic dopa melanin, these particles did not penetrate into the cells or produce any ultrastructural changes. These particles were in fact not even ingested by the cells

  18. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells

    DEFF Research Database (Denmark)

    Cheng, Chang; Edin, Nina F Jeppesen; Lauritzen, Knut H;

    2012-01-01

    Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tum...... tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma....

  19. Chromatin structure and epigenetics of tumour cells: A review

    Czech Academy of Sciences Publication Activity Database

    Bártová, Eva; Krejčí, Jana; Hájek, R.; Harničarová, Andrea; Kozubek, Stanislav

    2009-01-01

    Roč. 9, č. 1 (2009), s. 51-61. ISSN 1871-529X R&D Projects: GA AV ČR(CZ) 1QS500040508; GA ČR(CZ) GA204/06/0978 Grant ostatní: GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : tumour cells * chromatin * radiation Subject RIV: BO - Biophysics

  20. Diagnostic technologies for circulating tumour cells and exosomes

    OpenAIRE

    Shao, Huilin; Chung, Jaehoon; Issadore, David

    2016-01-01

    Circulating tumour cells (CTCs) and exosomes are promising circulating biomarkers. They exist in easily accessible blood and carry large diversity of molecular information. As such, they can be easily and repeatedly obtained for minimally invasive cancer diagnosis and monitoring. Because of their intrinsic differences in counts, size and molecular contents, CTCs and exosomes pose unique sets of technical challenges for clinical translation–CTCs are rare whereas exosomes are small. Novel techn...

  1. Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line.

    Science.gov (United States)

    Miyamoto, K; Wakabayashi, D; Minamino, T; Nomura, M; Wakusawa, S; Nakamura, S

    1996-01-01

    Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and clorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil. AH66 cells contained much glutahione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to clorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas. PMID:8702243

  2. POMB/ACE chemotherapy for mediastinal germ cell tumours.

    Science.gov (United States)

    Bower, M; Brock, C; Holden, L; Nelstrop, A; Makey, A R; Rustin, G J; Newlands, E S

    1997-05-01

    Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates. PMID:9291802

  3. Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.

    OpenAIRE

    Liebmann, J. E.; Cook, J. A.; Lipschultz, C.; Teague, D.; Fisher, J; Mitchell, J B

    1993-01-01

    The cytotoxicity of paclitaxel against eight human tumour cell lines has been studied with in vitro clonogenic assays. The fraction of surviving cells fell sharply after exposure for 24 h to paclitaxel concentrations ranging from 2 to 20 nM; the paclitaxel IC50 was found to range between 2.5 and 7.5 nM. Increasing the paclitaxel concentration above 50 nM, however, resulted in no additional cytotoxicity after a 24 h drug exposure. Cells incubated in very high concentrations of paclitaxel (10,0...

  4. Complications of the post-chemotherapy resection of retroperitoneal residual tumour mass in patients with non-seminomatous testicular germ cell tumours

    NARCIS (Netherlands)

    Gels, ME; Nijboer, AP; Hoekstra, HJ; Sleijfer, DT; Molenaar, WM; Plukker, JT; Droste, JHJ; Schraffordt Koops, H.

    1997-01-01

    Objective To evaluate the resection of the retroperitoneal residual tumour mass (RRTM) for histological examination after chemotherapy in patients with disseminated non-seminomatous testicular germ cell tumours (NSTGCTs), with particular attention to surgical morbidity. Patients and methods From 197

  5. Efficient Monte Carlo modelling of individual tumour cell propagation for hypoxic head and neck cancer

    Science.gov (United States)

    Tuckwell, W.; Bezak, E.; Yeoh, E.; Marcu, L.

    2008-09-01

    A Monte Carlo tumour model has been developed to simulate tumour cell propagation for head and neck squamous cell carcinoma. The model aims to eventually provide a radiobiological tool for radiation oncology clinicians to plan patient treatment schedules based on properties of the individual tumour. The inclusion of an oxygen distribution amongst the tumour cells enables the model to incorporate hypoxia and other associated parameters, which affect tumour growth. The object oriented program FORTRAN 95 has been used to create the model algorithm, with Monte Carlo methods being employed to randomly assign many of the cell parameters from probability distributions. Hypoxia has been implemented through random assignment of partial oxygen pressure values to individual cells during tumour growth, based on in vivo Eppendorf probe experimental data. The accumulation of up to 10 million virtual tumour cells in 15 min of computer running time has been achieved. The stem cell percentage and the degree of hypoxia are the parameters which most influence the final tumour growth rate. For a tumour with a doubling time of 40 days, the final stem cell percentage is approximately 1% of the total cell population. The effect of hypoxia on the tumour growth rate is significant. Using a hypoxia induced cell quiescence limit which affects 50% of cells with and oxygen levels less than 1 mm Hg, the tumour doubling time increases to over 200 days and the time of tumour growth for a clinically detectable tumour (109 cells) increases from 3 to 8 years. A biologically plausible Monte Carlo model of hypoxic head and neck squamous cell carcinoma tumour growth has been developed for real time assessment of the effects of multiple biological parameters which impact upon the response of the individual patient to fractionated radiotherapy.

  6. Efficient Monte Carlo modelling of individual tumour cell propagation for hypoxic head and neck cancer

    International Nuclear Information System (INIS)

    A Monte Carlo tumour model has been developed to simulate tumour cell propagation for head and neck squamous cell carcinoma. The model aims to eventually provide a radiobiological tool for radiation oncology clinicians to plan patient treatment schedules based on properties of the individual tumour. The inclusion of an oxygen distribution amongst the tumour cells enables the model to incorporate hypoxia and other associated parameters, which affect tumour growth. The object oriented program FORTRAN 95 has been used to create the model algorithm, with Monte Carlo methods being employed to randomly assign many of the cell parameters from probability distributions. Hypoxia has been implemented through random assignment of partial oxygen pressure values to individual cells during tumour growth, based on in vivo Eppendorf probe experimental data. The accumulation of up to 10 million virtual tumour cells in 15 min of computer running time has been achieved. The stem cell percentage and the degree of hypoxia are the parameters which most influence the final tumour growth rate. For a tumour with a doubling time of 40 days, the final stem cell percentage is approximately 1% of the total cell population. The effect of hypoxia on the tumour growth rate is significant. Using a hypoxia induced cell quiescence limit which affects 50% of cells with and oxygen levels less than 1 mm Hg, the tumour doubling time increases to over 200 days and the time of tumour growth for a clinically detectable tumour (109 cells) increases from 3 to 8 years. A biologically plausible Monte Carlo model of hypoxic head and neck squamous cell carcinoma tumour growth has been developed for real time assessment of the effects of multiple biological parameters which impact upon the response of the individual patient to fractionated radiotherapy

  7. PDT and tumour infiltrating immune cells

    International Nuclear Information System (INIS)

    Mechanisms involved in tumor destruction following PhotoDynamic Therapy are still under investigation. Direct killing of tumor cells by phototoxic action is not the only mechanism responsible for tumor destruction. When Photofrin is used as a photosensitizer a majority of tumor cells is killed by secondary mechanisms, expressed only if tumor is left in situ for at least 6-12 hours after light treatment. The indirect mechanism of tumor destruction by PDT has been described as a massive necrosis of tumor tissue resulting from hypoxia induced by destruction of tumor vasculature. Earliest changes in tumor vasculature already occur during the course of light illumination. They include accumulation of polymorphonuclear leukocytes (neutrophils), platelet aggregation, vasoconstriction followed by vascular stasis and hemorrhage. Release of mediators of inflammation (e.g. prostaglandin E2, thromboxane), cytokines, proteolytic enzymes and other substances was also demonstrated. These events are typical for inflammatory response. Nature and significance of this response has, however, not been studied in detail. Initial results on host immune cell infiltration into PDT treated murine tumor are reported here. (author). 16 refs., 1 fig., 1 tab

  8. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination.

    Science.gov (United States)

    Le, Caroline P; Nowell, Cameron J; Kim-Fuchs, Corina; Botteri, Edoardo; Hiller, Jonathan G; Ismail, Hilmy; Pimentel, Matthew A; Chai, Ming G; Karnezis, Tara; Rotmensz, Nicole; Renne, Giuseppe; Gandini, Sara; Pouton, Colin W; Ferrari, Davide; Möller, Andreas; Stacker, Steven A; Sloan, Erica K

    2016-01-01

    Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes. PMID:26925549

  9. Mixed germ cell tumour of testis: a case report with review of literature

    Directory of Open Access Journals (Sweden)

    S. V. Kumar

    2015-01-01

    Full Text Available Testicular tumours are rare neoplasm. Mixed germ cell tumour is the most common histological variant. Essentially, any admixture of the germ cell tumours as seen in pure form may be seen, one of the most common admixtures being embryonal carcinoma and teratoma. Unfortunately many of these patients present late usually with some complications. We present a rare case of mixed germ cell tumour with predominant embryonal carcinoma and yolk sac tumour in adolescent patient with multiple metastatic foci at the time of presentation. [Int J Res Med Sci 2015; 3(1.000: 327-330

  10. Juvenile granulosa cell tumour: a rare clinical entity

    Directory of Open Access Journals (Sweden)

    Kaliki Hymavathi Reddy

    2014-08-01

    Full Text Available Ovarian cancer is the third most common neoplasm of the female genital tract. Based on the cell type of origin, primary ovarian malignancies are classified into surface epithelium, germ cell, and sex cord tumors. Sex cord tumors account for 1% to 2% of ovarian malignancies. They may contain granulosa cells, theca cells, sertoli cells, or fibroblasts of gonadal stromal origin. Granulosa Cell Tumours (GCTs account for approximately 2-5% of all ovarian tumors and can be divided into adult (95% and juvenile (5% types based on histologic findings. GCTs secrete estrogen thus resulting in menstrual irregularities in the affected individual. More serious estrogen effects can occur in various end organs such as uterus resulting in endometrial hyperplasia, endometrial adenocarcinomas and increased risk of breast cancers. Androgen production is also reported but rare and produces virilization in the affected women. Juvenile Granulosa Cell Tumours (JGCTs are clinically and histopathologically distinct from the GCTs. They are rarely encountered but mostly in youngsters. Surgery is the primary modality of treatment with chemotherapy being reserved for advanced or recurrent disease states. We herewith report an interesting case of JGCT in a young teenage girl. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 1150-1154

  11. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    OpenAIRE

    Kumar, Saurabh; Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case present...

  12. In situ and in vitro profiling of brain tumour initiating cells of high-grade gliomas

    OpenAIRE

    Leidgens, Verena Jeannine

    2016-01-01

    High-grade gliomas, especially glioblastomas, are highly complex and heterogeneous primary brain tumours. Glioblastoma (GBM) is one of the most aggressive cancers with poor overall survival prognosis. Fast and widespread invasion of the brain parenchyma by a subpopulation of progenitor tumour cells is a main pathophysiological feature of these tumours. Invasion renders localised therapies ineffective and is a primary cause of tumour recurrence as well as associated morbidity. Identification o...

  13. Continuous cell lines and immune ascitic fluid pools in arbovirus detection

    OpenAIRE

    Digoutte, J. P.; Calvo-Wilson, M.A.; Mondo, M.; Traore-Lamizana, Moumouni; Adam, François

    1992-01-01

    Pour la recherche et l'isolement des arbovirus, des expérimentations successives nous ont amenés à utiliser, parmi les lignées de cellules en culture continue dont l'utilisation est préconisée par l'OMS, les deux systèmes cellulaires MOS61 (cellules de #Aedes pseudoscutellaris$) et Vero. La détection des virus dans les sytèmes cellulaires est réalisée à l'aide de 7 pools de 10 ascites hyperimmunes polyvalentes. Cette technique permet la mise en évidence de 70 sur 80 arbovirus transmis par le...

  14. The epigenetics of tumour initiation: cancer stem cells and their chromatin.

    Science.gov (United States)

    Avgustinova, Alexandra; Benitah, Salvador Aznar

    2016-02-01

    Cancer stem cells (CSCs) have been identified in various tumours and are defined by their potential to initiate tumours upon transplantation, self-renew and reconstitute tumour heterogeneity. Modifications of the epigenome can favour tumour initiation by affecting genome integrity, DNA repair and tumour cell plasticity. Importantly, an in-depth understanding of the epigenomic alterations underlying neoplastic transformation may open new avenues for chromatin-targeted cancer treatment, as these epigenetic changes could be inherently more amenable to inhibition and reversal than hard-wired genomic alterations. Here we discuss how CSC function is affected by chromatin state and epigenomic instability. PMID:26874045

  15. The influence of X radiation on the proliferation kinetics of Ehrlich ascites tumors of different ploidy (in vivo investigations following 500 ROD)

    International Nuclear Information System (INIS)

    The proliferation kinetics following a single irradiation (500 ROD) was investigated in the following work in two Ehrlich ascites tumors of different ploidy (diploid EAT and tetraploidy ELT). The H3 thymidine availiblity time hardly changed after irradiation, it was about 40 minutes as in untreated control tumours. The H3 thymidine incorporation rate, in contrast, was in reduced both tumours by about 75% of the value for the untreated control tumour. The H3 labelling index did not greatly deviate from the control vlues. In the investigation of the cell cycle in the %-labelled mitosis test and with the double labelling method, both tumours exhibited distinctly different behaviour: Whilst the tetraploid exhibited no considerable extension of the S-phase and the generation time changed only slightly, the doploid EAT showed an ectension of S-phase and generation time of about the factor 2. In further tests, after irradiating both ascites tumours, all counting showed a clearly slower cell multiplication was found compared to the untreated control tumour. Whilst this was especially due to a strangly increasing dealth rate with ELT, it was more likely the longer generation time at merely moderate death rate which can be assumed as inhibiting the proliferation in the case of EAT sub(dipl). The mitosis index exhibited a depression of over 5 hours for EATsub(dipl) and of over 20 hours for ELT. Here too a different behaviour can be seen for both tumours after irradiation. As a whole, the results obtained for the different ploidy ascites tumours after X-radiation are to be considered as expression of the individuality of various tumour cell strains. (orig./MG)

  16. Carcinoma in situ testis, the progenitor of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G;

    2005-01-01

    Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...

  17. Triple angiokinase inhibition, tumour hypoxia and radiation response of FaDu human squamous cell carcinomas

    International Nuclear Information System (INIS)

    Background and purpose: To test the effect of BIBF 1120, a novel small molecule inhibitor of multiple angiogenic receptor tyrosine kinases, on the hypoxia and radiation response of tumours. Materials and methods: Poorly differentiated human squamous cell carcinoma FaDu growing in nude mice was treated with BIBF 1120 and investigated by functional histology. To test the effect of BIBF 1120 on the radiobiological hypoxic fraction (rHF), the number and intrinsic radiation sensitivity of tumour stem cells and the outcome after fractionated irradiation, a series of local tumour control assays were performed. Results: BIBF 1120 significantly reduced the vessel area, vessel area with a perfusion signal and tumour growth rate but did not affect tumour hypoxia or the number and intrinsic radiation sensitivity of tumour stem cells. Concurrent BIBF 1120 had no effect on local tumour control after fractionated irradiation. Conclusion: Triple angiokinase inhibition resulted in a clear-cut decrease of angiogenesis, vessel area with a perfusion signal and tumour growth but did not change tumour hypoxia or radiation response of tumour stem cells. Further experiments into mechanisms of interaction between anti-angiogenic strategies and irradiation appear to be necessary to better define and exploit the potential of this strategy to improve local tumour control after fractionated radiotherapy.

  18. Possible interrelationship between changes in F-actin and myosin II, protein phosphorylation, and cell volume regulation in Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Pedersen, S F; Hoffmann, E K

    2002-01-01

    Osmotic shrinkage of Ehrlich ascites tumor cells (EATC) elicited translocation of myosin II from the cytosol to the cortical region, and swelling elicits concentration of myosin II in the Golgi region. Rho kinase and p38 both appeared to be involved in shrinkage-induced myosin II reorganization. In...... effects on F-actin. The subsequent F-actin depolymerization, however, appeared MLCK- and PKC-dependent, and the initial swelling-induced F-actin depolymerization was MLCK-dependent; both effects were apparently secondary to kinase-mediated effects on cell volume changes. NHE1 in EATC is activated both by...

  19. Effect of anti-glycolytic agents on tumour cells in vitro

    Science.gov (United States)

    Korshunov, D. A.; Kondakova, I. V.

    2016-08-01

    A metabolic change is one of the tumour hallmarks, which has recently attracted a great amount of attention. One of the main metabolic characteristics of tumour cells is a high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in a glycolysis pathway than that in a tricarboxylic acid cycle. The Warburg effect constitutes a fundamental adaptation of tumour cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumour glycolysis may become an attractive target for cancer therapy. Here, we research the effect of potential anticancer agents on tumour cells in vitro. In our study, we found a high sensitivity of tumour cells to anti-glycolityc drugs. In addition, tumour cells are more resistant to the agents studied in comparison with normal cells. We also observed an atypical cooperative interaction of tumour cells in the median lethal dose of drugs. They formed the specific morphological structure of the surviving cells. This behavior is not natural for the culture of tumour cells. Perhaps this is one of the mechanisms of cells' adaptation to the aggressive environment.

  20. Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach.

    OpenAIRE

    Niitsu, Y; Ito, N.; Kohda, K; Owada, M.; Morita, K.; Sato, S.; Watanabe, N.; Kohgo, Y; Urushizaki, I.

    1988-01-01

    Human gastric carcinomas were tested for their immunohistochemical reactivity with anti-type I procollagen antiserum. In all specimens of scirrhous carcinomas, staining of the tumour cells was strongly positive, while in medullary carcinomas staining of the tumour cells was generally poor. These results suggest that the tumour cells in scirrhous carcinomas produce collagen in their stroma. Images Figure 1 Figure 4 Figure 3 Figure 5

  1. Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo

    International Nuclear Information System (INIS)

    The effect of plumbagin, a naphthoquinone from the roots of the Indian medicinal plant Plumbago rosea, and cobalt-60 gamma radiation was studied on Ehrlich ascites carcinoma in vivo, taking cytogenetic damage and cell cycle changes as experimental endpoints. Plumbagin (5 mg/kg body wt, Pl) administered intraperitoneally produced a significant increase in the percentage of S-phase as well as G2-M cells with a corresponding decrease in the G1 phase at different post-treatment times. Radiation (7.5 Gy, RT) alone produced the classical G2 block at 1 hr, which persisted with a continuous increase throughout the post-treatment observation period. The combination treatment produced a similar effect as that of RT on G2-M cells, but its effect on the G1 phase was more pronounced than the latter. While Pl treatment produced a small increase in the percentage of labelled S-phase cells, combination treatment significantly reduced the labelled S-phase cells with a corresponding increase in the unlabelled fraction. Drug or radiation alone significantly increased micronuclei induction at various post-treatment times and the combination of the two further enhanced this effect additively. The mechanism of interaction of Pl with radiation in bringing about this effect is not clear. (author)

  2. Protective Effect of Propolis (Bee Glue) in Mice Bearing Ehrlich Ascites Carcinoma

    International Nuclear Information System (INIS)

    Cancer is considered one of the most common causes of morbidity and mortality worldwide. Many studies were carried out to investigate the discovery of natural and synthetic compounds that can be used in the prevention and/or treatment of cancer. Natural products of either plant or animal origin that exhibit antitumour activity have been discovered. The present study was undertaken to evaluate the protective effect of ethanolic extract of propolis without or with radiation exposure in Ehrlich ascites carcinoma- bearing female albino mice. The animals were randomly distributed into three major groups as follows: group A (control group): consists of 10 mice kept on normal standard rodent diet without any treatment and housed in two cages: mice of the first cage served as control for non tumour-bearing group and the second cage served as control for tumour-bearing group. Group B (non tumour-bearing group): consists of 15 mice and used to study the effect of the vehicle solution (gum acacia), propolis and gamma irradiation on normal mice. Mice of this group were equally distributed into three subgroups receiving gum acacia, propolis for two weeks and gamma irradiated. Group C (tumour bearing group): consists of 20 mice randomly and equally distributed into 4 subgroups: Ehrlich ascites carcinoma, Ehrlich ascites carcinoma and 2 Gy irradiated, Ehrlich ascites carcinoma and propolis treated, and Ehrlich ascites carcinoma and propolis irradiated. Plasma and hepatic lipid peroxidation index (TBARS), superoxide dismutase (SOD) and glutathione (GSH) were assessed in RBC and liver together with hepatic aspartate amino transferase (AST) and alanine amino transferase (ALT) and histopathological examination of liver sections. There was decrease in the levels of SOD and GSH as well as an increase in TBARS in mice bearing EAC in addition to increase in hepatic levels of AST and ALT. The microscopical examination of liver sections of mice bearing EAC showed various histopathological

  3. Evaluation of antitumour activity and antioxidant status in Dioscorea hispida, Dennst. leaves on Ehrlich Ascites Carcinoma in Swiss Albino Mice

    OpenAIRE

    Punith kumar. T. G; Panduranga Murthy. G; Suresh. A, Suresh. V; Senthil kumar N; Raviashankar. H. G

    2011-01-01

    Cancer’ is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumour, or proliferate throughout the body. Next to heart disease, cancer is a killer of mankind. The present study aims at a preliminary phytochemical analysis and anticancer evaluation of Dioscorea hispida, Dennst. against Ehrlich Ascites Carcinoma in animal model. The results indicate that ethanolic extract of Dioscorea hispida leaves (DhLE)...

  4. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  5. Galectin-3 coats the membrane of breast cells and makes a signature of tumours

    KAUST Repository

    Simone, Giuseppina

    2014-01-01

    Galectin-3, β-galactoside-binding lectin, coats the membrane of most cancer cells and is involved in metastasis and endothelium recognition as well as in evading immune surveillance through killing of activated T cells. To flag galectin as a biomarker of tumours and metastasis, it is pivotal to understand the role of this protein in different tumours and at different stages. Breast tumours have an anomalous behaviour of the galectin-3 compared to other tumour cells. Herein, FACS sorting and galactoside based assays were used to investigate the role of galectin-3 in metastasis and metastatisation of breast cancer cells. Breast galectin fingerprint at the FACS displayed a higher amount in healthy cells, compared to metastatic cells. The microfluidic assay was able to isolate tumour and metastatic cells more than healthy breast cells. Investigation was performed on samples from patients with breast tumours at stage I and stage III whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The readout of the conditioned medium (from culturing of stage I cells) fingerprint by FACS evidenced high expression of free galectin. Analysis of the results established that the galectin coating the membrane, by galactoside recognition of the breast cells, and engaged by the cells to form protein-carbohydrate complexes inside the microfluidic assay, resembled the tumour signature of tumours in breast cells whilst the galectin free is independent of those mechanisms. © 2014 The Royal Society of Chemistry.

  6. Role of metallothionein in cisplatin sensitivity of germ-cell tumours

    NARCIS (Netherlands)

    Meijer, C.; Timmer, A.; Vries, E.G.E.de; Groten, J.P.; Knol, A.; Zwart, N.; Dam, W.A.; Sleijfer, D.Th.; Mulder, N.H.

    2000-01-01

    Cisplatin (CDDP) is an extremely active drug in the treatment of germ- cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell tumour and 3 colon-carcinoma cell lines. Major components of the

  7. Tc(V)-DMS tumour imaging agent

    International Nuclear Information System (INIS)

    The data obtained by the authors provide good evidence of Tc(V)-DMS as a stable, large-molecular-size Tc-complex or polynuclear Tc-complex, comparable to Tc-cit and Ga-cit. A role for this polynuclear configuration in the generation of Tc-species with affinity for neoplastic cells was demonstrated using the dilution method as a promoter of Tc(V)-DMS dissociation. The concurrent Ehrlich ascites tumour cell uptake studies with TLC analysis revealed the chromatographically detected changes well traced by the biological cell utilization. The biological implications of dilution as one of the factors regulating radiopharmaceutical delivery to the tumour cell tissue were better demonstrated in the biodistribution studies carried out with Erhlich ascites-bearing mice. If, on the basis of the present data, the authors may take their postulate one step further, a more dissociated Tc-species, defined speculatively as TcO/sub 4//sup 3-/, might constitute an active Tc- species within the cell interacting with some tumour-specific substance or site. Research to find evidence of its presence is currently in progress

  8. Tumour cell proliferation after failed ruthenium plaque radiotherapy for posterior uveal melanoma

    International Nuclear Information System (INIS)

    Enucleation following ruthenium plaque radiotherapy for posterior uveal melanoma indicates failure of treatment. This study focused on the histopathological findings and remaining tumour cell growth fraction in 42 of 46 patients with failed ruthenium plaque treatment (of 266 patients treated) for melanoma of the choroid or ciliary body. The cause for enucleation was clinically detected tumour regrowth in 27 (64%) patients, treatment-related ocular side effects in 12 (29%) cases and the patient's personal preference in three (7%) cases. The median time elapsing from plaque radiotherapy to enucleation was not significantly different for patients with recurrent tumour growth (23 months) compared to those enucleated without clinical signs of regrowth (19 months). While all tumours showed some regressive features by histopathological examination, only five melanomas were completely necrotic and viable-appearing tumours cells were present in all of the remaining 37 (88%) irradiated tumours. Microwave processed PC-10 immunostaining increased the sensitivity to detect cycling cells compared to the sole use of mitotic cell counts. By the former technique, proliferating tumour cells were detected in 17 or 23 (74%) studied melanomas of eyes enucleated for tumour regrowth following brachytherapy. Also, the number of cycling melanoma cells was similar to that of non-irradiated controls managed solely by enucleation. In contrast, the proliferative compartment of irradiated, but non-recurrent, posterior uveal melanomas were significantly reduced compared to those of matched controls. Still, cycling tumour cells were present in four of 13 (31%) irradiated melanomas, clinically assumed to be successfully treated. (au) 43 refs

  9. Radical Resection of a Late-Relapsed Testicular Germ Cell Tumour: Hepatectomy, Cavotomy, and Thrombectomy

    OpenAIRE

    C. Ní Leidhin; Redmond, C. E.; Cahalane, A. M.; Heneghan, H. M.; R. Motyer; Ryan, E. R.; Hoti, E.

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. Thi...

  10. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  11. Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

    International Nuclear Information System (INIS)

    Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo

  12. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    Science.gov (United States)

    Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case presented malignant transformation of the epithelial component showing foci of squamous cell carcinoma within the GCT. PMID:26266228

  13. Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

    LENUS (Irish Health Repository)

    Tan, B

    2012-02-03

    BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

  14. Competition for cytotoxic immune capacity against a 'syngeneic' mouse tumour distributed at two sites.

    Science.gov (United States)

    Chassoux, D; MacLennan, I C; Munro, T R

    1977-06-15

    Normal C3H mice will develop fatal ascites after the intraperitoneal injection of as few as 100 BP8 cells. However, mice can be immunized so that they can specifically reject an intraperitoneal challenge of 10(7) of these C3H-derived tumour cells. This paper investigates a phenomenon in which the capacity of immunized mice to reject an intraperitoneal challenge of tumour cells is lost between two to seven days after tumour cells have been given subcutaneously. Investigation of this temporary loss of capacity to reject the intraperitoneal challenge of tumour suggests that this might be due to the attraction of cytotoxic immunity to the site of subcutaneous injection. The possibility that this phenomenon is due to blocking factors, tumour overload, suppressor cells or enhancing antibody has been investigated but experimental results are given which do not favour these explanations. PMID:873644

  15. Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites

    OpenAIRE

    Francés, R; Muñoz, C.; Zapater, P; Uceda, F; Gascón, I; Pascual, S.; Pérez-Mateo, M; J. Such

    2004-01-01

    Background and aims: Translocation of intestinal bacteria to ascitic fluid is probably the first step in the development of episodes of spontaneous bacterial peritonitis in patients with cirrhosis. We have recently reported the detection of bacterial DNA in blood and ascitic fluid from patients with advanced cirrhosis, what we consider as molecular evidence of bacterial translocation. Several studies have shown the immunogenic role of bacterial DNA in vitro, and we hypothesised that the prese...

  16. Mixed germ cell tumour of ovary presenting as pregnancy: a rare presentation

    Directory of Open Access Journals (Sweden)

    Kavita Mahadevappa

    2015-12-01

    Full Text Available Malignant mixed germ cell tumour of the ovary containing embryonal carcinoma and choriocarcinoma is a very rare entity. These tumours can present as precocious puberty or menstrual irregularities in adolescent girls. Here we report a case of 22 year old lady who presented as 5 months pregnancy in antenatal clinic. MRI Imaging and tumour markers revealed malignant ovarian tumour. Patient underwent surgicopathological staging and was found to have malignant mixed germ cell tumour stage IIIB, comprising of both choriocarcinoma and embryonal carcinoma components. Patient received one cycle of chemotherapy and was called for follow up. Mixed malignant germ cell tumour of the ovary is a highly aggressive neoplasm that can present in advanced stage. A high clinical suspicion is needed in patients presenting with pelvic mass associated with menstrual irregularity or amenorrhoea in adolescent and young women. [Int J Reprod Contracept Obstet Gynecol 2015; 4(6.000: 2084-2087

  17. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    Science.gov (United States)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  18. A single dividing cell population with imbalanced fate drives oesophageal tumour growth.

    Science.gov (United States)

    Frede, Julia; Greulich, Philip; Nagy, Tibor; Simons, Benjamin D; Jones, Philip H

    2016-09-01

    Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium. However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by Kras(G12D) expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity. PMID:27548914

  19. Rapid and quantitative discrimination of tumour cells on tissue slices.

    Science.gov (United States)

    Huang, Kai-Wen; Chieh, Jen-Jie; Liao, Shu-Hsien; Wei, Wen-Chun; Hsiao, Pei-Yi; Yang, Hong-Chang; Horng, Herng-Er

    2016-06-10

    After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology. PMID:27138705

  20. Rapid and quantitative discrimination of tumour cells on tissue slices

    Science.gov (United States)

    Huang, Kai-Wen; Chieh, Jen-Jie; Liao, Shu-Hsien; Wei, Wen-Chun; Hsiao, Pei-Yi; Yang, Hong-Chang; Horng, Herng-Er

    2016-06-01

    After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology.

  1. FIBULA AND ILIAC BONE GRAFTING WITH INTERNAL FIXATION FOR GAINT CELL TUMOUR OF PROXIMAL TIBIA

    OpenAIRE

    Nishant Gaonkar; Takale; Kolekar; Vaibhav Koli; Jimit Shah

    2015-01-01

    Middle aged old female with swelling in left knee suggestive of giant cell tumour was treated with excisional biopsy with curettage, phenol cauterisation , bone graft and proximal tibia locking plate fixation. Sample sent for histopathology was consistent with diagnosis of giant cell tumour. No recurrence has been seen after 1 year of follow up.

  2. FIBULA AND ILIAC BONE GRAFTING WITH INTERNAL FIXATION FOR GAINT CELL TUMOUR OF PROXIMAL TIBIA

    Directory of Open Access Journals (Sweden)

    Nishant Gaonkar

    2015-02-01

    Full Text Available Middle aged old female with swelling in left knee suggestive of giant cell tumour was treated with excisional biopsy with curettage, phenol cauterisation , bone graft and proximal tibia locking plate fixation. Sample sent for histopathology was consistent with diagnosis of giant cell tumour. No recurrence has been seen after 1 year of follow up.

  3. Giant cell tumour of the tendon sheath of the hand: a pictorial essay

    International Nuclear Information System (INIS)

    Giant cell tumour of the tendon sheath is a soft tissue mass found occasionally in the hand. Its diagnosis can be readily made preoperatively if the characteristic MRI features are appreciated. This pictorial essay demonstrates and describes the imaging findings correlated with histopathological findings in a group of patients with proven giant cell tumour of the tendon sheath. Copyright (2001) Blackwell Science Pty Ltd

  4. Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy, cavotomy, and thrombectomy.

    Science.gov (United States)

    Ní Leidhin, C; Redmond, C E; Cahalane, A M; Heneghan, H M; Motyer, R; Ryan, E R; Hoti, E

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation. PMID:25587480

  5. Radical Resection of a Late-Relapsed Testicular Germ Cell Tumour: Hepatectomy, Cavotomy, and Thrombectomy

    Directory of Open Access Journals (Sweden)

    C. Ní Leidhin

    2014-01-01

    Full Text Available Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation.

  6. Incomplete free fatty acid oxidation by ascites tumor cells under low oxygen tension.

    Science.gov (United States)

    Ookhtens, M; Baker, N

    1983-01-01

    We tried to understand why our earlier estimates of fatty acid (FA) oxidation rates under the nearly anaerobic state of the Ehrlich ascites tumor (EAT) in vivo were even greater than those found in vitro under aerobic conditions. Using tracers [1-14C]linoleate, [1-14C]-, and [9,10-3H]palmitate, and NaH14CO3, we estimated essential and nonessential FA oxidation rates to CO2 + H2O by EAT in living mice and in vitro under aerobic and anaerobic conditions. Sequestration of intraperitoneally (ip)-injected 14C-FFA allowed a selective labeling of the tumor versus the host; thus, breath 14CO2 could be used to estimate the maximum rate of FA oxidation in vivo by the tumor. Initially, we measured breath 14CO2 following NaH14CO3 injections and developed a multicompartmental model to simulate the tumor-host HCO-3-CO2 system. This model was integrated with our earlier model for tumor FA turnover. The integrated model was fitted to breath 14CO2 data from mice injected ip with 14C-FFA to compute tumor FA oxidation rates. Both essential and nonessential FA were oxidized to CO2 at similar rates. The maximum rate of total FA oxidation to CO2 was 5-6 nmol FA X min-1 X 7-ml tumor-1, about 5-10 times lower than all previous estimates obtained in vitro and in vivo. To resolve this dilemma we used doubly labeled [1-14C; 9,10-3H]palmitate and found that under aerobic conditions, in vitro, EAT formed 3H2O and 14CO2 at nearly equal rates. These rates were suppressed markedly but unequally at low PO2. Anaerobic suppression of 14CO2 formation greatly exceeded that of 3H2O formation. As a result 3H2O/14CO2 reached a value of congruent to 10 at low PO2. Our data indicate that under the nearly anaerobic conditions of a growing EAT in vivo, the partial beta-oxidation of FA to 2C + H2O takes place at a 5 to 10 times faster rate than the complete oxidation of FA to CO2 + H2O. This finding can account for earlier apparent inconsistencies in the literature, since aerobic studies of 14C-FA oxidation

  7. Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.;

    2012-01-01

    to determine whether this heterogeneity persisted in tumours established from these clones, and whether the response to radiation treatment was principally governed by cell intrinsic qualities or by factors pertaining to the tumour microenvironment, such as the degree of hypoxia and vascularisation....... Methods: Immune deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400mm3. Radiation was given as a single fraction of 0 to 15 Gy and the...... degree of tumour control and time to three times the treatment volume were noted. Tumours used for the microenvironmental assay had intratumoral hypoxia measured by the Eppendorf oxygen electrode and Pimonidazole staining, and the extent of vascularisation determined by a microvasculature density assay...

  8. Epidermal Langerhans` cell induction of immunity against an ultraviolet-induced skin tumour

    Energy Technology Data Exchange (ETDEWEB)

    Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M. [Royal Prince Alfred Hospital, Sydney, NSW (Australia). Dept. of Medicine (Dermatology)

    1996-03-01

    Lanerghans` cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia{sup +} EC and was tumour specific. Thus Ia{sup +} epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author).

  9. Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

    International Nuclear Information System (INIS)

    Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia+ EC and was tumour specific. Thus Ia+ epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

  10. Radiosensitization by cisplatin of RIF1 tumour cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Begg, A.C.; Kolk, P.J. van der; Dewit, L.; Bartelink, H.

    1986-11-01

    The ability of cis-diamminedichloroplatinum (II) (c-DDP) to enhance radiation-induced cell killing was tested on oxic RIF1 tumour cells in monolayer culture. Marked radiosensitization of the survivors of a 1 h drug treatment was found with all c-DDP doses tested, enhancement ratios increasing from 1.2 to 2.2 with increasing drug dose. Isobologram analyses showed that the interactions of c-DDP with X-rays were supra-additive. To test whether part of the enhancement was due to a selection of subpopulations, the diploid and tetraploid RIF1 cells, normally coexisting in culture, were separated by (a) unit gravity velocity sedimentation, and (b) by developing diploid and tetraploid clones. Both methods showed little difference in either drug sensitivity or radiation sensitivity between diploid and tetraploid cells. DNA histograms obtained by flow cytometry showed little or no cycle progression during the 1 h drug treatment. These data indicate that the radiosensitization was not the result of the drug exposure leaving cells in a radiosensitive phase. The observed radiosensitization, therefore, appears to have resulted from a true drug/X-ray interaction.

  11. Testicular germ cell tumours and parental occupational exposure to pesticides

    DEFF Research Database (Denmark)

    Le Cornet, Charlotte; Fervers, Béatrice; Oksbjerg Dalton, Susanne;

    2015-01-01

    controls per case were randomly selected from the general national populations, matched on year of birth. Information on parental occupation was collected through censuses or Pension Fund information and converted into a pesticide exposure index based on the Finnish National Job-Exposure Matrix. RESULTS......OBJECTIVES: A potential impact of exposure to endocrine disruptors, including pesticides, during intrauterine life, has been hypothesised in testicular germ cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large-scale registry-based case-control study aimed to investigate...... the association between parental occupational exposure to pesticides and TGCT risk in their sons. METHODS: Cases born in 1960 or onwards, aged between 14 and 49 years, and diagnosed between 1978 and 2013 in Denmark, Finland, Norway or Sweden, were identified from the respective nationwide cancer registries. Four...

  12. Two cases report of a malignant germ cell tumour of ovary and a granulosa cell tumour:Interest of tumoral immunochemistry in the identification and management.

    Directory of Open Access Journals (Sweden)

    Jean eBouquet De Jolinière

    2014-05-01

    Full Text Available Abstract Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23 year old female and a case of a bilateral undifferentiated granulosa cell tumor in a 71 year old female. The aim of these reports is to illustrate the interest of the immuno-histochemical analysis to define the correct diagnosis, to better classify these ovarian tumours and improve their management. Methods: This study we report two cases. The first case concern a 23 years old woman (A with a mixed germ cell tumour of the right ovary (dysgerminoma (75%, yolk sac tumour (20%, and a mature teratoma (5%, and the second case (B a bilateral non differentiated and necrotic granulosa cell tumour of both ovaries concerning a 71 year old patient. The staging system used was according to both classifications, the one of International Federation of Gynaecology and Obstetrics (FIGO 1987 for ovarian cancer, and the one of TNM code 2009. Results: The immunostaining establish the malignancy and the immunochemistry contribute to confirm effectively the right diagnosis (Table 2 and 3. Conclusion: An immuno-histochemical analysis is mandatory for the choice of chemotherapy to obtain the better response of the disease and improve the survival prognosis. The efficiency of the chemotherapy authorizes a conservative surgery including a unilateral salpingo-oophorectomy preserving fertility (A. Concerning the non-dysgerminoma tumour (B, and after a surgical staging and debulking, chemotherapy was recommended. The type of tumour and its histological feature conditioned the choice of treatment. The benefit of the immunohistological analysis in this case allowed the right adjuvant treatment. Key words: germ cell tumours, dysgerminoma, teratoma, yolk sac, ovarian cell tumour, and immunohistochemistry.

  13. Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

    International Nuclear Information System (INIS)

    Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC50=25±0.38) when compared to reference compound PTER (IC50=65±0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. - Highlights: • Conjugate was prepared by appending isothiocyanate moiety on pterostilbene backbone. • Conjugate showed anticancer effects at comparatively lower dose than pterostilbene. • Conjugate caused blockage of the Akt and ERK signaling pathways in MCF-7 cells. • Conjugate significantly reduced solid tumor volume as compared to pterostilbene

  14. Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Nikhil, Kumar; Sharan, Shruti; Chakraborty, Ajanta [Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand (India); Bodipati, Naganjaneyulu; Krishna Peddinti, Rama [Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand (India); Roy, Partha, E-mail: paroyfbs@iitr.ernet.in [Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand (India)

    2014-01-15

    Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC{sub 50}=25±0.38) when compared to reference compound PTER (IC{sub 50}=65±0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. - Highlights: • Conjugate was prepared by appending isothiocyanate moiety on pterostilbene backbone. • Conjugate showed anticancer effects at comparatively lower dose than pterostilbene. • Conjugate caused blockage of the Akt and ERK signaling pathways in MCF-7 cells. • Conjugate significantly reduced solid tumor volume as compared to pterostilbene.

  15. Glucose uptake-stimulatory activity of Tinospora cordifolia stem extracts in Ehrlich ascites tumor cell model system.

    Science.gov (United States)

    Joladarashi, Darukeshwara; Chilkunda, Nandini D; Salimath, Paramahans Veerayya

    2014-01-01

    Diabetes mellitus is a multifunctional disorder with several causes and multiple consequences. Nutraceuticals play a vital role in ameliorating diabetic condition. The stems of the plant, Tinospora cordifolia (T. cordifolia) are often used in Ayurvedic medicine for the management of diabetes. Earlier studies have shown that T. cordifolia to be a potent antidiabetic plant material by virtue of being rich in nutraceuticals. In the present study we were interested to know if, T. cordifolia stem extracts are able to promote glucose uptake through glucose transporters, 1 (GLUT1) and 3 (GLUT3), which are responsible for basal glucose uptake. Hence, Ehrlich ascites tumor (EAT) cells were chosen as a model which harbours both GLUT1 and GLUT3 and glucose uptake was measured using a fluorescent analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG). Serially, solvent extracted T. cordifolia stems, especially water, ethanol and methanol extracts showed glucose uptake activity. Uptake was stimulated in a dose dependent manner at dosages of 1-100 μg. Glucose-stimulating activity does not seem to be solely due to polyphenol content since methanol extract, with high amount of polyphenol content (9.5 ± 0.1 g kg(-1)), did not stimulate higher glucose uptake activity when compared to water extract. PMID:24426067

  16. Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer.

    OpenAIRE

    Alexandroff, A B; McIntyre, C A; Porter, J. C.; Zeuthen, J; Vile, R. G.; Taub, D. D.

    1998-01-01

    The Second Meeting of the British Society for Immunology Tumour Immunology Affinity Group (TIAG) took place at King's College (London, UK) on 17-18 June 1997 and brought together over 100 tumour immunologists from the UK and abroad. In contrast to previous meetings the focus of the meeting was on the role of adhesion in immunosurveillance and tumour dissemination. In addition, recent achievements in the areas of chemokines, cytotoxic T-lymphocyte (CTL) and natural killer (NK) cells, co-stimul...

  17. Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer

    OpenAIRE

    Goeppert, B; Frauenschuh, L; Zucknick, M; Stenzinger, A; Andrulis, M; Klauschen, F; Joehrens, K; Warth, A; Renner, M.; Mehrabi, A; Hafezi, M.; Thelen, A; Schirmacher, P; Weichert, W

    2013-01-01

    Background: Biliary tract cancers (BTC) are relatively rare malignant tumours with poor prognosis. It is known from other solid neoplasms that antitumour inflammatory response has an impact on tumour behaviour and patient outcome. The aim of this study was to provide a comprehensive characterisation of antitumour inflammatory response in human BTC. Methods: Tumour-infiltrating T lymphocytes (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes (CD20+), macrophages (CD68+) ...

  18. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    OpenAIRE

    Collins Hilary M; Abdelghany Magdy K; Messmer Marie; Yue Baigong; Deeves Sian E; Kindle Karin B; Mantelingu Kempegowda; Aslam Akhmed; Winkler G Sebastiaan; Kundu Tapas K; Heery David M

    2013-01-01

    Abstract Background Post-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on hi...

  19. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Adriana J Michielsen

    Full Text Available Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5 could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  20. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  1. The Preparation of Mice Ascites with Anti-HBs/a Monoclonal Antibody Hybridoma Cell Separated from Mice Ascites%分离小鼠腹水中抗HBs/a单克隆抗体杂交瘤细胞制备小鼠腹水

    Institute of Scientific and Technical Information of China (English)

    邹汉武; 刘琦

    2001-01-01

    探讨利用从小鼠腹水中分离获得的单克隆抗体杂交瘤细胞, 大量制备小鼠单克隆抗体腹水的方法:收集已接种单克隆抗体杂交瘤细胞的小鼠腹水,用淋巴细胞分离液离心分离腹水中的杂交瘤细胞;再将此分离出的杂交瘤细胞,注入其他小鼠腹腔又制得腹水。每只小鼠分离得到的杂交瘤细胞可供5只小鼠腹腔注射, 平均每只小鼠产腹水3.97 ml。此法可规模制备大量高效价的单克隆抗体腹水。%A large quantity of mice McAb ascites with monoclonal antibody (McAb) hybridoma cells separated from mice ascites was prepared. Ascites of mice inoculated with McAb hybridoma cells were collected, and the McAb hybridoma cells were isolated by centrifugation with lymphocyte separating fluid. McAb hybridoma cells then were injected into other mice abdominal cavity to prepare ascites again. McAb hybridoma cells separated from a mouse could be injected into the abdominal cavity of 5 mice. Each mouse could produce 3.97 ml ascites on average. This method could be used to prepare large quantity of high titer mice monoclonal anti-HBs/a ascites.

  2. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    International Nuclear Information System (INIS)

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

  3. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    International Nuclear Information System (INIS)

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer

  4. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cabeza, Laura [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Cano-Cortés, Victoria; Rodríguez, María J. [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Vélez, Celia; Melguizo, Consolación, E-mail: melguizo@ugr.es [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Sánchez-Martín, Rosario M., E-mail: rmsanchez@ugr.es [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Prados, Jose [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain)

    2015-01-15

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer.

  5. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral microenvironment.

    Science.gov (United States)

    Garibay-Cerdenares, O L; Hernández-Ramírez, V I; Osorio-Trujillo, J C; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype. PMID:26211665

  6. How does the metabolism of tumour cells differ from that of normal cells

    OpenAIRE

    Amoêdo, Nívea Dias; Valencia, Juan Perez; Rodrigues, Mariana Figueiredo; Galina, Antonio; Rumjanek, Franklin David

    2013-01-01

    Tumour cells thrive in environments that would be hostile to their normal cell counterparts. Survival depends on the selection of cell lines that harbour modifications of both, gene regulation that shifts the balance between the cell cycle and apoptosis and those that involve the plasticity of the metabolic machinery. With regards to metabolism, the selected phenotypes usually display enhanced anaerobic glycolysis even in the presence of oxygen, the so-called Warburg effect, and anabolic path...

  7. Circulating Cell-Free Tumour DNA in the Management of Cancer

    Science.gov (United States)

    Francis, Glenn; Stein, Sandra

    2015-01-01

    With the development of new sensitive molecular techniques, circulating cell-free tumour DNA containing mutations can be identified in the plasma of cancer patients. The applications of this technology may result in significant changes to the care and management of cancer patients. Whilst, currently, these “liquid biopsies” are used to supplement the histological diagnosis of cancer and metastatic disease, in the future these assays may replace the need for invasive procedures. Applications include the monitoring of tumour burden, the monitoring of minimal residual disease, monitoring of tumour heterogeneity, monitoring of molecular resistance and early diagnosis of tumours and metastatic disease. PMID:26101870

  8. Circulating Cell-Free Tumour DNA in the Management of Cancer

    Directory of Open Access Journals (Sweden)

    Glenn Francis

    2015-06-01

    Full Text Available With the development of new sensitive molecular techniques, circulating cell-free tumour DNA containing mutations can be identified in the plasma of cancer patients. The applications of this technology may result in significant changes to the care and management of cancer patients. Whilst, currently, these “liquid biopsies” are used to supplement the histological diagnosis of cancer and metastatic disease, in the future these assays may replace the need for invasive procedures. Applications include the monitoring of tumour burden, the monitoring of minimal residual disease, monitoring of tumour heterogeneity, monitoring of molecular resistance and early diagnosis of tumours and metastatic disease.

  9. RM-06IN VITRO CLONAL EVOLUTION OF GLIOBLASTOMA (GBM) BRAIN TUMOUR INITIATING CELLS (BTIC) TO MODEL TUMOUR RECURRENCE

    OpenAIRE

    Qazi, Maleeha; Vora, Parvez; Venugopal, Chitra; McFarlane, Nicole; Hallett, Robin; Singh, Sheila

    2014-01-01

    Glioblastoma (GBM) is the most common and highly aggressive primary adult brain tumour. Despite multimodal therapy, patients on average experience relapse at 9 months and median survival rarely extends beyond 15 months. Targeting the cells that drive GBM formation as well as its inevitable and rapid recurrence has remained a major challenge, likely due to intra-tumoral heterogeneity. At the genetic level, this heterogeneity has prompted a molecular classification of GBM based on differential ...

  10. How does the metabolism of tumour cells differ from that of normal cells.

    Science.gov (United States)

    Amoêdo, Nívea Dias; Valencia, Juan Perez; Rodrigues, Mariana Figueiredo; Galina, Antonio; Rumjanek, Franklin David

    2013-01-01

    Tumour cells thrive in environments that would be hostile to their normal cell counterparts. Survival depends on the selection of cell lines that harbour modifications of both, gene regulation that shifts the balance between the cell cycle and apoptosis and those that involve the plasticity of the metabolic machinery. With regards to metabolism, the selected phenotypes usually display enhanced anaerobic glycolysis even in the presence of oxygen, the so-called Warburg effect, and anabolic pathways that provide precursors for the synthesis of lipids, proteins and DNA. The review will discuss the original ideas of Otto Warburg and how they initially led to the notion that mitochondria of tumour cells were dysfunctional. Data will be presented to show that not only the organelles are viable and respiring, but that they are key players in tumorigenesis and metastasis. Likewise, interconnecting pathways that stand out in the tumour phenotype and that require intact mitochondria such as glutaminolysis will be addressed. Furthermore, comments will be made as to how the peculiarities of the biochemistry of tumour cells renders them amenable to new forms of treatment by highlighting possible targets for inhibitors. In this respect, a case study describing the effect of a metabolite analogue, the alkylating agent 3BP (3-bromopyruvate), on glycolytic enzyme targets will be presented. PMID:24079832

  11. Early growth of tumour cells in lung tissue

    International Nuclear Information System (INIS)

    As the treatment of metastases is a very important problem in human and veterinary medicine (for instance osteosarcoma is notorious for its high deathrate due to this problem), proof was sought for the hypothesis that the doubling time of early metastases is shorter than that of tumor cells of an older age. This is of fundamental importance for the therapeutic problem: is a favourable effect to be expected from a limited dose of radiation on the lungs when metastases are still very small or even invisible. If the hypothesis holds true, it would be justified to treat patients, even though a small group of patients will be treated unnecessarily; clinical experience shows that some patients have not developed metastases without adjuvant treatment. The interest was directed at the very early (1-cell, 2-cell etc.) stages. Obviously these are not detectable in patients and therefore an experimental study with tumourcells in the lungs of mice was devised. The expectation is that the theoretical approach may produce an additional basis for the radiotherapeutic and chemotherapeutic treatment of patients, in whom the tumourload has been diminished by treatment of the primary tumour but where metastases, although frequently not detectable must be expected. (Auth.)

  12. Prediction of radiosensitivity in tumour cells: use of the alkaline comet assay to assess radiosensitivity in bladder and colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Radiotherapy is the treatment of choice for a wide range of solid tumours yet it is impossible to predict which tumours will show a good response. We have investigated the radiosensitivity of a number of tumour cell lines (5 bladder and 4 colorectal) to verify whether the alkaline comet assay (ACA) can be used to predict tumour radiosensitivity. Preliminary studies showed that it is essential to carry out irradiations on cells pre-embedded in agarose to ensure that repair, prior to lysis, is kept to a minimum. Cells were embedded prior to irradiation, lysed and the comet tail moment analysed; this was compared to cell survival measured using a clonogenic assay. For all doses (0 - 6Gy) there was a good correlation between the two measures: r2 0.897 for bladder tumour cells and r2 = 0.929 for colorectal tumour cells. We also irradiated cells with 4Gy X-rays and measured initial damage, repair rate and residual damage. In both groups initial DNA damage and residual damage correlated with clonogenic survival; repair rate was very similar for the cell lines and was not predictive. One cell line (T24) had a pronounced shoulder on the radiation dose response curve such that there was a radioresistant response at 2 Gy and a radiosensitive response at 4 Gy. This change in response within the clinically relevant range emphasises that for a predictive test to have validity in the clinic it must be carried out in the clinically relevant range. The finding that initial damage varies between individual cell lines is consistent with some, but not all reports in the literature. We have also carried out nuclear texture analysis to measure phenotypic changes in DNA distribution and chromatin organisation. The results support the contention that organisation of nuclear chromatin is inherently different in different cell lines and may be significant in determining their response to radiation damage

  13. Chronic phase CML patients possess T cells capable of recognising autologous tumour cells.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2002-05-01

    Much circumstantial evidence points to the immunogenicity of chronic myloid leukemia (CML) cells, most impressively the well-established T cell-dependent GvL effect seen in bone marrow transplantation. However, only a small number of shared antigens expressed by CML cells have been identified as potential targets for T cell-mediated immune responses which might be exploited for immunotherapy. It may be that unique antigens expressed by individual tumours are more potent rejection antigens if the patient's own T cells could be encouraged to react against them. Work is reviewed here which documents that in vitro mixed cultures between autologous T cells and dendritic cells of chronic-phase CML patients can give rise to sensitised T cells capable of recognising the patient's tumour cells. Additionally, mixed autologous tumour cell/lymphocyte cultures, modified by the addition of cytokine cocktails, may also result in the generation of similarly sensitised T cells. These results could be exploited for adoptive immunotherapy, and possibly, after identification of the antigens recognised, also for active immunotherapy, i.e. including therapeutic vaccination. PMID:12148904

  14. Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation

    International Nuclear Information System (INIS)

    Purpose: To characterize irradiated murine tumor cells with respect to drug resistance, drug kinetics, and ATPase activity, and to evaluate the possible role of P-glycoprotein (PGP) and murine multidrug resistance associated protein (Mrp1) in the drug-resistant phenotype of these cells. Methods and Materials: Sensitive Ehrlich ascites tumor cells (EHR2) were in vitro exposed to fractionated irradiation (60 Gy). Western blot analysis was performed for determination of PGP and Mrp1, reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of mdr1a + b mRNA, and semiquantitative RT-PCR for Mrp1 mRNA. The clonogenic assay was applied to investigate sensitivity, whereas the steady-state drug accumulation of daunorubicin (DNR), 3H-vincristine (VCR), and 3H-etoposide (VP16) was measured by spectrofluorometry and scintillation counting, respectively. For determining of ATPase activity, the release of inorganic phosphate from ATP was quantified using a colorimetric method. Results: Compared with EHR2, the irradiated cell line EHR2/irr showed increased expression of PGP (threefold), Mrp1 (eightfold), and Mrp1 mRNA (sixfold), and a slight reduction of mdr1b mRNA, whereas mdr1a was present in EHR2 but could not be detected in EHR2/irr. EHR2/irr developed sixfold resistance to VP16, twofold resistance to vincristine, but remained sensitive to DNR. Addition of the PGP inhibitor, verapamil (VER) or depletion of glutathione by buthionine sulfoximine (BSO) partly reversed the resistance in EHR2/irr. In EHR2/irr, the steady-state accumulation of 3H-VCR and 3H-VP16 was significantly decreased as compared with EHR2, whereas the accumulation of DNR was unchanged. The ATPase activity of plasma membrane vesicles prepared from EHR2/irr cells was similar to that of wild-type EHR2 cells. The ATPase activity was neither stimulated by vinblastine nor VER. Conclusion: Irradiation induced a multidrug-resistant phenotype in sensitive tumor cells. This phenotype was

  15. Nonlinear modelling of cancer: bridging the gap between cells and tumours

    International Nuclear Information System (INIS)

    Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of

  16. [{sup 18}F]FDG PET monitoring of tumour response to chemotherapy: does [{sup 18}F]FDG uptake correlate with the viable tumour cell fraction?

    Energy Technology Data Exchange (ETDEWEB)

    Spaepen, Karoline; Stroobants, Sigrid; Dupont, Patrick; Bormans, Guy; Mortelmans, Luc [Department of Nuclear Medicine, UZ Gasthuisberg, Herestraat 49, 3000, Leuven (Belgium); Balzarini, Jan [Rega Institute, Katholieke Universiteit, Leuven (Belgium); Verhoef, Gregor; Vandenberghe, Peter [Department of Hematology, UZ Gasthuisberg, Leuven (Belgium); De Wolf-Peeters, Christine [Department of Pathology, UZ Gasthuisberg, Leuven (Belgium)

    2003-05-01

    Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [{sup 18}F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [{sup 18}F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10{sup 6} Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [{sup 18}F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [{sup 18}F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [{sup 18}F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [{sup 18}F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [{sup 18}F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells. (orig.)

  17. Clinical studies of hepatocellular carcinoma with liver cirrhosis and ascites.

    Directory of Open Access Journals (Sweden)

    Yuasa,Shiro

    1984-06-01

    Full Text Available A comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC accompanied with hepatocellular carcinoma (HCC (of which 35 had ascites and 24 did not at the time of admission and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not. HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96% died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.

  18. Host microenvironment in breast cancer development: Inflammatory and immune cells in tumour angiogenesis and arteriogenesis

    International Nuclear Information System (INIS)

    Breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated 'normal' cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In particular, infiltrating immune/inflammatory cells secrete a diverse repertoire of growth factors and proteases that enable them to enhance tumour growth by stimulating angiogenesis and, as we suggest here, by promoting 'tumour arteriogenesis' – enlargement of feeding vessels supplying the expanding tumour capillary bed. Macrophages and their chemoattractants (e.g. macrophage chemoattractant protein-1) are critical for the arteriogenic process in ischaemia, and probably also in breast neoplasia. A better understanding of these various cellular and molecular constituents of breast cancer neovascularization may be useful in designing more effective therapies

  19. The influence of membrane-active agents on the radiomodifying effect of glucose in x-irradiated Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    A study was made of the influence of membrane-active agents with different mechanisms of action (quercetine, amyloride, valinomycine, and digitonine), that modify the transmembrane transfer of inorganic ions, on a modifying effect of a glucose loading in X-irradiated Ehrlich ascites tumor cells. The combination of digitonine with glucose increased the damaging effect of radiation on tumor cells by 1.8-2.2 times as compared to glucose alone. Merely insignificant changes in the radiomodyfying effect of glucose were observed when it was combined with other membrane-active agents

  20. Cell Shrinkage is Essential in Lysophosphatidic Acid Signaling in Ehrlich Ascites

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Hoffmann, Else Kay; Hougaard, Charlotte;

    2000-01-01

    ; (ii) a subsequent cell shrinkage and increased polymerization of F-actin, and (iii) activation of a Na(+)/H(+) exchange, resulting in a concentration-dependent intracellular alkalinization. The EC(50) value for the LPA-induced rate of alkalinization was estimated at 0. 37 nm LPA. When cell shrinkage...

  1. Tumour-initiating cells vs. cancer "stem" cells and CD133: What's in the name?

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Stantic, M.; Zobalová, Renata; Chladová, Jaromíra; Wang, X. F.; Procházka, L.; Dong, L.; Anděra, Ladislav; Ralph, S.J.

    2007-01-01

    Roč. 255, č. 4 (2007), s. 855-859. ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : tumour-initiating cells * CD133 * resistance to treatment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.749, year: 2007

  2. Genomic profiling of papillary renal cell tumours identifies small regions of DNA alterations: a possible role of HNF1B in tumour development

    NARCIS (Netherlands)

    Szponar, A.; Yusenko, M.V.; Kuiper, R.P.; Geurts van Kessel, A.H.M.; Kovacs, G.

    2011-01-01

    AIMS: Papillary renal cell tumours (RCT) are characterized by specific trisomies. The aim of this study was to identify small regions of duplication marking putative tumour genes. METHODS AND RESULTS: Full-tiling path bacterial artificial chromosome (BAC) array hybridization of 20 papillary RCTs con

  3. Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer.

    Science.gov (United States)

    Berntsson, Jonna; Nodin, Björn; Eberhard, Jakob; Micke, Patrick; Jirström, Karin

    2016-09-01

    Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study. PMID:27074317

  4. Prospects for T cell immunotherapy of tumours by vaccination with immunodominant and subdominant peptides.

    Science.gov (United States)

    Melief, C J; Kast, W M

    1994-01-01

    Immunotherapy of tumours by adoptive transfer of cytotoxic T lymphocytes (CTL) is now feasible in experimental murine systems. These CTL recognize peptide sequences of defined length presented by major histocompatibility complex (MHC) class I molecules. Effective eradication of large tumour masses requires co-administration of interleukin 2. Tumour escape strategies are numerous but in various instances can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic virally induced tumours and other tumours requires novel strategies to overcome T cell inertia. We propose a strategy in which CTL are raised against target molecules of choice including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The steps proposed include: (1) identification of target molecules of choice. (2) Identification in these target molecules of peptides fitting MHC allele-specific peptide motifs involved in peptide binding to MHC molecules. (3) Evaluation of actual binding of such peptides to specific MHC class I molecules. (4) In vitro CTL response induction by such peptides, presented by highly efficient antigen-presenting cells such as antigen processing-defective cells carrying empty MHC class I molecules loaded with a single peptide or dendritic cells. Both types of cells are capable of primary CTL response induction in vitro. (5) Evaluation of proper processing by the demonstration of tumour cell lysis by these CTL. (6) Adoptive transfer of tumour-specific CTL generated in vitro or vaccination with peptides. These various steps have now been taken for several viruses, virally induced tumours and other types of tumours and the first indications that this strategy is useful have been obtained. PMID:7796678

  5. Re-programming tumour cell metabolism to treat cancer: no lone target for lonidamine.

    Science.gov (United States)

    Bhutia, Yangzom D; Babu, Ellappan; Ganapathy, Vadivel

    2016-06-01

    Tumour cell metabolism is very different from normal cell metabolism; cancer cells re-programme the metabolic pathways that occur in normal cells in such a manner that it optimizes their proliferation, growth and survival. Although this metabolic re-programming obviously operates to the advantage of the tumour, it also offers unique opportunities for effective cancer therapy. Molecules that target the tumour cell-specific metabolic pathways have potential as novel anti-cancer drugs. Lonidamine belongs to this group of molecules and is already in use in some countries for cancer treatment. It has been known for a long time that lonidamine interferes with energy production in tumour cells by inhibiting hexokinase II (HKII), a glycolytic enzyme. However, subsequent studies have uncovered additional pharmacological targets for the drug, which include the electron transport chain and the mitochondrial permeability transition pore, thus expanding the pharmacological effects of the drug on tumour cell metabolism. A study by Nancolas et al. in a recent issue of the Biochemical Journal identifies two additional new targets for lonidamine: the pyruvate transporter in the mitochondria and the H(+)-coupled monocarboxylate transporters in the plasma membrane (PM). It is thus becoming increasingly apparent that the anti-cancer effects of lonidamine do not occur through a single target; the drug works at multiple sites. Irrespective of the molecular targets, what lonidamine does in the end is to undo what the tumour cells have done in terms of re-programming cellular metabolism and mitochondrial function. PMID:27234586

  6. Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Nardou Katya

    2008-06-01

    Full Text Available Abstract Background Histone deacetylase inhibitors (HDACi are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. Results We show here that the HDACi Sodium Butyrate (NaB, suberoylanilide hydroxamic acid (SAHA and Trichostatin A (TSA strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. Conclusion HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.

  7. Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Poulsen, K A; Litman, Thomas; Eriksen, J;

    2002-01-01

    rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50-70 kDa region. A visible...... Ehrlich cells increased compared to the parental fibroblasts. It is concluded that the reduced taurine uptake in resistant Ehrlich cells reflects a down regulation of the taurine transporter at the mRNA and protein level and it is most probably not related to P-gp overexpression....

  8. Langerhans' cell histiocytosis: possible association with malignant germ cell tumour.

    OpenAIRE

    Ng, W K; Lam, K Y; Ng, I O

    1995-01-01

    A rare case of adult onset Langerhans' cell histiocytosis associated with dysgerminoma in a 35 year old Chinese woman is reported. The patient had a history of dysgerminoma of left ovary 15 years previously and had undergone surgery followed by radiotherapy and an uneventful recovery. She presented again in March 1994, this time with a left clavicular mass, which was shown histologically to be Langerhans' cell histiocytosis. The report illustrates the probable association between the two lesi...

  9. Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

    Directory of Open Access Journals (Sweden)

    Hiroaki Haga

    2015-01-01

    Full Text Available The contributions of mesenchymal stem cells (MSCs to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs. We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.

  10. A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

    OpenAIRE

    Farace, F.; Massard, C; Vimond, N.; Drusch, F; Jacques, N; Billiot, F.; Laplanche, A; Chauchereau, A; Lacroix, L; Planchard, D.; Le Moulec, S.; André, F.; Fizazi, K; Soria, J. C.; Vielh, P

    2011-01-01

    Background: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). Methods: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch accordin...

  11. Influence of neuraminidase and X-ray irradiation (2 Gy and 8 Gy) on microvilli and membrane invaginations of Ehrlich ascites tumor cells in monolayer culture

    International Nuclear Information System (INIS)

    A monolayer culture (Eagle basal medium plus 10% of fetal calf serum) of Ehrlich ascites tumor cells was exposed to X-radiation with 2 Gy and 8 Gy and treated with Vibrio cholerae neuraminidase alone or combined with sublethal X-ray irradiation (2 Gy). Pictures of the Ehrlich ascites tumor cells taken with the electron microscope were investigated in order to find out any cell surface modifications due to membrane invaginations and microvilli. The results showed that the rate of microvilli as well as that of membrane invaginations became higher with the increasing X-ray dose (2 Gy; 8 Gy). Following to neuraminidase treatment there was a considerable augmentation of membran invaginations as compared to control cells, whereas the number of microvilli was slightly reduced. As it has been already described before, the influence of neuraminidase produced an increased endocytosis activity and a strengthening of the cytoskeleton. Combined treatment with neuraminidase and sublethal X-radiation (2 Gy) caused a higher rate of membrane invaginations than each method alone; the number of microvilli was slightly increased by combined treatment. The conclusion is drawn that these structure modifications are due to reparation processes induced by radiation on the one hand and to an enzymic action of neuraminidase on the cell surface on the other hand. (orig.)

  12. Mixed germ cell tumour complicated by pulmonary thromboembolism: a case report

    Directory of Open Access Journals (Sweden)

    Hema Priya Kukreja

    2016-04-01

    Full Text Available Malignant ovarian germ cell tumours (MOGCTs are a heterogeneous group of tumours that have several histological different types derived from primordial germ cells of the embryonic gonad. They account for less than 5% of all ovarian malignancies, and are seen in the second and third decade of life. The majority of germ cell tumours are diagnosed in the early stages. Histology, FIGO stage and residual tumour after surgery are the most important prognostic factors. Recent multimodality therapy with staging laparotomy and conservative surgery, followed by platinum based chemotherapy, is associated with survival rates of 60 - 80%, even in patients with advanced disease. Mixed germ cell tumours are extremely rare and the prognosis depends on the size of each component of the tumour. The exact incidence of thrombo embolic events in patients with malignancy is difficult to determine. However ovarian malignancy is strongly associated with venous thrombo embolism. We report a case of a fourteen year old girl with a mixed GCT, with elements of yolk sac tumour and embryonal carcinoma, who succumbed to pulmonary thromboembolism. [Int J Reprod Contracept Obstet Gynecol 2016; 5(4.000: 1242-1244

  13. Tumour T1 changes in vivo are highly predictive of response to chemotherapy and reflect the number of viable tumour cells – a preclinical MR study in mice

    International Nuclear Information System (INIS)

    Effective chemotherapy rapidly reduces the spin–lattice relaxation of water protons (T1) in solid tumours and this change (ΔT1) often precedes and strongly correlates with the eventual change in tumour volume (TVol). To understand the biological nature of ΔT1, we have performed studies in vivo and ex vivo with the allosteric mTOR inhibitor, everolimus. Mice bearing RIF-1 tumours were studied by magnetic resonance imaging (MRI) to determine TVol and T1, and MR spectroscopy (MRS) to determine levels of the proliferation marker choline and levels of lipid apoptosis markers, prior to and 5 days (endpoint) after daily treatment with vehicle or everolimus (10 mg/kg). At the endpoint, tumours were ablated and an entire section analysed for cellular and necrotic quantification and staining for the proliferation antigen Ki67 and cleaved-caspase-3 as a measure of apoptosis. The number of blood-vessels (BV) was evaluated by CD31 staining. Mice bearing B16/BL6 melanoma tumours were studied by MRI to determine T1 under similar everolimus treatment. At the endpoint, cell bioluminescence of the tumours was measured ex vivo. Everolimus blocked RIF-1 tumour growth and significantly reduced tumour T1 and total choline (Cho) levels, and increased polyunsaturated fatty-acids which are markers of apoptosis. Immunohistochemistry showed that everolimus reduced the %Ki67+ cells but did not affect caspase-3 apoptosis, necrosis, BV-number or cell density. The change in T1 (ΔT1) correlated strongly with the changes in TVol and Cho and %Ki67+. In B16/BL6 tumours, everolimus also decreased T1 and this correlated with cell bioluminescence; another marker of cell viability. Receiver-operating-characteristic curves (ROC) for everolimus on RIF-1 tumours showed that ΔT1 had very high levels of sensitivity and specificity (ROCAUC = 0.84) and this was confirmed for the cytotoxic patupilone in the same tumour model (ROCAUC = 0.97). These studies suggest that ΔT1 is not a measure of cell density

  14. Studies on bleomycin-induced repair DNA synthesis in permeable mouse ascites sarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mori,Shigeru

    1989-04-01

    Full Text Available To study the mechanism of DNA excision repair, a DNA repair system employing permeable mouse sarcoma (SR-C3H/He cells was established and characterized. SR-C3H/He cells were permeabilized with a 0.0175% Triton X-100 solution. The permeable cells were treated with 1 mM ATP and 0.11 mM bleomycin, and then washed thoroughly to remove ATP and bleomycin. Repair DNA synthesis occurred in the bleomycin-damaged, permeable SR-C3H/He cells when incubated with ATP and four deoxyribonucleoside triphosphates. The repair nature of the DNA synthesis was confirmed by the BrdUMP density shift technique, and by the reduced sensitivity of the newly synthesized DNA to Escherichia coli exonuclease III. The DNA synthesis was optimally enhanced by addition of 0.08 M NaCl. Studies using selective inhibitors of DNA synthesis showed that aphidicolin-sensitive DNA polymerase (DNA polymerase alpha and/or delta and DNA polymerase beta were involved in the repair process. The present DNA repair system is thought to be useful to study nuclear DNA damage by bleomycin, removal of the damaged ends by an exonuclease, repair DNA synthesis by DNA polymerases and repair patch ligation by DNA ligase(s.

  15. Congenital chylous ascites

    OpenAIRE

    Romańska-Kita, Justyna; Borszewska-Kornacka, Maria Katarzyna; Dobrzańska, Anna; Rudzińska, Iwona; Czech-Kowalska, Justyna; Wawrzoniak, Tomasz

    2011-01-01

    Summary Congenital chylous ascites is a rare entity, conditioned by numerous factors and with changing dynamics of the disease. Because of the lack of therapeutic and diagnostic standards, this disease constitutes to be a medical challenge. This article presents current knowledge on pathogenesis, diagnostics and management of this disease, as well as a case of a newborn with primary congenital chylous ascites in the abdominal cavity.

  16. Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

    Directory of Open Access Journals (Sweden)

    Charlotte T A H Wetzels

    Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

  17. Mitogen-activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells.

    Science.gov (United States)

    Brown, Gabriella K; Tovar, Cesar; Cooray, Anne A; Kreiss, Alexandre; Darby, Jocelyn; Murphy, James M; Corcoran, Lynn M; Bettiol, Silvana S; Lyons, A Bruce; Woods, Gregory M

    2016-08-01

    Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8(+) T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll-like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo. PMID:27089941

  18. The effect of trocar composition on tumour cell adherence: and in vivo model

    International Nuclear Information System (INIS)

    Full text: Port site recurrence of tumour is a recognised complication of laparoscopic surgery for cancer. It has previously been shown that an increased number of tumour cells adhere to metal rather than plastic trocars and sites through which metal trocars had passed. In an extension of this study, adherence of such cells to trocars and trocar sites was investigated in an in vivo porcine model. 99mTc-HMPAO labelled LIM 1215 tumour cells were injected under direct laparoscopic vision into the pelvises of pigs, and then metal and plastic trocars were inserted through the anterior abdominal wall. Trocar type, removal and replacement, as well as site, were all examined for the presence of 99mTc-tumour cells by counting samples in a large volume counter. Greater contamination occurred with metal rather than plastic trocars, and after increased manipulation of the trocars. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.

    Science.gov (United States)

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  20. Radiation-Sensitising Effects of Antennapedia Proteins (ANTP-SmacN7 on Tumour Cells

    Directory of Open Access Journals (Sweden)

    Li Qing Du

    2013-12-01

    Full Text Available The objective of this study was to investigate the underlying mechanisms behind the radiation-sensitising effects of the antennapedia proteins (ANTP-smacN7 fusion protein on tumour cells. ANTP-SmacN7 fusion proteins were synthesised, and the ability of this fusion protein to penetrate cells was observed. Effects of radiation on the expression of X-linked inhibitor of apoptosis protein (XIAP were detected by western blotting. The radiation-sensitising effects of ANTP-SmacN7 fusion proteins were observed by a clonogenic assay. The effects of drugs and radiation on tumour cell apoptosis were determined using Annexin V/FITC double staining. Changes in caspase-8, caspase-9 and caspase-3 were detected by western blot before and after ANTP-SmacN7 inhibition of XIAP. The ANTP-SmacN7 fusion protein could enter and accumulate in cells; in vitro XIAP expression of radiation-induced tumour cells was negatively correlated with tumour radiosensitivity. The ANTP-SmacN7 fusion protein promoted tumour cell apoptosis through the activation of caspase3. ANTP-SmacN7 fusion protein may reduce tumour cell radioresistance by inducing caspase3 activation.

  1. Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

    International Nuclear Information System (INIS)

    TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor

  2. Giant cell tumour in the foot of a skeletally immature girl: a case report.

    LENUS (Irish Health Repository)

    Baker, Joseph F

    2009-08-01

    We present a case of delayed diagnosis of a benign giant cell tumour (GCT) of the third metatarsal in a skeletally immature girl. The patient underwent en bloc excision of the tumour. The tumour had replaced the third metatarsal and had infiltrated the surrounding soft tissue and the second and fourth metatarsal bases. Deep, lateral and medial margins were all involved. A high index of suspicion is needed when evaluating any tumours of the foot, because the compact structure of the foot may delay diagnosis. Early detection is important for avoiding amputation, as the hindfoot and midfoot are classified as one compartment and radical resection is impossible to achieve. Tumours grow faster in the foot than in other bones. GCT in this location and age-group are rare and should be considered in the differential diagnosis of a destructive bony lesion in skeletally immature patients.

  3. Influence of the products of radiolysis of uracil and thymidine on the biosynthesis of DNA of Ehrlich's ascites cells

    Energy Technology Data Exchange (ETDEWEB)

    Polverelli, M.; Teoule, R.

    1972-09-01

    From ninth annual meeting of the European society for Radiation Biology; Rome, Italy (26 8ep 1972). The effect of gamma radiolysis products in aqueous solution of uracil and thymidine on the normal replicative biosynthesis of DNA of Ehrlich's ascites cells incubated in vitro in the presence of radioactive precursors of DNA (/sup 14/C-methyl thymidine or (/sup 14/C/sub 2/-d esoxyrytidine) was studied. The inhibiting effect of the thymidine radiolysis products, desoxy-2' - BETA -D-ribofuranosyl-1-hydroxy-5methyl-5-barbituric acid and hydroxy-6-dihydro-5, 6-thymidine, and the uracil radiolysis products, alloxanne and parabanic acid, was shown. (JSR)

  4. Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes.

    OpenAIRE

    Lin, W.C.; O'Connor, K. L.; Culp, L. A.

    1993-01-01

    Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co-localisation and co-growth in nu...

  5. Aspects of Tumour Targeting : Preclinical Studies on Human Malignant Cells in vitro

    OpenAIRE

    Dahlström Wester, Maria

    2009-01-01

    Exclusive eradication of tumour cells causing minimal damage to healthy tissue, a concept referred to as targeting, is an interesting approach to improve the outcome for patients afflicted with cancer. The general aim of this thesis was to highlighten aspects that could be of importance in developing novel treatment regimens based on specific targeting of tumour cells. Two variants of targeting strategies, boron neutron capture therapy (BNCT) and platelet-derived growth factor receptor (PDGFR...

  6. Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

    International Nuclear Information System (INIS)

    Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC. In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue. While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced. Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours

  7. Tumours and tumourous diseases

    International Nuclear Information System (INIS)

    This book on tumours and tumourous diseases comprises two parts: 1. Bone tumours and tumourous lesions. 2. Soft tissue tumours and tumourous lesions. Details are presented on pathology, diagnosis, conservative and perioperative therapy, surgical therapy, complications after resection, indicators for amputation, recommendations for follow-up treatment, radiotherapy, radionuclide therapy, alternative therapies, therapy concepts in case of metastases, tissue engineering and plastic surgery. (uke)

  8. ROS activate KCl cotransport in nonadherent Ehrlich ascites cells but K+ and Cl- channels in adherent Ehrlich Lettré and NIH3T3 cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Klausen, Thomas Kjær; Bergdahl, Andreas;

    2009-01-01

    Addition of H2O2 (0.5 mM) to Ehrlich ascites tumor cells under isotonic conditions results within 25 min in a substantial (22 +/- 1 %) reduction in cell volume. The cell shrinkage is paralleled by net loss of K(+), which was significant within 8 min, whereas no concomitant increase in the K(+) or...... the electrochemical driving force for K(+). On the other hand, the H2O2-induced cell shrinkage was impaired in the presence of the KCl cotransport inhibitor DIOA, following substitution of NO3(-) for Cl(-), and when the driving force for KCl cotransport was omitted. It is suggested that H2O2 activates...... electro neutral KCl cotransport in Ehrlich ascites tumor cells and not K(+) and Cl(-) channels. Addition of H2O2 to hypotonically exposed cells accelerates the regulatory volume decrease and the concomitant net loss of K(+), whereas no additional increase in the K(+) and Cl(-) conductance was observed...

  9. [Favourable course of persisting malignant ascites].

    Science.gov (United States)

    Stange, Rainer; Jänsch, Annette; Schrag, Sabine; Pflugbeil, Christine; Schlodder, Dietrich; Pandey-Hoffmann, Ursula; Uehleke, Bernhard

    2009-02-01

    Malignant ascites is a frequent complication in oncological diseases. There are no standard therapies for any primary tumour. We report the case of a woman, aged 49 years at the time of primary diagnosis, who suffered from recurrent ascites resulting from liver metastasis of breast cancer. Based on the literature and former experience of our department, mistletoe extract was repeatedly applied intraperitoneally at the occasion of decompressive punctures. The further course of the disease suggests a significant role of mistletoe in achieved symptom control, which also resulted in a considerable improvement in quality of life. The mistletoe solution was well tolerated. Relevant mechanisms of action in addition to the well-known immunomodulating properties of mistletoe could be direct cytotoxic and adjuvant effects to the concomitantly administered chemotherapy of carboplatin/paclitaxel. PMID:19295230

  10. Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings.

    Science.gov (United States)

    Bagnasco, Giorgio; Properzi, Roberto; Porto, Roberto; Nardini, Vincenzo; Poli, Alessandro; Abramo, Francesca

    2003-04-01

    A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour. PMID:12662269

  11. Mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea

    Directory of Open Access Journals (Sweden)

    Kissová Viktória

    2015-09-01

    Full Text Available The aim of the study was to evaluate the distribution and number of mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea. The highest density of mast cells was found in cystic papillary adenocarcinomas of grade II. Eosinophils were detected only in the cystic papillary adenocarcinoma of grades I and II, in non-invasive cribriform adenocarcinoma and comedo-type carcinoma. Mast cell populations were observed perivascularly in the tumour stroma, in the host tumour interface, as well as in necrotic areas of neoplasms. Mast cells were observed to be intact according to their morphological changes, collectively referred to as degranulation. The obtained results indicate that mast cells and eosinophils play an important role in tumour micro-environment formation. The increased density of these cells in experimentally-induced rat mammary gland tumours suggests a poor prognosis in these cancers. Our results also confirmed that rat mammary gland tumours are good models for the study of breast cancers.

  12. Computed tomography evaluation of mast cell tumours; Avaliacao por tomografia computadorizada dos mastocitomas

    Energy Technology Data Exchange (ETDEWEB)

    Lorigados, Carla Aparecida Batista; Matera, Julia Maria; Macedo, Thais; Pinto, Ana Carolina Brandao Fonseca, E-mail: clorigados@usp.br [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Cirurgia

    2012-07-01

    The mast cell tumours are common tumours of the canine skin. Computed tomography (CT) has assumed an important role in tumours evaluation and staging. The aim of this study was to evaluate the role of CT as a method of assessing characteristics of mast cell tumors. Ten dogs with mast cell tumor were evaluated. CT was performed before and after the intravenous injection of hydro soluble ionic iodine. Attenuation, contrast enhancement, cleavage with adjacent tissues and the unidimensional measurement of each lesion was determined in it maximum diameter, in transversal plane. Concerning the attenuation characteristic, 50% were homogeneous and 50% heterogeneous. The contrast enhancement was homogeneous in 50% of cases, heterogeneous in 40% and peripheral in 10%. Fifty percent of the tumours showed loss of plane of cleavage and 30% partial loss. This information can help in directing the patients that will be undergoing chemotherapy or surgery. (author)

  13. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    International Nuclear Information System (INIS)

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells

  14. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Guangwen; Yang, Tianming [College of Pharmacy, South-Central University for Nationalities, Wuhan (China); Wang, Chaoyuan [College of Life Science, South-Central University for Nationalities, Wuhan (China); Su, Hanwen, E-mail: suhanwen-1@163.com [Renmin Hospital of Wuhan University, Wuhan (China); Xiang, Meixian, E-mail: xiangmeixian99@163.com [College of Pharmacy, South-Central University for Nationalities, Wuhan (China)

    2013-06-15

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells.

  15. New approaches to targeted drug delivery to tumour cells

    Science.gov (United States)

    Severin, E. S.

    2015-01-01

    Basic approaches to the design of targeted drugs for the treatment of human malignant tumours have been considered. The stages of the development of these approaches have been described in detail and theoretically substantiated, and basic experimental results have been reported. Considerable attention is paid to the general characteristic of nanopharmacological drugs and to the description of mechanisms of cellular interactions with nanodrugs. The potentialities and limitations of application of nanodrugs for cancer therapy and treatment of other diseases have been considered. The use of nanodrugs conjugated with vector molecules seems to be the most promising trend of targeted therapy of malignant tumours. The bibliography includes 122 references.

  16. New approaches to targeted drug delivery to tumour cells

    International Nuclear Information System (INIS)

    Basic approaches to the design of targeted drugs for the treatment of human malignant tumours have been considered. The stages of the development of these approaches have been described in detail and theoretically substantiated, and basic experimental results have been reported. Considerable attention is paid to the general characteristic of nanopharmacological drugs and to the description of mechanisms of cellular interactions with nanodrugs. The potentialities and limitations of application of nanodrugs for cancer therapy and treatment of other diseases have been considered. The use of nanodrugs conjugated with vector molecules seems to be the most promising trend of targeted therapy of malignant tumours. The bibliography includes 122 references

  17. Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

    International Nuclear Information System (INIS)

    Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEXGM-CSF, we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV. To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and β-galactosidase (lacZ). These vectors were tested in non-tumour cell lines in vitro and tumour cells that are moderately susceptible to HSV infection both in vitro and in mice xenografts in vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting. Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells in vitro and tumours in vivo, with the viruses expressing artificial miRNA being comprehensibly more effective. This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells in vitro and in vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials

  18. Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

    Directory of Open Access Journals (Sweden)

    Herbst Hermann

    2005-07-01

    Full Text Available Abstract Background Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic. Methods A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH was performed. Results Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH. Conclusion Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present

  19. Sensitivity of locally recurrent rat mammary tumour cell lines to syngeneic polymorphonuclear cell, macrophage and natural killer cell cytolysis.

    OpenAIRE

    Aeed, P. A.; Welch, D. R.

    1988-01-01

    Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose following subcutaneous inoculation into the mammary fat pad, sc1 and sc3; and the local recurrences (following surgical excision) LR1 and LR1a from sc1, and LR3 from sc3 were all...

  20. An integrated on-chip platform for negative enrichment of tumour cells.

    Science.gov (United States)

    Bhuvanendran Nair Gourikutty, Sajay; Chang, Chia-Pin; Poenar, Daniel Puiu

    2016-08-15

    The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps. PMID:27344255

  1. Lessons from T cell responses to virus induced tumours for cancer eradication in general.

    Science.gov (United States)

    Melief, C J; Kast, W M

    1992-01-01

    Immunotherapy of virus induced tumours by adoptive transfer of virus specific cytotoxic T cells (CTL) is now feasible in experimental murine systems. These CTL recognize viral peptide sequences of defined length presented in the groove of MHC class I molecules. Effective eradication of large tumour masses requires coadministration of IL-2. In essence, T cell immunity against virus induced tumours does not differ from anti-viral T cell immunity in general. Tumour escape strategies are numerous but, in various instances, can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic non-virus induced tumours (the majority of human cancer) requires novel strategies to overcome T cell inertia. Rather than waiting to see whether tumour specific CTL (against unknown antigens) can be cultured from TIL, we propose an alternative strategy in which CTL are raised against target molecules of choice, including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The various steps proposed include: (a) identification of target molecules of choice; (b) identification in these target molecules of MHC allele specific peptide motifs involved in peptide binding to MHC molecules; (c) evaluation of actual binding of such peptides to specific MHC class I molecules; (d) in vitro CTL response induction by such peptides, presented either by highly efficient antigen presenting cells (such as processing defective cells, which carry empty MHC class I molecules) loaded with a single peptide or by dendritic cells, both cell types being capable of primary CTL response induction in vitro and (e) adoptive transfer of tumour specific CTL generated in vivo or, more conveniently, vaccination with immunodominant peptides. The latter possibility seems to be feasible because peptide vaccination with a single immunodominant viral peptide can install CTL memory and confer protection against lethal virus

  2. Antitumour and antioxidant activity of some Red Sea seaweeds in Ehrlich ascites carcinoma in vivo.

    Science.gov (United States)

    Ahmed, Hanaa H; Hegazi, Muhammad M; Abd-Alla, Howaida I; Eskander, Emad F; Ellithey, Mona S

    2011-01-01

    The antitumour activities of extracts from the Red Sea seaweeds Jania rubens, Sargassum subrepandum, and Ulva lactuca were investigated in an in vivo mice model based on intramuscular injection of Ehrlich ascites tumour cells. In parallel, antioxidant activities were measured. Tumour marker levels, liver biochemical parameters, and hepatic oxidant/antioxidant status were measured to prove the anticancer and antioxidant nature of the algal extracts. Significant decreases in carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) levels, activities of liver enzymes, levels of nitric oxide (NO) and malondialdehyde (MDA), and an increase in total antioxidant capacity (TAC) were recorded in groups treated with the algal extracts. Jania rubens was selected for phytochemical screening of its phytoconstituents. In addition, carotenoids, halides, minerals, lipoidal matters, proteins, and carbohydrates were studied. Furthermore, 7-oxo-cholest-5(6)-en-3-ol (1) and cholesterol (2) were isolated from the dichloromethane fraction. PMID:21950161

  3. Chylous ascites in a hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Roh, Yoon-Seok; Kim, Eun-Ju; Cho, Ara; Kim, Min-Su; Cho, Ho-Seong; Lim, Chae Woong; Kim, Bumseok

    2014-12-01

    An African pygmy hedgehog (Atelerix albiventris) was diagnosed as chylous ascites with biliary cirrhosis. Abdomenocentesis revealed a milky fluid with a 324 mg/dl triglyceride level. On serum biochemical examination, the hedgehog had hypoalbuminemia, hypoglycemia, and high blood urea nitrogen. There was no cytologic or genomic evidence of infection, and a blood culture was negative. Histopathologic examination revealed a liver with proliferative bile ducts that were often surrounded by prominent septa of fibrous connective tissue. In the area of ductular reaction, proliferative cells positive for CD66, an embryogenic antigen of epithelial cells, were revealed. The potential association between chylous ascites and liver cirrhosis is undetermined but could be an aspect of future study. This is the first description of chylous ascites in a hedgehog. PMID:25632690

  4. Human germ cell tumours: expression of γ-glutamyl transpeptidase and sensitivity to cisplatin

    OpenAIRE

    Hanigan, M H; Frierson, H F; Abeler, V. M.; Kaern, J; Taylor, P T

    1999-01-01

    Previous studies have shown that the enzyme γ-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against ...

  5. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Elmpt, Wouter van; Zegers, Catharina M.L.; Reymen, Bart; Even, Aniek J.G.; Oellers, Michel; Troost, Esther G.C.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Wildberger, Joachim E.; Das, Marco [Maastricht University Medical Centre, Department of Radiology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Centre, Department of Nuclear Medicine, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); University Hospital RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

    2016-02-15

    Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. (orig.)

  6. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

    International Nuclear Information System (INIS)

    Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. (orig.)

  7. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression

    Directory of Open Access Journals (Sweden)

    Johannsen Manfred

    2008-06-01

    Full Text Available Abstract Background A Disintegrin And Metalloprotease (ADAM 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort. Methods 108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ2-test, correlations and univariate as well as multivariate survival analyses. Results ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis. Conclusion ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts.

  8. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression

    International Nuclear Information System (INIS)

    A Disintegrin And Metalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort. 108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ2-test), correlations and univariate as well as multivariate survival analyses. ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis. ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts

  9. [Current ascites therapy].

    Science.gov (United States)

    Ochs, A

    1997-01-21

    Ultrasonography detects ascites easily even in trace amounts. 80% of the cases are caused by hepatic disease, in the remaining 20% cancer, inflammation, pancreatic, renal, or cardiac disease can be found. The underlying disease should be investigated by few inexpensive laboratory test from serum, urine and ascites and by abdominal sonography. Hepatic ascites is caused by portal hypertension and disturbances of humoral factors. Sodium retention, peripheral, vasodilation, hyperdynamic circulation and progressive renal vasoconstriction lead to a stepwise deterioration of patients condition. Treatment with diuretics (furosemide, torsemide, or xipamide and spironolactone) and sodium-restriction (peritoneo-venous shunt is restricted to rare indications. In the future, new drugs such as antagonists of endothelins or of the antidiuretic hormone may offer new therapeutic options. PMID:9064726

  10. Ion Channels Involved in Cell Volume Regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay

    2011-01-01

    This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume...... regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation...

  11. The Na+/H+ exchanger, NHE1, differentially regulates mitogen-activated protein kinase subfamilies after osmotic shrinkage in Ehrlich Lettre Ascites cells

    DEFF Research Database (Denmark)

    Petersen, Stine Helene Falsig; Rasmussen, Maria; Darborg, Barbara Vasek;

    2007-01-01

    intracellular alkalinization, and p38 MAPK is activated in an NHE1-independent manner, and contributes to NHE1 activation and ERK inhibition. Shrinkage-induced ERK1/2 inhibition was attenuated in Ehrlich Lettre Ascites cells by NHE1 inhibitors (EIPA, cariporide) or removal of extracellular Na(+), and mimicked...... augmented at alkaline pH(i). Shrinkage-activation of p38 MAPK was NHE1-independent, and p38 MAPK inhibition (SB203580) attenuated NHE1 activation and ERK1/2 inhibition. Long-term shrinkage elicited caspase-3 activation and a loss of cell viability, which was augmented by ERK1/2 or JNK1/2 inhibition, and......Osmotic stress modulates mitogen activated protein kinase (MAPK) activities, leading to altered gene transcription and cell death/survival balance, however, the mechanisms involved are incompletely elucidated. Here, we show, using a combination of biochemical and molecular biology approaches, that...

  12. The Biochemical Effects of the Promising Hypoxic Cell radiosensitizers KIN-804, KIN-844, KIN-806 d TX-1877 in Mice Bearing Ehrlich Ascites Carcinoma

    International Nuclear Information System (INIS)

    The existence of hypoxic cells in solid tumors is one of the important limiting factors in the local control of malignant tumors by radiation therapy. A series of new analogues of 2-nitroimidazole has been synthesized. Among these 2-nitroimidazoles, the derivatives KIN-804, KIN-806 and their analogs KIN-844, TX-1877 were selected, evaluated and compared biochemically with these of misonidazole (MISO). The radiosensitizing activity and acute toxicity of those new hypoxic cell radiosensitizer were previously established both in vitro and in vivo . The present study was design to evaluate the effect of those compounds at dose level 0.4g/kg body weight, injected alone or in combination with g-irradiation on the liver reduced glutathione content, (GSH); glucose-6-phosphate dehydrogenase (G-6-PDH); superoxide dismutase (SOD), catalase and brain acetylcholinesterase (AChE) in Swiss albino mice bearing solid Ehrlich ascites carcinoma (EAC, 2.5 x 10 cells)

  13. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets

    Science.gov (United States)

    Yoon, Hyeun Joong; Kim, Tae Hyun; Zhang, Zhuo; Azizi, Ebrahim; Pham, Trinh M.; Paoletti, Costanza; Lin, Jules; Ramnath, Nithya; Wicha, Max S.; Hayes, Daniel F.; Simeone, Diane M.; Nagrath, Sunitha

    2013-10-01

    The spread of cancer throughout the body is driven by circulating tumour cells (CTCs). These cells detach from the primary tumour and move from the bloodstream to a new site of subsequent tumour growth. They also carry information about the primary tumour and have the potential to be valuable biomarkers for disease diagnosis and progression, and for the molecular characterization of certain biological properties of the tumour. However, the limited sensitivity and specificity of current methods for measuring and studying these cells in patient blood samples prevents the realization of their full clinical potential. The use of microfluidic devices is a promising method for isolating CTCs. However, the devices are reliant on three-dimensional structures, which limits further characterization and expansion of cells on the chip. Here we demonstrate an effective approach to isolating CTCs from blood samples of pancreatic, breast and lung cancer patients, by using functionalized graphene oxide nanosheets on a patterned gold surface. CTCs were captured with high sensitivity at a low concentration of target cells (73 +/- 32.4% at 3-5 cells per ml blood).

  14. Evidence of distinct tumour-propagating cell populations with different properties in primary human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Federico Colombo

    Full Text Available BACKGROUND AND AIMS: Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC compartments within human hepatocellular carcinoma (HCC. METHODS: After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice. RESULTS: The primary cell populations (hcc-1, -2 and -3 and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8 differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features. CONCLUSIONS: Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution.

  15. Studies into characteristics of cancer stem cells and their role in the origin of epithelial tumours.

    OpenAIRE

    Burkert, J.

    2008-01-01

    Tumours are organised in a cellular hierarchy, originating in and maintained by a minority of cells with stem cell characteristics, so-called 'cancer stem cells'. The Side Population (SP) phenotype, distinguished by its ability to efflux the nucleic acid dye Hoechst 33342, as well as surface markers CD44 and CD133 were evaluated as potential cancer stem cell markers in human colorectal cancer cell lines and primary adenocarcinomas by testing sorted cell fractions for phenotypical and behaviou...

  16. Tumour dose uniformity in radiotherapy: experimental evidence for cell response to non-uniform irradiation

    International Nuclear Information System (INIS)

    A common goal of radiotherapy is the application of uniform radiation dose to the tumour volume. Such a goal has been formalized by the ICRU (ICRU 50, 1993), based on the assumption that cells respond independently and any under-dosed region represents an area with a higher probability to act as a recurrence site. However, dose distributions provided by intensity-modulated radiotherapy (IMRT) and other techniques offer opportunities to escalate tumour doses and greatly reduce normal tissue doses, with these effects enhanced further if dose non-uniformity is allowed in the tumour. A study of the response of several tumour cell lines has suggested an averaging effect if those cells are exposed to a gradient rather then a uniform dose. A study was performed with cell cultures exposed in a 6 MV X-ray beam in full equilibrium conditions with the beam modulated by a wedge filter. With cell communication channels open, cells exposed at the lower or higher dose ends of the wedge responded as if irradiated to mean dose levels, with the severity of this effect dependent on cell type. A possible explanation for this effect is cellular communication. When cells are irradiated with communication channels physically blocked, the normal dose response experienced under uniform irradiation conditions results. There are significant implications of this result for radiotherapy treatment and prescription, dependent primarily on translation of the results to the clinical setting. The ability to deliver largely non-uniform doses to tumours would greatly facilitate normal tissue avoidance and enhance our ability to escalate doses to tumours. This result can also be used to explain some recent observations regarding dose-response extracted from clinical trial data

  17. Infrared laser pulse triggers increased singlet oxygen production in tumour cells

    Science.gov (United States)

    Sokolovski, S. G.; Zolotovskaya, S. A.; Goltsov, A.; Pourreyron, C.; South, A. P.; Rafailov, E. U.

    2013-12-01

    Photodynamic therapy (PDT) is a technique developed to treat the ever-increasing global incidence of cancer. This technique utilises singlet oxygen (1O2) generation via a laser excited photosensitiser (PS) to kill cancer cells. However, prolonged sensitivity to intensive light (6-8 weeks for lung cancer), relatively low tissue penetration by activating light (630 nm up to 4 mm), and the cost of PS administration can limit progressive PDT applications. The development of quantum-dot laser diodes emitting in the highest absorption region (1268 nm) of triplet oxygen (3O2) presents the possibility of inducing apoptosis in tumour cells through direct 3O2 --> 1O2 transition. Here we demonstrate that a single laser pulse triggers dose-dependent 1O2 generation in both normal keratinocytes and tumour cells and show that tumour cells yield the highest 1O2 far beyond the initial laser pulse exposure. Our modelling and experimental results support the development of direct infrared (IR) laser-induced tumour treatment as a promising approach in tumour PDT.

  18. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment.

    Science.gov (United States)

    Zhang, Tao; Tseng, Chieh; Zhang, Yan; Sirin, Olga; Corn, Paul G; Li-Ning-Tapia, Elsa M; Troncoso, Patricia; Davis, John; Pettaway, Curtis; Ward, John; Frazier, Marsha L; Logothetis, Christopher; Kolonin, Mikhail G

    2016-01-01

    White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression. PMID:27241286

  19. Management of ascites in cirrhosis.

    Science.gov (United States)

    Wong, Florence

    2012-01-01

    Ascites is a common complication of liver cirrhosis associated with a poor prognosis. The treatment of ascites requires dietary sodium restriction and the judicious use of distal and loop diuretics, sequential at an earlier stage of ascites, and a combination at a later stage of ascites. The diagnosis of refractory ascites requires the demonstration of diuretic non-responsiveness, despite dietary sodium restriction, or the presence of diuretic-related complications. Patients with refractory ascites require second-line treatments of repeat large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), and assessment for liver transplantation. Careful patient selection is paramount for TIPS to be successful as a treatment for ascites. Patients not suitable for TIPS insertion should receive LVP. The use of albumin as a volume expander is recommended for LVP of >5-6 L to prevent the development of circulatory dysfunction, although the clinical significance of post-paracentesis circulatory dysfunction is still debated. Significant mortality is still being observed in cirrhotic patients with ascites and relatively preserved liver and renal function, as indicated by a lower Model for End-Stage Liver Disease (MELD) score. It is proposed that patients with lower MELD scores and ascites should receive additional points in calculating their priority for liver transplantation. Potential new treatment options for ascites include the use of various vasoconstrictors, vasopressin V(2) receptor antagonists, or the insertion of a peritoneo-vesical shunt, all of which could possibly improve the management of ascites. PMID:21916992

  20. Chylous ascites following radical nephrectomy: a case report

    Directory of Open Access Journals (Sweden)

    Shah Shahzad S

    2008-01-01

    Full Text Available Abstract Introduction Chylous ascites may result from diverse pathologies. Ascites results either due to blockage of the lymphatics or leak secondary to inadvertent trauma during surgery. Case presentation We report the first case of chylous ascites following radical nephrectomy for a renal cell carcinoma involving the right half of a crossed fused renal ectopia. The patient was managed conservatively. Conclusion Post-operative chylous ascites is a rare complication of retroperitoneal and mediastinal surgery. Most cases resolve with conservative treatment which aims at decreasing lymph production and optimizing nutritional requirements along with palliative measures. Refractory cases need either open or laparoscopic ligation of the leaking lymphatic channels. A review of the current literature on the management of post-operative chylous ascites is presented.

  1. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting

    Directory of Open Access Journals (Sweden)

    Sander A. A. Kooijmans

    2016-03-01

    Full Text Available Background: Extracellular vesicles (EVs are attractive candidate drug delivery systems due to their ability to functionally transport biological cargo to recipient cells. However, the apparent lack of target cell specificity of exogenously administered EVs limits their therapeutic applicability. In this study, we propose a novel method to equip EVs with targeting properties, in order to improve their interaction with tumour cells. Methods: EV producing cells were transfected with vectors encoding for anti-epidermal growth factor receptor (EGFR nanobodies, which served as targeting ligands for tumour cells, fused to glycosylphosphatidylinositol (GPI anchor signal peptides derived from decay-accelerating factor (DAF. EVs were isolated using ultrafiltration/size-exclusion liquid chromatography and characterized using western blotting, Nanoparticle Tracking Analysis, and electron microscopy. EV–tumour cell interactions were analyzed under static conditions using flow cytometry and under flow conditions using a live-cell fluorescence microscopy-coupled perfusion system. Results: V analysis showed that GPI-linked nanobodies were successfully displayed on EV surfaces and were highly enriched in EVs compared with parent cells. Display of GPI-linked nanobodies on EVs did not alter general EV characteristics (i.e. morphology, size distribution and protein marker expression, but greatly improved EV binding to tumour cells dependent on EGFR density under static conditions. Moreover, nanobody-displaying EVs showed a significantly improved cell association to EGFR-expressing tumour cells under flow conditions. Conclusions: We show that nanobodies can be anchored on the surface of EVs via GPI, which alters their cell targeting behaviour. Furthermore, this study highlights GPI-anchoring as a new tool in the EV toolbox, which may be applied for EV display of a variety of proteins, such as antibodies, reporter proteins and signaling molecules.

  2. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  3. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg

    1995-01-01

    , the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells...

  4. Expression of core clock genes in colorectal tumour cells compared with normal mucosa

    DEFF Research Database (Denmark)

    Fonnes, S; Donatsky, A M; Gögenur, I

    2015-01-01

    AIM: Experimental studies have shown that some circadian core clock genes may act as tumour suppressors and have an important role in the response to oncological treatment. This study investigated the evidence regarding modified expression of core clock genes in colorectal cancer and its...... expression of colorectal cancer cells compared with healthy mucosa cells from specimens analysed by real-time or quantitative real-time polymer chain reaction. The expression of the core clock genes Period, Cryptochrome, Bmal1 and Clock in colorectal tumours were compared with healthy mucosa and correlated...... of Clock. Other core clock genes did not appear to be differentially expressed. Decreased Period gene expression was correlated to some clinicopathological features. CONCLUSION: The Period genes seemed to be modified in colorectal tumour cells compared with normal mucosa. Core clock genes might be...

  5. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    Science.gov (United States)

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up. PMID:27543869

  6. Small round blue cell tumours: diagnostic and prognostic usefulness of the expression of B7-H3 surface molecule

    OpenAIRE

    Gregorio, A.; Corrias, M V; R. Castriconi; Dondero, A; Mosconi, M.; Gambini, C; Moretta, A; Moretta, L; Bottino, C

    2008-01-01

    Aims: To assess whether the expression of B7-H3 surface molecule could improve differential diagnosis of small cell round tumours. Methods and results: One hundred and one well-characterized paraffin-embedded small round cell tumours, stored in the pathology archive of the Gaslini Institute, were immunohistochemically analysed with the 5B14 monoclonal antibody, which recognizes the surface molecule B7-H3. All lymphoblastic lymphomas and the blastematous component of Wilms’ tumours were comple...

  7. THE INHIBITORY EFFECT OF EXTRACT OF CAMELLIA SINENSIS AND EXTRACT OF CAMELLIA PTILOPHYLLA CHANG ON DNA POLYMERASE OF EHRLICH ASCITES CARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Xian Lijian; Liu Zongchao; Pan Qichao; Li Hanxi

    1998-01-01

    Objective:To detect the effect of extract of Camellia Sinensis (ECS) and extract of Camellia Ptilophylla Chang (ECPC) on DNA polymerase (Pol) of Ehrlich ascites tumor cells. Methods: Referring to the method of K.Ono, Pol was extracted from Ehrlich ascites tumor cells in mice. Pol α, β, and γ were separated by phosphocellulose column chromatography and were identified. The effect of ECPC and ECS on Pol was studied. Results: ECPC and ECS were shown to inhibit the activity of Pol α, β, and γ. IC50 values of ECS on Polα, β, and γ were 10.2μ g/ml, 9.9μ g/ml and 28.9 μ g/mlrespectively. IC50 values of ECPC on Pol α, Pol β and Pol γ were 5.6 μ g/ml, 15 μ g/ml and 14.7 μ g/mlrespectively. The modes of inhibition of ECPC on Pol α,Pol β and Pol γ were noncompetitive with respect to template DNA. The Ki values of ECPC on Pol α, β, and γ were 2.68± 0.12 μ g/ml, 2.24 ± 0. 12 μ g/ml , 2.56 ±0. 18 μ g/ml . Conclusion: ECPC and ECS were shown to have inhibitory effect on DNA polymerase of tumor cells. The mode of inhibition of ECPC on Pol α, Pol βand Pol γwere noncompetitive with respect to template DNA.

  8. Steroid hormones affect binding of the sigma ligand {sup 11}C-SA4503 in tumour cells and tumour-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van [University of Groningen, Nuclear Medicine and Molecular Imaging, University of Groningen Medical Center, Groningen (Netherlands); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Tokyo (Japan)

    2009-07-15

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist {sup 11}C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. {sup 11}C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of {sup 11}C-SA4503 to C6 cells was increased ({proportional_to}50%) upon removal and decreased ({proportional_to}60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC{sub 50} progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of {sup 11}C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of {sup 11}C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

  9. Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

    International Nuclear Information System (INIS)

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist 11C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. 11C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of 11C-SA4503 to C6 cells was increased (∝50%) upon removal and decreased (∝60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC50 progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of 11C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of 11C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

  10. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting

    OpenAIRE

    Sander A. A. Kooijmans; Gómez Aleza, Clara; Roffler, Steve R; van Solinge, Wouter W.; Vader, Pieter; Schiffelers, Raymond M.

    2016-01-01

    Background: Extracellular vesicles (EVs) are attractive candidate drug delivery systems due to their ability to functionally transport biological cargo to recipient cells. However, the apparent lack of target cell specificity of exogenously administered EVs limits their therapeutic applicability. In this study, we propose a novel method to equip EVs with targeting properties, in order to improve their interaction with tumour cells.Methods: EV producing cells were transfected with vectors enco...

  11. Diagnostic Efficacy of Radiology in the Diagnosis of Giant Cell Tumour of Bone

    OpenAIRE

    Afia Akhter; Mohammad Serajus Saleheen; Nadira Majid; Syed Salahuddin; Kwazi Dil Afroz; Md Rezwanur Rahman; Syed Makarram Ali

    2014-01-01

    Background: Giant cell tumour (GCT) is an aggressive and potentially malignant lesion. Microscopic feature reveals osteoclast like giant cells in a mononuclear stromal cells background. The mononuclear stromal cell is interpreted as neoplastic. Objective: As radiological diagnosis is non invasive and cost effective in comparison to histopathological diagnosis, considering the patients’ compliance, the aim of the study was to observe the diagnostic efficacy of radiology in diagnosis of GCT...

  12. Modelling tumour cell proliferation from vascular structure using tissue decomposition into avascular elements.

    Science.gov (United States)

    Besenhard, Maximilian O; Jarzabek, Monika; O'Farrell, Alice C; Callanan, John J; Prehn, Jochen Hm; Byrne, Annette T; Huber, Heinrich J

    2016-08-01

    Computer models allow the mechanistically detailed study of tumour proliferation and its dependency on nutrients. However, the computational study of large vascular tumours requires detailed information on the 3-dimensional vessel network and rather high computation times due to complex geometries. This study puts forward the idea of partitioning vascularised tissue into connected avascular elements that can exchange cells and nutrients between each other. Our method is able to rapidly calculate the evolution of proliferating as well as dead and quiescent cells, and hence a proliferative index, from a given amount and distribution of vascularisation of arbitrary complexity. Applying our model, we found that a heterogeneous vessel distribution provoked a higher proliferative index, suggesting increased malignancy, and increased the amount of dead cells compared to a more static tumour environment when a homogenous vessel distribution was assumed. We subsequently demonstrated that under certain amounts of vascularisation, cell proliferation may even increase when vessel density decreases, followed by a subsequent decrease of proliferation. This effect was due to a trade-off between an increase in compensatory proliferation for replacing dead cells and a decrease of cell population due to lack of oxygen supply in lowly vascularised tumours. Findings were illustrated by an ectopic colorectal cancer mouse xenograft model. Our presented approach can be in the future applied to study the effect of cytostatic, cytotoxic and anti-angiogenic chemotherapy and is ideally suited for translational systems biology, where rapid interaction between theory and experiment is essential. PMID:27155046

  13. Fluorescence and electron microscopic study of intracellular F-actin in concanavalin A-treated and cytochalasin B-treated Ehrlich ascites tumor cells.

    Directory of Open Access Journals (Sweden)

    Watanabe,Sadahiro

    1986-12-01

    Full Text Available To investigate the involvement of actin filaments in concanavalin A (Con A-induced cap formation and cytochalasin B (CB-induced zeiotic knob migration, the distribution of F-actin was studied in Con A-treated and CB-treated Ehrlich ascites tumor cells (EATC by fluorescence microscopy using heavy meromyosin conjugated with a fluorescent dye, N-(7-dimethylamino-4-methylcoumarinyl maleimide, (DACM-HMM. In non-treated cells, the diffuse fluorescence of DACM-HMM was observed in the cytoplasm, particularly intensely under the plasma membrane and around the nucleus. In Con A- and CB-treated cells, the fluorescence was seen at Con A-induced-capped and CB-induced-knob-accumulated regions. This fluorescence was more intense in CB-treated cells. To study the actin filaments in these fluorescent regions more clearly, the soluble components of the cells were eliminated by treatment with Triton X-100 or saponin solution containing a low concentration of glutaraldehyde, and the detergent-treated and saponin-treated cells were observed under a transmission electron microscope. Concentrated actin filaments were observed directly beneath the Con A-induced capping area and CB-induced zeiotic knob-accumulation area. The area of concentrated actin filaments appeared to correspond to the electron dense area observed in the identical region in the cells fixed without detergent treatment. More actin filaments were observed in CB-treated cells than in Con A-treated ones.

  14. Interferon regulatory factor-8 modulates the development of tumour-induced CD11b+Gr-1+ myeloid cells.

    Science.gov (United States)

    Stewart, Trina J; Greeneltch, Kristy M; Reid, Julia E; Liewehr, David J; Steinberg, Seth M; Liu, Kebin; Abrams, Scott I

    2009-09-01

    Tumour-induced myeloid-derived suppressor cells (MDSC) promote immune suppression and mediate tumour progression. However, the molecular basis for the generation of MDSC, which in mice co-express the CD11b(+) and Gr-1(+) cell surface markers remains unclear. Because CD11b(+)Gr-1(+) cells expand during progressive tumour growth, this suggests that tumour-induced events alter signalling pathways that affect normal myeloid cell development. Interferon regulatory factor-8 (IRF-8), a member of the IFN-gamma regulatory factor family, is essential for normal myelopoiesis. We therefore examined whether IRF-8 modulated tumour-induced CD11b(+)Gr-1(+) cell development or accumulation using both implantable (4T1) and transgenic (MMTV-PyMT) mouse models of mammary tumour growth. In the 4T1 model, both splenic and bone marrow-derived CD11b(+)Gr-1(+) cells of tumour-bearing mice displayed a marked reduction in IRF-8 expression compared to control populations. A causal link between IRF-8 expression and the emergence of tumour-induced CD11b(+)Gr-1(+) cells was explored in vivo using a double transgenic (dTg) mouse model designed to express transgenes for both IRF-8 and mammary carcinoma development. Despite the fact that tumour growth was unaffected, splenomegaly, as well as the frequencies and absolute numbers of CD11b(+)Gr-1(+) cells were significantly lower in dTg mice when compared with single transgenic tumour-bearing mice. Overall, these data reveal that IRF-8 plays an important role in tumour-induced development and/or accumulation of CD11b(+)Gr-1(+) cells, and establishes a molecular basis for the potential manipulation of these myeloid populations for cancer therapy. PMID:20196788

  15. An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy

    DEFF Research Database (Denmark)

    Bach, Lars Arve; Bentzen, Søren; Alsner, Jan;

    2001-01-01

    interpretations of gene therapy. Two prototypical strategies for gene therapy are suggested, both of them leading to extinction of the malignant phenotype: one approach would be to reduce the relative proportion of the cooperating malignant cell type below a certain critical value. Another approach would be to......Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent the...... analysis to allow for synergistic effects between cells. A mathematical model of a tumour cell population is presented in which population-level synergy is assumed to originate through the interaction of triplets of cells. A threshold of two cooperating cells is assumed to be required to produce a...

  16. The evolution of carrying capacity in constrained and expanding tumour cell populations

    Science.gov (United States)

    Gerlee, Philip; Anderson, Alexander R. A.

    2015-10-01

    Cancer cells are known to modify their micro-environment such that it can sustain a larger population, or, in ecological terms, they construct a niche which increases the carrying capacity of the population. It has however been argued that niche construction, which benefits all cells in the tumour, would be selected against since cheaters could reap the benefits without paying the cost. We have investigated the impact of niche specificity on tumour evolution using an individual based model of breast tumour growth, in which the carrying capacity of each cell consists of two components: an intrinsic, subclone-specific part and a contribution from all neighbouring cells. Analysis of the model shows that the ability of a mutant to invade a resident population depends strongly on the specificity. When specificity is low selection is mostly on growth rate, while high specificity shifts selection towards increased carrying capacity. Further, we show that the long-term evolution of the system can be predicted using adaptive dynamics. By comparing the results from a spatially structured versus well-mixed population we show that spatial structure restores selection for carrying capacity even at zero specificity, which poses a solution to the niche construction dilemma. Lastly, we show that an expanding population exhibits spatially variable selection pressure, where cells at the leading edge exhibit higher growth rate and lower carrying capacity than those at the centre of the tumour.

  17. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Almstrup, K; Nielsen, J E;

    2005-01-01

    AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG...

  18. Sex determination by SRY PCR and sequencing of Tasmanian devil facial tumour cell lines reveals non-allograft transmission.

    Science.gov (United States)

    Cui, Xianlan; Wang, Yunfeng; Hua, Bobby; Miller, Webb; Zhao, Yan; Cui, Hongyu; Kong, Xiangang

    2016-05-20

    Devil facial tumour disease (DFTD) is an infectious tumour disease and was hypothesised to be transmitted by allograft during biting based on two cytogenetic findings of DFTD tumours in 2006. It was then believed that DFTD tumours were originally from a female devil. In this study the devil sex-determining region Y (SRY) gene was PCR amplified and sequenced, and six pairs of devil SRY PCR primers were used for detection of devil SRY gene fragments in purified DFTD tumour cell lines. Using three pairs of devil SRY PCR primers, devil SRY gene sequence was detected by PCR and sequencing in genomic DNA of DFTD tumour cell lines from six male devils, but not from six female devils. Four out of six DFTD tumour cell lines from male devils contained nucleotides 288-482 of the devil SRY gene, and another two DFTD tumour cell lines contained nucleotides 381-577 and 493-708 of the gene, respectively. These results indicate that the different portions of the SRY gene in the DFTD tumours of the male devils were originally from the male hosts, rejecting the currently believed DFTD allograft transmission theory. The reasons why DFTD transmission was incorrectly defined as allograft are discussed. PMID:27084454

  19. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses.

    Science.gov (United States)

    Boks, Martine A; Ambrosini, Martino; Bruijns, Sven C; Kalay, Hakan; van Bloois, Louis; Storm, Gert; Garcia-Vallejo, Juan J; van Kooyk, Yvette

    2015-10-28

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)(X) which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. Le(X)-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro-inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280-288 peptide to CD8(+) T cells compared to non-glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280-288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8(+) T cell responses. These data demonstrate that adjuvant-containing glycoliposome-based vaccines targeting DC-SIGN(+) DC

  20. Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

    Directory of Open Access Journals (Sweden)

    Anesti Anna-Maria

    2010-09-01

    Full Text Available Abstract Background Delivery of small interfering RNA (siRNA to tumours remains a major obstacle for the development of RNA interference (RNAi-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV OncoVEXGM-CSF, we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV. Methods To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA or artificial microRNA (miRNA against the reporter genes green fluorescent protein (eGFP and β-galactosidase (lacZ. These vectors were tested in non-tumour cell lines in vitro and tumour cells that are moderately susceptible to HSV infection both in vitro and in mice xenografts in vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting. Results Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells in vitro and tumours in vivo, with the viruses expressing artificial miRNA being comprehensibly more effective. Conclusions This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells in vitro and in vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen

  1. Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

    International Nuclear Information System (INIS)

    Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

  2. Tumour cell growth inhibitory potential of mushroom extracts from the genus Suillus

    OpenAIRE

    Vaz, Josiana A.; Santos, Tiago; Tavares, Catarina; Almeida, Gabriela M.; Ferreira, Isabel C. F. R.; Vasconcelos, M. Helena

    2012-01-01

    Mushrooms are a source of compounds with promising antitumour activity [1]. We have been working on the identification of wild mushrooms with promising antitumour activity and a Clitocybe alexandri extract which induces cell cycle arrest and apoptosis in a lung cancer cell line has been previously identified by part of the team [2]. The objective of this work was to continue the identification of mushrooms from the Northeast of Portugal with tumour cell growth inhibitory potential. Thirty...

  3. The contribution of drug resistant cancer stem cells to paediatric brain tumours

    OpenAIRE

    Punjaruk, Wiyada

    2010-01-01

    Introduction: Recent studies have revealed that cancer stem cells (CSCs) exist in malignant disease. Additionally, it is proposed that these cells may survive following chemotherapy, and hence contribute to tumour relapse. A significant mechanism of drug resistance in CSCs is believed to be the expression of ATP-binding cassette (ABC) transporters that efflux cytotoxic agents out of cells. The objective of this study was to study the existence of CSCs in a panel of primary paediatric brain tu...

  4. Treatment with IL-2 and IL-12 inhibits tumour cell division in SL2 lymphoma

    NARCIS (Netherlands)

    Masztalerz, A; Van Luyn, M; Werner, N; Molema, G; Everse, LA; Den Otter, W

    2004-01-01

    We examined which mechanism plays a dominant role in the rejection of solid SL2 lymphoma treated with locally applied IL-2 and /or IL-12. This treatment resulted in about 80% cures. There was a moderate influx of leukocytes in the tissue surrounding tumours; yet these cells failed to invade the soli

  5. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    Energy Technology Data Exchange (ETDEWEB)

    Andergassen, Ulrich; Kölbl, Alexandra C.; Hutter, Stefan; Friese, Klaus; Jeschke, Udo, E-mail: udo.jeschke@med.uni-muenchen.de [Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Munich, Maistrasse 11, D-80337 Munich (Germany)

    2013-09-25

    Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.

  6. Tumour resistance in induced pluripotent stem cells derived from naked mole-rats

    Science.gov (United States)

    Miyawaki, Shingo; Kawamura, Yoshimi; Oiwa, Yuki; Shimizu, Atsushi; Hachiya, Tsuyoshi; Bono, Hidemasa; Koya, Ikuko; Okada, Yohei; Kimura, Tokuhiro; Tsuchiya, Yoshihiro; Suzuki, Sadafumi; Onishi, Nobuyuki; Kuzumaki, Naoko; Matsuzaki, Yumi; Narita, Minoru; Ikeda, Eiji; Okanoya, Kazuo; Seino, Ken-ichiro; Saya, Hideyuki; Okano, Hideyuki; Miura, Kyoko

    2016-01-01

    The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype—ARF suppression-induced senescence (ASIS)—that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR. PMID:27161380

  7. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    Directory of Open Access Journals (Sweden)

    Udo Jeschke

    2013-09-01

    Full Text Available Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs. The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.

  8. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W;

    1994-01-01

    Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA sequ...

  9. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    International Nuclear Information System (INIS)

    Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment

  10. Two cases report of a malignant germ cell tumour of ovary and a granulosa cell tumour:Interest of tumoral immunochemistry in the identification and management.

    OpenAIRE

    Jean eBouquet De Jolinière

    2014-01-01

    Abstract Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23 year old female and a case of a bilateral undifferentiated granulosa cell tumor in a 71 year old female. The aim of these reports is to illustrate the interest of the immuno-histochemical analysis to define the correct diagnosis, to better classify these ovarian tumours and improve their management. Methods: This study we report two cases. The first case...

  11. Ascites: Pathogenesis and therapeutic principles

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens; Bendtsen, Flemming

    2009-01-01

    Ascites is a classic complication of advanced cirrhosis and it often marks the first sign of hepatic decompensation. Ascites occurs in more than 50% of patients with cirrhosis, worsens the course of the disease, and reduces survival substantially. Portal hypertension, splanchnic vasodilatation...... with large volume paracentesis followed by plasma volume expansion or transjugular intrahepatic portosystemic shunt. Ascites complicated by spontaneous bacterial peritonitis requires adequate treatment with antibiotics. New potential treatment strategies include the use of vasopressin V(2)-receptor...

  12. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases.

    Science.gov (United States)

    Tandra, Varun Sharma; Kotha, Krishna Mohan Reddy; Satyanarayana, Moorthy Gadisetti Venkata; Vadlamani, Kali Varaprasad; Yerravalli, Vyjayanthi

    2015-01-01

    Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge. PMID:26106496

  13. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases

    Directory of Open Access Journals (Sweden)

    Varun Sharma Tandra

    2015-01-01

    Full Text Available Giant cell tumour (GCT is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge.

  14. Aromatase inhibitors - a viable option for recurrent granulosa cell tumour of ovary: overview and case report

    International Nuclear Information System (INIS)

    Granulosa cell tumour of the ovary in adults is a rare tumour of low malignant potential affecting middle aged peri or post menopausal patients. These tumours are often diagnosed at an early stage, due to their hormonally active nature. They, however, have unique distinguishing histologic features and behaviour of frequent and late local or systemic relapses. The diagnosis can be challenging with unusual presentations. There is high association of endometrial carcinoma. Surgery is the mainstay of management in early low risk disease, while radiotherapy and systemic platinum based chemotherapy are employed in higher stage with poor prognostic indices. Survival is good in early stage disease. Recurrent, progressive, and treatment refractory disease is not infrequent and poses management challenge. Endocrine manipulation and hormone treatment are employed in few cases with equivocal results, as reported in literature. We present a case of recurrent and treatment refractory GCT in a postmenopausal patient, managed by aromatase inhibitor Anastrozole with reasonable efficacy. (author)

  15. A case of inflammatory ascites

    Directory of Open Access Journals (Sweden)

    Marco Biolato

    2008-03-01

    Full Text Available Even ascites appears mainly as sign of portal hypertension in patiens with liver cirrhosis, in some case depends on a different lying condition such as right congestive heart failure, peritoneal carcinomatosis or tuberculosis. In these cases, paracentesis represents the key tool for diagnosis. We report a case of cardiac ascites in a 71-years-old woman who developed in four-month an abdominal distension. Preliminary exams showed exudative ascites related to portal hypertension, a pelvic mass with caseous apparence, and inflammatory status ad an elevation of CA-125. Successive evaluation exluded peritoneal carcinomatosis or tuberculosis, underlyng a tricuspidal regurgitation. The literature on ascites has also been reviewed.

  16. The relationship of DNA double-strand break induction to radiosensitivity in human tumour cell lines

    International Nuclear Information System (INIS)

    Recent data suggest that differences in radiosensitivity between cell lines can be related to differences in dsb induction (Radford 1986). The current authors set out to assess the extent to which differences in radiation survival between nine human tumour cell lines could be attributed to differences in dsb induction. The lines varied widely in sensitivity, ranging from a sensitive neuroblastoma (surviving fraction at 2 Gy, SF2 = 0.13) to a resistant bladder carcinoma (SF2 = 0.62). Dsb induction was found to vary between the cell lines, such that resistant cells generally suffered less damage than sensitive ones. The data suggest that, in human tumour cell lines, differences in radiosensitivity may at least in part be due to different levels of damage induction, but that some lines may vary in their tolerance of damage due to differences in biological characteristics such as repair capacity. (author)

  17. Case Report: Detection and quantification of tumor cells in peripheral blood and ascitic fluid from a metastatic esophageal cancer patient using the CellSearch® technology [v1; ref status: indexed, http://f1000r.es/2hr

    Directory of Open Access Journals (Sweden)

    Qian Tu

    2014-01-01

    Full Text Available Analysis of ascitic fluid should help to identify and characterize malignant cells in gastrointestinal cancer. However, despite a high specificity, the sensitivity of traditional ascitic fluid cytology remains insufficient, at around 60%. Since 2004 the CellSearch® technology has shown its advantages in the detection of circulating tumor cells (CTCs in peripheral blood, which can perform an accurate diagnosis and molecular analysis at the same time. To our knowledge, no previous study has explored the potential utility of this technology for the detection and quantification of tumor cells in ascitic fluid samples. Herein we report a case of metastatic esophageal adenocarcinoma in a 70-year-old man presenting with dysphagia and a large amount of fluid in the peritoneal cavity. Analysis of a peripheral blood sample and ascites sample with the CellSearch® technology both revealed the presence of putative tumor cells that were positive for epithelial cell adhesion molecule (EpCAM and cytokeratin (CK expression. This study confirmed the hematogenous dissemination of esophageal cancer by the detection of circulating tumor cells in the peripheral blood, and is the first to demonstrate that tumor cells can be identified in ascitic fluid by using CellSearch® technology.

  18. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Menon, I.A.; Persad, S.; Ranadive, N.S.; Haberman, H.F.

    1983-07-01

    The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of ''Celtic'' skin to UV radiation-induced skin damage and carcinogenesis.

  19. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells

    International Nuclear Information System (INIS)

    The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of ''Celtic'' skin to UV radiation-induced skin damage and carcinogenesis

  20. Mechanisms of activation of NHE by cell shrinkage and by calyculin A in Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Varming, Camilla; Hoffmann, E K;

    2002-01-01

    compartments. Osmotic cell shrinkage elicited a rapid intracellular alkalinization, the sensitivity of which to EIPA (IC50 0.19 microM) and HOE 642 (IC50 0.85 microM) indicated that it predominantly reflected activation of NHE1. NHE activation by osmotic shrinkage was inhibited by the protein kinase C...... inhibitors chelerythrine (IC50 12.5 microM), Gö 6850 (5 microM), and Gö 6976 (1 microM), and by the p38 MAPK inhibitor SB 203580 (10 microM). Furthermore, hypertonic cell shrinkage elicited a biphasic increase in p38 MAPK phosphorylation, with the first significant increase detectable 2 minutes after the......-inhibitable intracellular alkalinization, indicating NHE1 activation. Similarly, shrinkage-induced NHE activation was potentiated by calyculin A. The calyculin A-induced alkalinization was not associated with an increase in the free, intracellular calcium concentration, but was abolished by chelerythrine. It...

  1. Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-cell Communication

    Directory of Open Access Journals (Sweden)

    Claudia Campanella

    2014-06-01

    Full Text Available Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.

  2. Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system.

    Science.gov (United States)

    Papaevangelou, Efthymia; Whitley, Guy S; Johnstone, Alan P; Robinson, Simon P; Howe, Franklyn A

    2016-06-01

    Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour-derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2 /5% CO2 ) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2 *) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions from which the carbogen-induced ΔR2 * was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour-derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti-vascular cancer therapies. The combination of ΔR2 * response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non-invasively monitor treatment response to iNOS inhibitors. PMID:26756734

  3. Computer simulation of tumour control probabilities after irradiation for varying intrinsic radio-sensitivity using a single cell based model

    International Nuclear Information System (INIS)

    Background. Currently, optimisation of the dose distribution and clinical acceptance are almost entirely based on the physical dose distribution and tumour control probability modelling is far from being routinely used as objective in treatment planning. For future individualised radiotherapeutic strategies, a reliable patient specific simulation model, taking into account customised tumour features, is needed to predict and improve treatment outcome. Materials and methods. To approach these demands, a single cell and Monte-Carlo based model was developed, which enables three-dimensional tumour growth and radiation response simulation. Tumour cells were characterised by cell-associated features such as age, intrinsic radio-sensitivity, proliferation ability, and oxygenation status, while capillary cells were considered as sources of a radial-dependent oxygen profile. Response to radiation was simulated by the linear-quadratic model, taking into account the lower radio-sensitivity of poorly oxygenated tumour cells. Results. The present study shows the influence of the model components and demonstrates the impact of the intra- and inter-tumoural radio-sensitivity heterogeneity on the treatment response. Conclusion. The simulation model adequately delineates the importance of the above described selected parameters on tumour control probability, providing an insight into the interplay of different physical and biological parameters, and its relevance for an individual tumour response

  4. Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

    International Nuclear Information System (INIS)

    Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics. For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine. All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (Vmax) and affinity (Km) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells. In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system. (orig.)

  5. Steroid hormones affect binding of the sigma ligand C-11-SA4503 in tumour cells and tumour-bearing rats

    NARCIS (Netherlands)

    Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Ishiwata, Kiichi; de Jong, Johan R.; de Vries, Erik F.; Dierckx, Rudi A.; van Waarde, Aren

    2009-01-01

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined change

  6. Urothelial atypia and survival rate of 500 unselected patients with primary transitional-cell tumour of the urinary bladder

    DEFF Research Database (Denmark)

    Rosenkilde Olsen, P; Wolf, H; Schroeder, T; Fischer, A; Højgaard, K

    1988-01-01

    In a consecutive series of 500 unselected patients with primary urinary bladder tumours the influence of urothelial atypia on the 5 years survival-rate was examined. All tumours were transitional-cell tumours categorized according to the T-classification. Mucosal biopsies from 7 pre-selected sites...... were taken at the initial cystoscopy in 391 patients (78%) to identify urothelial atypia. The over-all cumulative 5 years survival-rate was 48%. Submucosal and muscle invasion had major influence on survival, whereas tumour grade was less important. Patients with urothelial atypia fared significantly...

  7. Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment.

    Science.gov (United States)

    Rausch, Vanessa; Liu, Li; Apel, Anja; Rettig, Theresa; Gladkich, Jury; Labsch, Sabrina; Kallifatidis, Georgios; Kaczorowski, Adam; Groth, Ariane; Gross, Wolfgang; Gebhard, Martha M; Schemmer, Peter; Werner, Jens; Salnikov, Alexei V; Zentgraf, Hanswalter; Büchler, Markus W; Herr, Ingrid

    2012-07-01

    Involvement of dysregulated autophagy in cancer growth and progression has been shown in different tumour entities, including pancreatic ductal adenocarcinoma (PDA). PDA is an extremely aggressive tumour characterized by a small population of highly therapy-resistant cancer stem cells (CSCs) capable of self-renewal and migration. We examined whether autophagy might be involved in the survival of CSCs despite nutrition and oxygen deprivation typical for the hypoxic tumour microenvironment of PDA. Immunohistochemistry revealed that markers for hypoxia, CSCs and autophagy are co-expressed in patient-derived tissue of PDA. Hypoxia starvation (H/S) enhanced clonogenic survival and migration of established pancreatic cancer cells with stem-like properties (CSC(high)), while pancreatic tumour cells with fewer stem cell markers (CSC(low)) did not survive these conditions. Electron microscopy revealed more advanced autophagic vesicles in CSC(high) cells, which exhibited higher expression of autophagy-related genes under normoxic conditions and relative to CSC(low) cells, as found by RT-PCR and western blot analysis. LC3 was already fully converted to the active LC3-II form in both cell lines, as evaluated by western blot and detection of accumulated GFP-LC3 protein by fluorescence microscopy. H/S increased formation of autophagic and acid vesicles, as well as expression of autophagy-related genes, to a higher extent in CSC(high) cells. Modulation of autophagy by inhibitors and activators resensitized CSC(high) to apoptosis and diminished clonogenicity, spheroid formation, expression of CSC-related genes, migratory activity and tumourigenicity in mice. Our data suggest that enhanced autophagy levels may enable survival of CSC(high) cells under H/S. Interference with autophagy-activating or -inhibiting drugs disturbs the fine-tuned physiological balance of enhanced autophagy in CSC and switches survival signalling to suicide. PMID:22262369

  8. Therapy of MHC Class I+ and Class I- HPV 16-Associated Tumours with Cytokines, Genetically Modified Tumour Vaccines and Dendritic Cells

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Šímová, Jana; Mikyšková, Romana; Vonka, V.

    2004-01-01

    Roč. 27, č. 4 (2004), s. 161D. ISSN 0147-958X. [International Congress of Immunology /12./ and Annual Conference of FOCIS /4./. Montreal, 18.07.2004-23.07.2004] Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV 16 * tumour vaccines * dendritic cells Subject RIV: EC - Immunology Impact factor: 1.051, year: 2004

  9. Inducible Protective Processes in Animal Systems XIII: Comparative Analysis of Induction of Adaptive Response by EMS and MMS in Ehrlich Ascites Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Periyapatna Vishwaprakash Mahadimane

    2014-01-01

    Full Text Available In order to investigate the presence of adaptive response in cancerous cells, two monofunctional alkylating agents, namely, ethyl methanesulfonate (EMS and methyl methanesulfonate (MMS, were employed to treat Ehrlich ascites carcinoma (EAC cells in vivo. Conditioning dose of 80 mg/kg body weight of EMS or 50 mg/kg body weight of MMS and challenging dose of 240 mg/kg body weight of EMS or 150 mg/kg body weight of MMS were selected by pilot toxicity studies. Conditioned EAC cells when challenged after 8 h time lag resulted in significant reduction in chromosomal aberrations compared to challenging dose of respective agents. As has been proved in earlier studies with normal organisms, even in cancerous cells (EAC, there is presence of adaptive response to methylating and ethylating agents. Furthermore, it is also interesting to note in the present studies that the methylating agent, MMS, is a stronger inducer of the adaptive response than the ethylating agent, EMS.

  10. Activity and characterization of sialyltransferase from serum of normal rats, of bearing Zajdela ascitic hepatoma, in normal host liver and in Zajdela hepatoma cells

    International Nuclear Information System (INIS)

    Comparative studies on the content of sialic acid and on the sialyltransferase activity in normal serum and in serum of rats with Zajdela ascitic in different phases of tumor development have been conducted. Unlike the serum from animals with tumors, in which the sialic acid quantity increases in dependence of the stage of tumor development, the activity of serum sialyltransferase statistically augmented only in serum of rats at the final stage of tumor progression. The sialyltransferase activity towards asialofetuin as an acceptor in normal liver and in Zajdela hepatoma cells, was measured and a decrease in this activity in tumor cells as well as in host liver was found. When lactose was used as acceptor, again lower activity in the tumor cells in comparison with that in liver was established, but in liver and in hepatoma cells the predominant 14C-labelled product of the sialyltransferase assay was alpha(2-6)sialyllactose isomer. The results contribute to the biochemical characterization of rat Zajdela hepatoma. (author)

  11. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

    OpenAIRE

    Flores, L M; Kindelberger, D W; Ligon, A H; Capelletti, M.; Fiorentino, M.; Loda, M; Cibas, E S; Jänne, P.A.; Krop, I. E.

    2010-01-01

    Background: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. Methods: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with meta...

  12. Giant cell tumour of tendon sheath with simultaneous two tendon involvement of the foot treated with excision of the tumour and reconstruction of the flexor retinaculum using tibialis posterior tendon in a paediatric patient: A rare case report.

    Science.gov (United States)

    Tiwari, Vivek; Ansari, Tahir; Mittal, Samarth; Sharma, Pankaj; Nalwa, Aasma

    2015-12-01

    Giant cell tumour of tendon sheath is a benign soft tissue tumour arising from the tendon sheath. The involvement of foot and ankle by such tumours is relatively rare. Children are not commonly afflicted by this condition. All such tumours are reported to arise either from a single tendon sheath or one joint. We report a case of giant cell tumour of tendon sheath in a 12-year-old child, arising simultaneously from the tendon sheaths of tibialis posterior and flexor digitorum longus tendons, as well as extending into the ankle joint. It was treated by complete excision of the mass along with the tendon sheaths with reconstruction of the flexor retinaculum. The location of the tumour, age of the patient, diffuse nature of the tumour and novel technique of reconstruction of the flexor retinaculum make this case extremely rare and the first to be reported in literature. PMID:26564735

  13. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    Science.gov (United States)

    Whelan, M C; Casey, G; MacConmara, M; Lederer, J A; Soden, D; Collins, J K; Tangney, M; O'Sullivan, G C

    2010-07-01

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development. PMID:20186173

  14. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    LENUS (Irish Health Repository)

    Whelan, M C

    2012-01-31

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

  15. Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice.

    OpenAIRE

    Lenti, L; Lipari, M.; Lombardi, D; Zicari, A.; Dotta, A.; Pontieri, G. M.

    1986-01-01

    The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl...

  16. The effect of Translationally Controlled Tumour Protein (TCTP) on programmed cell death in plants

    OpenAIRE

    Hoepflinger, Marion Christine; Reitsamer, Johannes; Geretschlaeger, Anja Maria; Mehlmer, Norbert; Tenhaken, Raimund

    2013-01-01

    Background: Translationally controlled tumour protein (TCTP), a well known protein of the animal kingdom, was shown to be a Ca2+-binding protein with important functions in many different cellular processes (e.g. protection against stress and apoptosis, cell growth, cell cycle progression, and microtubule organization). However, only little is known about TCTP in plants. Transcript and protein levels of plant TCTPs were shown to be altered by various stress conditions (e.g. cold, salt, draugh...

  17. Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival.

    OpenAIRE

    Ligthart, Sjoerd T.; Frank A W Coumans; Gerhardt Attard; Amy Mulick Cassidy; de Bono, Johann S.; Terstappen, Leon W. M. M.

    2011-01-01

    Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearch™ system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer t...

  18. Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma

    OpenAIRE

    Morris, M.

    2008-01-01

    Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidat...

  19. Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer

    OpenAIRE

    Lindsay, C. R.; Le Moulec, S.; Billiot, F.; Loriot, Y; Ngo-Camus, M.; Vielh, P; Fizazi, K; Massard, C; Farace, F.

    2016-01-01

    Background High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRP...

  20. Emerging roles of extracellular vesicles in the adaptive response of tumour cells to microenvironmental stress

    Directory of Open Access Journals (Sweden)

    Paulina Kucharzewska

    2013-03-01

    Full Text Available Cells are constantly subjected to various types of endogenous and exogenous stressful stimuli, which can cause serious and even permanent damage. The ability of a cell to sense and adapt to environmental alterations is thus vital to maintain tissue homeostasis during development and adult life. Here, we review some of the major phenotypic characteristics of the hostile tumour microenvironment and the emerging roles of extracellular vesicles in these events.

  1. Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases.

    NARCIS (Netherlands)

    Groot, J.W. de; Rikhof, B.; Doorn, J. van; Bilo, H.J.; Alleman, M.A.; Honkoop, A.H.; Graaf, W.T.A. van der

    2007-01-01

    This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused

  2. Non-islet cell tumour-induced hypoglycaemia : a review of the literature including two new cases

    NARCIS (Netherlands)

    De Groot, Jan Willem B.; Rikhof, Bart; Van Doom, Jaap; Bilo, Henk J. G.; Alleman, Maarten A.; Honkoop, Aafke H.; Van der Graaf, Winette T. A.

    2007-01-01

    This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused

  3. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby;

    2010-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may...

  4. Cybernetical investigations on the radiation effects on tumour cells

    International Nuclear Information System (INIS)

    The goal of this work was to find suitable conditions for the in-vitro investigations with these E.A.T. cells so that basic experiments carried out with yeast cells will also be possible. Systematic investigations on cell multiplication led to reliable and definite test conditions for these cells. For the evaluation of the data which had been measured with several sorts of radiation the cybernetic model was applied. (orig./MG)

  5. IMRT technique application in vertebra L3 giant cell tumour - a case report

    International Nuclear Information System (INIS)

    Giant cell tumour is a rare locally malignant neoplasm of the bone, which is characterised by a high risk of recurrence. The main management is surgery and, in the case of a nonradical operation, radiotherapy. The aim of the paper is to present the case of a 38-year old woman with a diagnosis of giant cell tumour localised in the 3rd vertebral body. For this rare localisation both surgery and radiotherapy are at high risk of neurological complications due to the close neighbourhood of critical organs (the spinal cone and cauda equina). The treatment of the patient consisted of a non radical operation and postoperative radiotherapy with a total dose of 54 Gy given in 27 fractions. In this case the intensity modulated radiotherapy (IMRT) technique seemed to be specially beneficial (a high dose gradient), enabling radiosensitive critical organs to be protected. After 3 months, in spite of the treatment, a recurrence was detected by CT and the patient was re operated on. The reason for the local regrowth of the tumour might be insufficient stabilization of the irradiated region. The literature reports only a few cases of IMRT usage for paraspinal tumour treatment. Immobilization body frames were used for these patients. Thus this modern radiotherapy technique requires not only a doctors experience but also improvement of ways of its application in new organ localizations. (authors)

  6. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

    Science.gov (United States)

    Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

    2016-08-01

    Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs. PMID:27189371

  7. The Role of TG2 in Regulating S100A4-Mediated Mammary Tumour Cell Migration

    OpenAIRE

    Zhuo Wang; Martin Griffin

    2013-01-01

    The importance of S100A4, a Ca(2+)-binding protein, in mediating tumour cell migration, both intracellularly and extracellularly, is well documented. Tissue transglutaminase (TG2) a Ca(2+)-dependent protein crosslinking enzyme, has also been shown to enhance cell migration. Here by using the well characterised non-metastatic rat mammary R37 cells (transfected with empty vector) and highly metastatic KP1 cells (R37 cells transfected with S100A4), we demonstrate that inhibition of TG2 either by...

  8. Specific transfer of oncolytic adenoviruses by mesenchymal stem cells for the elimination of pancreatic tumour stem cells

    OpenAIRE

    KACZOROWSKI, ADAM

    2014-01-01

    Abstract Pancreatic adenocarcinoma has a very poor prognosis with currently existing therapies prolonging patient life for only a few weeks. Therefore novel therapy options are urgently needed. Present theories maintain that only a small fraction of tumour cells (the cancer stem cells (CSC)) are responsible for the highly aggressive behaviour of pancreatic cancer. These cells show a stem cell like phenotype and a high resistance to chemotherapy. Oncolytic viruses are promising candidat...

  9. [Ascites and acute kidney injury].

    Science.gov (United States)

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  10. GIANT CELL TUMOUR OF THE TENDON SHEATH: A CASE REPORT

    OpenAIRE

    Ravikumar; Amit

    2014-01-01

    INTRODUCTION: The giant cell tumor of tendon sheath is among the more common soft tissue tumors of the hand. It is a slowly progressive, usually painless, rubbery mass predominating on the radial three digits of the hand and is typically identified adherent to the digital flexor tendon sheath of the hand. The histology is variable but the tumors consistently contain multinucleated giant cells and xanthoma cells. CASE PRESENTATION: A case report of a 57 years old female patient...

  11. Anti-Tumor Activity of Four Ayurvedic Herbs in Dalton Lymphoma Ascites Bearing Mice and Their Short-Term In Vitro Cytotoxicity on DLA-Cell-Line

    OpenAIRE

    Adhvaryu, Meghna R; Reddy, Narshimha; Parabia, Minoo H

    2008-01-01

    The anti-tumor activity and chemopreventive potential of four Ayurvedic herbs viz. Curcuma longa L., Ocimum sanctum L., Tinospora cordifolia (Wild) Miers ex Hook.f & Thomas and Zizyphus mauritiana Lam. were evaluated using Dalton Lymphoma ascites (DLA) tumor model in Swiss Albino mice. The outcome was assessed using survival time, peritoneal ascitic fluid (Tumor volume) and hematological indices as parameters. Animals were divided into five groups (n = 6) viz. one DLA control and four Herb + ...

  12. Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells

    OpenAIRE

    Shukla Deepa; Esteban Miguel A; Harten Sarah K; Ashcroft Margaret; Maxwell Patrick H

    2011-01-01

    Abstract Background 209 000 new cases of renal carcinoma are diagnosed each year worldwide and new therapeutic targets are urgently required. The great majority of clear cell renal cancer involves inactivation of VHL, which acts as a gatekeeper tumour suppressor gene in renal epithelial cells. However how VHL exerts its tumour suppressor function remains unclear. A gene expression microarray comparing RCC10 renal cancer cells expressing either VHL or an empty vector was used to identify novel...

  13. Anti tumor vaccination with hybrid dendritic-tumour cells

    International Nuclear Information System (INIS)

    Dendritic cells are the most potent antigen-presenting cells, and the possibility of their use for cancer vaccination has renewed the interest in this therapeutic modality. Nevertheless, the ideal immunization protocol with these cells has not been described yet. In this paper we describe the preliminary results of a protocol using autologous tumor and allogeneic dendritic hybrid cell vaccination every 6 weeks, for metastatic melanoma and renal cell carcinoma (RCC) patients. Thirty-five patients were enrolled between March 2001 and March 2003. Though all patients included presented with large tumor burdens and progressive diseases, 71% of them experienced stability after vaccination, with durations up to 19 months. Among RCC patients 3/22 (14%) presented objective responses. The median time to progression was 4 months for melanoma and 5.7 months for RCC patients; no significant untoward effects were noted. Furthermore, immune function, as evaluated by cutaneous delayed-type hypersensitivity reactions to recall antigens and by peripheral blood proliferative responses to tumor-specific and nonspecific stimuli, presented a clear tendency to recover in vaccinated patients. These data indicate that dendritic cell-tumor cell hybrid vaccination affects the natural history of advanced cancer and provide support for its study in less advanced patients, who should, more likely, benefit even more from this approach. (author)

  14. Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours

    International Nuclear Information System (INIS)

    Germ cell tumours (GCT) producing alpha fetoprotein (aFP) can be imaged by external scintigraphy after intraveneous administration of radiolabelled antibody directed against aFP. Antibody imaging (AI) by this method was used in an attempt to guide surgical resection of deposits of drug-resistant or recurrent GCT. 30 patients with GCT and raised aFP in whom site of tumour was not known were investigated by AI and conventional imaging methods. All but one were heavily pretreated. Where tumour appeared localised, resection was attempted. Tumour was found in all sites positive by both AI and conventional imaging. AI produced false-positive results in one of 30 patients and false-negative results in 9 patients. Computerised tomography was false-positive in one case and false-negative in three. In these patients, AI gave true-negative and true-positive results, respectively. Of 11 patients with positive AI in whom resection was attempted, 6 achieved sustained complete response with up to 5 years follow-up. We conclude AI and conventional imaging methods to be complementary in selection for surgery of patients with drug-resistant or recurrent GCT. (orig.)

  15. The relationship between induced chromosome aberrations and chromosome abnormality in tumour cells

    International Nuclear Information System (INIS)

    The occurrence of chromosome abnormalities in cancer cells and the induction of chromosome aberrations by many different carcinogenic agents are now well established facts and there are many detailed studies in both areas. It is known, however, whether or not there is any relationship between the induced aberrations and those seen in tumours. The purpose of this paper is to consider any evidence which might suggest that such a relationship does exist and the significance that this would have in the genesis of neoplasia. There are at least four chromosomal situations in human tumours: (a) cytogenetically normal, (b) clonal but unique, (c) clonal and specific for a particular neoplasm, (d) clonal and common to some tumours of different types. Any theory that we develop must take account of all four situations. A number of different suggestions have been made to try to explain the observation of chromosome abnormalities in human tumours. The one feature that does seem common to all situations is clonal evolution. A modified somatic mutation hypothesis to account for the chromosome changes occurring before and after malignant transformation is suggested

  16. Radiotherapeutic response of Ehrlich Ascites tumor cells perfused in agarose gel threads and implanted in mice. A 31P MR spectroscopy study

    International Nuclear Information System (INIS)

    Aim: In order to obtain better understanding of radiation-induced alterations in intracellular metabolism, a dynamic and noninvasive experimental model system is required. A serial study in cultured tumor cell line followed by verification in the in vivo samples may be of considerable value for non-invasive prediction and/or detection of tumor response to therapy. The present study was undertaken to evaluate the radiation response of perfused Ehrlich ascites tumors cells (EATC) immobilized in agarose gel matrix to that observed in mouse bearing EATC tumor, in order to identify biomarkers of radiation response. Materials and Methods: Perfused EAT cells, entrapped in agarose gel threads were irradiated in the perfusion assembly outside the magnet with fast electrons (6 Gy, 1 Gy/min) using 30 MeV Betatron. Solid EATC tumors implanted subcutaneously onto right hand limb of Swiss-albino strain 'A' mice, were focally irradiated using 60Co teletherapy (10 Gy, 0.4 Gy/min). Metabolites changes were monitored by 31P MR spectroscopic techniques. Results: A post-irradiation decrease in the levels of ATP and ADP along with an increase in inorganic phosphate and glycerophosphocholine levels was observed. The ratios of β-phosphate of ATP to inorganic phosphate (β-ATP-Pi), and phosphocholine to glycerophosphocholine (PC/GPC), declined during 1-5 hours following irradiation, in perfused EAT cells and in the solid tumors implanted in mice. Conclusion: Perfused cells could be used as a simple model of tumor for prediction of clinical radiotherapeutic response. The present study demonstrates that radiation damage may be occurring both at the DNA protein as well as the membrane lipid levels. Therefore, the bioenergetics and phospholipid profiles of tumor cells could be used as complimentary, reliable and sensitive indirect indicators for devising predictive assays for assessment and monitoring of radiation response, which will also facilitate the individualization and optimization of

  17. (Accumulation of methyl-deficient rat liver messenger ribonucleic acid on ethionine administration). Progress report. [Methyltransferase activity in Ehrlich ascites tumor cells and effects of phorbol ester on methyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Borek, E.

    1980-01-01

    Enzyme fractions were isolated from Ehrlich ascites cells which introduced methyl groups into methyl deficient rat liver mRNA and unmethylated vaccinia mRNA. The methyl groups were incorporated at the 5' end into cap 1 structures by the viral enzyme, whereas both cap 0 and cap 1 structures were formed by the Ehrlich ascites cell enzymes. Preliminary results indicate the presence of adenine N/sup 6/-methyltransferase activity in Ehrlich ascites cells. These results indicate that mRNA deficient in 5'-cap methylation and in internal methylation of adenine accumulated in rats on exposure to ethionine. The methyl-deficient mRNA isolated from the liver of ethionine-fed rats differed in its translational properties from mRNA isolated from control animals. Preliminary experiments indicate that single topical application of 17n moles of TPA to mouse skin altered tRNA methyltransferases. The extent of methylation was increased over 2-fold in mouse skin treated with TPA for 48 hours. These changes have been observed as early as 12 hours following TPA treatment. In contrast, the application of initiating dose of DMBA had no effect on these enzymes. It should be emphasized that the changes in tRNA methyltransferases produced by TPA are not merely an increase of the concentration of the enzyme, rather that they represent alterations of specificity of a battery of enzymes. In turn the change in enzyme specificity can produce alterations in the structure of tRNA. (ERB)

  18. Raman spectroscopy of single human tumour cells exposed to ionizing radiation in vitro

    International Nuclear Information System (INIS)

    This work investigates the capability of Raman spectroscopy (RS) to study the effects of ionizing radiation on single human tumour cells. Prostate tumour cells (cell line DU145) are cultured in vitro and irradiated to doses between 15 and 50 Gy with single fractions of 6 MV photons. Single-cell Raman spectra are acquired from irradiated and unirradiated cultures up to 5 days post-irradiation. Principal component analysis is used to distinguish the uniquely radiation-induced spectral changes from inherent sources of spectral variability arising from cell cycle differences and other known factors. We observe uniquely radiation-induced spectral changes which are correlated with both the irradiated dose and the incubation time post-irradiation. The spectral changes induced by radiation arise from biochemical differences in lipids, nucleic acids, amino acids and conformational protein structures between irradiated and unirradiated cells. To our knowledge, this study is the first use of RS to observe radiation-induced biochemical differences in single cells, and is the first use of vibrational spectroscopy to observe uniquely radiation-induced biochemical differences in single cells independent of concurrent cell-cycle- or cell-death-related processes.

  19. Repopulation of tumour cells following irradiation with X-rays or low energy neutrons

    International Nuclear Information System (INIS)

    The repopulation of C3H mouse mammary carcinoma cells following X-ray or fast neutron irradiation was investigated in vivo using TCD50 as an endpoint. Tumours in the C3H mouse leg were irradiated in air with an X-ray dose of 9.6, 28.8 or 48.0 Gy, or a neutron dose of 2.6 or 5.2 Gy, and, various times thereafter, graded X-ray doses were given under hypoxic conditions to determine TCD50. A significant finding was that the tumour cells treated with a neutron dose, either 2.6 or 5.2 Gy, appeared to repopulate slightly more rapidly than those irradiated with X-rays, and the doubling times following two different neutron doses were not significantly different. (author)

  20. Method validation of circulating tumour cell enumeration at low cell counts

    International Nuclear Information System (INIS)

    Circulating tumour cells (CTC) are receiving increasing attention as prognostic, predictive and pharmacodynamic biomarkers in cancer patients. However, their clinical significance can be dependent on an accurate determination of CTC around cut-off values at low cell counts (<10 cells/7.5 ml). Consequently, we have conducted method validation of the CellSearch™ system focusing on clinical samples containing CTC in the cut-off region. Analytical accuracy was first assessed employing quality controls (QC) and spiked healthy volunteer blood specimens. Results were analysed by β-expectation tolerance intervals (BETI). Inter-operator error (6 different readers) was then characterised in 38 different patient samples, 68% of which had ≤5 CTC and data were analysed by β-content γ-confidence tolerance intervals (BCTI). Results from QCs and spiked blood confirmed a 3-4-fold higher degree of imprecision at the low (48 cells, BETI = + 0.288/-0.345, β = 95%) compared to the high QC (987 cells, BETI = +0.065/-0.140, β = 95%). However, when data for individual analysts were interrogated characteristic systematic errors were detected. In the analysis of patient samples again individual analysts introduced a highly specific error into the interpretation of CTC images, which correlated to the level of training and experience. When readers were selected based on BETI and BCTI results, the high level of between-operator error (up to 170%) observed at CTC of ≤ 5 was reduced to < 30%. Inter-operator variability in enumeration of CTC at low cell counts can be considerable, but is also potentially avoidable by following simple guidance steps

  1. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

    OpenAIRE

    Silconi Žana Besser; Benazic Sasa; Milovanovic Jelena; Arsenijevic Aleksandar; Stojanovic Bojana; Milovanovic Marija; Kanjevac Tatjana

    2015-01-01

    Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity...

  2. Clinical evaluation of serum tumour marker CA 242 in non-small cell lung cancer.

    OpenAIRE

    Pujol, J L; Cooper, E H; Lehmann, M.; Purves, D. A.; Dan-Aouta, M.; Midander, J.; Godard, P.; Michel, F B

    1993-01-01

    CA 242, a novel tumour carbohydrate antigen present in serum (upper limit of normal values: 20.0 U ml-1), has been measured in a group of 102 pathologically confirmed non-small cell lung cancer patients. The aim of the present prospective study was to identify any relationship between pre-treatment serum CA 242 level and different features of lung cancer including prognosis. Serum CA 242 was measured using the delayed europium lanthanide fluoroimmunometric assay. Sensitivity and specificity w...

  3. HPV16-associated tumours: Therapy of surgical minimal residual disease with dendritic cell-based vaccines

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Indrová, Marie; Mendoza, Luis; Mikyšková, Romana; Bieblová, Jana; Bubeník, Jan; Šímová, Jana

    2004-01-01

    Roč. 25, č. 4 (2004), s. 1165-1170. ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA ČR GA301/04/0492; GA ČR GA301/01/0985; GA AV ČR IAA5052203 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * minimal residual tumour disease * dendritic cells Subject RIV: EC - Immunology Impact factor: 3.056, year: 2004

  4. Circulating Cell-Free Tumour DNA in the Management of Cancer

    OpenAIRE

    Glenn Francis; Sandra Stein

    2015-01-01

    With the development of new sensitive molecular techniques, circulating cell-free tumour DNA containing mutations can be identified in the plasma of cancer patients. The applications of this technology may result in significant changes to the care and management of cancer patients. Whilst, currently, these “liquid biopsies” are used to supplement the histological diagnosis of cancer and metastatic disease, in the future these assays may replace the need for invasive procedures. Applications ...

  5. Non-islet Cell Tumour Hypoglycaemia (NICTH) in Malignant Mesothelioma: Case Report

    OpenAIRE

    Wong, Wai Keat

    2015-01-01

    Non-islet cell tumour hypoglycaemia (NICTH) is an uncommon but important clinical condition. It can occur in a setting of known malignancy. Here, we report the case of a 56-year-old, non-diabetic, female patient with unresectable malignant pleural mesothelioma who presented with unexplained recurrent hypoglycaemia. Surreptitious use of insulin or other hypoglycaemic agents were ruled out. Investigations revealed markedly suppressed insulin-like growth factor-I, normal insulin-like growth fact...

  6. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  7. Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells

    Directory of Open Access Journals (Sweden)

    Takahashi Takashi

    2007-04-01

    Full Text Available Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

  8. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

    Directory of Open Access Journals (Sweden)

    Jason R Sutherland

    Full Text Available Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2, cytokines interleukin (IL -6, and -11 and vascular endothelial growth factor-A (VEGF-A. To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

  9. Desmoplastic small round cell tumour: Cytological and immunocytochemical features

    Directory of Open Access Journals (Sweden)

    Filho Adhemar

    2005-01-01

    Full Text Available Abstract Background Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive neoplasm. The cytological diagnosis of these tumors can be difficult because they show morphological features quite similar to other small round blue cells tumors. We described four cases of DSRCT with cytological sampling: one obtained by fine needle aspiration biopsy (FNAB and three from serous effusions. The corresponding immunocytochemical panel was also reviewed. Methods Papanicolaou stained samples from FNAB and effusions were morphologically described. Immunoreaction with WT1 antibody was performed in all cytological samples. An immunohistochemical panel including the following antibodies was performed in the corresponding biopsies: 34BE12, AE1/AE3, Chromogranin A, CK20, CK7, CK8, Desmin, EMA, NSE, Vimentin and WT1. Results The smears showed high cellularity with minor size alteration. Nuclei were round to oval, some of them with inconspicuous nucleoli. Tumor cells are clustered, showing rosette-like feature. Tumor cells in effusions and FNA were positive to WT1 in 3 of 4 cytology specimens (2 out 3 effusions and one FNA. Immunohistochemical reactions for vimentin, NSE, AE1/AE3 and WT1 were positive in all cases in tissue sections. Conclusion The use of an adjunct immunocytochemical panel coupled with the cytomorphological characteristics allows the diagnosis of DSRCT in cytological specimens.

  10. High-dose chemotherapy in germ cell tumours: a large single centre experience.

    Science.gov (United States)

    Rick, O; Beyer, J; Kingreen, D; Schwella, N; Krusch, A; Schleicher, J; Kirsch, A; Huhn, D; Siegert, W

    1998-11-01

    High-dose chemotherapy (HDCT) has evolved as a strategy to improve the treatment outcome in patients with relapsed and/or refractory germ cell tumours. Between August 1989 and September 1995, 150 consecutive patients with relapsed and/or refractory germ cell tumours were treated with conventional-dose salvage chemotherapy followed by one cycle of HDCT with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2 and ifosfamide 0-10 g/m2 and were retrospectively analysed. With a median follow-up time of 55 months (range 21-88 months) 51/150 (34%) patients are alive and disease free. The projected event-free and overall survival are 29% (confidence interval 22-37%) and 39% (confidence interval 31-47%) respectively. The relevance of prognostic variables for long-term survival after HDCT were prospectively confirmed. Persisting toxicities occurred in approximately one third of the long-term survivors. Treatment intensification with HDCT resulted in a significant proportion of the long-term survivors in patients with relapsed and/or refractory germ cell tumours. Trials to prospectively evaluate HDCT as an early intervention in these patients seem justified. PMID:10023310

  11. Cell survival and growth delay in rat R-1 tumours after radiation and vinblastine treatment

    International Nuclear Information System (INIS)

    The rat R-1 rhabdomyosarcoma with a capacity for colony growth in vitro after excision of the tumour and dissociation by a trypsin method was used to investigate the effectiveness of radio-chemotherapy. Growth delay data were compared with data on survival of cells derived from tumours treated in situ. An excess in growth delay was observed when vinblastine (1.5 mg/kg) was given at intervals of 0.3 to 2 d after or 4 d before a dose of 20 Gy of X-rays. Cell survival data indicated that the maximum effectiveness of the drug treatment and the combined treatment (vinblastine and a dose of 10 Gy) can be assessed 2 to 3 d after treatment. The fractions of surviving cells determined after combined therapy at 0,1 and 2 d intervals were not significantly different from the fractions expected on the basis of simple multiplication of the fractions surviving individual treatments. The data suggested that the excess in tumour growth delay observed cannot be accounted for by co-operative interaction of the doses of radiation and drug. (author)

  12. Equine Cutaneous Mast Cell Tumours Exhibit Variable Differentiation, Proliferation Activity and KIT Expression.

    Science.gov (United States)

    Ressel, L; Ward, S; Kipar, A

    2015-11-01

    Equine cutaneous mast cell tumours (CMCTs) are generally considered to be benign skin lesions, although recurrent and multicentric tumours have been described. For canine CMCTs, grading and prognostic approaches are well established and aberrant KIT expression as well as high proliferation indices are associated with poor outcome. However, in the case of equine CMCTs, morphological features, proliferative activity and KIT expression pattern have not been assessed or related to biological behaviour, and there is discussion as to whether CMCTs are true neoplastic processes. The present study describes 45 equine CMCTs in terms of their morphology and KIT and PCNA expression by immunohistochemistry. KIT expression was classified as membranous (I), cytoplasmic and focally stippled (II) or diffuse cytoplasmic (III). A large proportion of the tumours were multinodular or diffuse dermal infiltrates of mast cells with mild anisokaryosis, a low proliferative rate and a dominance of KIT pattern I, representing well-differentiated CMCTs. In approximately one third of the cases, the mast cells exhibited more infiltrative growth, moderate to marked anisokaryosis and a higher degree of proliferation. These were classified as poorly differentiated CMCTs and exhibited only KIT patterns II and III. These findings indicate that there is a subgroup of poorly differentiated equine CMCTs, in which there is an association between aberrant KIT expression, high proliferative rate and potential aggressive behaviour, all features that confirm at least the poorly differentiated CMCT as a true neoplastic processes. PMID:26292768

  13. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1 cell cycle arrest in EAC cells.

    Science.gov (United States)

    Fukumasu, Heidge; Latorre, Andreia Oliveira; Zaidan-Dagli, Maria Lucia

    2011-01-01

    The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant. PMID:20564499

  14. Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling

    DEFF Research Database (Denmark)

    Carl, J; Christensen, T B; von der Maase, H

    1992-01-01

    This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactate dehydrogenase (LDH...... faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses....

  15. Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK

    OpenAIRE

    Pereira, Lorena; Igea, Ana; Canovas, Begoña; Dolado, Ignacio; Nebreda, Angel R

    2013-01-01

    The p38 MAPK pathway is an important regulator of many cellular responses. It is well established that p38 MAPK signalling negatively regulates epithelial cell transformation, but enhanced p38 MAPK activity has been also correlated with bad clinical prognosis in some tumour types. Here, we provide genetic and pharmacological evidence showing that p38 MAPK inhibition cooperates with the chemotherapeutic agent cisplatin to kill tumour cells. We show that p38 MAPK inhibition results in ROS upreg...

  16. Imaging and radiation effects of gold nanoparticles in tumour cells

    Science.gov (United States)

    McQuaid, Harold N.; Muir, Mark F.; Taggart, Laura E.; McMahon, Stephen J.; Coulter, Jonathan A.; Hyland, Wendy B.; Jain, Suneil; Butterworth, Karl T.; Schettino, Giuseppe; Prise, Kevin M.; Hirst, David G.; Botchway, Stanley W.; Currell, Fred J.

    2016-01-01

    Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events.

  17. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    Directory of Open Access Journals (Sweden)

    Collins Hilary M

    2013-01-01

    Full Text Available Abstract Background Post-translational modifications (PTMs of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7. Methods Cell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR. Results Although treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2

  18. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    International Nuclear Information System (INIS)

    Post-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7. Cell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR. Although treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2, and was prevented by siRNA targeting of SUV420H2. In

  19. Comparison of CT scan and colour flow doppler ultrasound in detecting venous tumour thrombous in renal cell carcinoma

    International Nuclear Information System (INIS)

    Renal cell carcinoma has marked tendency to spread into renal vein, inferior vena cava and right side of heart. Extension of tumour thrombus into these veins will alter the surgical approach. We have compared the CT scan with Colour flow Doppler ultrasound in detecting venous tumour thrombus in renal vein and inferior vena cava. This cross-sectional study included 30 adult patients presenting with renal tumour. Patients of either gender were included in the study. Non probability convenience sampling was used. All patients underwent colour flow Doppler ultrasound and CT scan with contrast to asses the renal vein and inferior vena cava. The results were confirmed by intra operative findings and histopathology. The data was analyzed using SPSS version 12. Out of 30 patients, 20 (66%) were males and 10 (34%) female. The tumour was predominantly on the right side (60%), as was renal venous tumour thrombus (44%). Inferior vena cava was involved in 4 cases predominantly due to right sided tumours. The sensitivity of Doppler ultrasound in detecting renal venous tumour thrombus (88% on right and 100% on left side) was higher than CT scan (63% on right and 60% on left side). Doppler ultrasound was also superior to CT scan in detecting vena caval thrombus. The overall sensitivity of Doppler sonography was higher than CT scan in detecting tumour extension into renal veins and inferior vena cava. Therefore, it can be used as a complementary tool in equivocal cases. (author)

  20. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  1. HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bieblová, Jana; Rossowska, J.; Kuropka, P.; Pajtasz-Piasecka, E.; Bubeník, Jan; Reiniš, Milan

    2009-01-01

    Roč. 34, č. 1 (2009), s. 173-180. ISSN 1019-6439 R&D Projects: GA ČR GA301/06/0774 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant ostatní: Polish Ministry of Science and Higher Education(PL) N401 235334 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * vaccines * tumour-infiltrating cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.447, year: 2009

  2. Genetic profiling of tumours using both circulating free DNA and circulating tumour cells isolated from the same preserved whole blood sample.

    Science.gov (United States)

    Rothwell, Dominic G; Smith, Nigel; Morris, Daniel; Leong, Hui Sun; Li, Yaoyong; Hollebecque, Antoine; Ayub, Mahmood; Carter, Louise; Antonello, Jenny; Franklin, Lynsey; Miller, Crispin; Blackhall, Fiona; Dive, Caroline; Brady, Ged

    2016-04-01

    Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumours via analysis of circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed. This dictates for ctDNA analysis EDTA blood samples must be processed with 4 h of draw, severely limiting the use of ctDNA in multi-site trials. Here we describe a blood collection protocol that is amenable for analysis of both CTCs and ctDNA up to four days after blood collection. We demonstrate that yields of circulating free DNA (cfDNA) obtained from whole blood CellSave samples are equivalent to those obtained from conventional EDTA plasma processed within 4 h of blood draw. Targeted and genome-wide NGS revealed comparable DNA quality and resultant sequence information from cfDNA within CellSave and EDTA samples. We also demonstrate that CTCs and ctDNA can be isolated from the same patient blood sample, and give the same patterns of CNA enabling direct analysis of the genetic status of patients' tumours. In summary, our results demonstrate the utility of a simple approach that enabling robust molecular analysis of CTCs and cfDNA for genotype-directed therapies in multi-site clinical trials and represent a significant methodological improvement for clinical benefit. PMID:26639657

  3. Changes of hepatic biochemical parameters and proteomics in broilers with cold-induced ascites.

    Science.gov (United States)

    Wang, Yongwei; Guo, Yuming; Ning, Dong; Peng, Yunzhi; Cai, Hong; Tan, Jianzhuang; Yang, Ying; Liu, Dan

    2012-01-01

    Ascites syndrome is still a problem for chicken industry in various parts of the world. Despite the intensive investigations of this syndrome for many years, its pathogenesis remains unclear. The objective of this study was to analyze the difference in hepatic proteomics between ascites and healthy broilers by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Changes of biochemical parameters of liver and blood were also determined. The results indicated that red blood cell counts (RBC), hematocrit (HCT) and haemoglobin (HGB) of ascites broilers were significantly greater than healthy broilers. Hepatic malondialdehyde (MDA) level of ascites broilers was significantly increased, and the activity of total superoxide dismutase (T-SOD) was significantly decreased. Hepatic lactic acid (LD) level of ascitic broilers were significantly lower than healthy ones. Serum glucose and cholesterol level of ascites broilers were significantly increased, and serum globulin level was significantly decreased in ascites broilers. There was no significant difference in triglyceride (TG) and blood urea nitrogen (BUN) level. The activity of liver hexokinase (HK) and succinodehydrogenase (SDH) in ascites broilers was significantly decreased, and there was no significant difference in the activity of liver pyruvate kinase (PK) and Na+-K+-ATPase. The hepatic proteomics analysis showed that 18 proteins expression difference were identified between ascites and healthy broilers. These proteins were mainly involved in: 1) cytoskeleton; 2) glucose, lipids and amino acid metabolism; 3) cell secretion; 4) cell apoptosis; 5) signal transduction; 6) immune and inflammatory response; and 7) cellular redox homeostasis. Mitochondrial isoform phosphoenolpyruvate carboxykinase (M-PEPCK) mainly participates in gluconeogenesis of chicken liver. In conclusion, liver oxidative damage was significantly aggravated, but

  4. Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone

    International Nuclear Information System (INIS)

    Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts. In this study, we have examined clinical and radiological outcomes of treatment with aminobisphosphonates on 25 cases of aggressive primary, recurrent and metastatic GCTB derived from four European centres. We also analysed in vitro the inhibitory effect of zoledronic acid on osteoclasts isolated from GCTBs. Treatment protocols differed with several different aminobisphosphonates being employed, but stabilisation of disease was achieved in most of these cases which were refractory to conventional treatment. Most inoperable sacral/pelvic tumours did not increase in size and no further recurrence was seen in GCTBs that had repeatedly recurred in bone and soft tissues. Lung metastases did not increase in size or number following treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived osteoclasts in vitro. Our findings suggest that bisphosphonates may be useful in controlling disease progression in GCTB and that these agents directly inhibit GCTB - derived osteoclast resorption. These studies highlight the need for the establishment of standardised protocols to assess the efficacy of bisphosphonate treatment of GCTB

  5. Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumours.

    Science.gov (United States)

    Anand, Kushi; Asthana, Pallavi; Kumar, Anup; Ambasta, Rashmi K; Kumar, Pravir

    2011-01-01

    Diet-derived flavonoids, in particular quercetin, may play advantageous roles by preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can elicit various properties depending on the cell type. The aim of this study was to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours and to identify the target(s) of action. We addressed this question by inducing subcutaneous solid tumours in Swiss albino mice and investigated whether the quercetin affects essential biological processes that are responsible for tumour growth, morphology, angiogenesis and apoptosis. We also studied influence on several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour administration of quercetin results in decreased volume/weight. Furthermore, we demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin might result in triggering of caspase-3 in treated tumours. Moreover, it also down-regulated the expression of major key angiogenic or pro-angiogenic factors, like HIF-1α and VEGF In addition, H and E staining together with immunofluorescence of fixed tumour tissue provided evidence in support of increased cell death in quercetin-treated mice. PMID:22393949

  6. Dendritic cells and T cells deliver oncolytic reovirus for tumour killing despite pre-existing anti-viral immunity

    OpenAIRE

    Ilett, EJ; Prestwich, RJ; Kottke, T; Errington, F; Thompson, JM; Harrington, KJ; Pandha, HS; Coffey, M; Selby, PJ; Vile, RG; Melcher, AA

    2009-01-01

    Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour...

  7. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts

    OpenAIRE

    Zheng, M H; ROBBINS, P; Xu, J.; Huang, Liping; Wood, D. J.; Papadimitriou, J M

    2001-01-01

    Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, un...

  8. Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

    Science.gov (United States)

    Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

    1991-02-01

    Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories. PMID:1707715

  9. Effects of a cloned cell line with NK activity on bone marrow transplants, tumour development and metastasis in vivo

    Science.gov (United States)

    Warner, John F.; Dennert, Gunther

    1982-11-01

    Natural killer (NK) cells cloned in vitro have been transferred into NK-deficient hosts. These cells have been shown to have a role in the rejection of allogeneic bone marrow grafts, resistance to both radiation-induced thymic leukaemia and challenge with melanoma tumour cells. It appears that NK cells have an important role in immune surveillance.

  10. Anorexia nervosa and pancreatic ascites.

    OpenAIRE

    Isaacs, P.; Saunders, A J; Rosen, B. K.; Sladen, G E

    1986-01-01

    Acute alcoholic pancreatitis was undiagnosed in a patient with anorexia nervosa who subsequently developed pancreatic ascites and oedema, wrongly attributed to protein malnutrition alone. She became hyperphagic in an attempt to reverse the malnutrition and hence the abdominal swelling, indicating that the goal of attaining a thin shape was the major determinant of the eating disorder in this patient. Measurement of ascitic fluid amylase concentration should be carried out in all patients with...

  11. A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

    Science.gov (United States)

    Farace, F; Massard, C; Vimond, N; Drusch, F; Jacques, N; Billiot, F; Laplanche, A; Chauchereau, A; Lacroix, L; Planchard, D; Le Moulec, S; André, F; Fizazi, K; Soria, J C; Vielh, P

    2011-01-01

    Background: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). Methods: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer's protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies. Results: Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients. Conclusion: Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma. PMID:21829190

  12. Genetic modification of cancer cells using non-viral, episomal S/MAR vectors for in vivo tumour modelling.

    Directory of Open Access Journals (Sweden)

    Orestis Argyros

    Full Text Available The development of genetically marked animal tumour xenografts is an area of ongoing research to enable easier and more reliable testing of cancer therapies. Genetically marked tumour models have a number of advantages over conventional tumour models, including the easy longitudinal monitoring of therapies and the reduced number of animals needed for trials. Several different methods have been used in previous studies to mark tumours genetically, however all have limitations, such as genotoxicity and other artifacts related to the usage of integrating viral vectors. Recently, we have generated an episomally maintained plasmid DNA (pDNA expression system based on Scaffold/Matrix Attachment Region (S/MAR, which permits long-term luciferase transgene expression in the mouse liver. Here we describe a further usage of this pDNA vector with the human Ubiquitin C promoter to create stably transfected human hepatoma (Huh7 and human Pancreatic Carcinoma (MIA-PaCa2 cell lines, which were delivered into "immune deficient" mice and monitored longitudinally over time using a bioluminometer. Both cell lines revealed sustained episomal long-term luciferase expression and formation of a tumour showing the pathological characteristics of hepatocellular carcinoma (HCC and pancreatic carcinoma (PaCa, respectively. This is the first demonstration that a pDNA vector can confer sustained episomal luciferase transgene expression in various mouse tumour models and can thus be readily utilised to follow tumour formation without interfering with the cellular genome.

  13. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  14. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  15. Generation of hydroxyl radicals during ascites experimentally induced in broilers.

    Science.gov (United States)

    Arab, H A; Jamshidi, R; Rassouli, A; Shams, G; Hassanzadeh, M H

    2006-04-01

    Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the most important features of the ascites syndrome in broiler chickens. However, the mechanism of cell injury causing the pathogenesis of the syndrome is not clearly understood. Our study aimed to examine the generation of hydroxyl radicals (OH*) in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens were purchased from a local hatchery and reared in an open poultry house for 46 d. They were divided at random into three groups and ascites was induced in two groups by exposing them to low temperature or administration of triiodothyronine (T(3)). The third group served as control and was reared normally. Haematological, biochemical and pathological tests were used to determine the incidence of ascites: including total red blood cell (RBC), packed cell volume (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and ratio of right ventricular weight to total ventricular weight (RV/TV). A salicylate hydroxylation method was used to examine the generation of hydroxyl radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites, 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to detect the generation of OH*. An ascites syndrome was observed in T(3) and low-temperature treated groups, as shown by necropsy changes and increases in f RBC, PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were increased in groups experiencing ascites compared to control group. It is suggested that reactive oxygen species that is OH* ions, may be involved in the pathogenesis of the ascites syndrome in broiler chickens. PMID:16641033

  16. A case of chronic lymphocytic leukemia with massive ascites

    Science.gov (United States)

    Yonal, Ipek; Nazlıgul, Esra; Tas, Gulsum; Agan, Mehmet Ramazan; Yenerel, Mustafa Nuri; Nalcaci, Meliha

    2012-01-01

    An 81-year old woman with a history of chronic lymphocytic leukemia (CLL) was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC) count 28.5×109/L and platelets 38.4×109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely granular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites. PMID:23372915

  17. A case of chronic lymphocytic leukemia with massive ascites

    Directory of Open Access Journals (Sweden)

    Meliha Nalcaci

    2012-10-01

    Full Text Available An 81-year old woman with a history of chronic lymphocytic leukemia (CLL was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC count 28.5x109/L and platelets 38.4x109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely gran- ular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites.

  18. Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

    Science.gov (United States)

    Zhou, Ming-Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard; Tai, Yu-Chong; Zheng, Si-Yang

    2014-12-01

    The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

  19. Molecular mechanisms of the killing effects on Ehrlich ascites tumor cells by sono-chemical-activated protoporphyrin Ⅸ

    OpenAIRE

    LIU Quan-Hong, XIAO Li-Na; Li, Xiao-ying; Wang, Pan; Wang, Xiao-Bing; Wang, Yu; LI Chen-Di

    2008-01-01

    We studied the Ehrlich ascetic tumor (EAT) cell line killing effects by ultrasound activating protoporphyrin Ⅸ (PPⅨ) and its mechamism. The cellular uptake and subcellular localization of protoporphyrin Ⅸ were estimated by fluorescence photometer and laser scanning confocal microscopy (LSCM) respectively. The trypan blue exclusion method was used to analyze the relative viability of EAT cells after ultrasonically activated protoporphyrin Ⅸ. Changes of ultra-microstructure of the treated cell...

  20. Occult leydig cell tumour and androgen-receptor positive breast cancer in a woman with severe hyperandrogenism

    OpenAIRE

    Saraceno, Giovanna; Barresi, Valeria; Trimarchi, Francesco; Cannavo, Salvatore

    2013-01-01

    Leydig cell tumours represent more than 75% of all testosterone-secreting ovarian masses. These benign tumours are frequently occult or very small, but cause dramatic virilization. Chronic hyperandrogenism can also induce systemic complications, which increase morbidity and mortality risk. One of the most obvious effects of increased testosterone levels is polycythemia, a complication which induces dermatologic, osteoarticular and gastrointestinal manifestations and is associated with increas...

  1. O 6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts

    OpenAIRE

    Clemons, M.; Kelly, J.; Watson, A.J.; Howell, A.; McElhinney, R S; McMurry, T B H; Margison, G P

    2005-01-01

    Tumour resistance to chemotherapy involving methylating agents such as DTIC (dacarbazine) and temozolomide is linked to expression of the DNA repair protein O 6-alkylguanine-DNA alkyltransferase (MGMT). There is considerable interest in improving the efficacy of such O 6-alkylating chemotherapy by the prior inactivation of MGMT. We have examined the effect of the modified guanine base, O 6-(4-bromothenyl)guanine (PaTrin-2, Patrin™, Lomeguatrib) on MGMT activity and cell or xenograft tumour gr...

  2. Effect of Echis carinatus snake venom and its purified fractions F and F on the evolution of Ehrlich ascites tumor (EAT cells

    Directory of Open Access Journals (Sweden)

    Nabil A. Soliman

    2002-09-01

    Full Text Available The present study was undertaken to investigate the effects of Echis carinatus crude venom and some of its isolated toxic fractions on Ehrlich ascites tumor (EAT cells transplanted into the peritoneal cavity of the white female mice as an experimental model of fast growing tumor. The fractionation of the crude venom by gel filtration on sephadex G- %&' , F , Fand F while, the refractionation of these fractions by ion exchange chromatography using diethylamino ethyl cellulose (DEAE-cellulose gave nine subfractions (F (, F , F (, F , F *, F ( F , F ( and F .All these separated subfractions were pure when tested by a third chromatographic step using SDS-PAGE and scanned with densitometer scan. Some in vitro biological properties of the crude venom and its isolated fractions were studied. It was found that F showed the highest value of protein content, followed by F and F (. On the other hand, it was found that no interrelationship between phospholipase enzyme activity (PLA and the protein contents of the crude venom and its isolated fractions. Toxicity studies were conducted on adult female Swiss albino mice to determine the approximate acute median lethal dose (LD% of the crude venom and its purified fractions. LD% of crude venom, F and F+,-.%% /g/g b.w. In addition, F and F were non-lethal, while after ion exchange chromatography, the only toxic fraction was F ( (LD% 0 #% /g/g b.w.. The inhibitory effect of crude venom, F and F ( on tumor growth was studied by treatment of EAT bearing mice with two intraperitoneul injections of the sublethal &1 23% of crude venom and its purified fractions F and F (. The +,123% of the crude venom, Fand F ( was confirmed by a remarkable decrease of the viable tumor cells. This was accompanied by a significant increase in the number of dead cells, and increased percentage of survivals. On the other hand, the animals inoculated by EAT cells showed a significant increase in polymorphonuclear (PMN and mononuclear (MN

  3. Differentiation of tumour and inflammation: characterisation of [methyl-{sup 3}H]methionine (MET) and O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

    Energy Technology Data Exchange (ETDEWEB)

    Stoeber, Barbara; Tanase, Ursula; Herz, Michael; Seidl, Christof; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich (Germany)

    2006-08-15

    Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics. For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine. All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V{sub max}) and affinity (K{sub m}) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells. In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system. (orig.)

  4. Oestrogen receptors and small nuclear ring finger protein 4 (RNF4) in malignant ovarian germ cell tumours.

    Science.gov (United States)

    Salonen, Jonna; Butzow, Ralf; Palvimo, Jorma J; Heikinheimo, Markku; Heikinheimo, Oskari

    2009-08-13

    The peak incidence of malignant ovarian germ cell tumours occurs soon after puberty. Thus, gonadal steroids may play a role in their development. Oestrogen receptors (ERalpha and ERbeta) and their co-regulators, including small nuclear ring finger protein 4 (SNURF/RNF4) mediate oestrogen actions. While ERbeta and SNURF are down-regulated in testicular germ cell tumours, their role in the ovarian germ cell tumours remains unknown. We herein studied the different subtypes of malignant ovarian germ cell tumours, and found that they all express ERalpha, ERbeta, and SNURF. Stimulation with oestradiol (E2), ERalpha, ERbeta and SNURF significantly up-regulated mRNA expression in the human germinoma derived NCC-IT cells. Further, the effects of E2 were counteracted by an anti-oestrogen (ICI 182,780). Neither E2 nor ICI 182,780 had an effect on the proliferation of NCC-IT cells as assessed by flow cytometric analysis. Our results suggest that oestrogen signalling has a role in malignant ovarian germ cell tumours. PMID:19524139

  5. ROS Induce Cardiomyocyte Apoptosis in Ascitic Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Zhaofang Xi§, Shijin Yang§, Dongyang Liu, Liming Wu, Xiaodong Liu, Jing Zhao and Dingzong Guo*

    2012-10-01

    Full Text Available It is believed that ascitic broilers die of right heart failure caused by pulmonary hypertension, but the underlying mechanisms of right heart failure are unknown. However, recent studies have shown that reactive oxygen species have the ability to damage heart cells. This study aimed to determine the changes of reactive oxygen species in serum and plasma, and the effect of this variation on myocardial cells during broiler ascites. We used hypoxia and a low-temperature method to induce broiler ascites in the fast-growing group. For controls, we treated a slow-growing group of broilers with 70% restricted feeding under the same circumstances as the fast-growing group. The results showed that hypoxia is a more effective and better way to induce broiler ascites than a low-temperature environment and high growth rate. In addition, reactive oxygen species levels were significantly increased in the fast-growing group compared with those in the slow-growing group. This significant increase in reactive oxygen species resulted in myocardial cell apoptosis in the fast-growing group. Our results suggest that cardiomyocyte apoptosis caused by increased reactive oxygen species levels of ascitic broilers is one of the most important reasons for causing heart failure.

  6. Proving tumour cells by acute nutritional/energy deprivation as a survival threat: a task for microscopy

    Czech Academy of Sciences Publication Activity Database

    Janečková, H.; Veselý, Pavel; Chmelík, R.

    2009-01-01

    Roč. 29, č. 6 (2009), s. 2339-2345. ISSN 0250-7005 Institutional research plan: CEZ:AV0Z50520514 Keywords : tumour cell * nutritional deprivation * energy deprivation * cell survival * cell death * digital holographic microscopy * dynamic phase difference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.428, year: 2009

  7. Molecular mechanisms of the killing effects on Ehrlich ascites tumor cells by sono-chemical-activated protoporphyrin Ⅸ

    Directory of Open Access Journals (Sweden)

    LIU Quan-Hong, XIAO Li-Na

    2008-10-01

    Full Text Available We studied the Ehrlich ascetic tumor (EAT cell line killing effects by ultrasound activating protoporphyrin Ⅸ (PPⅨ and its mechamism. The cellular uptake and subcellular localization of protoporphyrin Ⅸ were estimated by fluorescence photometer and laser scanning confocal microscopy (LSCM respectively. The trypan blue exclusion method was used to analyze the relative viability of EAT cells after ultrasonically activated protoporphyrin Ⅸ. Changes of ultra-microstructure of the treated cells were examined by transmission electron microscopy.Mitochondrial membrane potential(MMP, intracellular reactive oxygen species (ROS levels, and the level of lipid peroxidation were determined by Rhodamine 123, 2′,7′- dichlorodihydrofluorescin diacetate (DCFH-DA and thiobarbituric acid reaction method respectively. Results showed that there is a selective uptake and retention of the PPⅨ in tumor cells. CLSM revealed that PPⅨ localize mainly in the mitochondria. In the ultrasound plus PPⅨ group, the survival rate of cells was significantly lower. The ultra-microstructural damage of treated cells was the most remarkable, the loss of mitochondria membrane potential was the most noticeable, levels of ROS and lipid peroxides were remarkably increased. These results indicate that there is significant synergistic killing effect with ultrasound activating PPⅨ. The decreased mitochondria membrane potential and the increased level of lipid peroxidation in the ultrasound plus PPⅨ group may be associated with reactive oxygen species. In summary, reactive oxygen species might be involved in mediating the killing effect of EAT cells in SDT [Acta Zoologica Sinica 54(5: 846– 854, 2008

  8. Variation in sensitizing effect of caffeine in human tumour cell lines after γ-irradiation

    International Nuclear Information System (INIS)

    We have investigated whether the protective role of the G2 checkpoint has increasing importance when the p53-dependent G1 checkpoint is inactivated. We have studied the differential effect of caffeine by clonogenic assays and flow cytometry in three human tumour cell lines with different functionality of p53 protein. The radiosensitizing effect of caffeine (2 mM) expressed itself as a significant decrease in surviving fraction at 2 Gy and a significant increase in α-values in RT112 and TE671, both with non-functional p53. However, no radiosensitizing effect was seen in cells with a normal p53 function (MCF-7 BUS). Two millimoles of caffeine also caused important changes in the cell cycle progression after irradiation. MCF-7 BUS showed a G1 arrest after irradiation and an early G2 arrest but those cells that reached the second G2 did not arrest significantly. In contrast, TE671 exhibited radiosensitization by caffeine, no G1 arrest, a G2 arrest in those cells irradiated in G2, no significant accumulation in the second G2 but an overall delay in release from the first cell cycle, which could be abrogated by caffeine. RT112 was similar to TE671 except that the emphasis in a G2 arrest was shifted from the block in cells irradiated in G2 to those irradiated at other cell cycle phases. The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. (author)

  9. KCNK5 is Functionally Down-Regulated Upon Long-Term Hypotonicity in Ehrlich Ascites Tumor Cells

    DEFF Research Database (Denmark)

    Kirkegaard, S. S.; Wulff, Tune; Gammeltoft, S.;

    2013-01-01

    Background/Aims: Regulatory volume decrease (RVD) in response to acute cell swelling is well described and KCNK5 (also known as TASK-2 or K2P5.1) has been shown to be the volume sensitive K+ channel in Ehrlich cells. Very little is, on the other hand, known about the effects of long-term hypotoni...... physiological impairment of KCNK5 in Ehrlich cells after long-term hypotonic stimulation is predominantly due to down-regulation of the KCNK5 protein synthesis.© 2013 S. Karger AG, Basel...

  10. Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques

    DEFF Research Database (Denmark)

    Issinger, O G; Beier, H

    1978-01-01

    Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according to a ...

  11. In vitro activity of bortezomib in cultures of patient tumour cells--potential utility in haematological malignancies.

    Science.gov (United States)

    Wiberg, Kristina; Carlson, Kristina; Aleskog, Anna; Larsson, Rolf; Nygren, Peter; Lindhagen, Elin

    2009-01-01

    Bortezomib represents a new class of anti-cancer drugs, the proteasome inhibitors. We evaluated the in vitro activity of bortezomib with regard to tumour-type specificity and possible mechanisms of drug resistance in 115 samples of tumour cells from patients and in a cell-line panel, using the short-term fluorometric microculture cytotoxicity assay. Bortezomib generally showed dose-response curves with a steep slope. In patient cells, bortezomib was more active in haematological than in solid tumour samples. Myeloma and chronic myeloid leukaemia were the most sensitive tumour types although with great variability in drug response between the individual samples. Colorectal and kidney cancer samples were the least sensitive. In the cell-line panel, only small differences in response were seen between the different cell lines, and the proteasome inhibitors, lactacystin and MG 262, showed an activity pattern similar to that of bortezomib. The cell-line data suggest that resistance to bortezomib was not mediated by MRP-, PgP, GSH-; tubulin and topo II-associated MDR. Combination experiments indicated synergy between bortezomib and arsenic trioxide or irinotecan. The data support the current use of bortezomib but also points to its potential utility in other tumour types and in combination with cytotoxic drugs. PMID:19016012

  12. 腹水细胞HBV DNA荧光PCR检测方法的建立及意义研究%Studying and the significance of the HBV DNA from ascite cells with time fluoresceence quantitative PCR

    Institute of Scientific and Technical Information of China (English)

    李妍; 马洪滨; 朱剑功; 王海滨; 洪炜; 庞君丽; 王大刚; 杨宁; 李永利; 刘立明; 王雪飞; 陈厦

    2011-01-01

    Objective:The Cyto- megalovirus CMV Lysis Solution , which can extraction the HBV DNA from ascite cells, has been used in detecting HBV DNA with time fluoresceence quantitative PCR , and then we can study the change and the clinical significance. Methods: 10 ml ascite from cirrhosis patients originating hepatitis B infection centrifuged immediately by 1500 g for 5 minutes. The liquid supernatant was discarded thoroughly. The HBV DNA in ascite cells from the bottom of tube is detected with real time PCR technology. Results:The detected numerical attain abilities was 102 IU/ml, which using fluorescence PCR technology testing ascite cell HBV DNA it showed theoretical gradient according to the terms of diluted times. and then the Correlation coefficient is 0.91, making it clear that the method has a good sensitivity. By making repeated study we find that the 5 repeated times leafs CV is 14.4% ,9.8% and 11.2%, and the declination meet the NCCL Requirements. There is about 0.5 to 1. 5 LOG of HBV DNA in different ascite cells from patients with cirrhosis,which explaining ascite cells not only contains a lot of HBV, but also has much individual differences apparently. The HBV DNA in three times of dynamic detecting in one case of hepatocellular carcinoma is gradually decreased both in ascite and ascite cells along with the deterioration of disease. Conclusion:Our real - time PCR system of HBV DNA detection from ascite cells by the Cyto - megalo virus CMV Lysis Solution , can provide an accurate and highly sensitive rapid method to quantify Hepatitis B virus with low artificial positive and lower negative artificial results. It is suitable for studying the significance of HBV DNA from ascite cells in clinic.%目的:采用细胞病毒裂解液快速提取腹水细胞内的HBV DNA,建立实时荧光定量PCR检测HBV DNA的技术,并初步研究其临床意义.方法:采用乙肝肝硬化患者腹水10 ml,1500 g/min离心5 min,全部吸出上清,对沉渣细胞进

  13. Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Svingen, Terje; Nielsen, John Erik;

    2014-01-01

    , elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2γ, SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal...... tumour (PDPN, GATA4). All YSTs expressed AFP and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2 and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma markers AP-2γ, OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We further report a previously...... unrecognised pathogenetic relationship between AFP and SALL4 in YST in that different populations of YST cells express either SALL4 or AFP, which suggests variable differentiation status. We also show that AP-2γ is expressed in the granulosa layer of ovarian follicles and weakly expressed in immature but not...

  14. Prognosis after salvage treatment for unselected male patients with germ cell tumours.

    OpenAIRE

    Gerl, A; Clemm, C.; Schmeller, N.; Hartenstein, R.; Lamerz, R.; Wilmanns, W.

    1995-01-01

    Long-term outcome of salvage treatment was reviewed in 67 unselected male patients relapsing during or after their primary cisplatin-based chemotherapy for metastatic germ cell tumours. Seven patients underwent only surgery and/or radiotherapy as curatively intended salvage treatment. Thirty-five patients (52%) had a complete or partial response to salvage treatment, 20 (57%) of whom relapsed again. With a median follow-up of 90 months (range 3-143 months) 20 patients (30%) are alive with no ...

  15. Dendritic cell-based vaccines for therapy of HPV16-induced tumours

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Šímová, Jana; Vonka, V.; Šmahel, M.; Mikyšková, Romana; Mendoza, Luis

    2001-01-01

    Roč. 495, - (2001), s. 359-363. ISSN 0065-2598 R&D Projects: GA MZd NC5526; GA ČR GA312/98/0826; GA ČR GA312/99/0542; GA ČR GA301/00/0114; GA ČR GA301/01/0985; GA AV ČR IAA7052002 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * dendritic cells * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.513, year: 2000

  16. Pharmacological characterization of β2-adrenoceptor in PGT-β mouse pineal gland tumour cells

    OpenAIRE

    Suh, Byung-Chang; Chae, Hee-Don; Chung, Joo-Ho; Kim, Kyong-Tai

    1999-01-01

    The adrenoceptor in a mouse pineal gland tumour cell line (PGT-β) was identified and characterized using pharmacological and physiological approaches.Adrenaline and noradrenaline, adrenoceptor agonists, stimulated cyclic AMP generation in a concentration-dependent manner, but had no effect on inositol 1,4,5-trisphosphate production. Adrenaline was a more potent activator of cyclic AMP generation than noradrenaline, with half maximal-effective concentrations (EC50) seen at 175±22 nM and 18±2 μ...

  17. Spermatogonial Nature of the Germ Cell Component of Canine Testicular Mixed Germ Cell-Sex Cord Stromal Tumours.

    Science.gov (United States)

    Mizukami, S; Murakami, T; Tanaka, T; Machida, N; Nomura, K; Yoshida, T; Shibutani, M

    2016-07-01

    The present study has characterized the germ cell component of canine testicular mixed germ cell-sex cord stromal tumours (MGSCTs) by examining the histological nature and histochemical and immunohistochemical features using gonocytic and spermatogonial cellular markers, c-Kit, placental alkaline phosphatase (PLAP), protein gene product 9.5 (PGP9.5), Sal-like protein 4 (SALL4), and the periodic acid-Schiff (PAS) reaction. Histologically, all 45 examples of MGSCTs were classified as spermatocytic seminomas (SSs) and Sertoli cell tumours in combination. The germ cell component of all MGSCTs was negative by PAS staining. Immunohistochemically, PLAP immunoreactivity was lacking in the germ cell component of all MGSCTs, which is not consistent with a gonocytic origin. The germ cell component was positive for PGP9.5 and SALL4 in all MGSCTs and positive for c-Kit in 53% of MGSCTs, which is consistent with the phenotype of spermatogonia. Furthermore, the germ cell component in 71% of MGSCTs had moderate immunoreactivity for SALL4, which is suggestive of a spermatogonial phenotype. Conversely, 29% of cases had a minor population of germ cells showing strong SALL4 immunoreactivity, suggesting a phenotype similar to prespermatogonia. The results suggest that the germ cell component of canine MGSCTs is morphologically classified as SS, with the majority of cases showing the spermatogonial phenotype and some cases containing a small population of prespermatogonia. PMID:27241073

  18. Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours

    DEFF Research Database (Denmark)

    Lassen, U; Daugaard, G; Eigtved, A; Højgaard, L; Nielsen, Knud Damsgaard; Rørth, M

    2003-01-01

    negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative......Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour...... markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty...

  19. New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

    Directory of Open Access Journals (Sweden)

    Branka Zorc

    2012-01-01

    Full Text Available Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1, 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethylphenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1. Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

  20. Ascite quilosa traumática Traumatic chylous ascites

    Directory of Open Access Journals (Sweden)

    João Baptista de Resende Neto

    2002-02-01

    Full Text Available Chylous ascites is a rare clinical entity. In infancy it is less commom still. The etiology of most of them is usually congenital or idiopathic; trauma is a less frequent cause. It has been implicated in about 10% of all cases 1-5. There have been less than one hundred cases published in the English literature, including 12 in children. We report a pediatric case of chylous ascites as a result of blunt abdominal trauma managed by ligation of the lymphatic leak.

  1. Juvenile granulosa cell tumour of the ovary presenting with hyperprolactinaemic amenorrhoea and galactorrhoea

    Science.gov (United States)

    Iqbal, Ahmed; Lubina-Solomon, Alexandra; Kew, Fiona M; Webster, Jonathan

    2016-01-01

    Summary Secondary amenorrhoea and galactorrhoea represent a common endocrine presentation. We report a case of an oestrogen-producing juvenile granulosa cell tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following surgical resection of the tumour. This patient presented with a 9-month history of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l) were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with undetectable β-human chorionic gonadotropin. MRI showed a bulky pituitary with no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the right ovary with no evidence of metastatic disease. Serum inhibin B was elevated at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post-operatively, oestrogen and prolactin levels were normalised, and she subsequently had a successful pregnancy. In summary, we present a case of an oestrogen-secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical state analogous to pregnancy. To the best of our knowledge, this is the first report of hyperprolactinaemia as a result of excessive oestrogen production in the context of a JGCT. Learning points Hyperprolactinaemia with bilateral galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is not always caused by a prolactin secreting pituitary adenoma.Significantly elevated serum oestradiol levels in the range seen in this case, in the absence of pregnancy, are indicative

  2. The genomic landscape of testicular germ cell tumours: from susceptibility to treatment.

    Science.gov (United States)

    Litchfield, Kevin; Levy, Max; Huddart, Robert A; Shipley, Janet; Turnbull, Clare

    2016-07-01

    The genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk and are highly polygenic in nature. Secondly KIT-KITLG signalling is currently the major pathway that is implicated in TGCT formation, both as a predisposition risk factor and a somatic driver event. Results from genome-wide association studies have also consistently suggested that other closely related pathways involved in male germ cell development and sex determination are associated with TGCT risk. Thirdly, the method of disease formation is unique, with tumours universally stemming from a noninvasive precursor lesion, probably of fetal origin, which lies dormant through childhood into adolescence and then eventually begins malignant growth in early adulthood. Formation of a 12p isochromosome, a hallmark of TGCT observed in nearly all tumours, is likely to be a key triggering event for malignant transformation. Finally, TGCT have been shown to have a distinctive somatic mutational profile, with a low rate of point mutations contrasted with frequent large-scale chromosomal gains. These four hypotheses by no means constitute a complete model that explains TGCT tumorigenesis, but advances in genomic technologies have enabled considerable progress in describing and understanding the disease. Further advancing our understanding of the genomic basis of TGCT offers a clear opportunity for clinical benefit in terms of preventing invasive cancer arising in young men, decreasing the burden of chemotherapy-related survivorship issues and reducing mortality in the minority of patients who have treatment-refractory disease. PMID:27296647

  3. Immunology of naturally transmissible tumours

    OpenAIRE

    Siddle, Hannah V; Kaufman, Jim

    2014-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonise a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, Canine Transmissible Venereal Tumour (CTVT) that spreads among dogs and Devil Facial Tumour Disease (D...

  4. Wild mushrooms Clitocybe alexandri and Lepista inversa: in vitro antioxidant activity and growth inhibition of human tumour cell lines.

    Science.gov (United States)

    Vaz, Josiana A; Heleno, Sandrina A; Martins, Anabela; Almeida, Gabriela M; Vasconcelos, M Helena; Ferreira, Isabel C F R

    2010-10-01

    The in vitro antioxidant and growth inhibitory activity of extracts obtained from two Portuguese wild mushrooms (Clitocybe alexandri and Lepista inversa) was studied in human tumour cell lines. The extracts were phenolic (methanolic and ethanolic) and polysaccharidic (boiling water). The antioxidant activity assays included evaluation of radical-scavenging capacity, reducing power and inhibition of lipid peroxidation measured in liposome solutions. Extract-induced cell growth inhibition was measured in four different tumour cell lines (lung, breast, colon and gastric cancer) using the SRB assay. The polysaccharidic extract of L. inversa was the most potent as antioxidant (EC(50)mushrooms are promising sources of bioactive compounds. PMID:20647028

  5. CYTOLOGICAL DIAGNOSIS OF GELATINOUS ASCITES

    Directory of Open Access Journals (Sweden)

    Samith

    2013-04-01

    Full Text Available ABSTRACT: Pseudomyxoma peritonei (PMP is a condition characte rized by the accumulation of mucinous material in the peritoneal cavity (gela tinous ascites. Pseudomyxoma peritonei is an uncommon condition in which mucinous ascites causes progressive abdominal distension and gastrointestina l dysfunction. We present a case of 44 year old female who presented with gradually progres sive abdominal distension since 6 months. An ascitic tap was performed and the fluid wa s sent for cytological study. Cytology showed pools of acellular mucin. On laparotomy there was mucinous material in the abdomen that was evacuated. Appendix and omentum were found t o be thickened, hence appendicectomy was done and omental biopsy taken. Histopathological diagnosis of well differentiated mucinous adenocarcinoma of appendix with rupture and mucinous ascitis was made.

  6. The role of meiotic cohesin REC8 in chromosome segregation in {gamma} irradiation-induced endopolyploid tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Erenpreisa, Jekaterina [Latvian Biomedicine Research and Study Centre, Riga, LV-1067 (Latvia); Cragg, Mark S. [Tenovus Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton SO16 6YD (United Kingdom); Salmina, Kristine [Latvian Biomedicine Research and Study Centre, Riga, LV-1067 (Latvia); Hausmann, Michael [Kirchhoff Inst. fuer Physik, Univ. of Heidelberg, D-69120 Heidelberg (Germany); Scherthan, Harry, E-mail: scherth@web.de [Inst. fuer Radiobiologie der Bundeswehr in Verbindung mit der Univ. Ulm, D-80937 Munich (Germany); MPI for Molec. Genetics, 14195 Berlin (Germany)

    2009-09-10

    Escape from mitotic catastrophe and generation of endopolyploid tumour cells (ETCs) represents a potential survival strategy of tumour cells in response to genotoxic treatments. ETCs that resume the mitotic cell cycle have reduced ploidy and are often resistant to these treatments. In search for a mechanism for genome reduction, we previously observed that ETCs express meiotic proteins among which REC8 (a meiotic cohesin component) is of particular interest, since it favours reductional cell division in meiosis. In the present investigation, we induced endopolyploidy in p53-dysfunctional human tumour cell lines (Namalwa, WI-L2-NS, HeLa) by gamma irradiation, and analysed the sub-cellular localisation of REC8 in the resulting ETCs. We observed by RT-PCR and Western blot that REC8 is constitutively expressed in these tumour cells, along with SGOL1 and SGOL2, and that REC8 becomes modified after irradiation. REC8 localised to paired sister centromeres in ETCs, the former co-segregating to opposite poles. Furthermore, REC8 localised to the centrosome of interphase ETCs and to the astral poles in anaphase cells where it colocalised with the microtubule-associated protein NuMA. Altogether, our observations indicate that radiation-induced ETCs express features of meiotic cell divisions and that these may facilitate chromosome segregation and genome reduction.

  7. Effector memory T-cell frequencies in relation to tumour stage, location and HPV status in HNSCC patients

    NARCIS (Netherlands)

    A.W. Turksma; H.J. Bontkes; H. van den Heuvel; T.D. de Gruijl; B.M.E. von Blomberg; B.J.M. Braakhuis; C.R. Leemans; E. Bloemena; C.J.L.M. Meijer; E. Hooijberg

    2013-01-01

    Background The immune system plays an important role in tumour immune surveillance. Head and neck squamous cell carcinoma patients are often immune compromised. Objective To chart the baseline levels of T-cell subpopulation frequencies in patients with cancer prior to treatment. Subjects and methods

  8. Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells

    International Nuclear Information System (INIS)

    We have previously documented that transient polyploidy is a potential cell survival strategy underlying the clonogenic re-growth of tumour cells after genotoxic treatment. In an attempt to better define this mechanism, we recently documented the key role of meiotic genes in regulating the DNA repair and return of the endopolyploid tumour cells (ETC) to diploidy through reduction divisions after irradiation. Here, we studied the role of the pluripotency and self-renewal stem cell genes NANOG, OCT4 and SOX2 in this polyploidy-dependent survival mechanism. In irradiation-resistant p53-mutated lymphoma cell-lines (Namalwa and WI-L2-NS) but not sensitive p53 wild-type counterparts (TK6), low background expression of OCT4 and NANOG was up-regulated by ionising radiation with protein accumulation evident in ETC as detected by OCT4/DNA flow cytometry and immunofluorescence (IF). IF analysis also showed that the ETC generate PML bodies that appear to concentrate OCT4, NANOG and SOX2 proteins, which extend into complex nuclear networks. These polyploid tumour cells resist apoptosis, overcome cellular senescence and undergo bi- and multi-polar divisions transmitting the up-regulated OCT4, NANOG and SOX2 self-renewal cassette to their descendents. Altogether, our observations indicate that irradiation-induced ETC up-regulate key components of germ-line cells, which potentially facilitate survival and propagation of the tumour cell population.

  9. A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients

    Science.gov (United States)

    Rodenhizer, Darren; Gaude, Edoardo; Cojocari, Dan; Mahadevan, Radhakrishnan; Frezza, Christian; Wouters, Bradly G.; McGuigan, Alison P.

    2016-02-01

    The profound metabolic reprogramming that occurs in cancer cells has been investigated primarily in two-dimensional cell cultures, which fail to recapitulate spatial aspects of cell-to-cell interactions as well as tissue gradients present in three-dimensional tumours. Here, we describe an engineered model to assemble three-dimensional tumours by rolling a scaffold-tumour composite strip. By unrolling the strip, the model can be rapidly disassembled for snapshot analysis, allowing spatial mapping of cell metabolism in concert with cell phenotype. We also show that the establishment of oxygen gradients within samples that are shaped by oxygen-dependent signalling pathways, as well as the consequential variations in cell growth, response to hypoxic gradients extending from normoxia to severe hypoxia, and therapy responsiveness, are consistent with those of tumours in vivo. Moreover, by using liquid chromatography tandem mass spectrometry, we mapped cellular metabolism and identified spatially defined metabolic signatures of cancer cells to reveal both known and novel metabolic responses to hypoxia.

  10. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    International Nuclear Information System (INIS)

    Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells

  11. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Garrido Federico

    2008-03-01

    Full Text Available Abstract Background Protein-bound polysaccharide (PSK is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

  12. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer

    OpenAIRE

    Lecharpentier, A; Vielh, P; Perez-Moreno, P; Planchard, D.; Soria, J. C.; Farace, F.

    2011-01-01

    Background: Circulating tumour cells (CTC) have a crucial role in metastasis formation and can consistently provide information on patient prognosis. Epithelial-mesenchymal transition (EMT) is considered as an essential process in the metastatic cascade, but there is currently very few data demonstrating directly the existence of the EMT process in CTCs. Methods: CTCs were enriched by blood filtration using ISET (isolation by size of epithelial tumour cells), triply labelled with fluorescent ...

  13. Oncological and functional results following operation for giant cell tumour of bone

    Institute of Scientific and Technical Information of China (English)

    Yongzhong Wei; Eugene T.H. Ek; Lipeng Yu; Guoyong Yin

    2008-01-01

    Objective:Giant cell tumours(GCT) represent one of the most common benign turnouts of bone. However, despite its benign nature they are aggressive lesions that have a tendency to recur. This study aims to report experience with the treatment of GCTs, and reviews the relationship between surgical management and clinical outcome. Methods:A retrospective review was performed with 70 patients (32 males and 38 females) who presented to our institution between 1991 and 2001 with GCT of bone. An evaluation of the oncological and functional results was conducted and patients were divided into three groups according to the treatment method; Group Ⅰ:(46 patients) intralesional curettage and adjuvant therapy and packing with filling materials. Group Ⅱ:(18 patients) en-bloc resection and arthrodesis or reconstruction. Group Ⅲ:(6 patients) amputation. Results:The mean follow-up period was 10 years (range, 5-15 years). The overall rate of local recurrence was 14%, 22% in Group Ⅰ, and only 4% in Group Ⅱ and Group Ⅲ According to the Musculoskeletal Tumour Society(MSTS) score for functional outcome, the mean overall score for Group Ⅰ was 27.9 (out of 30), 15.9 for Group Ⅱ. Of note, the 9 patients within Group Ⅱ who received endoprosthetic reconstruction, the mean overall MSTS functional score was 25.5. Conclusion:Intralesional curettage with adjuvant therapies and filling agents is often associated with a relatively high recurrence rate, however joint function is well preserved. Patients with more extensive, biologically aggressive, and/or recurrent tumours are best treated with en-bloc resection.

  14. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour. The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient. TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol. Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72). TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy

  15. Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further

  16. Tumour Cell Membrane Poration and Ablation by Pulsed Low-Intensity Electric Field with Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Lijun Wang

    2015-03-01

    Full Text Available Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs, the effective pulse amplitude was reduced to 50 V/cm (main field/15 V/cm (alignment field at the optimized pulse frequency (5 Hz of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses.

  17. Ehrlich and sarcoma 180 tumour characterisation and early detection by {sup 1}H NMR-based metabonomics of mice serum

    Energy Technology Data Exchange (ETDEWEB)

    Grandizoli, Caroline W.P. da S.; Simonelli, Fabio; Nagata, Noemi; Barison, Andersson, E-mail: andernmr@ufpr.br [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Carrenho, Luise Z.B.; Francisco, Thais M.G. de; Campos, Francinete R. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Farmacia; Santana Filho, Arquimedes P. de; Sassaki, Guilherme L. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Bioquimica; Kreuger, Maria R.O. [Universidade do Vale do Itajai (UNIVALI), (Brazil). Centro de Ciencias da Saude

    2014-05-15

    The success of cancer treatment is directly related to early detection before symptoms emerge, although nowadays few cancers can be detected early. In this sense, {sup 1}H nuclear magnetic resonance ({sup 1}H NMR)-based metabonomics was used to identify metabolic changes in biofluid as a consequence of tumours growing in mice. Through partial least squares discriminant analysis (PLS-DA) analysis of {sup 1}H NMR spectra from serum samples it was possible to diagnose Ehrlich ascites and Sarcoma 180 tumours five and ten days after cell inoculation, respectively. Lipids, lipoproteins and lactate were the main biomarkers at onset as well as in the progress of carcinogenic process. Thus, NMR-based metabonomics can be a valuable tool to study the effects of tumour establishment on the chemical composition of biofluids. (author)

  18. The role of TG2 in regulating S100A4-mediated mammary tumour cell migration.

    Directory of Open Access Journals (Sweden)

    Zhuo Wang

    Full Text Available The importance of S100A4, a Ca(2+-binding protein, in mediating tumour cell migration, both intracellularly and extracellularly, is well documented. Tissue transglutaminase (TG2 a Ca(2+-dependent protein crosslinking enzyme, has also been shown to enhance cell migration. Here by using the well characterised non-metastatic rat mammary R37 cells (transfected with empty vector and highly metastatic KP1 cells (R37 cells transfected with S100A4, we demonstrate that inhibition of TG2 either by TG2 inhibitors or transfection of cells with TG2 shRNA block S100A4-accelerated cell migration in the KP1cells and in R37 cells treated with exogenous S100A4. Cell migration was also blocked by the treatment with the non-cell permeabilizing TG2 inhibitor R294, in the human breast cancer cell line MDA-MB-231 (Clone 16, which has a high level of TG2 expression. Inhibition was paralleled by a decrease in S100A4 polymer formation. In vitro co-immunoprecipitation and Far Western blotting assays and cross-linking assays showed not only the direct interaction between TG2 and S100A4, but also confirmed S100A4 as a substrate for TG2. Using specific functional blocking antibodies, a targeting peptide and a recombinant protein as a competitive treatment, we revealed the involvement of syndecan-4 and α5β1 integrin co-signalling pathways linked by activation of PKCα in this TG2 and S100A4-mediated cell migration. We propose a mechanism for TG2-regulated S100A4-related mediated cell migration, which is dependent on TG2 crosslinking.

  19. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Silconi Žana Besser

    2015-09-01

    Full Text Available Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity, ototoxicity, and neurotoxicity. Although cisplatin is one of the most successful anticancer drugs to date, its biochemical mechanism of action is still unclear. Cisplatin is generally accepted as having the ability to interact with the purine bases on the DNA, causing DNA damage, interfering with DNA repair mechanisms, and subsequently inducing apoptosis in cancer cells.

  20. The sensitivity of human tumour cells to quinone bioreductive drugs: what role for DT-diaphorase?

    Science.gov (United States)

    Robertson, N; Stratford, I J; Houlbrook, S; Carmichael, J; Adams, G E

    1992-08-01

    15 human tumour cell lines (lung, breast and colon) have been evaluated for their sensitivity to the quinone based anti-cancer drugs Mitomycin C, Porfiromycin, and EO9 (3-hydroxymethyl-5-aziridinyl-1-methyl-2-(IH-indole-4,7-dione)prop-beta- en-alpha-ol). Sensitivity has been compared with the intra-cellular levels of DT-diaphorase, an enzyme thought to be important in the reductive activation of these quinones. No correlation exists between levels of DT-diaphorase and sensitivity to Mitomycin C or Porfiromycin. However, for EO9 those cell lines showing highest levels of DT-diaphorase activity tend to be the most sensitive. PMID:1510692

  1. Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours

    DEFF Research Database (Denmark)

    Poulsen, Grete Lottrup; Nielsen, John E; Skakkebæk, Niels E; Juul, Anders; Rajpert-De Meyts, Ewa

    2015-01-01

    cells (LCs), and masses consisting of such cells are occasionally misclassified as malignant testicular tumours, which may lead to erroneous orchiectomy in these patients. DESIGN: In this study, we aimed to investigate the potential of LC developmental markers and adrenal steroidogenic markers in the......OBJECTIVE: Testicular adrenal rest tumours (TARTs) are a common finding in patients with congenital adrenal hyperplasia (CAH). These tumours constitute a diagnostic and management conundrum and may lead to infertility. TART cells share many functional and morphological similarities with Leydig...... differential diagnosis of TARTs and malignant LC tumours (LCTs). METHODS: We investigated mRNA and protein expression of testicular steroidogenic enzymes; CYP11A1 and HSD3B1/2, markers of adrenal steroidogenesis; CYP11B1, CYP21A2 and ACTH receptor/melanocortin 2 receptor (MC2R), and markers of LC maturation...

  2. Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines.

    LENUS (Irish Health Repository)

    Anoopkumar-Dukie, S

    2009-10-01

    Oxygen-dependent radiosensitivity of tumour cells reflects direct oxidative damage to DNA, but non-nuclear mechanisms including signalling pathways may also contribute. Mitochondria are likely candidates because not only do they integrate signals from each of the main kinase pathways but mitochondrial kinases responsive to oxidative stress communicate to the rest of the cell. Using pharmacological and immunochemical methods, we tested the role of mitochondrial permeability transition (MPT) and the Bcl-2 proteins in oxygen-dependent radiosensitivity. Drug-treated or untreated cervical cancer HeLa, breast cancer MCF-7 and melanoma MeWo cell lines were irradiated at 6.2 Gy under normoxic and hypoxic conditions then allowed to proliferate for 7 days. The MPT blocker cyclosporin A (2 microM) strongly protected HeLa but not the other two lines against oxygen-dependent radiosensitivity. By contrast, bongkrekic acid (50 microM), which blocks MPT by targeting the adenine nucleotide transporter, had only marginal effect and calcineurin inhibitor FK-506 (0.1 microM) had none. Nor was evidence found for the modulation of oxygen-dependent radiosensitivity by Bax\\/Bcl-2 signalling, mitochondrial ATP-dependent potassium (mitoK(ATP)) channels or mitochondrial Ca(2+) uptake. In conclusion, calcineurin-independent protection by cyclosporin A suggests that MPT but not mitoK(ATP) or the mitochondrial apoptosis pathway plays a causal role in oxygen-dependent radiosensitivity of HeLa cells. Targeting MPT may therefore improve the effectiveness of radiotherapy in some solid tumours.

  3. Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment.

    Science.gov (United States)

    Wu, Amy; Liao, David; Tlsty, Thea D; Sturm, James C; Austin, Robert H

    2014-08-01

    Preventing relapse is the major challenge to effective therapy in cancer. Within the tumour, stromal (ST) cells play an important role in cancer progression and the emergence of drug resistance. During cancer treatment, the fitness of cancer cells can be enhanced by ST cells because their molecular signalling interaction delays the drug-induced apoptosis of cancer cells. On the other hand, competition among cancer and ST cells for space or resources should not be ignored. We explore the population dynamics of multiple myeloma (MM) versus bone marrow ST cells by using an experimental microecology that we call the death galaxy, with a stable drug gradient and connected microhabitats. Evolutionary game theory is a quantitative way to capture the frequency-dependent nature of interactive populations. Therefore, we use evolutionary game theory to model the populations in the death galaxy with the gradients of pay-offs and successfully predict the future densities of MM and ST cells. We discuss the possible clinical use of such analysis for predicting cancer progression. PMID:25097749

  4. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2015-12-01

    Full Text Available Adult stem cells (ASCs reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014. Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013. Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice, we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014. Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155.

  5. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation.

    Science.gov (United States)

    Foronda, Miguel; Morgado-Palacin, Lucia; Gómez-López, Gonzalo; Domínguez, Orlando; Pisano, David G; Blasco, Maria A

    2015-12-01

    Adult stem cells (ASCs) reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014). Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013). Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4 (cKO) mice), we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC) activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4 (cKO) mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014). Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155. PMID:26697322

  6. Increased exosome production from tumour cell cultures using the Integra CELLine Culture System.

    Science.gov (United States)

    Mitchell, J Paul; Court, Jacqueline; Mason, Malcolm David; Tabi, Zsuzsanna; Clayton, Aled

    2008-06-01

    Exosomes are nanometer-sized vesicles, secreted from most cell types, with documented immune-modulatory functions. Exosomes can be purified from cultured cells but to do so effectively, requires maintenance of cells at high density in order to obtain sufficient accumulation of exosomes in the culture medium, prior to purification. Whilst high density cultures can be achieved with cells in suspension, this remains difficult with adherent cells, resulting in low quantity of exosomes for subsequent study. We have used the Integra CELLine culture system, originally designed for hybridoma cultures, to achieve a significant increase in obtainable exosomes from adherent and non-adherent tumour cells. Traditional cultures of mesothelioma cells (cultured in 75 cm(2) flasks) gave an average yield of 0.78 microg+/-0.14 microg exosome/ml of conditioned medium. The CELLine Adhere 1000 (CLAD1000) flask, housing the same cell line, increased exosome yield approximately 12 fold to 10.06 microg+/-0.97 microg/ml. The morphology, phenotype and immune function of these exosomes were compared, and found to be identical in all respects. Similarly an 8 fold increase in exosome production was obtained from NKL cells (a suspension cell line) using a CELLine 1000 (CL1000) flask. The CELLine system also incurred ~5.5 fold less cost and reduced labour for cell maintenance. This simple culture system is a cost effective, useful method for significantly increasing the quantity of exosomes available from cultured cells, without detrimental effects. This tool should prove advantageous in future studies of exosome-immune modulation in cancer and other settings. PMID:18423480

  7. Inhibitory effect of STAT3 gene combined with CDDP on growth of human Wilms tumour SK-NEP-1 cells.

    Science.gov (United States)

    Wang, Junrong; Zhang, Nina; Qu, Haijiang; You, Guangxian; Yuan, Junhui; Chen, Caie; Li, Wenyi; Pan, Feng

    2016-07-01

    To investigate the effects of signal transducer and activator of transcription 3 (STAT3) combined with cisplatin (CDDP) on the growth of human Wilms tumour (WT) SK-NEP-1 cell subcutaneous xenografts in nude mice and the possible mechanisms. Human WT SK-NEP-1 cells were subcutaneously transplanted to establish the BALB/c nude mice xenograft model. Mice were randomly divided into five groups: blank control group, adenovirus control group (NC group), STAT3 group, CDDP group and STAT3 plus CDDP group (combination group). Tumour volume and tumour weight were observed during the therapeutic process. The expression levels of STAT3, glucose regulatory protein 78 (GRP78) and BCL2-associated X protein (BAX) were evaluated by immunohistochemical analysis. Compared with the STAT3 group or CDDP group, the tumour weight and volume was significantly reduced in the combination group (Pstatistical significance was found in NC group compared with the blank control group (P > 0.05). Immunohistochemical analysis showed that STAT3, GRP78 and BAX protein levels in the combination group were significantly higher than those in STAT3 group and CDDP group (P<0.05). Exogenous STAT3 and CDDP may synergistically inhibit the xenograft tumour growth through up-regulation of BAX protein via GRP78. PMID:27129294

  8. Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Junichi Sakamoto; Tsutomu Namikawa; Ken Okamoto; Takehiro Okabayashi; Kengo Ichikawa; Keijiro Araki

    2006-01-01

    AIM: To examine the paclitaxel concentrations in plasma and ascites after its intravenous administration in patients with ascites due to peritonitis carcinomatosa resulting from advanced gastric cancer.METHODS: Two patients with ascites due to peritonitis carcinomatosa resulting from gastric cancer were included in this study. The paclitaxel concentrations in plasma and ascites were investigated for 72 h in case 1 and 168 h in case 2 after intravenous administration.RESULTS: The paclitaxel concentration in plasma peaked immediately after administration, followed by rapid decrease below the threshold value of 0.1 μmol (85 ng/mL) within 24 h. In contrast, the paclitaxel concentration in ascites increased gradually for 24 h after administration to a level consistent with the level found in plasma. After 24 h the level of paclitaxel in ascites and plasma became similar, with the optimal level being maintained up to 72 h following administration.CONCLUSION: The concentration of paclitaxel in ascites is maintained within the optimal level for the treatment of cancer cells for up to 72 h after intravenous administration. Paclitaxel is a promising drug for the treatment of malignant ascites of gastric cancer.

  9. Light-oxygen effect in cells and its potential applications in tumour therapy (review)

    International Nuclear Information System (INIS)

    The light-oxygen effect (POE) represents damage (and at low optical doses, activation) of cells by photogeneration of molecular singlet oxygen from O2 dissolved in cells, in accordance with the reaction: 3O2+hν→1O2→ biological effect. The phases of evolution of the LOE are similar to the phases, observed in cell experiments, of the photodynamic effect (PDE) the mechanism of which is the basis of the familiar method of photodynamic cancer therapy. The reported proofs of the occurrence of the LOE are in the form of detailed spectra of the biological action of optical radiation on cells recorded in four spectral intervals with the aid of tunable lasers. Allowances are made for the relationships governing a new type of cell excitation, associated with reversible structural transitions in the biomembrane. A demonstration is reported of the same efficiency of cw and pulsed irradiation. An analysis is made of the reasons why the optical doses initiating the PDE and the LOE are comparable. The results are given of the first experimental applications of the LOE in tumour therapy. Identification of the primary photoacceptor (O2) in cell biostimulation and photodestruction provides a scientific basis for the development of low-intensity laser light-oxygen cancer therapy methods. (lasers in medicine)

  10. A case of Sertoli-Leydig cell tumour of the ovary with a multilocular cystic appearance on CT and MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Asako [Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto (Japan); Kameda Medical Center, Department of Radiology, Kamogawa (Japan); Koyama, Takashi [Kyoto University Hospital, Department of Radiology, Kyoto (Japan); Mikami, Yoshiki [Kyoto University Hospital, Laboratory of Anatomic Pathology, Kyoto (Japan); Tamai, Ken; Fujimoto, Koji; Morisawa, Nobuko; Togashi, Kaori [Kyoto University, Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto (Japan); Nagano, Fusaka; Yoshioka, Shinya [Graduate School of Medicine, Kyoto University Hospital, Department of Gynecology and Obstetrics, Kyoto (Japan)

    2008-08-15

    We present a case of Sertoli-Leydig cell tumour of the ovary in a 14-year-old girl who presented with abdominal distension. Ultrasonography showed a multilocular cystic lesion filled with finely echogenic fluid. Contrast-enhanced CT demonstrated a huge multilocular cystic mass with thickened septa. At MR imaging, the capsule of the cyst was focally thickened, showing intermediate signal intensity on T2-W images. Although extensive cyst formation of Sertoli-Leydig cell tumour is rare, this tumour should be considered in the differential diagnosis of a multilocular cystic ovarian tumour in a young female. (orig.)

  11. A case of Sertoli-Leydig cell tumour of the ovary with a multilocular cystic appearance on CT and MR imaging

    International Nuclear Information System (INIS)

    We present a case of Sertoli-Leydig cell tumour of the ovary in a 14-year-old girl who presented with abdominal distension. Ultrasonography showed a multilocular cystic lesion filled with finely echogenic fluid. Contrast-enhanced CT demonstrated a huge multilocular cystic mass with thickened septa. At MR imaging, the capsule of the cyst was focally thickened, showing intermediate signal intensity on T2-W images. Although extensive cyst formation of Sertoli-Leydig cell tumour is rare, this tumour should be considered in the differential diagnosis of a multilocular cystic ovarian tumour in a young female. (orig.)

  12. YOLK SAC TUMOUR IN A PREMENARCHAL GIRL : A CASE REPORT

    OpenAIRE

    Sourav; Avishek; Pallab Kumar; Bandana; Mrinmoyee

    2015-01-01

    Yolk sac tumour, otherwise known as endodermal sinus tumour, is a rare and highly malignant germ cell tumour accounting for approximately 10% of malignant germ cell tumours. The tumour usually presents as a rapidly growing mass in young women. Here we present a case of a young premenarchal girl with a huge ovarian tumour which pro...

  13. Immunotherapeutic efficacy of vaccines generated by fusion of dendritic cells and HPV16-associated tumour cells

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Indrová, Marie; Jandlová, Táňa

    2005-01-01

    Roč. 51, č. 1 (2005), s. 19-24. ISSN 0015-5500 R&D Projects: GA AV ČR(CZ) IAA5052203; GA ČR(CZ) GA301/04/0492 Grant ostatní: Liga proti rakovině, Praha(CZ) - Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * DC-tumour hybrids * immunotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.719, year: 2005

  14. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141(+)XCR1+ dendritic cells.

    Science.gov (United States)

    Silk, K M; Silk, J D; Ichiryu, N; Davies, T J; Nolan, K F; Leishman, A J; Carpenter, L; Watt, S M; Cerundolo, V; Fairchild, P J

    2012-10-01

    Monocyte-derived dendritic cells (moDC) have been widely used in cancer immunotherapy but show significant donor-to-donor variability and low capacity for the cross-presentation of tumour-associated antigens (TAA) to CD8(+) T cells, greatly limiting the success of this approach. Given recent developments in induced pluripotency and the relative ease with which induced pluripotent stem (iPS) cell lines may be generated from individuals, we have succeeded in differentiating dendritic cells (DC) from human leukocyte antigen (HLA)-A(*)0201(+) iPS cells (iPS cell-derived DC (ipDC)), using protocols compliant with their subsequent clinical application. Unlike moDC, a subset of ipDC was found to coexpress CD141 and XCR1 that have been shown previously to define the human equivalent of mouse CD8α(+) DC, in which the capacity for cross-presentation has been shown to reside. Accordingly, ipDC were able to cross-present the TAA, Melan A, to a CD8(+) T-cell clone and stimulate primary Melan A-specific responses among naïve T cells from an HLA-A(*)0201(+) donor. Given that CD141(+)XCR1(+) DC are present in peripheral blood in trace numbers that preclude their clinical application, the ability to generate a potentially unlimited source from iPS cells offers the possibility of harnessing their capacity for cross-priming of cytotoxic T lymphocytes for the induction of tumour-specific immune responses. PMID:22071967

  15. Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR. Four male and three female patients of age 42-74 years were evaluated. All cases were incidentally detected by ultrasound and ranged 1.8-3.5 cm. Microscopic examination showed variably tubulopapillary, tubular acinar, cystic architecture and the characteristic linear arrangement of nuclei. The cells were reactive with CK7 (strong), CA IX (cup-shape) and 34 β E12. CD10, AMACR/RACEMASE and GATA3 were negative. There were no mutations on any of the investigated genes. This preliminary observation supports the concept that CCPRCC might be indeed an indolent tumour worth it to be named as clear cell papillary neoplasm of low potential. PMID:26941183

  16. Microimaging FT-IR of oral cavity tumours. Part III: Cells, inoculated tissues and human tissues

    Science.gov (United States)

    Conti, C.; Ferraris, P.; Giorgini, E.; Pieramici, T.; Possati, L.; Rocchetti, R.; Rubini, C.; Sabbatini, S.; Tosi, G.; Mariggiò, M. A.; Lo Muzio, L.

    2007-05-01

    The biochemistry of healthy and tumour cell cultures, inoculated tissues and oral cavity tissues have been studied by FT-IR Microscopy with the aim to relate spectral patterns with microbiological and histopathological findings. 'Supervised' and 'unsupervised' procedures of data handling afforded a satisfactory degree of accordance between spectroscopic and the other two techniques. In particular, changes in frequency and intensity of proteins, connective and nucleic acids vibrational modes as well as the visualization of biochemical single wave number or band ratio images, allowed an evaluation of the pathological changes. The spectroscopic patterns of inoculated tissues resulted quite similar to human tissues; differences of both types of sections with cellular lines could be explained by the influence of the environment.

  17. A Rare Case of Metastatic Desmoplastic Small Round Cell Tumour: Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Shahzaib Nabi

    2015-01-01

    Full Text Available A 26-year-old male without any significant past medical history presented to the hospital with shortness of breath, cough, pleuritic chest pain, and weight loss for the past 3 months. On chest CT, he was found to have extensive mediastinal and hilar lymphadenopathy and multiple pulmonary nodules. On physical examination, a right groin mass was noted which had been slowly growing for the past 2 years. Ultrasound of the groin showed complex solid mass with internal vascular channels. CT guided biopsy of the mass showed desmoplastic small round cell tumour. His hospital course was complicated by hypoxic respiratory failure requiring emergent intubation and ICU admission where he completed one cycle of vincristine, cyclophosphamide, and doxorubicin with subsequent improvement, followed by extubation. His condition continued to improve after second cycle of chemotherapy and he was ultimately discharged in a stable condition to continue outpatient chemotherapy after a 2-month inpatient stay.

  18. Effect of reconstituted basement membrane components on the growth of a panel of human tumour cell lines in nude mice.

    OpenAIRE

    Topley, P.; Jenkins, D C; Jessup, E. A.; Stables, J. N.

    1993-01-01

    Previous reports have indicated that reconstituted basement membrane (matrigel), when co-injected with either established or primary human tumour cells, can improve the growth of subcutaneous xenografts in nude mice. The human adenocarcinoma cell lines A549, SW480, and WiDr, and the human fibrosarcoma cell line HT1080scc2 exhibit varying degrees of tumourigenicity in nude mice. All these lines showed increased tumorigenicity and/or growth rate, together with a change towards a more differenti...

  19. Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model

    International Nuclear Information System (INIS)

    The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models

  20. Simultaneous removal of a tumour of the right atrium and inferior vena cava and coronary bypass-grafting in a patient with recurrent clear renal cell carcinoma

    Science.gov (United States)

    Pietrzyk, Edward; Głuszek, Stanisław; Michta, Kamil; Kot, Marta; Wożakowska-Kapłon, Beata

    2015-01-01

    Metastatic cardiac tumours are the most common malignant cardiac tumours. In the early stages they are usually asymptomatic, but their consequences can be very serious, and the prognosis is poor. We present a patient with recurrent renal cell carcinoma as a tumour of the right atrium and the vena cava inferior in whom cancerous masses were removed with simultaneously coronary artery bypass-grafting. PMID:26855653

  1. Histone H1x is highly expressed in human neuroendocrine cells and tumours

    International Nuclear Information System (INIS)

    Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation. Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study. We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues. We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate

  2. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015). ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.362, year: 2014

  3. Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance.

    Science.gov (United States)

    Salam, M A; Crocker, J; Morris, A

    1995-02-01

    p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours. PMID:7788934

  4. Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C;

    2009-01-01

    A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from ...

  5. Pre-treatment number of clonogenic cells and their radiosensitivity are major determinants of local tumour control after fractionated irradiation

    International Nuclear Information System (INIS)

    Objective: The response of tumours to fractionated radiotherapy is determined by many factors including repopulation, reoxygenation, the number of clonogenic cells, and their intrinsic radiosensitivity. However, after single radiation doses given under conditions of clamp hypoxia, the dose to control a tumour locally is dependent only on the number of clonogenic cells and their cellular radiosensitivity. Therefore, these parameters were investigated using local control after single doses given under hypoxia, to predict the outcome of fractionated irradiation. Materials and methods: Ten hSCC cell lines (FaDu, UT-SCC-15, UT-SCC-14, XF354, UT-SCC-5, UT-SCC-45, SAS, CAL-33, UT-SCC-8, and HSC-4) were transplanted subcutaneously into the right hind-leg of NMRI nude mice. At 7 mm in diameter, tumours were irradiated either with graded single doses under clamp blood flow conditions (n = 873) or with 30 graded fractions within 6 weeks (n = 905) under ambient conditions. Local tumour control was determined 120 days after irradiation. Radiation response was quantified in terms of TCD50, i.e. the dose required to control 50% of tumours locally. Results: Ten tumour lines investigated showed a pronounced heterogeneity in both TCD50(30fx/6w) after fractionated irradiation and TCD50(SDclamp) after single dose irradiation. TCD50(30fx/6w) varied between 45 Gy for UT-SCC-45 and 127 Gy for SAS; TCD50(SDclamp) varied between 42 Gy for UT-SCC-14 and 66 Gy for CAL-33. Two tumours were excluded from further analysis due to immunogenicity or non-defined TCD50. Linear regression analysis revealed a significant positive correlation between TCD50(SDclamp) and TCD50(30fx/6w) (R 2 = 0.82, p = 0.002). Conclusions: Significant association between TCD50(SDclamp) and TCD50(30fx/6w) suggests that the pre-treatment number of clonogenic tumour cells and their cellular radiosensitivity have a major impact on local control after fractionated radiotherapy

  6. Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, Balaji; Miles, Ken [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Division of Clinical and Laboratory Investigation, Brighton, East Sussex (United Kingdom); Panayiotou, Elleny; Burnand, Kate [Brighton and Sussex University Hospitals NHS Trust, Brighton (United Kingdom); Dizdarevic, Sabina [Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton (United Kingdom)

    2012-04-15

    To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing {sup 18}F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. (orig.)

  7. Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression

    Science.gov (United States)

    Zhang, Wen Cai; Chin, Tan Min; Yang, Henry; Nga, Min En; Lunny, Declan Patrick; Lim, Edwin Kok Hao; Sun, Li Li; Pang, Yin Huei; Leow, Yi Ning; Malusay, Shanneen Rossellini Y; Lim, Priscilla Xin Hui; Lee, Jeravan Zili; Tan, Benedict Jian Wei; Shyh-Chang, Ng; Lim, Elaine Hsuen; Lim, Wan Teck; Tan, Daniel Shao Weng; Tan, Eng Huat; Tai, Bee Choo; Soo, Ross Andrew; Tam, Wai Leong; Lim, Bing

    2016-01-01

    The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets. PMID:27325363

  8. Location of tumour cells in colon tissue by Texas red labelled pentosan polysulphate, an inhibitor of a cell surface protease.

    Science.gov (United States)

    Anees, M

    1996-01-01

    Pentosan polysulphate (PPS), a highly negatively charged polysaccharide, is a significant inhibitor of an isoenzymic form of a cell surface protease referred to as guanidinobenzoatase GB, associated with colonic carcinoma tissues in frozen sections and free GB in solution, in a concentration-dependent manner. However PPS failed to recognise and bind to the isoenzymic form of GB associated with normal colon epithelial cell surfaces. Texas red labelled PPS (TR-PPS) binds to the tumour cell surfaces of colonic carcinoma and colonic polyps and these cells fluoresce red, whilst the normal colon cell surfaces failed to bind the TR-PPS, and hence lacked red fluorescence. Polysulphonated suramin also selectively recognised and inhibited the colonic carcinoma GB isoenzyme. The kinetic data indicated that this inhibition was not caused by a mere polyanionic effect, since highly sulphated heparin failed to show a significant inhibition of colonic carcinoma GB, however trypan blue did show 50% inhibition. Kinetic studies have also shown that PPS is a non-competitive, reversible inhibitor of colonic carcinoma GB, with an apparent Km 6.8 x 10(-7) M. Gel analysis has shown that PPS binds to another site, distinct from the active centre, and after binding PPS changed the conformation of GB. These studies suggest that TR-PPS is a potent inhibitor of colonic carcinoma GB, and can be used as a novel fluorescent probe for the location of tumour cells in frozen sections of human colon tissues. PSS could also have potential as a vehicle for the transport of cytotoxic compounds to carcinoma cells of the colon. PMID:8835946

  9. Radiosensitization by misonidazole, pimonidazole and azomycin and intracellular uptake in human tumour cell lines

    International Nuclear Information System (INIS)

    Radiosensitization of two human tumour cell lines, HT-1080 and LoVo was compared with Chinese hamster line V73-379A. Although the two human lines were more radiosensitive than V79, enhancement ratios for misonidazole, pimonidazole and azomycin were similar for all three. In all cells uptake of misonidazole and azomycin was very rapid; that of pimonidazole was initially much slower before reaching a plateau. The ratios of intracellular concentration of radiosensitizer to extracellular concentration (Ci to Ce)for misonidazole were 0.8 (HT-1080) and 0.7 (LoVo and V79); for azomycin 0.9 (HT-1080 and LoVo) and 0.8 (V79). CiCe for pimonidazole varied with cell line [1.8 (LoVo), 2.6 (HT-1080) and 3.3 (V79)]. When average cell volume was taken into consideration, concentrations of non-protein sulphydryl were very similar [4.2 (HT-1080), 5.6 (LoVo), 5.7 (V79) m mol dm-3]. MPSH levels expressed as n mol/mg protein were also similar. (author)

  10. The bromine enhancement ratio in mammalian cells in vitro and experimental mouse tumours

    International Nuclear Information System (INIS)

    Human kidney cells in culture and cells of mouse sarcoma-180 were allowed to incorporate bromine into their DNA. Cultured cells with and without incorporated BUdR were irradiated with electromagnetic radiations ranging in energy from 12 keV X-rays to 60Co γ-rays to find out whether or not there exists any energy dependence of the bromine dose enhancement ratio BER. Such a dependence should show in the immediate neighbourhood of the K-absorption edge of bromine (13.5 keV). Any influence of the Auger effect triggered in bromine by external irradiation should show by a significant increase of the BER for energies rising from slightly below to slight above the bromine K-edge. Values of D37, D0 and the extrapolation numbers of the cell survival curves served as biological endpoints. Measured values of BER ranged from 1.12-2.00 without any significant dependence on energy. A weakly pronounced peak was found for 50 kV X-rays of 26 keV mean energy. Sarcoma-180 were irradiated with 14 keV X-rays and 60C γ-rays. BUdR was administered i.v., i.p. and directly into the tumours in quantities of up to 1 ml of a 10-3M solution. (Auth.)

  11. Glucocorticoid regulation of SLIT/ROBO tumour suppressor genes in the ovarian surface epithelium and ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Rachel E Dickinson

    Full Text Available The three SLIT ligands and their four ROBO receptors have fundamental roles in mammalian development by promoting apoptosis and repulsing aberrant cell migration. SLITs and ROBOs have emerged as candidate tumour suppressor genes whose expression is inhibited in a variety of epithelial tumours. We demonstrated that their expression could be negatively regulated by cortisol in normal ovarian luteal cells. We hypothesised that after ovulation the locally produced cortisol would inhibit SLIT/ROBO expression in the ovarian surface epithelium (OSE to facilitate its repair and that this regulatory pathway was still present, and could be manipulated, in ovarian epithelial cancer cells. Here we examined the expression and regulation of the SLIT/ROBO pathway in OSE, ovarian cancer epithelial cells and ovarian tumour cell lines. Basal SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 expression was lower in primary cultures of ovarian cancer epithelial cells when compared to normal OSE (P<0.05 and in poorly differentiated SKOV-3 cells compared to the more differentiated PEO-14 cells (P<0.05. Cortisol reduced the expression of certain SLITs and ROBOs in normal OSE and PEO-14 cells (P<0.05. Furthermore blocking SLIT/ROBO activity reduced apoptosis in both PEO-14 and SKOV-3 tumour cells (P<0.05. Interestingly SLIT/ROBO expression could be increased by reducing the expression of the glucocorticoid receptor using siRNA (P<0.05. Overall our findings indicate that in the post-ovulatory phase one role of cortisol may be to temporarily inhibit SLIT/ROBO expression to facilitate regeneration of the OSE. Therefore this pathway may be a target to develop strategies to manipulate the SLIT/ROBO system in ovarian cancer.

  12. Treatment of transplanted CT26 tumour with dendritic cell vaccine in combination with blockade of vascular endothelial growth factor receptor 2 and CTLA-4

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Buus, S; Claesson, M H

    2005-01-01

    We investigated the anti CT26 tumour effect of dendritic cell based vaccination with the MuLV gp70 envelope protein-derived peptides AH1 and p320-333. Vaccination lead to generation of AH1 specific cytotoxic lymphocytes (CTL) and some decrease in tumour growth of simultaneously inoculated CT26 ce...... of mice with already established tumours was only obtained after combination of vaccination, DC101 and 9H10 treatment in which setting 80% of the mice rejected their tumours....

  13. Fluorodeoxyglucose positron emission tomography in the initial staging of germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hain, S.F.; O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospitals, London (United Kingdom); Timothy, A.R.; Leslie, M.D.; Partridge, S.E. [Dept. of Clinical Oncology, Guy' s and St Thomas' Hospitals, London (United Kingdom); Huddart, R.A. [Dept. of Radiotherapy and Oncology, Royal Marsden, Surrey (United Kingdom)

    2000-05-01

    Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease. (orig.)

  14. Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high-grade serous ovarian cancer that distinguish malignant, tumour-sustaining and chemo-resistant ovarian tumour cells.

    Science.gov (United States)

    Chapman-Rothe, N; Curry, E; Zeller, C; Liber, D; Stronach, E; Gabra, H; Ghaem-Maghami, S; Brown, R

    2013-09-19

    In embryonic stem (ES) cells, bivalent chromatin domains containing H3K4me3 and H3K27me3 marks silence developmental genes, while keeping them poised for activation following differentiation. We have identified gene sets associated with H3K27me3 and H3K4me3 marks at transcription start sites in a high-grade ovarian serous tumour and examined their association with epigenetic silencing and malignant progression. This revealed novel silenced bivalent marked genes, not described previously for ES cells, which are significantly enriched for the PI3K (P<10(-7)) and TGF-β signalling pathways (P<10(-5)). We matched histone marked gene sets to gene expression sets of eight normal fallopian tubes and 499 high-grade serous malignant ovarian samples. This revealed a significant decrease in gene expression for the H3K27me3 and bivalent gene sets in malignant tissue. We then correlated H3K27me3 and bivalent gene sets to gene expression data of ovarian tumour 'stem cell-like' sustaining cells versus non-sustaining cells. This showed a significantly lower expression for the H3K27me3 and bivalent gene sets in the tumour-sustaining cells. Similarly, comparison of matched chemo-sensitive and chemo-resistant ovarian cell lines showed a significantly lower expression of H3K27me3/bivalent marked genes in the chemo-resistant compared with the chemo-sensitive cell line. Our analysis supports the hypothesis that bivalent marks are associated with epigenetic silencing in ovarian cancer. However it also suggests that additional tumour specific bivalent marks, to those known in ES cells, are present in tumours and may potentially influence the subsequent development of drug resistance and tumour progression. PMID:23128397

  15. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

    DEFF Research Database (Denmark)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B;

    2013-01-01

    development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression......Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis...

  16. Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice

    Directory of Open Access Journals (Sweden)

    Debajit Bhowmick

    2016-01-01

    Full Text Available Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP, generation of reactive oxygen species (ROS, and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.

  17. Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice.

    Science.gov (United States)

    Bhowmick, Debajit; Bhar, Kaushik; Mallick, Sanjaya K; Das, Subhadip; Chatterjee, Nabanita; Sarkar, Tuhin Subhra; Chakrabarti, Rajarshi; Das Saha, Krishna; Siddhanta, Anirban

    2016-01-01

    Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma. PMID:27293892

  18. Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice

    Science.gov (United States)

    Bhowmick, Debajit; Bhar, Kaushik; Mallick, Sanjaya K.; Das, Subhadip; Chatterjee, Nabanita; Sarkar, Tuhin Subhra; Chakrabarti, Rajarshi; Das Saha, Krishna; Siddhanta, Anirban

    2016-01-01

    Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma. PMID:27293892

  19. Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110-kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells

    DEFF Research Database (Denmark)

    Schneider, H R; Reichert, G H; Issinger, O G

    1986-01-01

    mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (cAMP- and cGMP-dependent protein kinases) only show a basal level of enzyme...

  20. Cancer-derived VEGF plays no role in malignant ascites formation in the mouse

    Institute of Scientific and Technical Information of China (English)

    Bayasi Guleng; Tsuneo Ikenoue; Yasushi Fukushima; Keita Morikane; Makoto Miyagishi; Kazunari Taira; Takao Kawabe; Masao Omata; Keisuke Tateishi; Fumihiko Kanai; Amarsanaa Jazag; Miki Ohta; Yoshinari Asaoka; Hideaki Ijichi; Yasuo Tanaka; Jun Imamura

    2005-01-01

    AIM: Vascular endothelial growth factor (VEGF) is a potent mediator of peritoneal fluid accumulation following tumor progression. This study investigated the role of VEGF secreted by cancerous cells in the formation of malignant ascites.METHODS: VEGF expression was eliminated byknockdown in the pancreas cancer cell-line PancO2 using vector-based short-hairpin type RNA interference (RNAi).Malignant ascites formation in the mouse was analyzed by intraperitoneal injection of PancO2 cells expressing VEGF or with expression knockdown.RESULTS: The VEGF knockdown PancO2 cell was successfully established. Knockdown of VEGF did not affect cancer cell proliferation in vitro or in vivo. The volume of ascites following peritoneal expansion of the tumor in VEGF knockdown cells and control cells did not differ statistically in this in vivo study. Moreover, the VEGF concentration in the ascites did not differ statistically.CONCLUSION: Malignant ascites formation might be mediated by VEGF production in noncancerous tissues,such as stromal compartments. An anti-VEGF strategy against malignant ascites could be applied to various tumors regardless of whether they secrete VEGF.

  1. Role of Ethanol Extract of Bidens Pilosa L. Against Ehrlich Ascites Carcinoma Bearing Mice Exposed to Gamma Radiation

    International Nuclear Information System (INIS)

    Bidens pilosa L. is one of the dominant families of plants contributing to medicinal species worldwide. The present study was performed to investigate the role of ethanolic extract of B. pilosa (BpE) against Ehrlich ascites carcinoma (EAC)-induced hepatic dysfunction in gamma irradiated mice. BpE was orally administered to mice for eight consecutive days at the dose of 250 mg/kg body weight (one day before and eight days after tumour inoculation). On the 3rd day of tumour inoculation, animals were exposed to whole body gamma radiation at dose of 6 Gy. The results obtained in the present study revealed that both EAC and/or gamma radiation induced liver biochemical and histopathological alterations. In vitro short term toxicity study, Bidens pilosa extract at different experimental dose levels increased the percentage of non-viable cell count. Gamma radiation and/or EAC induced oxidative stress, inflammation and biochemical alteration in liver function. The liver oxidative stress was manifested by increase in lipid peroxidation concomitant with decrease in glutathione and superoxide dismutase levels. Liver inflammation was manifested by increased levels of tumour necrosis factor-a (TNF-a), interlukin-2 (IL-2) and alteration in leukocyte count (LC). Biochemical alteration in liver function manifested by significant increase in liver transaminases (AST and ALT) and lactate dehydrogenase (LDH). Moreover, radiation and EAC induced liver oxidative stress and significant increase in caspase-3. In vivo studies showed that BpE restored the hepatic function profile in tumour bearing mice. Histopathological studies showed that EAC and radiation caused fatty degeneration, enlargement of liver cells nuclei and presence of necrosis. Treatment with BpE modulates most of the pathological alterations. It could be concluded that the hepato protective effect of BpE is related to its phyto chemical components, which were claimed to be the mechanism of hepatic protection.

  2. Optimisation of immunofluorescence methods to determine MCT1 and MCT4 expression in circulating tumour cells

    International Nuclear Information System (INIS)

    The monocarboxylate transporter-1 (MCT1) represents a novel target in rational anticancer drug design while AZD3965 was developed as an inhibitor of this transporter and is undergoing Phase I clinical trials (http://www.clinicaltrials.gov/show/NCT01791595). We describe the optimisation of an immunofluorescence (IF) method for determination of MCT1 and MCT4 in circulating tumour cells (CTC) as potential prognostic and predictive biomarkers of AZD3965 in cancer patients. Antibody selectivity was investigated by western blotting (WB) in K562 and MDAMB231 cell lines acting as positive controls for MCT1 and MCT4 respectively and by flow cytometry also employing the control cell lines. Ability to detect MCT1 and MCT4 in CTC as a 4th channel marker utilising the Veridex™ CellSearch system was conducted in both human volunteer blood spiked with control cells and in samples collected from small cell lung cancer (SCLC) patients. Experimental conditions were established which yielded a 10-fold dynamic range (DR) for detection of MCT1 over MCT4 (antibody concentration 6.25 μg/mL; integration time 0.4 seconds) and a 5-fold DR of MCT4 over MCT 1 (8 μg/100 μL and 0.8 seconds). The IF method was sufficiently sensitive to detect both MCT1 and MCT4 in CTCs harvested from cancer patients. The first IF method has been developed and optimised for detection of MCT 1 and MCT4 in cancer patient CTC

  3. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Skakkebaek, N E

    1994-01-01

    , CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect...... addition, we propose that the c-kit protein product is a new marker for carcinoma-in-situ of the testis....

  4. In vitro growth inhibitory activity of the Portuguese wild mushroom Clitocybe alexandri in human tumour cell lines

    OpenAIRE

    Vaz, Josiana A.; Almeida, Gabriela M.; Martins, Anabela; Vasconcelos, M. Helena; Ferreira, Isabel C. F. R.

    2010-01-01

    Some mushrooms are a powerful source of bioactive compounds. lndeed, many pre-clinical studies have been conducted in human tumour cell lines and in some cases a number of compounds extracted from mushrooms have entered clinical trials [1]. Our previous results showed that phenolic (methanolic and ethanolic) and polissacharidic extracts from Clitocybe alexandri inhibited the growth of four human cell lines (lung, breast, colon and gastric cancer) [2]. The aim of the present wor...

  5. Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells

    Directory of Open Access Journals (Sweden)

    Shukla Deepa

    2011-07-01

    Full Text Available Abstract Background 209 000 new cases of renal carcinoma are diagnosed each year worldwide and new therapeutic targets are urgently required. The great majority of clear cell renal cancer involves inactivation of VHL, which acts as a gatekeeper tumour suppressor gene in renal epithelial cells. However how VHL exerts its tumour suppressor function remains unclear. A gene expression microarray comparing RCC10 renal cancer cells expressing either VHL or an empty vector was used to identify novel VHL regulated genes. Findings NMU (Neuromedin U is a neuropeptide that has been implicated in energy homeostasis and tumour progression. Here we show for the first time that VHL loss-of-function results in dramatic upregulation of NMU expression in renal cancer cells. The effect of VHL inactivation was found to be mediated via activation of Hypoxia Inducible Factor (HIF. Exposure of VHL expressing RCC cells to either hypoxia or dimethyloxalylglycine resulted in HIF activation and increased NMU expression. Conversely, suppression of HIF in VHL defective RCC cells via siRNA of HIF-α subunits or expression of Type 2C mutant VHLs reduced NMU expression levels. We also show that renal cancer cells express a functional NMU receptor (NMUR1, and that NMU stimulates migration of renal cancer cells. Conclusions These findings suggest that NMU may act in an autocrine fashion, promoting progression of kidney cancer. Hypoxia and HIF expression are frequently observed in many non-renal cancers and are associated with a poor prognosis. Our study raises the possibility that HIF may also drive NMU expression in non-renal tumours.

  6. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST) mimicking hereditary GIST syndromes

    OpenAIRE

    Mafalda Costa Neves; Gordon Stamp; Satvinder Mudan

    2015-01-01

    Introduction: Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. Case report: 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4 cm GIST in the gastric fundus. Pathology of the resecte...

  7. In silico modelling of a cancer stem cell-targeting agent and its effects on tumour control during radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2016-01-01

    Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA’s cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy. PMID:27573059

  8. Presence of both Mesenchymal and Carcinomatous Features in an In-vitro Model of Ovarian Carcinosarcoma Derived from Patients' Ascitic Fluid

    OpenAIRE

    2015-01-01

    ABSTRACT We have refined the technique for isolating and propagating cultures of primary ovarian carcinosarcoma cells (OSCs) derived from ascites, which allowed the cells to obtain the biphasic features of carcinosarcoma in cell culture conditions (presence of both carcinoma and mesenchymal morphologic types). This protocol involves a simple yet rapid method for the growth and propagation of ascites OSC in a basal culture medium. Autologous ascitic fluid was used as source of growth factors, ...

  9. Isolated Fetal Ascite Associated with Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    Vehbi Doğan

    2014-12-01

    Full Text Available Fetal ascite is defined as fluid accumulation in peritoneal cavity. It can be seen as isolated disease or an early sign of hydrops fetalis. Once fetal ascite is detected, a careful examination for hydops fetalis and possible underlying disease is necessary, since its prognosis and treatment depends mostly on the cause. Non-immunologic fetal ascite is an uncommon problem occurring for many reasons, such as urinary tract obstruction, congenital infections, genetic and metabolic diseases, gastrointestinal diseases and cardiovascular diseases. Here in this report we present two isolated fetal ascite that occurred secondary to cardiac diseases.

  10. Perivascular epithelioid cell tumour of the vagina in an 8 year old girl.

    Science.gov (United States)

    Ong, Lin Yin; Hwang, Wei Sek; Wong, Adelina; Chan, Mei Yoke; Chui, Chan Hon

    2007-03-01

    Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor with an unpredictable natural history. We present the first reported case of PEComa of the vagina diagnosed in an 8-year-old girl. This was initially diagnosed on biopsy as an embryonal rhabdomyosarcoma, and the patient underwent 3 cycles of chemotherapy according to the Mesenchymal Malignant Tumour 1989 protocol. A repeat scan, however, revealed an increase in tumor size. Total resection was achieved via a transvaginal (vertical sleeve) partial vaginectomy. The resected tumor had the typical appearance of a PEComa. Immunostains showed positive staining of tumor cells for HMB45, neuron-specific enolase, and calponin but were negative for S100 protein, melaninA, chromogranin, smooth muscle actin, desmin, caldesmon, epithelial membrane antigen, AE1/3, and synaptophysin. Six months after surgery, she remains free of tumor and is on follow-up with regular local examinations under anesthesia and computed tomography scans. Our case highlights the importance of an accurate initial diagnosis, and we stress the importance of regular surveillance over a significant period. PMID:17336201

  11. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    International Nuclear Information System (INIS)

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC

  12. Merkel cell polyomavirus: molecular insights into the most recently discovered human tumour virus.

    Science.gov (United States)

    Stakaitytė, Gabrielė; Wood, Jennifer J; Knight, Laura M; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian

    2014-01-01

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC. PMID:24978434

  13. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    Directory of Open Access Journals (Sweden)

    Gabrielė Stakaitytė

    2014-06-01

    Full Text Available A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC, a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.

  14. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis.

    Science.gov (United States)

    Hyde, C A C; Missailidis, S

    2009-06-01

    Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated. This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention. PMID:19239926

  15. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Piché Alain

    2011-05-01

    Full Text Available Abstract Background The acellular fraction of epithelial ovarian cancer (EOC ascites promotes de novo resistance of tumor cells and thus supports the idea that tumor cells may survive in the surrounding protective microenvironment contributing to disease recurrence. Levels of the pro-inflammatory cytokines IL-6 and IL-8 are elevated in EOC ascites suggesting that they could play a role in tumor progression. Methods We measured IL-6 and IL-8 levels in the ascites of 39 patients with newly diagnosed EOC. Commercially available enzyme-linked immunosorbent assay (ELISA was used to determine IL-6 and IL-8 ascites levels. Ascites cytokine levels were correlated with clinicopathological parameters and progression-free survival. Results Mean ascites levels for IL-6 and IL-8 were 6419 pg/ml (SEM: 1409 pg/ml and 1408 pg/ml (SEM: 437 pg/ml respectively. The levels of IL-6 and IL-8 in ascites were significantly lower in patients that have received prior chemotherapy before the surgery (Mann-Whitney U test, P = 0.037 for IL-6 and P = 0.008 for IL-8. Univariate analysis revealed that high IL-6 ascites levels (P = 0.021, serum CA125 levels (P = 0.04 and stage IV (P = 0.009 were significantly correlated with shorter progression-free survival. Including these variables in a multivariate analysis revealed that elevated IL-6 levels (P = 0.033 was an independent predictor of shorter progression-free survival. Conclusion Elevated IL-6, but not IL-8, ascites level is an independent predictor of shorter progression-free survival.

  16. Advantages of assaying telomerase activity in ascites for diagnosis of digestive tract malignancies

    Institute of Scientific and Technical Information of China (English)

    Chung-Pin Li; Tze-Sing Huang; Yee Chao; Full-Young Chang; Jacquline Whang-Peng; Shou-Dong Lee

    2004-01-01

    AIM: To evaluate the diagnostic value of assaying telomerase activity in ascites cells for the differential diagnosis of malignant and non-malignant ascites.METHODS: Ascites from 40 patients with hepatocellular carcinoma (HCC), 31 with non-HCC gastrointestinal carcinoma (CA), and 24 with liver cirrhosis (LC) were analyzed for telomerase activity. The telomerase activities in cell pellets from ascites were measured according to the Telomeric Repeat Amplification Protocol (TRAP) and quantified with a densitometer.RESULTS: Positive telomerase activity was detected in 16 of 31 (52%) CA patients, 10 of 40 (25%) HCC patients, and 1 of 24 (4%) LC patients (P<0.001). The telomerase activity was higher in the ascites of CA patients than in the ascites of HCC or LC patients (CA: 22.9±5.8, HCC: 6.7±2.5, LC:1.3±1.3, P= 0.001). Cytology was positive in 18 CA patients (58%) and 1 HCC patient (2.5%), respectively. The positive telomerase activity was not related to patients' age, gender,and ascitic protein concentration, but to white blood count (r= 0.31, P= 0.002), neutrophil count (r= 0.29, P= 0.005),and the C-reactive protein level (r= 0.29, P= 0.018). When the results of both cytological examination and telomerase assay were considered together, the sensitivity increased to 77% for CA patients, 25% for HCC patients, and 48% for all 71 gastrointestinal cancer patients.CONCLUSION: Combining cytological examination of ascites with telomerase activity assay significantly improves the differential diagnosis between malignant and non-malignant ascites.

  17. The tumour distribution of bromodeoxyuridine labelled S-phase cells is found to be strongly dose dependant

    International Nuclear Information System (INIS)

    Bromodeoxyurdine (BrdU) is used extensively to measure the fraction of S-phase cells in tumours. Unlike endogenous markers of proliferation, such as PCNA and Ki-67, BrdU is exogenously administered and reaches the tumour via vasculature where it must then distribute throughout the tissue in order to label S-phase cells. Interest in using BrdU labelling of histological sections to evaluate the distribution of the effect of different treatment modalities on tumours led us to study the ability of BrdU to distribute within tissue. The study used SiHa (human cervix squamous cell carcinoma) xenografts, a tumour that exhibits cords of cells extending up to 150 μm away from blood vessels. A quantitative microscopy-based technique was employed to determine the distribution of S-phase labelled cells relative to the vasculature over a dose range of 25-2000 mg/kg BrdU. Detection of BrdU incorporation in DNA was carried out immunohistochemically and vasculature was identified using perfusion of carbocyanine, a fluorescent perivascular stain. Analysis of BrdU labelling distribution in the tissue found that a dose of 1000 mg/kg was required to label cells furthest from vasculature. Dosing at lower levels resulted in only the cells close to blood vessels being labelled. This result is surprising since 100 mg/kg BrdU is commonly used in flow cytometry studies. Results were compared with penetration seen in vitro using multilayered cell culture, a three-dimensional tissue culture model of solid tumours. Using multilayered cell culture, an exposure of 100 μM BrdU for 1 hour was required for labelling of S-phase cells 150 μm into the tissue, while cells adjacent to the edge of the tissue could be adequately labelled with just 5 μM BrdU for 1 hour. The AUC for a 100 mg/kg BrdU dose in mice was found to be ∼30 μM x h

  18. Parallel evolution of tumour subclones mimics diversity between tumours.

    Science.gov (United States)

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  19. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours

    Science.gov (United States)

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-01-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise. PMID:23125021

  20. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    Directory of Open Access Journals (Sweden)

    Nicolas Goudin

    Full Text Available Natural regulatory T (Treg cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy.