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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. Employment of synchronized cells and flow microfluorometry in investigations on the JB-1 ascites tumour chalones.

    Science.gov (United States)

    Bichel, P; Barfod, N M; Jakobsen, A

    1975-11-01

    In most experimental ascites tumours the growth rate decreases with increasing age and cell number. This decrease is caused by a prolongation of the cell cycle and an increasing accumulation of non-cycling cells in resting (or quiescent) G1 and G2 compartments. In cell-free ascitic fluid from the JB-1 ascites tumour in the plateau phase of growth lowmolecular-weight substances have been found which reversibly and specifically arrest JB-1 cells in G1 and G2. The present paper describes an in-vitro model for testing the effect of the humoral growth inhibitors contained in the ascitic fluid. The test system is based on synchronized JB-1 cells analysed by flow-through cytofluorometry. Addition to the synchronous cells of a ultrafiltrate (less than 50000 Daltons) of the JB-1 ascitic fluid was found to induce a complete, but temporary arrest of the cells at the G1-S border.

  5. A flow cytometric in vivo chalone assay using retransplanted old murine JB-1 ascites tumour cells.

    Science.gov (United States)

    Barfod, N M

    1981-07-01

    A flow cytometric in vivo chalone assay is described. Transplantation of old JB-1 ascites tumour cells to new hosts induced an influx of tumour cells, with G1 DNA content, to the S phase. This induction could be reversibly and specifically blocked by injections of an ultrafiltrate of old JB-1 ascites fluid. The method described is superior to a previously published in vivo chalone assay using regenerating ascites tumours. Owing to a reduced variability in time of onset of DNA synthesis, a smaller scatter of observations is achieved and thus the number of mice per group may be reduced using the new method. In contrast to the older technique, the present one does not necessitate killing of mice during the observation period.

  6. 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

  7. 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)

  8. Tumour cell recruitment of the JB-1 and L 1210 ascites tumour determined directly by double labelling with [14C]- and [3H]-thymidine.

    Science.gov (United States)

    Maurer-Schultze, B; Kondziella, U; Böswald, M

    1988-07-01

    Tumour cell recruitment of the JB-1 and L 1210 ascites tumour has been demonstrated directly by a double-labelling method with [14C]- and [3H]-thymidine (TdR). After [14C]-labelling of all proliferating tumour cells by multiple injections of [14C]TdR, recruitment of resting cells was stimulated by removal of the majority of tumour cells, i.e. by maximum aspiration of ascitic fluid. The number of recruited resting cells in the remaining tumour that re-enter the cell cycle after stimulation was demonstrated directly by a single injection of [3H]TdR given at different times after stimulation. The increase in the percentage of purely [3H]-labelled cells, i.e. recruited cells, with increasing time after stimulation, shows that recruitment is not a synchronous but a continuous process, the maximum of which occurs earlier in the case of the L 1210 than the JB-1 tumour. This suggests that there seems to be a relationship between the time required for maximum recruitment and the corresponding cell cycle parameters of the unperturbed tumour. There is a transitory increase of the growth fraction to about 100% and a considerable shortening of the cycle time at the maximum of recruitment.

  9. 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

  10. 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+)=benzam......-sensitive and -insensitive channels. In addition, because of its pharmacological profile, it may possibly be related to epithelial Na+ channels (ENaCs)....

  11. 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...

  12. Recycling of resting cells in the JB-1 ascites tumour after treatment with 1-beta-D-arabinofuranosylcytosine (ara-C).

    Science.gov (United States)

    Dombernowsky, P; Bichel, P

    1976-01-01

    Resting cells in tumours present a major problem in cancer chemotherapy. In the plateau phase of grwoth of the murine JB-1 ascites tumour (i.e. 10 days after 2-5 X 10(6) cells i.p.) large fractions of non-cycling cells with G1 and G2 DNA content (Q1 and Q2 cells) are present, and the fate of these resting cells was investigated after treatment with 1-beta-D-arabinofuranosylcytosine (Ara-C). The experimental work of growth curves, percentage of labelled mitoses curves after continuous labelling with 3H-TdR, and cytophotometric determination of single-cell DNA content in unlabelled tumour cells. Treatment with an i.p. single injection of Ara-C 200 mg/kg in the plateau JB-1 tumour resulted in a significant reduction in the number of tumour cells 1 and 2 days later as compared with untreated controls, while no difference in the number of tumour cells was observed after 3 days. In tumours prelabelled with 3H-TdR 24 hr before Ara-C treatment, a significant decrease in the percentage of labelled mitoses was observed 6-8 hr later followed by a return to the initial value after 12 hr, and a new pronounced fall from 20 hr after Ara-C. The second fall in the percentage of labelled mitoses disappeared when the labelling with 3H-TdR was continued also after Ara-C treatment. Cytophotometry of unlabelled tumour cells prelabelled for 24 hr with 3H-TdR before Ara-C treatment showed 20 hr after Ara-C a pronounced decrease in the fraction of Q1 cells paralleled by an increase in the fraction of unlabelled cells with S DNA content. The results indicate recycling of resting cells first with G2 and later with G1 DNA content, which contribute to the regrowth of the tumours.

  13. Specific chalone inhibition of the regeneration of the JB-1 ascites tumour studied by flow microfluorometry.

    Science.gov (United States)

    Bichel, P; Barfod, N M

    1977-03-01

    The variation in the DNA distribution in the JB-1 and the Lla2 ascites tumour was investigated by means of flow microfluorometry (FMF) in the plateau stage and during the initiation of the regenerative growth induced by percutaneous aspiration. The study showed that a considerable influx of cells with G1DNA content into the S phase occurred in both tumours about 10 hr after aspiration. In the JB-1 tumour, these initial regenerative changes could be reversibly blocked by injections of cell-free plateau JB-1 ascitic fluid or an ultrafiltrate of this ascites. In contrast to these observations no delay in the regenerative changes was observed in the L1a2 tumour after treatment with JB-1 ascites or the ultrafiltrate. The study supports the assumption of a specific growth regulation of the JB-1 ascites tumour and emphasizes the suitability of FMF analyses in cell-kinetic studies in which short-term fluctuations take place in the distribution of cells with different DNA content.

  14. 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

  15. 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)

  16. 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...

  17. 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

    showed moderate sensitisation to mitoxantrone on treatment with verapamil or cyclosporin A. Compared with EHR2, the multidrug resistance-associated protein mRNA was increased 13-fold in EHR2/MITOX. Western blot analysis showed an unchanged, weak expression of P-glycoprotein. Topoisomerase IIalpha......(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...

  18. Ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, Søren

    -stage congestive heart failure. The addition of complications like the hepatorenal syndrome and bacterial peritonitis, whether spontaneous or secondary, adds heavily to the bad prognosis. Since hepatic ascites are by far the most complex with respect to pathophysiology, complications, and treatment, emphasis...... is put on the description of this entity. Ascites of other aetiologies are mentioned along with hepatic ascites, in particular, if the pathophysiology differs from ascites of hepatic origin. Table of Contents: Abbreviations / Introduction / Pathophysiology of Ascites / Systemic Elements in the Ascites...

  19. An imaging study using laminin peptide 99mTc-YIGSR in mice bearing Ehrlich ascites tumour

    Institute of Scientific and Technical Information of China (English)

    HU Jia; ZHANG Yong-xue; LAN Xiao-li; QIN Guang-ming; ZHANG Jun; HU Zhi-hong

    2005-01-01

    Background The YIGSR is a pentapeptide, from the laminin-1 of the β1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of 99mTc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour.Methods Using S-Acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with 99mTc. 99mTc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged. Results Through reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-Acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. 99mTc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P<0.001). Conclusions Using S-Acetly-NH3-MAG3, we radiolabelled YIGSR with 99mTc. 99mTc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest 99mTc-YIGSR is a promising tumour radiotracer.

  20. Targeting tumour Cell Plasticity

    Institute of Scientific and Technical Information of China (English)

    Elizabeth D. WILLIAMS

    2009-01-01

    @@ Her research is focused on understanding the mechanisms of tumour progression and metastasis, particularly in uro-logical carcinomas (bladder and prostate). Tumour cell plasticity, including epithelial-mesenchymal transition, is a cen-tral theme in Dr Williams' work.

  1. 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

  2. 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...

  3. Hospicells (ascites-derived stromal cells) promote tumorigenicity and angiogenesis.

    Science.gov (United States)

    Pasquet, Marlene; Golzio, Muriel; Mery, Eliane; Rafii, Arash; Benabbou, Nadia; Mirshahi, Pezhman; Hennebelle, Isabelle; Bourin, Philippe; Allal, Ben; Teissie, Justin; Mirshahi, Massoud; Couderc, Bettina

    2010-05-01

    The microenvironment is known to play a dominant role in cancer progression. Cells closely associated with tumoral cells, named hospicells, have been recently isolated from the ascites of ovarian cancer patients. Whilst these cells present no specific markers from known cell lineages, they do share some homology with bone marrow-derived or adipose tissue-derived human mesenchymal stem cells (CD9, CD10, CD29, CD146, CD166, HLA-1). We studied the role of hospicells in ovarian carcinoma progression. In vitro, these cells had no effect on the growth of human ovarian carcinoma cell lines OVCAR-3, SKOV-1 and IGROV-1. In vivo, their co-injection with adenocarcinoma cells enhanced tumor growth whatever the tumor model used (subcutaneous and intraperitoneally established xenografts in athymic mice). In addition, their injection increased the development of ascites in tumor-bearing mice. Fluorescent macroscopy revealed an association between hospicells and ovarian adenocarcinoma cells within the tumor mass. Tumors obtained by coinjection of hospicells and human ovarian adenocarcinoma cells presented an increased microvascularization indicating that the hospicells could promote tumorigenicity of ovarian tumor cells in vivovia their action on angiogenesis. This effect on angiogenesis could be attributed to the increased HIF1alpha and VEGF expression associated with the presence of the hospicells. Collectively, these data indicate a role for these ascite-derived stromal cells in promoting tumor growth by increasing angiogenesis.

  4. 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

  5. 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.

  6. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B

    1997-01-01

    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic t

  7. 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.

  8. 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

  9. Artemisinin-derived sesquiterpene lactones as potential antitumour compounds : Cytotoxic action against bone marrow and tumour cells

    NARCIS (Netherlands)

    Beekman, AC; Wierenga, PK; Woerdenbag, HJ; Van Uden, W; Pras, N; Konings, AWT; El-Feraly, FS; Galal, AM; Wikstrom, HV

    1998-01-01

    We determined the in vitro cytotoxic activity of the sesquiterpene lactone endoperoxide artemisinin (1) and some chemically prepared derivatives, which have been found to display cytotoxicity to cloned murine Ehrlich ascites tumour (EAT) cells and human HeLa cells and against murine bone marrow usin

  10. 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)

  11. Desmoplastic small round cell tumour

    Energy Technology Data Exchange (ETDEWEB)

    Tan, T.H.L. [North District Hospital, Fanling, Kowloon (Hong Kong). Radiology Department; Ong, K.L. [Prince of Wales Hospital, Shatin, Kowloon (Hong Kong). Accident and Emergency Department; Au, Y.M.C. [Princess Margarete Hospital, Kowloon, (Hong Kong). Department of Radiology

    1998-11-01

    The present report describes a rare case of primary desmoplastic small cell tumour of the recto-sigmoid colon with hepatic metastases and lymphadenopathy. There are no pathognomonic radiological features and often their features overlap with other diseases including lymphoma. Histology is necessary to confirm this diagnosis. Unfortunately despite aggressive therapy, the prognosis for this disease is poor. Copyright (1998) Blackwell Science Pty Ltd 8 refs., 1 fig.

  12. Coordinated regulation of myeloid cells by tumours.

    Science.gov (United States)

    Gabrilovich, Dmitry I; Ostrand-Rosenberg, Suzanne; Bronte, Vincenzo

    2012-03-22

    Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.

  13. Myeloid cells in tumour-immune interactions.

    Science.gov (United States)

    Kareva, Irina; Berezovskaya, Faina; Castillo-Chavez, Carlos

    2010-07-01

    Despite highly developed specific immune responses, tumour cells often manage to escape recognition by the immune system, continuing to grow uncontrollably. Experimental work suggests that mature myeloid cells may be central to the activation of the specific immune response. Recognition and subsequent control of tumour growth by the cells of the specific immune response depend on the balance between immature (ImC) and mature (MmC) myeloid cells in the body. However, tumour cells produce cytokines that inhibit ImC maturation, altering the balance between ImC and MmC. Hence, the focus of this manuscript is on the study of the potential role of this inhibiting mechanism on tumour growth dynamics. A conceptual predator-prey type model that incorporates the dynamics and interactions of tumour cells, CD8(+) T cells, ImC and MmC is proposed in order to address the role of this mechanism. The prey (tumour) has a defence mechanism (blocking the maturation of ImC) that prevents the predator (immune system) from recognizing it. The model, a four-dimensional nonlinear system of ordinary differential equations, is reduced to a two-dimensional system using time-scale arguments that are tied to the maturation rate of ImC. Analysis shows that the model is capable of supporting biologically reasonable patterns of behaviour depending on the initial conditions. A range of parameters, where healing without external influences can occur, is identified both qualitatively and quantitatively.

  14. 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...

  15. Stochastic Gompertz model of tumour cell growth.

    Science.gov (United States)

    Lo, C F

    2007-09-21

    In this communication, based upon the deterministic Gompertz law of cell growth, a stochastic model in tumour growth is proposed. This model takes account of both cell fission and mortality too. The corresponding density function of the size of the tumour cells obeys a functional Fokker--Planck equation which can be solved analytically. It is found that the density function exhibits an interesting "multi-peak" structure generated by cell fission as time evolves. Within this framework the action of therapy is also examined by simply incorporating a therapy term into the deterministic cell growth term.

  16. 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.

  17. CYTOTOXICITY OF ARTEMISININ-RELATED ENDOPEROXIDES TO EHRLICH ASCITES TUMOR-CELLS

    NARCIS (Netherlands)

    WOERDENBAG, HJ; MOSKAL, TA; PRAS, N; MALINGRE, TM; ELFERALY, FS; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 muM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3],

  18. Effect of TNF gene-transfected LAK cells on the ascitic liver carcinoma-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Guo Liang Lou; Xue Tao Cao; Bi He Min; Wei Ping Zhang; Pei Lin Meng

    2000-01-01

    AIM To investigate the therapeutic effect of TNF gene transfected LAK cells on ascitic liver carcinoma-bearing mice.METHODS TNF gene was transfected into murine LAK cells by retrovirus. Low dose TNF gene-transfectcdLAK cells and IL-2 were i.p. injected into murine model. Cytotoxicity of gene transfected LAK cells wasstudied in vitro growth and the survival time of murine model was observed.RESULTS TNF gene-transfected LAK cells secreted higher level of TNF than that of normal LAK cells orcontrol gene-transfected LAK ceils. The in vitro growth ability and cytotoxicity of TNF gene-transfectedLAK cells were markedly inhibited by anti-TNF monoclonal antibodies. Significant therapeutic effect onascitic liver carcinoma-bearing mice was achieved.CONCLUSION TNF gene-transfected LAK cells have therapeutic effect on ascitic liver carcinoma-bearingmice.

  19. Tumour markers in germ cell tumours and thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mann, K.

    1988-02-01

    In patients with germ cell tumours of gonadal and extragonadal origin both markers, human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) are madatory for diagnosis and control of treatment. In seminoma, we found preoperatively elevated levels of hCG(+hCG-..beta..) in 42/349 patients (12%) up to 1200 mlU/ml using a polyclonal radioimmunoassay (1. IRP hCG standard 75/537). Lactatedehydrogenase can be useful in marker negative patients. Serum levels reflect tumour burden even if not highly specific. Presently, placental alkaline phosphatase is under discussion for seminoma. However, commercial kits are not available. As a relatively high secretion of hCG/..beta../hCG was found in gestational trophoblastic diseases, this parameters may be useful for differential diagnosis in pregnancy. In the follow-up of patients with differentiated thyroid carcinoma the determination of thyroglobulin (Tg) in combination with ultrasound of the thyroid and X-ray of the chest is sufficient. For Tg-determination thyroid hormone replacement therapy must be discontinued only in rare single cases with borderline levels, which need radioiodtesting additionally. Calcitonin is the most important marker in medullary thyroid carcinoma. Pentagastrin stimulated calcitonin as screening test is necessary, if multiple endocrine adenomatosis or the familial forms are suspected. In single cases benefit came from new scintigraphic methods such as /sup 131/I-metaiodo-benzylguanidine or /sup 201/thallium-chloride.

  20. Ascites bacterial burden and immune cell profile are associated with poor clinical outcomes in the absence of overt infection.

    Directory of Open Access Journals (Sweden)

    Kevin J Fagan

    Full Text Available Bacterial infections, most commonly spontaneous bacterial peritonitis in patients with ascites, occur in one third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality. Bacteria are isolated from less than 40% of ascites infections by culture, necessitating empirical antibiotic treatment, but culture-independent studies suggest bacteria are commonly present, even in the absence of overt infection. Widespread detection of low levels of bacteria in ascites, in the absence of peritonitis, suggests immune impairment may contribute to higher susceptibility to infection in cirrhotic patients. However, little is known about the role of ascites leukocyte composition and function in this context. We determined ascites bacterial composition by quantitative PCR and 16S rRNA gene sequencing in 25 patients with culture-negative, non-neutrocytic ascites, and compared microbiological data with ascites and peripheral blood leukocyte composition and phenotype. Bacterial DNA was detected in ascitic fluid from 23 of 25 patients, with significant positive correlations between bacterial DNA levels and poor 6-month clinical outcomes (death, readmission. Ascites leukocyte composition was variable, but dominated by macrophages or T lymphocytes, with lower numbers of B lymphocytes and natural killer cells. Consistent with the hypothesis that impaired innate immunity contributes to susceptibility to infection, high bacterial DNA burden was associated with reduced major histocompatibility complex class II expression on ascites (but not peripheral blood monocytes/macrophages. These data indicate an association between the presence of ascites bacterial DNA and early death and readmission in patients with decompensated cirrhosis. They further suggest that impairment of innate immunity contributes to increased bacterial translocation, risk of peritonitis, or both.

  1. 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.

  2. 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.

  3. 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.

  4. Regional tumour glutamine supply affects chromatin and cell identity.

    Science.gov (United States)

    Højfeldt, Jonas W; Helin, Kristian

    2016-09-28

    Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-resistant state of the tumour cells.

  5. 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...

  6. 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...

  7. Granular cell tumour of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Christoph von Klot

    2012-04-01

    Full Text Available With only 16 cases reported in the literature, the mostly benign granular cell tumour of the urinary bladder is exceptionally rare. We present the case of a 68-year old patient with one of these lesions demonstrating our histological findings including several immunohistochemical stainings used to differentiate between other more common entities.

  8. 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.)

  9. 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

  10. [Possibility of achieving the Pasteur effect by ascites carcinoma cells in vivo].

    Science.gov (United States)

    Tagi-zade, S B; Shapot, V S

    1971-01-01

    Possibility of Pasteur effect in cancer cells in vivo was studied on mice with Ehrlich ascites carcinoma and rats with carcinoma of ovaries++. The experiments were run in two series. In the first series, all animals were saturated with oxygen through inhalation. In this series, part of the animals were given glucose subcutaneously. In the second series, all animals were given oxygen intraperitoneally and some of the animals with carcinoma of ovaries++ were given glucose subcutaneously. Values of inhibition of glycolytic activity in cancer cells under various experimental conditions were estimated through a calculated coefficient. Results of the experiment evidenced that inhalational saturation of animals with oxygen did not inhibit glycolysis of ascites cells in vivo while after intraperitoneal administration of oxygen, coefficient of inhibition of glycolytic activity in mice with Ehrlich ascites++ carcinoma after 45-65 min was 50-615, respectively. Experiments on rats showed that inhibition of glycolytic activity in rats can be revealed during simultaneous administration of oxygen intraperitoneally and of glucose subcutaneously. The authors reached the conclusion that under adequate supply of cancer cells with oxygen respiration can suppress glycolysis at the level of organism as well.

  11. 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.

  12. 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

  13. 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...

  14. Ovarian Steroid Cell Tumour: Correlation of Histopathology with Clinicopathologic Features

    Directory of Open Access Journals (Sweden)

    Ghazala Mehdi

    2011-01-01

    Full Text Available Ovarian steroid cell tumours (not otherwise specified are rare neoplasms of the ovary and are classified under lipid cell tumours. Their diagnosis can be considered as one of exclusion. Histopathologically, the tumour should carefully be evaluated for microscopic features of malignancy, but it is essential for the clinician and the pathologist to remember that in these tumours, pathologically benign histomorphology does not exclude the possibility of clinically malignant behaviour. Our case study focuses on the comparative findings in a postmenopausal female diagnosed with an ovarian steroid tumour (not otherwise specified. A careful correlation between clinical and surgical evaluation and microscopic analysis is necessary, as is a regular followup.

  15. 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.

  16. Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration

    Science.gov (United States)

    Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul

    2016-01-01

    We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour.

  17. 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

    In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal...... gene product P-glycoprotein (P-gp). Using 5 progressively DNR resistant Ehrlich cell sublines with different P-gp expression pattern no correlation between taurine uptake and P-gp expression was found. Taurine uptake in MDR1 transfected NIH/3T3 mouse fibroblasts was in contrast to the findings...... reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1...

  18. 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.

  19. 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

    with the pH-sensitive dye BCECF, substitution of Na+ was observed to upregulate the activity of the Na+/H+ exchanger NHE1 as well as of Na+-independent acid extrusion mechanisms, facilitating intracellular pH (pH(i)) recovery after acid loading and increasing pH(i). Results using the potential sensitive dye...... 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 fine...

  20. 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

  1. 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......Cytochalasins have been used extensively to probe the role of F-actin in different aspects of cellular function. Most of the data obtained are interpreted on the basis of the well-established depolymerizing effects of cytochalasins on F-actin preparations in vitro. However, some evidence indicates......) cells. After a 3-min exposure to 0.5 microM cytochalasin D, B, or E, F-actin content was equally reduced in all cases and this correlated with a reduction in the amount of cortical F-actin associated with the EAT cell membrane. However, only with CE was cell morphology markedly altered...

  2. THE STUDY OF ELEMENE OF INDUCTION APOPTOSIS ON ASCITES HEPATOMA CELL LINE Hca-F25/CL-16A3

    Institute of Scientific and Technical Information of China (English)

    Zuo Yunfei; Zhang Yaozheng; Zhang Hong

    1998-01-01

    Objective: To investigate the effect of inducing apoptosis of Elemene on ascites hepatoma cell line HcaF25/cL-16A3. By using immunhistochemistry and DNA electrophoresis, the mechanism of Elemene antitumor was studied. Results: The results showed that the Elemene can inhibit expression of bcl-2 in ascites hepatoma cell line Hca-F25/CL-16A3, and the Eiemene also can make DNA fragmentation in this cell line in vitro and in vivo.Conclusion: The data suggest that Elemene can inhibit the growth of tumor by inducing apoptosis.

  3. Desmoplastic nested spindle cell tumours and nested stromal epithelial tumours of the liver.

    Science.gov (United States)

    Misra, Sunayana; Bihari, Chhagan

    2016-04-01

    Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal-epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis.

  4. 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.

  5. 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

  6. 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.)

  7. 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.

  8. 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...

  9. Sirolimus Therapy for Patients With Lymphangioleiomyomatosis Leads to Loss of Chylous Ascites and Circulating LAM Cells.

    Science.gov (United States)

    Harari, Sergio; Elia, Davide; Torre, Olga; Bulgheroni, Elisabetta; Provasi, Elena; Moss, Joel

    2016-08-01

    A young woman received a diagnosis of abdominal, sporadic lymphangioleiomyomatosis (LAM) and multiple abdominal lymphangioleiomyomas and was referred for recurrent chylous ascites responding only to a fat-free diet. On admission, pulmonary function test (PFT) results showed a moderate reduction in the transfer factor for carbon monoxide with normal exercise performance. The serum vascular endothelial growth factor D (VEGF-D) level was 2,209 pg/mL. DNA sequences, amplified at loci kg8, D16S3395, D16S3024, D16S521, and D16S291 on chromosome 16p13.3, showed a loss of heterozygosity (LOH) only for kg8. Fat-free total parenteral nutrition in association with sirolimus (2 mg po daily) was initiated. Serum sirolimus levels were maintained at concentrations between 5 and 15 ng/mL. After 1 month, reintroduction of a low-fat oral feeding was achieved without recurrence of ascites. PFT results were stable. Interestingly, clinical improvement was associated with a reduction in the VEGF-D serum level (1,558 pg/mL). LOH at the kg8 biomarker in blood LAM cells was no longer detected.

  10. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O;

    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...... 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...... 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...

  11. 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...

  12. 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

  13. 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.

  14. 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....... Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused...... of the 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....

  15. Fractionation and characterization of euchromatin isolated from mouse ascites sarcoma cells

    Directory of Open Access Journals (Sweden)

    Inaba,Kozo

    1978-12-01

    Full Text Available Euchromatin specimen prepared by the usual method formed large clumps and had various shapes under electron microscopy. A method of separation of the euchromatin specimen into chromatin fractions having relatively homogeneous form was examined and partial characterization of these fractions was carried out. The heavy euchromatin fraction was a large network of thin fibrils (about 100 A in diameter and various thick fibers. The intermediate euchromatin fraction consisted of relatively homogeneous networks of thick knobby fibers (about 250 A in diameter. The light euchromatin fraction had metworks of thick fibers. These chromatin fractions were quantitatively prepared from sonicated nuclei of mouse ascites sarcoma cells. Twenty-one or twenty-two bands of non-histone proteins besides histones were detected in these chromatin fractions by SDS-polyacrylamide gel electrophoresis. There were significant differences in the electrophoretic patterns of non-histone proteins among these chromatin fractions.

  16. Anti-tumour activity of Ruta graveolens extract.

    Science.gov (United States)

    Preethi, K C; Kuttan, Girija; Kuttan, Ramadasan

    2006-01-01

    An extract of Ruta graveolens was found to be cytotoxic to Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and L929 cells in culture (IC100=16 mg/ml) and also to increase the lifespan of tumour bearing animals. The extract further decreased solid tumours developing from DLA and EAC cells when given simultaneously with elongation of the lifespan of tumour-bearing animals. A homeopathic preparation of Ruta graveolens (200 c) was equally effective. Neither was effective for reducing already developed tumours. The Ruta graveolens extract was found to scavenge hydroxyl radicals and inhibit lipid peroxidation at low concentrations. However, at higher concentrations the extract acted as a prooxidant as inhibition of lipid peroxidation and scavenging of hydroxyl radical was minimal. These data indicates that the prooxidant activity of Ruta graveolens may be responsible for the cytocidal action of the extract and its ability to produce tumour reduction.

  17. Anti-tumour activity of Ruta graveolens extract.

    Science.gov (United States)

    Preethi, K C; Kuttan, Girija; Kuttan, Ramadasan

    2006-01-01

    An extract of Ruta graveolens was found to be cytotoxic to Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and L929 cells in culture (IC100=16 mg/ml) and also to increase the lifespan of tumour bearing animals. The extract further decreased solid tumours developing from DLA and EAC cells when given simultaneously with elongation of the lifespan of tumour-bearing animals. A homeopathic preparation of Ruta graveolens (200 c) was equally effective. Neither was effective for reducing already developed tumours. The Ruta graveolens extract was found to scavenge hydroxyl radicals and inhibit lipid peroxidation at low concentrations. However, at higher concentrations the extract acted as a prooxidant as inhibition of lipid peroxidation and scavenging of hydroxyl radical was minimal. These data indicates that the prooxidant activity of Ruta graveolens may be responsible for the cytocidal action of the extract and its ability to produce tumour reduction. PMID:17059340

  18. 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

  19. Immunohistochemical detection of tumour cell proliferation and intratumoural microvessel density in canine malignant mammary tumours

    Directory of Open Access Journals (Sweden)

    Sennazli Gulbin

    2015-06-01

    Full Text Available The objective of this study was to investigate the correlation between different histological types and grades of canine malignant mammary tumours, tumour cell proliferation and their angiogenic activity using immunohistochemical markers. Mammary tissue samples from 47 bitches with mammary cancer were evaluated. The expression of cellular proliferation marker Ki-67 and endothelial marker Von Willebrand’s factor (vWF were immunohistochemically demonstrated. The tumours with the highest Ki-67 and vWF expressions were found to share similar histomorphological features. Simple solid carcinoma had the highest levels of Ki-67, vWF, and higher histological grade while complex carcinomas, osteosarcomas, and carcinosarcomas had the lowest ones. The differences between the expressions of Ki-67 and vWF in different tumour types were considered to be of great importance in determination of biological behaviour and prognosis of these tumours. This study is one of the few studies that evaluate these differences among the subtypes of malignant canine mammary tumours

  20. Isolation and partial identification of eight endogenous G1 inhibitors of JB-1 ascites tumor cell proliferation.

    Science.gov (United States)

    Barfod, N M

    1982-06-01

    Eight endogenous G1 inhibitors of the proliferation of JB-1 ascites tumor cells have been isolated and characterized. The activity of the inhibitors has been analyzed on synchronized JB-1 (murine plasmacytoma) and L1A2 (murine sarcoma) cells in vitro using flow cytometry. The purified inhibitors have been tested for in vivo activity on partially synchronized JB-1 and L1A2 ascites tumors in situ. Four of the inhibitors exhibited a high degree of cell specificity (chalone-like inhibitors) and were chemically related, whereas the other four showed no cell specificity. In most extractions, the amount of cell-specific activity is more than 50% of the total G1-inhibitory activity. Most of the inhibitors are low-molecular-weight peptides and glycopeptides.

  1. Antitumour activity of Prosopis cineraria (L.) Druce against Ehrlich ascites carcinoma-induced mice.

    Science.gov (United States)

    Robertson, Stellaa; Narayanan, N; Raj Kapoor, B

    2011-04-01

    The antitumour activity of the hydroalcoholic extract of the leaf (PCL) and stem bark (PCB) of Prosopis cineraria (L.) in Swiss albino mice was evaluated against an Ehrlich ascites carcinoma (EAC) tumour model. The activity was assessed using survival time, peritoneal cells, haematological studies, lipid peroxidation, antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, solid tumour mass and in vitro cytotoxicity. PCL and PCB were found to be potent and possessed significant cytotoxicity towards EAC tumour cells.

  2. Migratory behaviour of tumour cells: a scanning electron microscopy study

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2015-06-01

    Full Text Available BACKGROUND: Tumour cells utilize different migration strategies to invade surrounding tissues and elude anticancer treatments. It is therefore important to understand the mechanisms underlying migration process, in order to aid the development of therapies aimed at blocking the dissemination of cancer cells. AIMS: In this study tumour cell lines of different histological origin were analysed by combining 2D and 3D in vitro assays, biochemical tests and high resolution imaging by scanning electron microscopy (SEM in order to look insight strategies adopted by tumour cells to invade extracellular matrix. RESULTS: Quantitative (computer-assisted colour camera equipped-light microscopy and qualitative analysis (SEM indicated that the most aggressive tumour cells adopt an "individual" behaviour. The analysis of intracellular signalling demonstrated that the highest invasive potential was associated with the activation of AKT, ERK, FAK and ERM proteins. The "individual" behaviour was positively related to the expression of VLA-2 and inversely related with the E-cadherin expression. CONCLUSIONS: The combination of 2D and 3D in vitro assays, biochemical tests and ultrastructural investigations proved to be a suitable test for the investigation of tumour cell migration and invasion. The high resolution imaging by SEM highlighted the interrelationships between cells in different migratory behaviours of tumour cells.

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. Biosynthesis of ascites sialoglycoprotein-1, the major O-linked glycoprotein of 13762 rat mammary adenocarcinoma ascites cells

    Energy Technology Data Exchange (ETDEWEB)

    Spielman, J.

    1987-01-01

    The present studies were undertaken to determine the timing of the major events in biosynthesis, and to characterize the contributions of chain initiation and elongation in maturation of the glycoprotein. Initiation of the earliest O-linked chains was detected by analysis of conversion of {sup 3}H-thr to {sup 3}H 2-aminobutyrate following mild alkaline borohydride elimination of O-linked sugars from peanut lectin-precipitated ASGP-1. Initiation was detected within 5 min of translation; amino sugar analysis of GlcNH{sub 2}-labeled, trypsinized cells also showed that GalNAc was added as late as 5 min prior to arrival of ASGP-1 at the cell surface. Thus initiation occurs throughout biosynthesis. Maturation of the glycoprotein from a lightly-glycosylated immature form to the heavily-glycosylated mature from involved both continued initiation of new chains and chain elongation, and occurred with a half-time of about 30 min. Analysis of labeled ASGP-1 released from the cell surface by trypsinization showed that although some newly-synthesized ASGP-1 reached the cell surface within 70-80 min of protein synthesis, the half-time for appearance of mature glycoprotein was in excess of 4 hr, indicating that most molecules reside in an intracellular compartment(s) for a considerable time.

  8. Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle;

    2007-01-01

    Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle......-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude....

  9. 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

    growth in ascitic fluid in which the cells had no intimate contact. Ascitic fluid from E1.95-bearing animals or radiation-killed E1.95 cells had no effect on the growth of E1.15, and no remote effect was seen when the two cell lines were growing in opposite flanks. This indicates that only viable E1...... 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....

  10. 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...

  11. 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

  12. 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....

  13. 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...

  14. 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...

  15. 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)

  16. 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...

  17. 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-state...

  18. A short-term in vitro test for tumour sensitivity to adriamycin based on flow cytometric DNA analysis

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1983-01-01

    on an adriamycin-sensitive Ehrlich ascites tumour and two adriamycin-resistant tumours. Adriamycin caused a dose-related accumulation of tumour cells in the G2 + M phase in the sensitive tumour. Drug concentrations greater than or equal to 100-fold higher were required to induce similar changes in the resistant...... tumours. The dose level causing maximum accumulation in the G2 + M phase is suggested as a parameter for quantifying the sensitivity. The results indicate that the method can be extended to sensitivity testing of human tumours....

  19. Ca2+ transport by mitochondria from L1210 mouse ascites tumor cells.

    Science.gov (United States)

    Reynafarje, B; Lehninger, A L

    1973-06-01

    Mitochondria isolated from the ascites form of L1210 mouse leukemia cells readily accumulate Ca(2+) from the suspending medium and eject H(+) during oxidation of succinate in the presence of phosphate and Mg(2+), with normal stoichiometry between Ca(2+) uptake and electron transport. Ca(2+) loads up to 1600 ng-atoms per mg of protein are attained. As is the case in mitochondria from normal tissues, Ca(2+) uptake takes precedence over oxidative phosphorylation. However, Ca(2+) transport by the L-1210 mitochondria is unusual in other respects, which may possibly have general significance in tumor cells. The apparent affinity of the L1210 mitochondria for Ca(2+) in stimulation of oxygen uptake is about 3-fold greater than in normal liver mitochondria; moreover, the maximal rate of Ca(2+) transport is also considerably higher. Furthermore, when Ca(2+) pulses are added to L1210 mitochondria in the absence of phosphate or other permeant anions, much larger amounts of Ca(2+) are bound and H(+) ejected per atom of oxygen consumed than in the presence of phosphate; up to 7 Ca(2+) ions are bound per pair of electrons passing each energy-conserving site of the electron-transport chain. Such "superstoichiometry" of Ca(2+) uptake can be accounted for by two distinct types of respiration-dependent interaction of Ca(2+) with the L1210 mitochondria. One is the stimulation of oxygen consumption, which is achieved by relatively low concentrations of Ca(2+) (K(m) congruent with 8 muM) and is accompanied by binding of Ca(2+) up to 40 ng-atoms per mg of protein. The second process, also dependent on electron transport, is the binding of further Ca(2+) from the medium in exchange with previously stored membrane-bound protons, in which the affinity for Ca(2+) is much lower (K(m) congruent with 120 muM).

  20. 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.

  1. 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

  2. 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.)

  3. 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.

  4. 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.

  5. 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.

  6. 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;

    2011-01-01

    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...... 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...... 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...

  7. 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.

  8. 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

  9. NANOG priming before full reprogramming may generate germ cell tumours

    Directory of Open Access Journals (Sweden)

    I Grad

    2011-11-01

    Full Text Available Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

  10. Ayurvedic management of cirrhotic ascites.

    Science.gov (United States)

    Aswathy, G; Dharmarajan, Prasanth; Sharma, Ananth Ram; Sasikumar, V K; Vasudevan Nampoothiri, M R

    2016-01-01

    Cirrhosis is the final stage of most of the chronic liver diseases and is most invariably complicated by portal hypertension resulting in ascites. A case of chronic liver disease with portal hypertension (cryptogenic cirrhosis), managed at Amrita School of Ayurveda is discussed in this paper. The clinical picture was that of an uncomplicated cirrhotic ascites. Snehapāna (therapeutic oral administration of lipids) followed by virecana (purgation) was done after an initial course of nityavirecana (daily purgation). Later Vardhamāna pippalī rasāyana [administration of single drug - pippalī (piper longum) in a structured dose pattern] was administered with an intention of rejuvenating liver cells. Ascites and lower limb oedema were completely resolved after the therapy. No recurrence of ascites has been reported after a follow up period of one year. PMID:27621523

  11. 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...

  12. 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 ...

  13. Glioblastoma stem-like cells give rise to tumour endothelium

    NARCIS (Netherlands)

    R. Wang; K. Chadalavada; J. Wilshire; U. Kowalik; K.E. Hovinga; A. Geber; B. Fligelman; M. Leversha; C. Brennan; V. Tabar

    2010-01-01

    Glioblastoma (GBM) is among the most aggressive of human cancers(1). A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia(2). Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poo

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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)

  20. Characterization of native 40 S particles from Krebs II mouse ascites tumor cells: resolution, nomenclature and molecular weights of the nonribosomal proteins

    DEFF Research Database (Denmark)

    Reichert, G; Issinger, O G

    1981-01-01

    Native 40 S particles from Krebs II mouse ascites tumor cells were isolated on a large scale. A nonribosomal protein moiety of about 30 proteins could be removed from the ribosomal particles by treatment with 250 mM KCl. These proteins were analysed by two-dimensional polyacrylamide gel electroph......Native 40 S particles from Krebs II mouse ascites tumor cells were isolated on a large scale. A nonribosomal protein moiety of about 30 proteins could be removed from the ribosomal particles by treatment with 250 mM KCl. These proteins were analysed by two-dimensional polyacrylamide gel...

  1. Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    Neelam Siddiqui; Saeed Al-Amoudi; Aamer Aleem; Maha Arafah; Layla Al-Gwaiz

    2008-01-01

    Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.

  2. 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

  3. 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

  4. 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...

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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...

  10. 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

  11. 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

  12. 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

  13. 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...

  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. Management of cirrhotic ascites.

    Science.gov (United States)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-05-01

    The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains the ultimate treatment and early referral of the patient to a highly specialized hepatology unit should always be considered. PMID:25954497

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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)...

  2. Cytological grading of canine cutaneous mast cell tumours.

    Science.gov (United States)

    Scarpa, Filippo; Sabattini, Silvia; Bettini, Giuliano

    2016-09-01

    A cytological grading for mast cell tumours (MCTs) would be highly desirable, allowing to select the most appropriate therapeutic intervention prior to surgery. This study evaluates the applicability on fine-needle aspirations (FNAs) of the novel Kiupel grading system, based on number of mitoses, multinucleated cells, bizarre nuclei and presence of karyomegaly. Fifty consecutive cases with pre-operative cytological diagnosis were included. In cytological specimens, approximately 1000 cells were evaluated, and the histological grade was assessed on the corresponding resected specimens. On cytology, the above parameters were significantly different between histologically low-grade and high-grade tumours (P < 0.001). The cytograding correctly predicted the histological grade in 47 cases (accuracy, 94%; sensitivity, 84.6%; specificity, 97.3%). Two high-grade MCTs (4%) were not detected on cytology. The cytograding can provide helpful insights to assist clinical decisions in most cases. However, the risk of underestimation in a minority of patients represents a limit to the overall utility of the technique.

  3. 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)

  4. Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

    Directory of Open Access Journals (Sweden)

    Marina Rios Araújo

    2012-08-01

    Full Text Available This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes are required for definitive diagnosis of round cell tumours in dogs.

  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. CSF Ascites: Review of articles and a case presentation

    Directory of Open Access Journals (Sweden)

    R Pourkhalili

    2005-09-01

    Full Text Available Cerebrospinal fluid (CSF ascites is a rare complication after ventriculopritoneal (VP shunts. Most patients have gradual abdominal protrusion without any neurological sign or symptom of shunt malfunction. We presented a girl with posterior third ventricle glioblastoma and acute hydrocephalus who developed increasingly abdominal protrusion one month after VP shunt operation. Ascites fluid examination showed characteristic findings similar to CSF with no evidence of infection or malignant cells. Ventriculo-atrial shunt revision cured patient's ascites. Review articles of patients with CSF ascites after VP shunt were presented in details. Key words: Cerebrospinal fluid, Ascites, Ventriculopritoneal Shunt

  7. 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

  8. An in vitro model for purging of tumour cells from ovarian tissue

    NARCIS (Netherlands)

    Schroder, CP; Timmer-Bosscha, H; Wijchman, JG; de Leij, LFMH; Hollema, H; Heineman, MJ; de Vries, EGE

    2004-01-01

    BACKGROUND: Cryopreservation and autografting of ovarian tissue may preserve fertility after cancer treatment, but could be hampered by tumour cell contamination. Epithelial tumour cell lysis can be obtained with cytotoxic T cell retargeting through the bispecific antibody BIS-1, with combined affin

  9. Rapid and non-enzymatic in vitro retrieval of tumour cells from surgical specimens.

    Directory of Open Access Journals (Sweden)

    Brigitte Mack

    Full Text Available The study of tumourigenesis commonly involves the use of established cell lines or single cell suspensions of primary tumours. Standard methods for the generation of short-term tumour cell cultures include the disintegration of tissue based on enzymatic and mechanical stress. Here, we describe a simple and rapid method for the preparation of single cells from primary carcinomas, which is independent of enzymatic treatment and feeder cells. Tumour biopsies are processed to 1 mm(3 cubes termed explants, which are cultured 1-3 days on agarose-coated well plates in specified medium. Through incisions generated in the explants, single cells are retrieved and collected from the culture supernatant and can be used for further analysis including in vitro and in vivo studies. Collected cells retain tumour-forming capacity in xenotransplantation assays, mimic the phenotype of the primary tumour, and facilitate the generation of cell lines.

  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. 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...

  12. 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

  13. 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.

  14. Management of cirrhotic ascites

    DEFF Research Database (Denmark)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic...... ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains...

  15. 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

  16. 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.

  17. 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

  18. DNA damage induction and tumour cell radiosensitivity : PFGE and halo measurements

    NARCIS (Netherlands)

    Woudstra, EC; Driessen, C; Konings, AWT; Kampinga, HH

    1998-01-01

    Purpose: To test whether induction of DNA damage is correlated with tumour-cell radiosensitivity. Materials and methods: Initial DNA damage caused by X-irradiation was measured in ten human tumour cell lines, which largely differed in radiosensitivity, using either the pulsed-field gel electrophores

  19. Sox2 expression in breast tumours and activation in breast cancer stem cells.

    Science.gov (United States)

    Leis, O; Eguiara, A; Lopez-Arribillaga, E; Alberdi, M J; Hernandez-Garcia, S; Elorriaga, K; Pandiella, A; Rezola, R; Martin, A G

    2012-03-15

    The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires self-renewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

  20. 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

  1. 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

  2. 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.

  3. Diagnostic technologies for circulating tumour cells and exosomes.

    Science.gov (United States)

    Shao, Huilin; Chung, Jaehoon; Issadore, David

    2015-11-24

    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 technologies are underway to overcome these specific challenges to fully harness the clinical potential of these circulating biomarkers. Herein, we will overview the characteristics of CTCs and exosomes as valuable circulating biomarkers and their associated technical challenges for clinical adaptation. Specifically, we will describe emerging technologies that have been developed to address these technical obstacles and the unique clinical opportunities enabled by technological innovations.

  4. 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

    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...... 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......: A total of 9569 cases and 32 028 controls were included. No overall associations were found for either maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95% CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific estimates and stratification by birth cohorts...

  5. 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.

  6. 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.

  7. 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...

  8. Influence of SLYWG on malignant tumor ascites

    Institute of Scientific and Technical Information of China (English)

    YANG Tian; XU Feng; WU Tian-yu

    2008-01-01

    Objective To search the effect of Chinese traditional medicine "Shang Lu Yu Wang Gao" (SLY-WG) on the ascites induced by tumor, and its mechanism. Methods The tumor aseites model and diuretic experiments were introduced to evaluate the effect of SLYWG. Physical eharacteristics,the tumor cell counting, volume of the ascites, protein content in ascites, the characters of ascites, the life duration of S180 tumor bearing animals as the indexes of evaluation, the diurtie experiments were performed on rats nad rabbits, the osmotic pressure, K+, Na+, Cl-, Ca2+ and pH in urine were determined. Results The inhibitions to ascites of SLYWG were displayed in three dosage (30 g·kg-1, 15 g·kg-1 and 7.5 g·kg-1). Ascites caused by tumor was significantly inhibited by the local administration of SLYWG. The increase of mice ascites was slow down, the content of ALB and the TP in ascites were decreased, the surviving time of mice was extended. SLYWG had remarkable diuresis effect on the rats and rabbits, it could reduce the osmotic pressure of urine, decrease the exclude of K+ but had no effect on the Na+, Cl-, Ca2+ and pH in urine. Conclusions Tumor ascites was significantly inhibited by the ventral administration of SLYWG. SLYWG had diuretic effect in rats and rabbits, it reduced the osmotic pressure of urine, decrease the exclude of K+ but had no effect on Na+, Cl-, Ca2+ and pH of urine.

  9. 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.

  10. 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.

  11. 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

  12. 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).

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

    Energy Technology Data Exchange (ETDEWEB)

    Klymenko, Olena

    2014-02-26

    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).

  14. 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.

  15. 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.

  16. 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

    with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting...

  17. Optical diagnostics of tumour cells at different stages of pathology development

    Energy Technology Data Exchange (ETDEWEB)

    Shcheglova, L S; Maryakhina, V S [Orenburg State University, Orenburg (Russian Federation); Abramova, L L [Orenburg State Agrarian University, Orenburg (Russian Federation)

    2013-11-30

    The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 – 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions. (optical methods in biology and medicine)

  18. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-06-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease manage‐ ment and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluores‐ cence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasi‐ bility of the assay was established by testing blood samples from a small cohort of patients, where we detected popu‐ lations of both CD138pos and CD138neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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 ...

  4. PROGNOSIS OF EPITHELIAL OVARIAN CANCER RELATED TO ITS ASCITES

    Institute of Scientific and Technical Information of China (English)

    宋水勤; 张国楠; 吴艳丽; 周红; 赵素兰; 谢方; 陈毅男

    2001-01-01

    Objective: To investigate the relationship between the prognosis of Epithelial Ovarian Cancer (EOC) and its ascites. Methods: Retrospectively analysis is performed for the clinical, pathological and followed up data of 101 in-patients suffering from epithelial ovarian cancer and operated with tumor debulking surgery in our hospital from January 1986 to December 1993. The patients was divided into two groups based upon the first laparotomy finding with ascites(62) or without(39). Age average, cell type, advanced proportion and survival rate of the patients are evaluated by a c2 test. Results: For age average and cell type, no statistical difference was noted. However, there were more advanced cases in ascites group than in the other (P<0.01). The 3-, 4- and 5-year survival in the no-ascites group were 87.02%, 73.42%, 57.10% respectively compared with 65.02%, 38.66%, 28.12% in the ascites group. The 5-year survival rate of stage I, II,III, IV patients in no-ascites group are 77%, 70%, 41.1%, 0 respectively, compared with that of 60%, 56.8%, 15.46%, 0 respectively in the ascites group. The results shows that 3-, 4-, and 5-year survival in no-ascites group were significantly higher than those in ascites group(P<0.01). Conclusion: Presence of ascites is a factor of poor prognosis for EOC.

  5. 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.)

  6. 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

  7. 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...... CIS; therefore, contralateral biopsy is recommended at the time of orchidectomy. Further research is warranted to identify causal factors explaining the increasing incidence of TGCT and to obtain a method of non-invasive CIS detection....

  8. 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...

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Diagnosis and therapy of ascites in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Erwin Biecker

    2011-01-01

    Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.

  14. 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

    Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline....... Because they are rare, histology of paediatric GCTs is poorly documented, and it remains unclear to what extent they differ from adult GCTs. We have analysed 35 paediatric germ cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients aged 0-15 years, to gain further knowledge......, 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...

  15. Tumour length is an independent prognostic factor of esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    WU Ning; PANG Lie-wen; CHEN Zhi-ming; MA Qin-yun; CHEN Gang

    2012-01-01

    Background The latest version of the American Joint Committee on Cancer (AJCC) TNM staging system has not comprehensively evaluated the impact of tumour length on survival in patients with esophageal squamous cell carcinoma.Our study explored the relationship between tumour length and clinicopathological characteristics as well as long-term survival.Methods All 202 cases of esophageal resections done from January 1,2004 to December 31,2008 in Huashan Hospital,Fudan University were reviewed and followed up.Results Patients with tumour length >3 cm were related to more advanced tumour stage (X2=55.9,P <0.001),more metastatic lymph nodes (X2=14.6,P <0.001),increased metastatic lymph node ratio (x2=16.1,P <0.001) and worse overall TNM stage (X2=48.1,P <0.001).Univariate and multivariate analyses indicated that tumour length was a significant prognostic risk factor (95% CI 0.235-0.947,P=0.035).Subgroup analyses disclosed that tumour length was a valuable prognostic predictor in patients with lower T stage,absence of metastatic lymph nodes and lower TNM stage.Conclusions Esophageal tumour length is a predictive factor for long-term survival especially for lower tumour stage,absence of metastatic lymph nodes and lower TNM stage patients.Tumour length should be incorporated in the staging system as an important grouping factor for better prognostic evaluation.

  16. 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

  17. 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...

  18. 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.

  19. 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

  20. 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

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

    Science.gov (United States)

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

    2016-01-01

    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

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. 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...

  8. 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.)

  9. Germ cell tumours of the ovary. A clinical study of 15 cases.

    Science.gov (United States)

    Friedman, M; Browde, S; Nissenbaum, M M

    1984-04-14

    Our experience with germ cell tumours of the ovary is reviewed. Over the last 10 years, 15 cases, representing 6,4% of all our referred patients with malignant ovarian tumours, have been analysed. The type of tumour, histological appearances, stage, treatment and results of treatment are presented. The tumour most commonly seen was the dysgerminoma, comprising 60% of all cases (9 patients). Multimodal treatment generally consisted of surgery and radiotherapy for dysgerminoma with the addition of chemotherapy for the non-dysgerminomas. Survival depends on the stage and histological appearances of the tumour. Patients in whom the disease is at advanced stages have a poor prognosis, irrespective of histological features. A general review of this subject is also given.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. Human tumour antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells

    Science.gov (United States)

    Vose, Brent M.; Bonnard, Guy D.

    1982-03-01

    The long-term goal of many laboratories has been to develop cellular reagents having specific reactivity against human tumour cells. Such immune cells should prove useful for defining the antigenicity of human malignancies and may have important therapeutic potential, as has been clearly shown in some animal models1. Here we describe methods of initiating continued lymphocyte cultures (CLC) having specific anti-tumour reactivity using conditioned media containing interleukin-2 (IL-2).

  16. 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.

  17. In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells

    DEFF Research Database (Denmark)

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

    1994-01-01

    A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their abi......A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well...... with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens......, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53...

  18. 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)

  19. 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...

  20. Clinical studies of resistant ascites in liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Yuasa,Shiro

    1984-06-01

    Full Text Available Resistant ascites was studied in 34 patients with liver cirrhosis and ascites. The patients were initially divided into 3 groups on the basis of the weekly cumulative ascites retention curve: patients relieved of ascites within 3 weeks of admission, patients relieved between 4 and 12 weeks and patients with ascites persisting beyond 13 weeks. "Resistant ascites" was defined as "ascites persisting for more than 13 weeks after admission to the hospital". The patients were then reclassified into 3 groups : Group A being those patients relieved of ascites within 12 weeks, Group B being those with resistant ascites and group C being those who died within 12 weeks of admission. There were no differences in age and sex distribution, etiology of liver cirrhosis, past medical history or physical findings among the 3 groups. However, Group B had higher levels of serum creatinine and blood urea nitrogen than Group A on admission. Serum bilirubin was higher and serum albumin was lower in Group C than in Group B, which indicates that Group C had greater liver cell failure.

  1. Changes in the template activity of chromatin isolated from sarcoma-180 ascites cells treated with mitomycin C and gamma irradiation in vivo.

    Science.gov (United States)

    Karuri, A; Mukherji, S

    1989-01-01

    The murine ascites sarcoma 180 cells were used to test the in vivo effectiveness of mitomycin C (MMC) and gamma-radiation applied in combination. The action of intraperitoneal administration of MMC and/or whole-body gamma irradiation on sarcoma 180 tumor bearing Swiss albino mice was investigated by studying the template activity of isolated tumor chromatin. The Km value for transcription of 10 Gy-irradiated chromatin was found to decrease with time implying an increase in the template efficiency with respect to that of the unirradiated control. Maximum decrease in Km was observed after 24 h of irradiation. MMC treatment (7 mg/kg body weight of mouse) for 18 h resulted in an inhibition of the transcription rate. Severe inhibition in the template activity was found when cells were subjected to MMC treatment 18 h prior to irradiation with 10 Gy. Susceptibility of tumor chromatin to DNase II followed the same pattern as observed in the case of transcription indicating structural alteration of the treated chromatin. The data showed that DNA damage and its consequences produced in the ascites cells by prior treatment of MMC were not repaired during the 18 h period after which the application of radiation enhanced cytotoxicity.

  2. The attractive Achilles heel of germ cell tumours : an inherent sensitivity to apoptosis-inducing stimuli

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

    2003-01-01

    Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact, apo

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Ascites: Pathogenesis and therapeutic principles

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens; Bendtsen, Flemming

    2009-01-01

    , liver insufficiency, and cardiovascular dysfunction are major pathophysiological hallmarks. Modern treatment of ascites is based on this recognition and includes modest salt restriction and stepwise diuretic therapy with spironolactone and loop-diuretics. Tense and refractory ascites should be treated...

  12. 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

  13. 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

  14. 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...

  15. 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

  16. [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

  17. 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.)

  18. Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

    Science.gov (United States)

    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, and programmed cell death.

  19. 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.

  20. Analysis of normal-tumour tissue interaction in tumours: prediction of prostate cancer features from the molecular profile of adjacent normal cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    Full Text Available Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the tissue microenvironment in specifying tumour physiology. Because of the importance of normal cells in shaping the tissue microenvironment we formulate the hypothesis that molecular components of the profile of normal epithelial cells adjacent the tumour are predictive of tumour physiology. We addressed this hypothesis by developing statistical models that link gene expression profiles representing the molecular state of adjacent normal epithelial cells to tumour features in prostate cancer. Furthermore, network analysis showed that predictive genes are linked to the activity of important secreted factors, which have the potential to influence tumor biology, such as IL1, IGF1, PDGF BB, AGT, and TGFβ.

  1. Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

    DEFF Research Database (Denmark)

    Rance, A J; Thönnes, M; Issinger, O G

    1985-01-01

    The phosphorylation of ribosomal protein S6 in fibroblasts, primary human tumour cells, established and SV40-transformed human cell lines was compared after the addition of 12-O-tetradecanoylphorbol 13-acetate (TPA). In fibroblasts and primary tumour cell cultures, stimulation of S6 phosphorylati...

  2. Three Dimensional Simulation Method in Early Process of Division and Growth for Tumour Cells

    Institute of Scientific and Technical Information of China (English)

    XIA Zhi-qiu; ZHAO Ting-ting

    2014-01-01

    The process of division, growth and death for tumour cell mass in the early is simulated. An integrated GUI is provided for users to set the value of each parameters, which are cell growth rates, cell mass division rates, cell mass death rates, simulate type, maximum running time, polarity and cell colour. It can display the growth process of each cell on result GUI. Also, it can display the values of each parameters for observing and analysing in current life cycle on result GUI, which are cell mass division times, cell mass death rate, cell mass division rate and cell mass growth rate. In the process of simulation, The cell growth rate is described by the approach to combine the exponential model with the linear model. In addition, a linked list data structure to store the tumour cells is used by the cellular automata for a reference to determine the position of each cell. It sets up two linked list to store the cells, one of them save the new small division cells and the other one save the big cell. That can make the painting process of cells on result GUI clearer and more organized. At last, the polarity of tumour growth is described for determining the growth direction of cells.

  3. A rare case of combined placental site trophoblastic tumour with mature cystic teratoma and mixed germ cell tumour in the testis.

    Science.gov (United States)

    Leow, Wei Qiang; Loh, Hwai Liang Alwin; Lee, Lui Shiong; Goh, Chin Hong Ronald

    2015-08-01

    A 20-year-old male presented with persistent right testicular pain. Following ultrasound detection of testicular nodules and biopsy for intraoperative consultation which yielded germ cell tumour, he underwent radical orchidectomy. A predominantly whitish cyst and a lobulated, variegated nodule were identified. Histology showed a mature cystic teratoma with a focus of infiltrative epithelioid cells containing eosinophilic cytoplasm and pleomorphic nuclei, invading ectatic vessel wall associated with fibrinoid change. These cells were positive for cytokeratin, human placental lactogen and inhibin, while negative for Melan-A, p63 and alpha-fetoprotein, consistent with placental site trophoblastic tumor (PSTT). The variegated nodule was a mixed germ cell tumour composed of embryonal carcinoma and immature teratoma. Aside from choriocarcinoma, primary trophoblastic tumors such as PSTT, which are derived from intermediate trophoblasts, are extremely rare in the testis. Aside from a case of pure testicular PSTT, 2 other cases have been described in association with germ cell tumour, of which one is a mature teratoma with PSTT that demonstrated gain of chromosome 12p. The other presented with PSTT in retroperitoneal recurrence of a testicular mixed germ cell tumour. We discussed the features of this tumour in the testis and important differentials in its diagnosis.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Kooijmans, Sander A. A.; Aleza, Clara Gómez; 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 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 EV 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. PMID:26979463

  10. 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.

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

    NARCIS (Netherlands)

    Ligthart, S.T.; Coumans, F.A.W.; Attard, G.; Mukick Cassidy, A.; Bono, de J.S.; Terstappen, L.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

  12. 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...

  13. 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.

  14. 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

  15. 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...

  16. Fc-receptor-bearing cells in spleen of mice injected with cell-free Ehrlich ascites fluid (EAF).

    Science.gov (United States)

    Gabrilovac, J; Pachmann, K; Thierfelder, S

    1980-10-01

    The kinetics of different cell populations (T and B) and subpopulations (one bearing easily releasable FcR and one bearing stable FcR) was followed in spleens of mice after one single i.p. injection of EAF. The number of FcR bearing cells doubled within 2-7 days after EAF injection. This increase was due to cells bearing temperature sensitive FcR and was accompanied by the doubling of theta positive cells. These results, supported by the demonstration of doubly labeled (theta+FcR+) cells, suggest that EAF injected into normal mice causes the appearance of T-cells expressing easily releasable FcR. These cells, according to Fridman et al. (1977) are suppressor cells. Maximal increase of theta positive cells and of cells with temperature sensitive FcR detected in vitro coincided with the maximum of the suppressive activity of EAF detected in vivo.

  17. 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.)

  18. 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.)

  19. 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.

  20. 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...

  1. 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

  2. SENSITIZING FOR CIS-DIAMMINEDICHLOROPLATINUM(II) ACTION BY HYPERTHERMIA IN RESISTANT CELLS

    NARCIS (Netherlands)

    KONINGS, AWT; HETTINGA, JVE; LEMSTRA, W; HUMPHREY, GB; KAMPINGA, HH

    1993-01-01

    cDDP-resistant Ehrlich ascites tumour (EAT) cells (ER cells) were tested for cellular content of total glutathione, heat sensitivity, cDDP sensitivity and synergistic effects of a combined treatment of heat and chemotherapy. In comparison with the non-resistant EAT cells (EN) the ER cells had an ele

  3. 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

  4. So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis.

    Science.gov (United States)

    Sano, K; Matsutani, M; Seto, T

    1989-06-01

    We investigated 110 cases of intracranial germ cell tumours (up to the end of 1986), 56% of which showed monotypic histological patterns and 44% were shown to be mixed tumours. All these cases underwent surgery followed by radiation and/or chemotherapy. All cases of choriocarcinoma and embryonal carcinoma died within 2 yr: cases of endodermal sinus tumour also showed poor results (4 yr survival rate was 12.5%). Mature teratoma had a 5 yr survival rate (5YSR) and a 10 yr survival rate (10YSR) of 78.3% each: immature teratoma showed a 5YSR of 44.9%. Two-cell pattern tumours (PTC) showed a 5YSR of 85.8% and a 10YSR of 82.4%. They (PTC) can be divided into two groups (i) germinoma and (ii) pinealoma of pineal parenchyma origin (pineocytoma with lymphocytic infiltration) on the basis of the difference in the tumour cell-stroma relationship and also placental alkaline phosphatase stain. In the pineal region, 70% of PTC belonged to the category of pinealoma and in the suprasellar region, 92% of PTC were germinoma. Germinoma showed a 5YSR of 91.4% and a 10YSR of 91.4%, whereas those of the pinealoma were 78.2% and 68.4% respectively. This suggests that the biological characteristics of germinoma and pinealoma may be different. All these results may bring into question the validity of the germ cell theory, since germinoma, which should be the most undifferentiated according to the theory, was the most benign and choriocarcinoma and endodermal sinus tumour, which should be the most differentiated, were the most malignant in the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2569683

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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.

  11. 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

  12. True precocious puberty following treatment of a Leydig cell tumour: two case reports and literature review

    Directory of Open Access Journals (Sweden)

    Alberto eVerrotti

    2015-11-01

    Full Text Available Leydig cell testicular tumours are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumour causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin releasing hormone analogues. Only 6 other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumour causing precocious pseudo puberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumour presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with gonadotropin releasing hormone analogues appears to be the most effective medical treatment.

  13. 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.

  14. 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

  15. 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.

  16. Carpal tunnel syndrome caused by a giant cell tumour of the flexor tendon sheath.

    Science.gov (United States)

    Meek, Marcel F; Sheikh, Zahid A; Quinton, David N

    2014-02-01

    A 76-year-old woman developed right carpal tunnel syndrome after being conservatively treated for tenosynovitis of the flexor tendons with associated mild carpal tunnel syndrome. A magnetic resonance imaging scan showed a tumour in the carpal tunnel. Re-exploration showed that the median nerve was being compressed by a giant cell tumour of the flexor tendon sheaths. Appropriate imaging is advised in patients with additional findings (such as swelling) or in patients with secondary carpal tunnel syndrome and incomplete response to conservative treatment, to exclude a space-occupying lesion.

  17. 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...

  18. Two cases of breast carcinoma with osteoclastic giant cells: Are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

    Directory of Open Access Journals (Sweden)

    Shishido-Hara Yukiko

    2010-08-01

    Full Text Available Abstract Breast carcinoma with osteoclastic giant cells (OGCs is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1 had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2 with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K and a histiocyte marker (CD68, but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

  19. 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)

  20. 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

  1. Engineering Salmonella as intracellular factory for effective killing of tumour cells.

    Science.gov (United States)

    Camacho, Eva María; Mesa-Pereira, Beatriz; Medina, Carlos; Flores, Amando; Santero, Eduardo

    2016-01-01

    Salmonella have many desirable properties as antitumour-agent due to its ability to proliferate inside tumours and induce tumour regression. Additionally, this bacterium can be genetically engineered to deliver therapeutic proteins intratumourally. The main limitation of this approach is the efficient release of therapeutic molecules from intratumoural bacteria. Here we have developed an inducible autolysis system based in the lysis operon of the lambda phage that, in response to anhydrotetracycline, lysates Salmonella thus releasing its content. The system was combined with a salicylate cascade system that allows efficient production of therapeutic molecules in response to aspirin and with a sifA mutation that liberates bacteria from the vacuoles to a cytosolic location. The combination of these three elements makes this strain a putative powerful instrument in cancer treatment. We have used this engineered strain for the intracellular production and delivery of Cp53 peptide. The engineered strain is able to sequentially produce and release the cytotoxic peptide while proliferating inside tumour cells, thus inducing host cell death. Our results show that temporal separation of protein production from protein release is essential to efficiently kill tumour cells. The combined system is a further step in the engineering of more efficient bacteria for cancer therapy. PMID:27464652

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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)

  8. 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.

  9. 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

  10. 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

  11. 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...

  12. 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...

  13. 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.

  14. 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...

  15. 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...

  16. 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.

  17. 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

  18. The effect of PLC-γ2 inhibitors on the growth of human tumour cells.

    Science.gov (United States)

    Feng, Linda; Reynisdóttir, Inga; Reynisson, Jóhannes

    2012-08-01

    The phosphoinositide specific-phospholipase C-γ (PLC-γ1 and 2) enzymes are plausible anticancer targets implicated in cell motility important to invasion and dissemination of tumour cells. A host of known PLC-γ2 inhibitors were tested against the NCI60 panel of human tumour cell lines as well as their commercially available structural derivatives. A class of thieno[2,3-b]pyridines showed excellent growth arrest with derivative 3 giving GI(50) = 58 nM for the melanoma MDA-MB-435 cell line. The PLC-γ2 is uniquely expressed in haematopoietic cells and the leukaemia tumour cell lines were growth restricted on average GI(50) = 275 nM by derivative 3 indicating a specific interaction with this isoform. Furthermore, a moderate growth inhibition was found for compound classes of indoles and 1H-pyrazoles. It is likely that the active compounds do not only inhibit the PLC-γ2 isoform but other PLCs as well due to their conserved binding site. The compounds tested were identified by applying the tools of chemoinformatics, which supports the use of in silico methods in drug design.

  19. [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.

  20. [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

  1. 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...

  2. 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...

  3. 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...

  4. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion.

    Science.gov (United States)

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars

    2014-01-01

    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression. PMID:25080976

  5. Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back

    Directory of Open Access Journals (Sweden)

    Luis León-Mateos

    2016-09-01

    Full Text Available Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice.

  6. 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

    sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace......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...... that a significant direct involvement of HPV and EBV in human testicular germ cell carcinogenesis is unlikely. However, a putative growth-stimulating role of EBV-transformed lymphocytes, which are frequently present in the stromal tissues of testicular tumours, cannot be excluded....

  7. Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back

    Science.gov (United States)

    León-Mateos, Luis; Vieito, María; Anido, Urbano; López López, Rafael; Muinelo Romay, Laura

    2016-01-01

    Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice. PMID:27657044

  8. 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.

  9. (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)

  10. VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells.

    Science.gov (United States)

    Fernández-Martínez, Ana B; Carmena, María J; Bajo, Ana M; Vacas, Eva; Sánchez-Chapado, Manuel; Prieto, Juan C

    2015-02-01

    The nuclear factor κB (NF-κB) is a powerful activator of angiogenesis, invasion and metastasis. Transactivation and nuclear localisation of NF-κB is an index of recurrence in prostate cancer. Vasoactive intestinal peptide (VIP) exerts similar effects in prostate cancer models involving increased expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) which are related to NF-κB transactivation. Here we studied differential mechanisms of VIP-induced NF-κB transactivation in non-tumour RWPE-1 and tumour LNCaP and PC3 human prostate epithelial cells. Immunofluorescence studies showed that VIP increases translocation of the p50 subunit of NF-κB1 to the nucleus, an effect that was inhibited by curcumin. The signalling transduction pathways involved are different depending on cell transformation degree. In control cells (RWPE1), the effect is mediated by protein kinase A (PKA) activation and does not implicate extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3-K) pathways whereas the opposite is true in tumour LNCaP and PC3 cells. Exchange protein directly activated by cAMP (EPAC) pathway is involved in transformed cells but not in control cells. Curcumin blocks the activating effect of VIP on COX-2 promoter/prostaglandin E2 (PGE2) production and VEGF expression and secretion. The study incorporates direct observation on COX-2 promoter and suggests that VIP effect on VEGF may be indirectly mediated by PGE2 after being synthesised by COX-2, thus amplifying the initial signal. We show that the signalling involved in VIP effects on VEGF is cAMP/PKA in non-tumour cells and cAMP/EPAC/ERK/PI3K in tumour cells which coincides with pathways mediating p50 nuclear translocation. Thus, VIP appears to use different pathways for NF-κB1 (p50) transactivation in prostate epithelial cells depending on whether they are transformed or not. Transformed cells depend on pro-survival and pro-proliferative signalling pathways

  11. 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...

  12. 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...

  13. 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 ...

  14. 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.

  15. 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.

  16. 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

  17. 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)

  18. 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....

  19. 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...... 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......; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring...

  20. 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.

  1. 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...

  2. 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)

  3. 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

  4. Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity.

    Science.gov (United States)

    O'Leary, L; van der Sloot, A M; Reis, C R; Deegan, S; Ryan, A E; Dhami, S P S; Murillo, L S; Cool, R H; Correa de Sampaio, P; Thompson, K; Murphy, G; Quax, W J; Serrano, L; Samali, A; Szegezdi, E

    2016-03-10

    Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand cytokine known for its cytotoxic activity against malignantly transformed cells. TRAIL induces cell death through binding to death receptors DR4 and DR5. The inhibitory decoy receptors (DcR1 and DcR2) co-expressed with death receptor 4 (DR4)/DR5 on the same cell can block the transmission of the apoptotic signal. Here, we show that DcRs also regulate TRAIL sensitivity at a supracellular level and thus represent a mechanism by which the microenvironment can diminish tumour TRAIL sensitivity. Mathematical modelling and layered or spheroid stroma-extracellular matrix-tumour cultures were used to model the tumour microenvironment. By engineering TRAIL to escape binding by DcRs, we found that DcRs do not only act in a cell-autonomous or cis-regulatory manner, but also exert trans-cellular regulation originating from stromal cells and affect tumour cells, highlighting the potent inhibitory effect of DcRs in the tumour tissue and the necessity of selective targeting of the two death-inducing TRAIL receptors to maximise efficacy. PMID:26050621

  5. 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

  6. Eosinophilic ascites: a diagnostic challenge.

    Science.gov (United States)

    Khalil, Hesham; Joseph, Moby

    2016-01-01

    Eosinophilic ascites is a rare feature of eosinophilic gastroenteritis. We would like to highlight this increasingly recognised diagnosis in a case of unexplained ascites. We present a challenging case of a woman aged 25 years who presented with nausea, vomiting, diarrhoea, generalised abdominal pain and swelling 8-week following delivery of her first baby. Her symptoms were primarily aggravated by eating, and she had also noticed postprandial itching and self-limiting generalised rash. She had a strong history of atopy. Physical examination revealed abdominal tenderness and distension with shifting dullness. Urticarial skin rash was noted on the face, neck, chest and abdomen. Routine biochemistry was normal apart from peripheral eosinophilia. Imaging confirmed moderate ascites. Diagnostic paracentesis showed exudative ascites with numerous eosinophils. Histology of the upper and lower gastrointestinal tract showed infiltration of the oesophageogastroduodenal and rectosigmoid mucosa with eosinophils. The patient significantly improved following a course of steroids and six-food elimination diet. PMID:27600059

  7. 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

  8. 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

  9. 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...

  10. 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.

  11. 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.

  12. 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

  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 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

  14. 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

  15. 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.

  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. Heterogeneity of vascular endothelial cells with relevance to diagnosis of vascular tumours.

    Science.gov (United States)

    Kuzu, I.; Bicknell, R.; Harris, A. L.; Jones, M.; Gatter, K. C.; Mason, D. Y.

    1992-01-01

    AIMS: To determine the distribution of factor VIII related antigen, CD31, CD34 and CD36 in normal and malignant human vascular tissues using a panel of well characterised monoclonal antibodies. METHODS: Frozen and fixed material from a wide range of normal tissues and routinely processed material from 43 benign and malignant vascular tumours were examined. Single immunocytochemical labelling was performed using the APAAP technique. Double staining involved the sequential use of APAAP with the peroxidase method. RESULTS: Human vascular endothelium was antigenically heterogeneous. One of the most restricted markers was factor VIII related antigen, despite its having been widely used in diagnostic pathology as a marker of vascular endothelium and of the tumours which arise from it. Three antibodies against factor VIII related antigen, CD31 (JC70) and CD34 (QBend 10) were identified as immunostaining routinely processed, formalin fixed, paraffin wax sections. Each antibody gave different staining when tested on a range of vascular tumours, both benign and malignant. CONCLUSIONS: A small panel of three reagents (factor VIII related antigen, CD31 (JC70) and CD34 (QBend 10)) should be used by diagnostic pathologists who want to show the presence of cells of endothelial origin in routine material. Images PMID:1371777

  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. 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...

  20. 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...

  1. In vitro immunopotentiating properties and tumour cell toxicity induced by Lophophora williamsii (peyote) cactus methanolic extract.

    Science.gov (United States)

    Franco-Molina, M; Gomez-Flores, R; Tamez-Guerra, P; Tamez-Guerra, R; Castillo-Leon, L; Rodríguez-Padilla, C

    2003-11-01

    Lophophora williamsii, also known as peyote, is found primarily in dry regions from Central Mexico, including the Mexican States of Nayarit, San Luis Potosí, Zacatecas, Nuevo León, Chihuahua, Coahuila and Tamaulipas, to Texas particularly in regions along Rio Grande. Peyote extracts have been associated with stimulating the central nervous system and regulating blood pressure, sleep, hunger and thirst. However, there is no evidence of any effect of peyote on the immune system or against tumour cell growth. The present study was designed to evaluate the in vitro effects of peyote methanolic extracts on some parameters of mouse and human leukocyte immunocompetence and tumour cell growth. Peyote extract (0.18-18 micro g/mL) activated nitric oxide production by murine macrophages, and stimulated up to 2.4-fold proliferation of murine thymic lymphocytes. In addition, peyote extract induced up to 1.85-, 2.29- and 1.89-fold increases in mRNA signal of IL-1, IL-6 and IL-8 by human leukocytes. Also examined were the effects of peyote extracts on murine lymphoma L5178Y-R and fi broblastoma L929, and human myeloid U937 and mammary gland MCF7 tumour cell growth using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Peyote extracts were toxic for MCF7, L5178Y-R, U937 and L929 (18 mg/mL peyote extract caused 1.3%, 8%, 45% and 60% viability respectively) cell lines.

  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. 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...

  4. 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 ...

  5. 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...

  6. 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

    correlation to clinicopathological features and survival. METHOD: A systematic review was conducted without meta-analysis according to the PRISMA guidelines on 24 March 2014 using PubMed and EMBASE. Eligibility criteria were: study design, original research article, English language, human subjects and gene...... 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...... with clinicopathological features and survival. RESULTS: Seventy-four articles were identified and 11 studies were included. Overall, gene expression of Period was significantly decreased in colorectal cancer cells compared with healthy mucosa cells. This tendency was also seen in the gene expression of Clock. Other core...

  7. 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

  8. Improved cytotoxic effects of Salmonella-producing cytosine deaminase in tumour cells

    Science.gov (United States)

    Mesa-Pereira, Beatriz; Medina, Carlos; Camacho, Eva María; Flores, Amando; Santero, Eduardo

    2015-01-01

    In order to increase the cytotoxic activity of a Salmonella strain carrying a salicylate-inducible expression system that controls cytosine deaminase production, we have modified both, the vector and the producer bacterium. First, the translation rates of the expression module containing the Escherichia coli codA gene cloned under the control of the Pm promoter have been improved by using the T7 phage gene 10 ribosome binding site sequence and replacing the original GUG start codon by AUG. Second, to increase the time span in which cytosine deaminase may be produced by the bacteria in the presence of 5-fluorocytosine, a 5-fluorouracyl resistant Salmonella strain has been constructed by deleting its upp gene sequence. This new Salmonella strain shows increased cytosine deaminase activity and, after infecting tumour cell cultures, increased cytotoxic and bystander effects under standard induction conditions. In addition, we have generated a purD mutation in the producer strain to control its intracellular proliferation by the presence of adenine and avoid the intrinsic Salmonella cell death induction. This strategy allows the analysis and comparison of the cytotoxic effects of cytosine deaminase produced by different Salmonella strains in tumour cell cultures. PMID:25227763

  9. 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

  10. 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

    -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....../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...

  11. 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

  12. 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.

  13. LINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines.

    Science.gov (United States)

    Aschacher, T; Wolf, B; Enzmann, F; Kienzl, P; Messner, B; Sampl, S; Svoboda, M; Mechtcheriakova, D; Holzmann, K; Bergmann, M

    2016-01-01

    A hallmark of cancer cells is an activated telomere maintenance mechanism, which allows prolonged survival of the malignant cells. In more than 80% of tumours, telomeres are elongated by the enzyme telomerase, which adds de novo telomere repeats to the ends of chromosomes. Cancer cells are also characterized by expression of active LINE-1 elements (L1s, long interspersed nuclear elements-1). L1 elements are abundant retrotransposons in the eukaryotic genome that are primarily known for facilitating aberrant recombination. Using L1-knockdown (KD), we show for the first time that L1 is critical for telomere maintenance in telomerase-positive tumour cells. The reduced length of telomeres in the L1-KD-treated cells correlated with an increased rate of telomere dysfunction foci, a reduced expression of shelterin proteins and an increased rate of anaphase bridges. The decreased telomere length was associated with a decreased telomerase activity and decreased telomerase mRNA level; the latter was increased upon L1 overexpression. L1-KD also led to a decrease in mRNA and protein expression of cMyc and KLF-4, two main transcription factors of telomerase and altered mRNA levels of other stem-cell-associated proteins such as CD44 and hMyb, as well as a corresponding reduced growth of spheroids. The KD of KLF-4 or cMyc decreased the level of L1-ORF1 mRNA, suggesting a specific reciprocal regulation with L1. Thus, our findings contribute to the understanding of L1 as a pathogenicity factor in cancer cells. As L1 is only expressed in pathophysiological conditions, L1 now appears to be target in the rational treatment of telomerase-positive cancer.

  14. The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

    Science.gov (United States)

    Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

    2014-04-01

    Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

  15. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis.

    Science.gov (United States)

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management. PMID:27610194

  16. MANAGEMENT OF SYMPTOMATIC MALIGNANT ASCITES WITH DIURETICS AND PARACENTESIS: CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Amer Hayat Khan

    2012-10-01

    Full Text Available Malignant ascites is a widespread impediment of advanced cancer but to 20% of all cases of malignant ascites have unknown primary tumours. With the exception of ovarian cancer, the response of the ascites to treatment of the tumor is unsatisfactory and treatment related morbidity is common. The intent of most treatments for malignant ascites should be palliative with diuretics paracentesis were the common approach. A 53 years old, male patients who was admitted with history of abdominal distention for past 3 month associated with altered bowel habit and mucus per rectum and significant loss weight. Patients was diagnosed as malignant ascites with multicentric hepatoma with abdominal lymphodenopathy, lung, liver and vertebral body metastasis and left portal vein thrombosis. Patient was managed with temporary external paracentesis (pigtail catheter and oral furosemide 40 mg daily and spironolactone 100 mg daily. Although abdominal paracentesis, diuretics and peritoneovenous shunting are commonly used procedures in management of malignant ascites, there are no randomized controlled trials evaluating the efficacy and safety of these therapies.

  17. 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...... 145 patients with invasive (n = 116) or in situ (n = 29) penile squamous cell carcinoma were subjected to systematic histological evaluation and were PCR-tested for 14 hrHPV types and 23 low-risk HPV types. Around half (52%) of invasive and nine-tenths (90%) of in situ lesions were positive for an hrHPV...... type, of which HPV 16 was by far the predominant type (91% of hrHPV-positive lesions). In relation to histological characteristics, hrHPV positivity was statistically significantly more common in high-grade tumours, lesions dominated by small tumour cells, lesions with a high number of multinucleated...

  18. 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

  19. 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.

  20. 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.

  1. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    Science.gov (United States)

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  2. In vitro anti-tumour activity of tumour necrosis serum

    NARCIS (Netherlands)

    Bloksma, N.; Schetters, Th.P.; Figdor, C.; Dijk, H. van; Willers, J.M.

    1980-01-01

    A method measuring 3H-thymidine incorporation in Meth A sarcoma cells was used to quantify in vitro anti-tumour activity of tumour necrosis serum and compared with a method using cell viability as a parameter. Tumour necrosis serum obtained from mice pretreated with Corynebacterium parvum and elicit

  3. 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.

  4. 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.

  5. 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 ...

  6. 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)

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

    Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study......, 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...... in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells...

  12. 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.

  13. Deregulation of the RB pathway in human testicular germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S;

    2003-01-01

    Deregulation of the RB pathway is shared by most human malignancies. Components upstream of the retinoblastoma tumour suppressor (pRB), namely the INK4 family of cyclin-dependent kinase (CDK) inhibitors, the D-type cyclins, their partner kinases CDK4/CDK6, and pRB as their critical substrate......, are differentially targeted in diverse types of cancer. An 'unorthodox' spectrum of defects within this cascade occurs in testicular germ cell tumours (TGCTs), including silencing of pRB transcription, overexpression of cyclin D2, and loss of p18INK4c. To improve understanding of the role of this pathway...... in spermatogenesis, and its subversion in TGCTs, we examined immunohistochemical expression patterns of CDK4, p16INK4a, p15INK4b, and pRB, and established an in situ assay for cyclin D-mediated phosphorylation of serine795, a phosphorylation event critical for neutralization of pRB's growth-restraining ability. pRB...

  14. 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.

  15. 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.

  16. 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.

  17. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  18. 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.)

  19. 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.)

  20. 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)

  1. Prevalence of human papillomavirus (HPV in oesophageal squamous cell carcinoma in relation to anatomical site of the tumour.

    Directory of Open Access Journals (Sweden)

    Hedvig E Löfdahl

    Full Text Available BACKGROUND: The prevalence and role of human papillomavirus (HPV in the aetiology of oesophageal squamous cell carcinoma is uncertain. Based on the presence of HPV in the oral cavity and its causal association with squamous cell carcinoma of the oropharynx, we hypothesised that HPV is more strongly associated with proximal than distal oesophageal squamous cell carcinoma. METHODS: A population-based study comparing HPV infection in relation to tumour site in patients diagnosed with oesophageal squamous cell carcinomas in the Stockholm County in 1999-2006. Multiplex polymerase chain reaction genotyping (PCR with Luminex was conducted on pre-treatment endoscopic biopsies to identify type specify HPV. Carcinogenic activity of HPV was assessed by p16(INK4a expression. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: Among 204 patients, 20 (10% had tumours harbouring HPV DNA, almost all (90% of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2-1.9. P16(INK4a expression was similarly common (24% and 16% in the HPV-positive and HPV-negative groups. CONCLUSION: This study found a limited presence of HPV in oesophageal squamous cell carcinoma of uncertain oncogenic relevance and did not demonstrate that HPV was more strongly associated with proximal than distal tumours.

  2. 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.

  3. 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

  4. Second primary tumours after a squamous cell carcinoma of the oral cavity or oropharynx using the cumulative incidence method

    NARCIS (Netherlands)

    van der Haring, I. S.; Schaapveld, M. S.; Roodenburg, J. L. N.; de Bock, G. H.

    2009-01-01

    The aim of this study was to define the incidence of second primary tumours (SPTs) after treatment of a first primary oral or oropharyngeal squamous cell carcinoma (SCC) and to define patient groups with an increased or decreased risk of developing SPT with adjustment for competing risks. Cancer reg

  5. 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.)

  6. 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

  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. Radiosensitization by misonidazole, pimonidazole and azomycin and intracellular uptake in human tumour cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Watts, M.E.; Dennis, M.F.; Roberts, I.J. (Mount Vernon Hospital, Northwood (UK). Gray Lab.)

    1990-02-01

    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 (C{sub i} to C{sub e})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). C{sub i}C{sub e} 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{sup -3}). MPSH levels expressed as n mol/mg protein were also similar. (author).

  9. Immediate diagnostic criteria for bacterial infection of ascitic fluid. Evaluation of ascitic fluid polymorphonuclear leukocyte count, pH, and lactate concentration, alone and in combination.

    Science.gov (United States)

    Stassen, W N; McCullough, A J; Bacon, B R; Gutnik, S H; Wadiwala, I M; McLaren, C; Kalhan, S C; Tavill, A S

    1986-05-01

    We prospectively evaluated the ascitic fluid (AF) polymorphonuclear cell (PMN) count, pH, and lactate concentration in single ascitic fluids from 60 patients to determine their relative predictive values for the immediate diagnosis of ascitic fluid infection. Nine of the 60 ascitic fluids were malignant. Of the remaining 51 samples, nine from cirrhotic patients were infected. The mean AF pH, lactate concentration, and PMN count in the infected group were 7.20 +/- 0.19, 80 +/- 51 mg/dl, and 18,199 +/- 19,650 cells/mm3, respectively, and all were significantly different from the corresponding values in noninfected ascites. Mean arterial blood-ascitic fluid (B-AF) pH and lactate gradients in the infected group were 0.23 +/- 0.17 and -46 +/- 31 mg/dl, respectively, and were significantly different from the corresponding values in noninfected ascites (p less than 0.05). Significant differences were not found between infected and malignant ascites, except for the AF PMN count (p less than 0.001). In cirrhosis with ascites, an AF pH less than or equal to 7.34 was the most specific single test (100%) and had the highest diagnostic accuracy (98%). In the larger group of patients with ascites of diverse etiology, a B-AF pH gradient greater than or equal to 0.10 or an AF PMN count greater than or equal to 500 cells/mm3 were the single tests with the highest diagnostic accuracy (92%). Combining an AF PMN count greater than 500 cells/mm3 with any of the other diagnostic criteria increased the specificity and diagnostic accuracy (up to 98%) compared to the best single criterion. Although our data support the use of a number of different combinations of AF measurements for the immediate diagnosis of infection, the simplest and most readily obtainable measurements are the pH and PMN count. Therefore, in the clinical setting we recommend the use of either an AF pH less than or equal to 7.34 or a B-AF pH gradient greater than or equal to 0.10 in combination with an AF PMN count

  10. 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

  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. 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.)

  13. 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

  14. Chylous ascites as a complication of nephroureterectomy

    Directory of Open Access Journals (Sweden)

    Chi-Hang Hsiao

    2015-06-01

    Full Text Available Chylous ascites may be the result of many pathological conditions, including congenital defects of the lymphatic system, nonspecific bacterial, parasitic and tuberculous peritoneal infection, liver cirrhosis, malignant neoplasm, blunt abdominal trauma, and surgical injury. A 62-year-old woman presented with chylous ascites after undergoing nephroureterectomy and bladder cuff excision for her left ureteral urothelial carcinoma. The diagnosis of chylous ascites is made when the ratio of ascitese versus serum triglyceride is > 2. Patients with chylous ascites may be treated conservatively with total parenteral nutrition and/or a diet containing low fat and medium chain triglycerides. Refractory cases may require more aggressive intervention. We report a case of postoperative chylous ascites that was treated successfully with total parenteral nutrition for 14 days. A review of the relevant literature is presented and chylous ascites treatment is also discussed.

  15. Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate.

    Science.gov (United States)

    Motevaseli, Elahe; Shirzad, Mahdieh; Akrami, Seyed Mohammad; Mousavi, Azam-Sadat; Mirsalehian, Akbar; Modarressi, Mohammad Hossein

    2013-07-01

    Cervical cancer is a human papilloma virus (HPV)-related cancer, but most HPV infections are transient or intermittent and resolve spontaneously. Thus, other factors, such as cervical microflora, which are dominated by lactobacilli, must be involved in invasive cervical carcinoma development after HPV infection. Previous studies have demonstrated that lactobacilli have antitumour effects, and it is possible that vaginal lactobacilli prevent cervical cancer. Here we examined the proliferative and apoptotic responses of normal and tumour cervical cells to common vaginal lactobacilli components by investigating human normal fibroblast-like cervical (normal cervical) and HeLa (cervical tumour) cell responses to Lactobacillus gasseri and Lactobacillus crispatus. The effects of different lactobacilli components, such as culture supernatants, cytoplasmic extracts, cell-wall extracts and live cells, were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, trypan blue staining, lactate dehydrogenase assay and colorimetric caspase-3 activity assay. Changes in caspase-3 and human chorionic gonadotropin β (hCGβ) expression were analysed by quantitative RT-PCR. Tumour cell growth inhibition by culture supernatants was higher than that by pH- and lactate-adjusted controls. However, the effects of the supernatants on normal cells were similar to those of lactate-adjusted controls. Apoptosis was inhibited by supernatants, which was consistent with higher hCGβ expression since hCG inhibits apoptosis. Our study demonstrated that common vaginal lactobacilli exert cytotoxic effects on cervical tumour cells, but not on normal cells, and that this cytotoxicity is independent of pH and lactate. Our results encourage further studies on the interaction between lactobacilli and cervical cells, and administration of common vaginal lactobacilli as probiotics.

  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. Efficacy and toxicity management of CAR-T-cell immunotherapy: a matter of responsiveness control or tumour-specificity?

    Science.gov (United States)

    Alonso-Camino, Vanesa; Harwood, Seandean Lykke; Álvarez-Méndez, Ana; Alvarez-Vallina, Luis

    2016-04-15

    Chimaeric antigen receptor (CAR)-expressing T-cells have demonstrated potent clinical efficacy in patients with haematological malignancies. However, the use of CAR-T-cells targeting solid tumour-associated antigens (TAAs) has been limited by organ toxicities related to activation of T-cell effector functions through the CAR. Most existing CARs recognize TAAs, which are also found in normal tissues. CAR-T-cell-mediated destruction of normal tissues constitutes a major roadblock to CAR-T-cell therapy, and must be avoided or mitigated. There is a broad range of strategies for modulating antigen responsiveness of CAR-T-cells, with varying degrees of complexity. Some of them might ameliorate the acute and chronic toxicities associated with current CAR constructs. However, further embellishments to CAR therapy may complicate clinical implementation and possibly create new immunogenicity issues. In contrast, the development of CARs targeting truly tumour-specific antigens might circumvent on-target/off-tumour toxicities without adding additional complexity to CAR-T-cell therapies, but these antigens have been elusive and may require novel selection strategies for their discovery.

  19. Pro- and anti-tumour effects of B cells and antibodies in cancer: a comparison of clinical studies and preclinical models.

    Science.gov (United States)

    Guy, Thomas V; Terry, Alexandra M; Bolton, Holly A; Hancock, David G; Shklovskaya, Elena; Fazekas de St. Groth, Barbara

    2016-08-01

    The primary immune role of B cells is to produce antibodies, but they can also influence T cell function via antigen presentation and, in some contexts, immune regulation. Whether their roles in tumour immunity are similar to those in other chronic immune responses such as autoimmunity and chronic infection, where both pro- and anti-inflammatory roles have been described, remains controversial. Many studies have aimed to define the role of B cells in antitumor immune responses, but despite this considerable body of work, it is not yet possible to predict how they will affect immunity to any given tumour. In many human cancers, the presence of tumour-infiltrating B cells and tumour-reactive antibodies correlates with extended patient survival, and this clinical observation is supported by data from some animal models. On the other hand, T cell responses can be adversely affected by B cell production of immunoregulatory cytokines, a phenomenon that has been demonstrated in humans and in animal models. The isotype and concentration of tumour-reactive antibodies may also influence tumour progression. Recruitment of B cells into tumours may directly reflect the subtype and strength of the anti-tumour T cell response. As the response becomes chronic, B cells may attenuate T cell responses in an attempt to decrease host damage, similar to their described role in chronic infection and autoimmunity. Understanding how B cell responses in cancer are related to the effectiveness of the overall anti-tumour response is likely to aid in the development of new therapeutic interventions against cancer.

  20. Impaired innate immune response of leukocytes from ascitic fluid of patients with spontaneous bacterial peritonitis.

    Science.gov (United States)

    Nieto, Juan Camilo; Sánchez, Elisabet; Romero, Cristina; Román, Eva; Poca, Maria; Guarner, Carlos; Juárez, Cándido; Soriano, Germán; Vidal, Silvia

    2015-11-01

    An ascitic microenvironment can condition the immune response of cells from cirrhotic patients with spontaneous bacterial peritonitis. To characterize this response, we determined the cytokine concentrations in ascitic fluid and analyzed the phenotype and function of ascitic leukocytes at diagnosis and after antibiotic-induced resolution in sterile ascites and ascitic fluid of 2 spontaneous bacterial peritonitis variants: positive and negative bacteriological culture. At diagnosis, a high concentration was found of IL-6 and IL-10 in the ascitic fluid from negative and positive bacteriological culture. The IL-6 concentration correlated with the percentage of neutrophils (R = 0.686, P peritonitis burst was fully recovered. Higher concentrations of IL-6 and IL-10 correlated with the presence of low granular CD 14(low) macrophages (R = -0.436, P = 0.005 and R = 0.414, P = 0.007, respectively). Positive culture spontaneous bacterial peritonitis macrophages expressed the lowest levels of CD16, CD86, CD11b and CD206, and HLA-DR, suggesting an impaired global function. Treatment increased all markers on the positive culture macrophages and CD11b and CD86 on negative culture macrophages. In negative culture spontaneous bacterial peritonitis, this increase was accompanied by phagocytic function recovery. The antibiotics then reverted the marker levels on positive and negative culture macrophages to the levels on sterile ascitis macrophages and restored ascitic negative culture cell function.

  1. 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

  2. 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 modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. "three-dimensional" gel...... electrophoresis; 2. two-dimensional gel electrophoresis at pH 4.K/pH 8.6 in SDS. The molecular weights for 40S proteins ranged from 10,000 to 39,000 dalton (number average molecular weight: 21,000). The molecular weights for the 60S proteins ranged from 14,000 to 44,000 dalton (number average molecular weight: 23...

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. Activation of tumour cell ECM degradation by thrombin-activated platelet membranes: potentially a P-selectin and GPIIb/IIIa-dependent process.

    Science.gov (United States)

    Pang, J H; Coupland, L A; Freeman, C; Chong, B H; Parish, Christopher R

    2015-06-01

    The promotion of tumour metastasis by platelets may occur through several mechanisms including the induction of a more metastatic phenotype in tumour cells and assisted extravasation of circulating tumour cells. Whilst the mechanisms underlying platelet-assisted extravasation have been extensively studied, much less attention has been paid to the mechanisms underlying platelet promotion of an aggressive phenotype within a tumour cell population. Herein, we demonstrate in vitro that MDA-MB-231 breast carcinoma cells incubated with washed thrombin-activated platelet membranes adopt a Matrigel-degrading phenotype in a dose- and contact time-dependent manner. The same phenotypic change was observed with three other human tumour cell lines of diverse anatomical origin. Moreover, tumour cell lines that had been cultured with washed thrombin-activated platelet membranes had a greater metastatic capacity when injected into mice. This in vivo effect was reliant upon a co-incubation period of >2 h implying a mechanism involving more than platelet membrane binding that occurred within 5 min. Upon further investigation it was found that simultaneous blocking of the platelet-membrane proteins P-selectin and GPIIb/IIIa prevented interactions between platelet membranes and MDA-MB-231 cells but also significantly reduced the ability of tumour cells to degrade Matrigel. These results confirm that platelets induce a more aggressive phenotype in tumour cells but also identify the platelet proteins involved in this effect. P-selectin and GPIIb/IIIa also play a role in assisting tumour cell extravasation and, thus, are ideal targets for the therapeutic intervention of both stages of platelet-assisted metastasis.

  8. 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.

  9. 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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Afia Akhter

    2014-01-01

    Full Text Available 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. Materials and method: This cross sectional study was carried out in the department of Pathology, Delta Hopital Ltd., Dhaka, Bangladesh from July 2011 to December 2012. A total of 30 study subjects were enrolled in the study irrespective of age and sex. Biopsy material and relevant data of clinically suspected cases of GCT along with radiology report were sent from National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR, Dhaka, Bangladesh. Histopathological diagnosis was made by expert pathologists. Results: Mean (±SD age of the study subjects was 29.20 (±7.34 years with highest number of patients were observed in 3rd decade and female was predominant (60% with a male female ratio of 1:1.5. Common site of GCT was around knee (50%. Among 30 clinically diagnosed GCT, 25 (83.3% cases were radiologically diagnosed as GCT, 2 (6.7% diagnosed as fibrous dysplasia, 1 (3.3% as chondroblastoma, 1 (3.3% as simple bone cyst and 1 (3.3% as aneurysmal bone cyst. However among 30 clinically diagnosed GCT, 28 (93.3% patients were histopathologically diagnosed as Giant cell lesion and rest 2 (6.7% patients diagnosed as fibrous dysplasia. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological diagnosis of GCT were found to be 92.6%, 100.0%, 100.0%, 40.0% and 90.0%, respectively. Conclusion: Radiology can be effectively used as a screening tool in diagnosing GCT.

  12. 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

  13. A logistic model for the detection of circulating tumour cells in human metastatic colorectal cancer

    Science.gov (United States)

    Barbazán, Jorge; Vieito, María; Abalo, Alicia; Alonso-Alconada, Lorena; Muinelo-Romay, Laura; Alonso-Nocelo, Marta; León, Luís; Candamio, Sonia; Gallardo, Elena; Anido, Urbano; Doll, Andreas; los Ángeles Casares, María; Gómez-Tato, Antonio; Abal, Miguel; López-López, Rafael

    2012-01-01

    The accuracy in the diagnosis of metastatic colorectal cancer (mCRC) represents one of the challenges in the clinical management of patients. The detection of circulating tumour cells (CTC) is becoming a promising alternative to current detection techniques, as it focuses on one of the players of the metastatic disease and it should provide with more specific and sensitive detection rates. Here, we describe an improved method of detection of CTC from mCRC patients by combining immune-enrichment, optimal purification of RNA from very low cell numbers, and the selection of accurate PCR probes. As a result, we obtained a logistic model that combines GAPDH and VIL1 normalized to CD45 rendering powerful results in the detection of CTC from mCRC patients (AUROC value 0.8599). We further demonstrated the utility of this model at the clinical setting, as a reliable prognosis tool to determine progression-free survival in mCRC patients. Overall, we developed a strategy that ameliorates the specificity and sensitivity in the detection of CTC, resulting in a robust and promising logistic model for the clinical management of metastatic colorectal cancer patients. PMID:22304365

  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. 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, ...

  16. 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...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

  17. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients

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    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.

  18. 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.

  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. Evaluation of magnetization transfer ratio in ascites and pelvic cystic masses

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Susumu [Nippon Medical School, Inba, Chiba (Japan). Chiba-Hokuso Hospital; Kato, Tomoyasu; Yamashita, Takashi [and others

    1997-12-01

    To investigate the feasibility of magnetization transfer contrast (MTC) in characterization of pelvic cystic masses and ascites, in vitro studies were performed. Cystic fluids were taken from operative specimens of ten ovarian cystic masses (five mucinous cystadenomas, one cystadenocarcinoma, two serous cystadenocarcinomas, two clear cell carcinomas) and three non-ovarian pelvic cysts (one paraovarian cyst, one pseudomyxoma peritonei, one pelvic abscess). Samples of ascitic flied were drawn by peritoneal puncture in twenty patients (thirteen with peritonitis carcinomatosa, five with liver dysfunction, two with renal dysfunction). Total protein content in ascitic fluids was measured. Magnetization transfer ratio (MTR) was calculated by the signal intensities under the gradient echo sequence with and without the application of off-resonance pulses. The relative signal intensities (RSI) relative to water in T{sub 1} and T{sub 2} weighted images were obtained using spin echo sequence. There was no correlation between histological type of pelvic mass and MTR and RSI. Good correlation (R{sup 2}=0.761) was obtained between MTR and protein content in ascitic fluids, whereas no correlation was noted between RSI and protein content in ascitic fluids. These results suggest that MTC is not useful in the characterization of pelvic masses but is applicable in the differentiation between exudative ascites and transudative ascites. (author)

  1. Changes of hepatic biochemical parameters and proteomics in broilers with cold-induced ascites

    Directory of Open Access Journals (Sweden)

    Wang Yongwei

    2012-12-01

    Full Text Available Abstract 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

  2. 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.

  3. 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.

    Science.gov (United States)

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly

    2016-01-01

    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. PMID:27341421

  4. A strategy to eradicate well-developed Krebs-2 ascites in mice.

    Science.gov (United States)

    Potter, Ekaterina A; Dolgova, Evgenia V; Proskurina, Anastasia S; Minkevich, Alexandra M; Efremov, Yaroslav R; Taranov, Oleg S; Omigov, Vladimir V; Nikolin, Valeriy P; Popova, Nelly A; Bayborodin, Sergey I; Ostanin, Alexander A; Chernykh, Elena R; Kolchanov, Nikolay A; Shurdov, Mikhail A; Bogachev, Sergey S

    2016-03-01

    We describe the strategy, which allows curing experimental mice engrafted with Krebs-2 ascites. The strategy is based on the facts that i) Krebs-2 tumor-initiating stem cells (TISCs) are naturally capable of internalizing fragments of extracellular double-stranded DNA (dsDNA); ii) upon delivery into TISCs, these dsDNA fragments interfere with the on-going DNA repair process so that TISCs either die or lose their tumorigenic potential. The following 3-step regimen of therapeutic procedures leading to eradication of Krebs-2 ascites is considered. Firstly, three timed injections of cyclophosphamide (CP) exactly matching the interstrand cross-link (ICL) repair phases that lead to synchronization of ascites cells in late S/G2/M. Secondly, additional treatment of ascites 18 hours post each CP injection (at NER/HR transition timepoint) with a composite dsDNA-based preparation interfering with the NER and HR repair pathways, so that tumorigenic properties of ascites cells are compromised. Thirdly, final treatment of mice with a combination of CP and dsDNA injections as ascites cells undergo apoptotic destruction, and the surviving TAMRA+ TISCs arrested in late S/G2/M phases massively enter into G1/S, when they regain sensitivity to CP+dsDNA treatment. Thus, this regimen assures that no viable cells, particularly Krebs-2 TISCs, remain.

  5. Influence of X-rays on early response gene expression in rat astrocytes and brain tumour cell lines

    International Nuclear Information System (INIS)

    The effects of ionizing radiation on c-fos, c-jun and jun-B mRNA levels were determined in cultures of rat perinatal type 1 astrocytes and two rat brain tumour cell lines, 175A and 9L. In astrocyte cultures X-ray doses as low as 1 Gy induced the expression of c-fos and jun-B but had essentially no effect on c-jun. The maximum increase in expression was found 1 h after irradiation, which then rapidly returned to control levels. These findings suggest that astrocytes may play a role in mediating the radiation response of the central nervous system via X-ray-induced changes in gene expression. In contrast, doses of up to 20 Gy had no effect on c-fos, c-jun and jun-B mRNA levels in the two brain tumour cell lines. In addition, whereas 12-0-tetradecanoylphorbol-13-acetate induced the expression of these genes in astrocytes, it had little or no effect on fos or jun expression in 9L or 175A cells. These results suggest that the signal transduction pathways mediating radiation-induced genes expression may be different in normal astrocytes and brain tumour cells. (author)

  6. The prosurvival activity of ascites against TRAIL is associated with a shorter disease-free interval in patients with ovarian cancer

    Directory of Open Access Journals (Sweden)

    Lane Denis

    2010-01-01

    Full Text Available Abstract Background The production of ascites is a common complication of ovarian cancer. Ascites constitute a unique tumor microenvironment that may affect disease progression. In this context, we recently showed that ovarian cancer ascites may protect tumor cells from TRAIL-induced apoptosis. In this study, we sought to determine whether the prosurvival effect of ascites affects disease-free intervals. Methods Peritoneal fluids were obtained from 54 women undergoing intra-abdominal surgery for suspected ovarian cancer (44 cancers and 10 benign diseases. The ability of peritoneal fluids to protect from TRAIL was assessed in the ovarian cancer cell line CaOV3, and IC50 were determined. The anti-apoptotic activity of 6 ascites against cisplatin, paclitaxel, doxorubicin, etoposide and vinorelbine was also assessed in CaOV3 cells, and the prosurvival activity of two ascites was assessed in 9 primary ovarian cancer cultures. Results Among the 54 peritoneal fluids tested, inhibition of TRAIL cytotoxicity was variable. Fluids originating from ovarian cancer were generally more protective than fluids from non-malignant diseases. Most of the 44 ovarian cancer ascites increased TRAIL IC50 and this inhibitory effect did not correlate strongly with the protein concentration in these ascites or the levels of serum CA125, a tumor antigen which is used in the clinic as a marker of tumor burden. The effect of ascites on cisplatin- and paclitaxel-induced cell death was assessed with 4 ascites having inhibitory effect on TRAIL-induced cell death and 2 that do not. The four ascites with prosurvival activity against TRAIL had some inhibitory on cisplatin and/or paclitaxel. Two ovarian cancer ascites, OVC346 and OVC509, also inhibited TRAIL cytotoxicity in 9 primary cultures of ovarian tumor and induced Akt activation in three of these primary cultures. Among a cohort of 35 patients with ascites, a threshold of TRAIL IC50 with ascites/IC50 without ascites > 2 was

  7. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

    Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

  8. Effect of administration of some antitumor extracts on Ehrlich ascites carcinoma-bearing mice

    International Nuclear Information System (INIS)

    Cancer is considered one of the most common causes of morbidity and mortality worldwide. Many researches have been studied on the discovery of natural and synthetic compounds that can be used in the prevention and/or treatment of cancer. Many chemo preventive agents have been associated with antiproliferative and apoptotic effects on cancer cells because of their high antioxidant activity. The present study was undertaken to investigate the antioxidant and antitumor effects of three natural extracts including (propolis, green tea and Chlorella vulgaris) without or with radiation exposure in Ehrlich ascites carcinoma (EAC) - bearing female albino mice. The animals were randomly distributed into three major groups as follows:- Group A (control group).This 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 tumor-bearing group and the second cage served as control for tumor-bearing group. Group B (Non tumor - bearing group).This group consists of 30 mice and used to study the effect of the vehicle solutions (gum acacia, DMSO), propolis, green tea, Chlorella vulgaris and gamma irradiation on normal mice. Mice of this group were equally distributed into six subgroups receiving gum acacia, DMSO, propolis, green tea and Chlorella vulgaris for two weeks and whole body gamma irradiated. Group C (Tumor- bearing group): This group consists of 160 mice randomly and equally distributed into 8 subgroups: Ehrlich ascites carcinoma(mice were inoculated with 2.5 x 106 intra-peretoneally(i.p), Ehrlich ascites carcinoma and 2 Gy irradiated, Ehrlich ascites carcinoma and propolis treated (150 mg/kg b.w), Ehrlich ascites carcinoma, propolis treated and irradiated, Ehrlich ascites carcinoma and green tea treated (150 mg/kg b.w), Ehrlich ascites carcinoma, green tea treated and irradiated, Ehrlich ascites carcinoma and Chlorella vulgaris treated (150 mg/kg b.w) and Ehrlich ascites

  9. Antiproliferative activity and apoptotic effects of Filipendula ulmaria pollen against C26 mice colon tumour cells

    Directory of Open Access Journals (Sweden)

    Mărgăoan Rodica

    2016-06-01

    Full Text Available Honeybee collected pollen exhibits high nutritional and pharmaceutical benefits for the human diet and medicine. Pollen’s antioxidant, anti-ageing, anti-inflammatory, anti-atherosclerosis, and cardioprotective activity, depending on the floral origin, are well known. Recent studies proposed that pollen may also be an excellent cancer-fighting candidate, as pollen harbours high amounts of phenolic substances. In our study, Filipendula ulmaria pollen (bee collected was methanol-water extracted and used to verify its in vitro pharmacological activities on C26 mice cancer tumour cells. Three different concentrations of the extract were tested in antitumour assays. Monitoring was done after 6, 12, 24, and 48 hours. Promising results were obtained for antiproliferative and apoptotic activity of the pollen extracts, with high efficiency for the highest concentration (1 mg/mL. For both activities, time and concentration-dependent effects were observed. Pollen extracts or bee collected pollen has a high potential as an antitumour agent for use in human medicine, because they are both rich in bioactive compounds.

  10. Influence of Coloured Correlated Noises on Probability Distribution and Mean of Tumour Cell Number in the Logistic Growth Model

    Institute of Scientific and Technical Information of China (English)

    HAN Li-Bo; GONG Xiao-Long; CAO Li; WU Da-Jin

    2007-01-01

    An approximate Fokker-P1anck equation for the logistic growth model which is driven by coloured correlated noises is derived by applying the Novikov theorem and the Fox approximation. The steady-state probability distribution (SPD) and the mean of the tumour cell number are analysed. It is found that the SPD is the single extremum configuration when the degree of correlation between the multiplicative and additive noises, λ, is in -1<λ ≤ 0 and can be the double extrema in 0<λ<1. A configuration transition occurs because of the variation of noise parameters. A minimum appears in the curve of the mean of the steady-state tumour cell number, 〈x〉, versus λ. The position and the value of the minimum are controlled by the noise-correlated times.

  11. Mathematical analysis and simulations involving chemotherapy and surgery on large human tumours under a suitable cell-kill functional response.

    Science.gov (United States)

    Rodrigues, Diego Samuel; de Arruda Mancera, Paulo Fernando

    2013-02-01

    Dosage and frequency of treatment schedules are important for successful chemotherapy. However, in this work we argue that cell-kill response and tumoral growth should not be seen as separate and therefore are essential in a mathematical cancer model. This paper presents a mathematical model for sequencing of cancer chemotherapy and surgery. Our purpose is to investigate treatments for large human tumours considering a suitable cell-kill dynamics. We use some biological and pharmacological data in a numerical approach, where drug administration occurs in cycles (periodic infusion) and surgery is performed instantaneously. Moreover, we also present an analysis of stability for a chemotherapeutic model with continuous drug administration. According to Norton and Simon [22], our results indicate that chemotherapy is less efficient in treating tumours that have reached a plateau level of growing and that a combination with surgical treatment can provide better outcomes.

  12. The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

    Science.gov (United States)

    Hunter, J E; Butterworth, J A; Zhao, B; Sellier, H; Campbell, K J; Thomas, H D; Bacon, C M; Cockell, S J; Gewurz, B E; Perkins, N D

    2016-06-30

    The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eμ-Myc lymphoma cells but, counterintuitively, c-rel-/- Eμ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel-/- Eμ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eμ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel-/- TCL1-Tg mice and RelA Thr505Ala mutant Eμ-Myc mice. Analysis of wild-type Eμ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel-/- mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-κB/IκB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-κB signalling in

  13. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  14. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.

    Science.gov (United States)

    Grover, P K; Cummins, A G; Price, T J; Roberts-Thomson, I C; Hardingham, J E

    2014-08-01

    Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.

  15. A spatio-temporal simulation model of the response of solid tumours to radiotherapy in vivo: parametric validation concerning oxygen enhancement ratio and cell cycle duration

    Science.gov (United States)

    Antipas, Vassilis P.; Stamatakos, Georgios S.; Uzunoglu, Nikolaos K.; Dionysiou, Dimitra D.; Dale, Roger G.

    2004-04-01

    Advanced bio-simulation methods are expected to substantially improve radiotherapy treatment planning. To this end a novel spatio-temporal patient-specific simulation model of the in vivo response of malignant tumours to radiotherapy schemes has been recently developed by our group. This paper discusses recent improvements to the model: an optimized algorithm leading to conformal shrinkage of the tumour as a response to radiotherapy, the introduction of the oxygen enhancement ratio (OER), a realistic initial cell phase distribution and finally an advanced imaging-based algorithm simulating the neovascularization field. A parametric study of the influence of the cell cycle duration Tc, OER, OERbgr for the beta LQ parameter on tumour growth, shrinkage and response to irradiation under two different fractionation schemes has been made. The model has been applied to two glioblastoma multiforme (GBM) cases, one with wild type (wt) and another one with mutated (mt) p53 gene. Furthermore, the model has been applied to a hypothetical GBM tumour with agr and bgr values corresponding to those of generic radiosensitive tumours. According to the model predictions, a whole tumour with shorter Tc tends to repopulate faster, as is to be expected. Furthermore, a higher OER value for the dormant cells leads to a more radioresistant whole tumour. A small variation of the OERbgr value does not seem to play a major role in the tumour response. Accelerated fractionation proved to be superior to the standard scheme for the whole range of the OER values considered. Finally, the tumour with mt p53 was shown to be more radioresistant compared to the tumour with wt p53. Although all simulation predictions agree at least qualitatively with the clinical experience and literature, a long-term clinical adaptation and quantitative validation procedure is in progress.

  16. Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

    OpenAIRE

    Ahitagni Biswas; Pramod Kumar Julka

    2016-01-01

    Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13 year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the...

  17. Hypoxia and prostaglandin E receptor 4 signalling pathways synergise to promote endometrial adenocarcinoma cell proliferation and tumour growth.

    Directory of Open Access Journals (Sweden)

    Rob D Catalano

    Full Text Available The prostaglandin endoperoxide synthase (PTGS pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG E(2. PTGS2 expression and PGE(2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE(2 regulate endometrial tumour growth is unknown. Here we investigated (a the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3 and PGE receptors (PTGER1-4 in endometrial adenocarcinomas compared with normal endometrium and (b the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE(2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE(2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells.

  18. Effect of Honey and Eugenol on Ehrlich Ascites and Solid Carcinoma

    OpenAIRE

    Saravana Kumar Jaganathan; Dilip Mondhe; Wani, Z. A.; Pal, Harish C.; Mahitosh Mandal

    2010-01-01

    Ehrlich ascites carcinoma is a spontaneous murine mammary adenocarcinoma adapted to ascites form and carried in outbred mice by serial intraperitoneal (i/p) passages. The previous work from our laboratory showed that honey having higher phenolic content was potent in inhibiting colon cancer cell proliferation. In this work, we extended our research to screen the antitumor activity of two selected honey samples and eugenol (one of the phenolic constituents of honey) against murine Ehrlich asci...

  19. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  20. Antioxidant activity and cytotoxicity on tumour cells of the essential oil from Cedronella canariensis var. canariensis (L.) Webb & Berthel. (Lamiaceae).

    Science.gov (United States)

    Zorzetto, Christian; Sánchez-Mateo, Candelaria C; Rabanal, Rosa M; Lupidi, Giulio; Bramucci, Massimo; Quassinti, Luana; Iannarelli, Romilde; Papa, Fabrizio; Maggi, Filippo

    2015-01-01

    Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic to the Canary Islands where it is used in the traditional medicine to prepare infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant, hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this work we investigated for the first time the antioxidant activity of the essential oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116) proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed by GC-ionisation flame detector and GC-MS, was characterised by pinocarvone (58.0%) and β-pinene (10.8%) as the major constituents, being typical of the chemotype 'canariensis'. Noteworthy was the cytotoxic activity of the oil against the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 μg/mL on A375, MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging activity against the ABTS radical (IC50 of 10.5 μg/mL). PMID:25560780

  1. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

    1992-07-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

  2. A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer

    International Nuclear Information System (INIS)

    In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage. Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case. We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the “Reverse Warburg effect” in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor

  3. Analysis of Normal-Tumour Tissue Interaction in Tumours: Prediction of Prostate Cancer Features from the Molecular Profile of Adjacent Normal Cells

    OpenAIRE

    Trevino, Victor; Tadesse, Mahlet G.; Vannucci, Marina; Al-Shahrour, Fatima; Antczak, Philipp; Durant, Sarah; Bikfalvi, Andreas; Dopazo, Joaquin; Campbell, Moray J.; Falciani, Francesco

    2011-01-01

    Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the t...

  4. Efficacy of temoporfin-loaded invasomes in the photodynamic therapy in human epidermoid and colorectal tumour cell lines.

    Science.gov (United States)

    Dragicevic-Curic, Nina; Gräfe, Susanna; Gitter, Burkhard; Fahr, Alfred

    2010-12-01

    In the case of cutaneous malignant or non-malignant diseases, topical photodynamic therapy (PDT) with a temoporfin (mTHPC)-containing formulation would be advantageous. Unfortunately, mTHPC is a highly hydrophobic drug with low percutaneous absorption and novel mTHPC-loaded invasomes for enhanced skin delivery were developed. The purpose of this study was to investigate photodynamic efficacy of mTHPC-loaded invasomes in vitro in two cell lines, i.e. the human colorectal tumour cell line HT29 and the epidermoid tumour cell line A431. Invasomes are vesicles containing besides phospholipids a mixture of terpenes or only one terpene and ethanol. Dark toxicity, phototoxicity and intracellular localization of mTHPC were studied. Laser scanning microscopy indicated perinuclear localization of mTHPC. Results revealed that mTHPC-invasomes and mTHPC-ethanolic solution used at a 2μM mTHPC-concentration and photoirradiation at 20J/cm(2) were able to reduce survival of HT29 cells and especially of A431 cells, being more sensitive to PDT. In contrast to HT29 cells, where there was not a significant difference between cytotoxicity of mTHPC-ethanolic solution and mTHPC-invasomes, in A431 cells mTHPC-invasomes were more cytotoxic. Survival of about 16% of A431 cells treated with mTHPC-invasomes is very promising, since it demonstrates invasomes' potential to be used in topical PDT of cutaneous malignant diseases.

  5. Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours

    DEFF Research Database (Denmark)

    Lassen, U; Daugaard, G; Eigtved, A;

    2003-01-01

    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 tumo...... predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.......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......-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false...

  6. Cell swelling activates K+ and Cl- channels as well as nonselective, stretch-activated cation channels in ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Christensen, Ove; Hoffmann, Else Kay

    1992-01-01

    external K+ is estimated at about 7 pS. A K+ channel with similar properties can be activated in the cellattached mode by addition of Ca2+ plus ionophore A23187. The channel is also activated by cell swelling, within 1 min following hypotonic exposure. No evidence was found of channel activation...... by membrane stretch (suction). The time-averaged number of open K+ channels during regulatory volume decrease (RVD) can be estimated at 40 per cell. The number of open K+ channels following addition of Ca2+ plus ionophore A23187 was estimated at 250 per cell. Concurrent activation in cell-attached patches...... in the cell-attached mode could be activated by addition of Ca2+ plus ionophore A23187. The channel is also activated by hypotonic exposure with a single-channel conductance at 7 pS (or less) and with a time delay at about 1 min. The number of open channels during RVD is estimated at 80 per cell. Two other...

  7. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

    DEFF Research Database (Denmark)

    Kristensen, Dina Graae; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa;

    2013-01-01

    Foetal development of germ cells is a unique biological process orchestrated by cellular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study....... In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3......K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigenetic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic...

  8. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, Q; Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Lum, J J [Deeley Research Centre, BC Cancer Agency, Vancouver Island Centre, Victoria BC V8R 6V5 (Canada); Brolo, A G, E-mail: qmatthew@uvic.ca, E-mail: jirasek@uvic.ca [Department of Chemistry, University of Victoria, Victoria BC V8W 3V6 (Canada)

    2011-11-07

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF{sub 2} > 0.6) and the R3 cell lines are radiosensitive (SF{sub 2} < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1

  9. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    Science.gov (United States)

    Matthews, Q.; Jirasek, A.; Lum, J. J.; Brolo, A. G.

    2011-11-01

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF2 > 0.6) and the R3 cell lines are radiosensitive (SF2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the regulated synthesis and

  10. The Anti-tumor Immunity of Dendritic Cells Modified by IFN γ Gene on Mice Bearing Ascite Hepatoma Cell H22

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 Introduction Dendritc cell (DC)-based cancer vaccines have shown to been effective both in clinical trials and in animal tumor models. Some clinical trials have been on the phase Ⅲ, but some problems are challenging now. The functions of DC from patient with malignant tumor were depressed by tumor-secreting cytokines such as IL-10. it is critical to find out some methods to improve DC differentiation maturation for priming naive T cells and initiating the specific anti-tumor immunity effectively. IFNγ is ...

  11. The Anti-tumor Immunity of Dendritic Cells Modified by IFN γ Gene on Mice Bearing Ascite Hepatoma Cell H22

    Institute of Scientific and Technical Information of China (English)

    Zi-You CUI; Hong-Yan YANG; You-Tian HUANG; Zhi-min ZHENG; Ming-Yao ZHAO; Zi-Ming DONG

    2005-01-01

    @@ 1 Introduction Dendritc cell (DC)-based cancer vaccines have shown to been effective both in clinical trials and in animal tumor models. Some clinical trials have been on the phase Ⅲ , but some problems are challenging now. The functions of DC from patient with malignant tumor were depressed by tumor-secreting cytokines such as IL-10. it is critical to find out some methods to improve DC differentiation maturation for priming naive T cells and initiating the specific anti-tumor immunity effectively. IFNγ is a pluripotent cytokine that can exert more the expressions of different molecules in various cells. Now, some data have shown that DCs can produce IFNγ and IFNγ can promote the maturation of DCs, which plays very important roles in promoting protective immune response as the same as IFNγ produced in NK and NKT cells. In our research,we transfected IFNγ gene into DCs in order to investigate the effect of IFNγ on DCs and monitor the anti-tumor response of the tumor bearing mice after vaccination by IFNγ-modified DCs.

  12. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    Science.gov (United States)

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-07-16

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer.

  13. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    Science.gov (United States)

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-09-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer. PMID:26183450

  14. Molecular characterization of c-Abl/c-Src kinase inhibitors targeted against murine tumour progenitor cells that express stem cell markers.

    Directory of Open Access Journals (Sweden)

    Thomas Kruewel

    Full Text Available BACKGROUND: The non-receptor tyrosine kinases c-Abl and c-Src are overexpressed in various solid human tumours. Inhibition of their hyperactivity represents a molecular rationale in the combat of cancerous diseases. Here we examined the effects of a new family of pyrazolo [3,4-d] pyrimidines on a panel of 11 different murine lung tumour progenitor cell lines, that express stem cell markers, as well as on the human lung adenocarcinoma cell line A549, the human hepatoma cell line HepG2 and the human colon cancer cell line CaCo2 to obtain insight into the mode of action of these experimental drugs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with the dual kinase inhibitors blocked c-Abl and c-Src kinase activity efficiently in the nanomolar range, induced apoptosis, reduced cell viability and caused cell cycle arrest predominantly at G0/G1 phase while western blot analysis confirmed repressed protein expression of c-Abl and c-Src as well as the interacting partners p38 mitogen activated protein kinase, heterogenous ribonucleoprotein K, cyclin dependent kinase 1 and further proteins that are crucial for tumour progression. Importantly, a significant repression of the epidermal growth factor receptor was observed while whole genome gene expression analysis evidenced regulation of many cell cycle regulated genes as well integrin and focal adhesion kinase (FAK signalling to impact cytoskeleton dynamics, migration, invasion and metastasis. CONCLUSIONS/SIGNIFICANCE: Our experiments and recently published in vivo engraftment studies with various tumour cell lines revealed the dual kinase inhibitors to be efficient in their antitumour activity.

  15. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  16. p53 Expression Helps Identify High Risk Oral Tongue Pre- malignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases.

    Science.gov (United States)

    Viveka, Thangaraj Soundara; Shyamsundar, Vidyarani; Krishnamurthy, Arvind; Ramani, Pratibha; Ramshankar, Vijayalakshmi

    2016-01-01

    Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.

  17. Cell Biological Markers in Breast Tumours: Applications in cyto- and histopathology

    NARCIS (Netherlands)

    V. Kuenen-Boumeester (Vibeke)

    1998-01-01

    textabstractBreast cancer is the most common malignant tumour among women in the western world, affecting 8-12 % of the female population. In the Netherlands, breast cancer occurs yearly in IOOO per IOO,OOO women with an absolute incidence of 9,000 new cases per year. The etiology is multifactorial.

  18. Evaluation of CD25-positive cells in relation to the subtypes and prognoses in various lymphoid tumours in dogs.

    Science.gov (United States)

    Mizutani, Noriyuki; Goto-Koshino, Yuko; Tsuboi, Masaya; Kagawa, Yumiko; Ohno, Koichi; Uchida, Kazuyuki; Tsujimoto, Hajime

    2016-05-01

    Interleukin-2 receptor alpha chain (CD25) expression has been reported in human lymphoid tumours and suggested to correlate with the prognosis. In this study, we detected CD25-positive cells in various types of lymphoid tumours in dogs. Immunohistochemical analyses of the tissues from diffuse large B-cell lymphoma (DLBCL) (n = 6), T-zone lymphoma (TZL) (n = 5), and follicular lymphoma (FL) (n = 2) revealed that cells strongly positive for CD25 were observed generally in accordance with lymphoma cell localization. CD25-positive cells were consistently detected in TZL and FL cases; however, the number of CD25-positive cells was variable among DLBCL cases. Furthermore, we evaluated the rate of CD25-positive cells by flow cytometric analysis in 29 dogs with lymphoid malignancies, including high-grade B-cell lymphoma (n = 17), TZL (n = 5), FL (n = 2), cutaneous lymphoma (n=2), and acute lymphoblastic leukaemia (ALL) (n = 3). CD25-positivity in the lymph node cells was significantly higher in dogs with high-grade B-cell lymphoma (mean ± SD, 49.6 ± 31.3%) or TZL (mean ± SD, 80.2 ± 10.0%) than that in healthy dogs (mean ± SD, 9.8 ± 2.8%). In prognostic analysis of 15 cases with high-grade B-cell lymphoma, the progression-free survival was significantly shorter in CD25-high group than that in CD25-low group. The results obtained in this study are useful for subtype differentiation and prognostic analysis of canine lymphomas and future development of molecular-targeted therapy directed at CD25.

  19. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours

    OpenAIRE

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-01-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the V600 EBRAF-driven mouse lung model that develop premalignant lesions to understand stroma–tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalign...

  20. 超声引导经皮门静脉穿刺干细胞移植治疗肝硬化顽固性腹水的疗效观察%Clinical observation of hepatic stem cell transplantation on liver cirrhosis with refractory ascites by ultrasonic guided percutaneous portal vein puncture

    Institute of Scientific and Technical Information of China (English)

    孙厚坦; 杨峰; 赵威武; 闫保华; 陈朝旻; 徐晓燕

    2012-01-01

    Objective To observe the clinical curative effect of autologous stem cells transplantation for decompensated on liver cirrhosis with refractory ascites by ultrasonic guided percutaneous portal vein puncture. Methods For treatment group A ( 64 cases ) of liver cirrhosis with refractory ascites, autologous stem cell was transplanted in liver by ultrasonic guided percutaneous portal vein puncture in the conventional therapy. We gathered materials of 87 cases with liver cirrhosis with refractory ascites of infectious disease department of our hospital and transplanted autologous stem cell into hepatic artery multilevel branch by pipe in the conventional therapy as control group( Bl ); Control group( B2 )was given conventional therapy. Observe the clinical symptoms after transplantation, postoperative adverse reaction, time of ascites continued tonormal, liver and kidney function, compared with the control materials and made statistical analysis. Results The ascites had a certain degree of relief after stem cells transplantation, the increment speed of ascites slowed after treatment; both treatment group( A )and control group ( Bl )patients'liver and kidney function got better obviously,laboratory indicators were better,there was no significant difference between contrast P > 0. 05 ). But treatment group ( A ) was better than that of control group ( B2 )( P 0.05).与对照组(B2)比较,腹水增长速度、肝肾功能、实验室指标改善改善情况均优于对照组(B2),差异有统计学意义(P<0.05).术后不良反应及并发症治疗组(A)少于对照组(B1),差异有统计学意义(P<0.05).结论 自体骨髓干细胞移植治疗肝硬化是目前治疗肝硬化顽固性腹水的一种有效手段,采用超声引导经皮门静脉穿刺干细胞移植治疗肝硬化与肝动脉多级分支自体骨髓干细胞移植疗效一致;经皮门静脉穿刺干细胞移植治疗肝硬化腹水安全有效且不良反应小,可作为中晚期肝硬化患者的临床治疗方案.

  1. Differential Diagnosis of a Severe Late Onset Ovarian Hyperstimulation Syndrome Associated with Prolonged Ascites Production – a Case Report

    Directory of Open Access Journals (Sweden)

    Ujvari E

    2005-01-01

    Full Text Available Capsule: A case of severe late onset ovarian hyperstimulation syndrome (OHSS with prolonged ascites production. Difficulties of differential diagnosis and management. Objective: This report describes a case of extremely prolonged, severe ovarian hyperstimulation syndrome. Results: 17 litres of ascites have been removed from the abdominal cavity by repeated paracenteses until the 25th week of pregnancy, which progressed after the complete resolution of symptoms to the 34th week, when cesarean section was done. Conclusion: Severe ovarian hyperstimulation syndrome can occasionally follow an unusually prolonged course. Chronic formation of abundant ascites, the presence of ovarian enlargement and elevated levels of certain tumour markers might raise the probability of ovarian cancer. Adequate differential diagnosis and management resulted in delivery of a healthy newborn.

  2. EXPERIENCE WITH INTRAPERITONEAL CHEMOTHERAPY USING ASCITIC FLUID AS A SOLVENT OF CHEMICALS IN THE TREATMENT OF OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2009-01-01

    Full Text Available Thirty two with the ascitic form of Stages IIIC—IV ovarian cancer underwent 1 to 3 courses of intraperitoneal multidrug therapy using a protein ascitic fluid concentrate (PAFC as a solvent of drugs (cisplatin, cyclophosphan, doxorubicin according to the CAP regimen. The induction chemotherapy allowed remission to be achieved in 78.1% of cases (against 40% with standard intraperitoneal therapy, the stan- dard volume of surgical treatment was performed in 28 (87.5% patients (21 (70% receiving the control regime; with the use of PAFC, the size of minimum residual tumour (less than 1 cm was achieved in 81.3% versus 63.3% with standard intraperitoneal chemotherapy. This treatment enables the use large-dose chemotherapy regimens that cause no severe systemic toxic reactions. The method is highly-effective, low-toxic and may be recommended for the treatment of patients with the ascitic form of Stages III—IV ovarian cancer.

  3. Eosinophil-activating factor (EAF) production by a human cell line (ESH 98) stimulated with tumour necrosis factor.

    Science.gov (United States)

    Thorne, K J; Richardson, B A; Butterworth, A E; Stanley, M

    1988-03-01

    A new cell line has been produced by fusing human cervical keratinocytes with HeLa cells. This cell line secretes eosinophil-activating activity upon stimulation with tumour necrosis factor (TNF). About one-third of the eosinophil-activating activity co-purifies with eosinophil-activating factor (EAF) from mononuclear cell supernatants. The purification procedure indicates that it resembles EAF in molecular weight and acidity. It also resembles EAF in its effect on eosinophils. Not only does it enhance the cytotoxic activity of eosinophils to antibody-coated schistosomula of Schistosoma mansoni, but it also increases the oxidative activity of eosinophils, as measured by reduction of nitroblue tetrazolium, and changes the morphology of eosinophils, affecting the distribution of F-actin in the cell.

  4. Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

    Science.gov (United States)

    Yeku, Oladapo O; Brentjens, Renier J

    2016-04-15

    Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the 'armor' agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms.

  5. Anti-tumour efficacy of mouse spleen cells separated with Dolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells.

    OpenAIRE

    Okada, T.; Higuchi, M.; Takano, M; Maruyama, T.; Imai, Y; Osawa, T

    1990-01-01

    Anti-tumour effector cells were generated through 4 days culture of normal C57BL/6 splenocytes in a medium containing concanavalin A supernatant and then fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (non-agglutinable with DBA) cells. The DBA- cells, infused intravenously into mice together with B16 melanoma cells, or adoptively transferred into mice 3 days after the injection of B16 cells, caused a marked decrease in the number of lung nodules, w...

  6. Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin

    Science.gov (United States)

    Medina, Carlos; Harmon, Shona; Inkielewicz, Iwona; Santos-Martinez, Maria Jose; Jones, Michael; Cantwell, Paula; Bazou, Despina; Ledwidge, Mark; Radomski, Marek W; Gilmer, John F

    2012-01-01

    BACKGROUND AND PURPOSE Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the pharmacological effects of a new group of isosorbide-based aspirin prodrugs on TCIPA. EXPERIMENTAL APPROACH TCIPA was induced in human platelets by mixing with human adenocarcinoma or fibrosarcoma cells under no flow and flow conditions. The release of gelatinases and P-selectin expression during TCIPA were studied by zymography and flow cytometry respectively. KEY RESULTS Tumour cells caused platelet aggregation. This aggregation resulted in the release of MMP-2 and a significant up-regulation of P-selectin on platelets, indicative of platelet activation. Pharmacological modulation of TCIPA revealed that ST0702, one of the aspirin prodrugs, down-regulated TCIPA while aspirin was ineffective. The deacetylated metabolite of ST0702, 5-nicotinate salicylate (ST0702 salicylate), down-regulated both ADP-stimulated platelet aggregation and TCIPA. CONCLUSIONS AND IMPLICATIONS Our results show that ST0702 was an effective inhibitor of TCIPA in vitro. Its deacetylated metabolite may contribute to the effects of ST0702 by inhibiting ADP-mediated TCIPA. PMID:22122360

  7. Molecular profiling of tumour budding implicates TGFβ-mediated epithelial–mesenchymal transition as a therapeutic target in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, David Hebbelstrup; Dabelsteen, Erik; Specht, Lena;

    2015-01-01

    collected from oral squamous cell carcinoma (OSCC) specimens using laser capture microdissection and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature comprising factors involved...

  8. Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

    Directory of Open Access Journals (Sweden)

    VIVIAN M. RUMJANEK

    2001-03-01

    Full Text Available Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed.A resistência a múltiplos fármacos é o principal obstáculo no tratamento de pacientes com câncer. O mecanismo responsável pela resistência múltipla mais bem caracterizado envolve a expressão do produto do gene MDR-1, a glicoproteína P. Entretanto, o processo de resistência tem fatores múltiplos. Estudos de mecanismos de resistência m��ltipla a fármacos têm dependido da análise de linhagens celulares tumorais que foram selecionadas e apresentam reatividade cruzada a uma ampla faixa de agentes anti-tumorais. Este trabalho caracteriza uma linhagem celular com múltipla resistência a fármacos, selecionada originalmente pela resistência ao alcalóide de Vinca vincristina e derivado

  9. Cytokines and soluble tumour necrosis factor I receptor levels during pretransplant conditioning in allogeneic stem-cell transplantation

    DEFF Research Database (Denmark)

    Andersen, Johnny; Heilmann, Carsten; Jacobsen, Niels;

    2005-01-01

    The inflammatory response induced by the conditioning regime may be related to the outcome in allogeneic stem-cell transplantation (SCT). However, previous statements concerning the prognostic significance of cytokine measurements during conditioning have not been conclusive. We investigated...... a broad range of cytokines in plasma samples drawn daily immediately before start of pretransplant conditioning and during the conditioning. The presented data indicate that single-day measurements of inflammatory cytokines during conditioning may lead to unreliable conclusions concerning their prognostic...... significance. However, serial quantitation of soluble tumour necrosis factor receptor I (sTNFRI) is more likely to reflect the degree of inflammatory activation induced by pretransplant conditioning....

  10. The radiation response of V79 and human tumour multicellular spheroids - cell survival and growth delay studies

    International Nuclear Information System (INIS)

    Chinese hamster cells (V79 379A), cells from a human small cell carcinoma of the lung (ME/MAR) and two xenografted human melanomas (HX117 and HX118) have been grown as multicellular spheroids in vitro. The radiation response of these four cell types has been compared when grown as spheroids (200 or 400 μm in diameter) and as single cells from disaggregated spheroids. The radiation sensitivity of the three human lines irradiated as single cells in air, is similar. In comparison, the V79 cells are more radioresistant. Only the V79 and HX118 cells show a spheroid size dependent radiation response. The radiation response of spheroids has been assayed using both cell survival and growth delay. V79, ME/MAR and HX117 cells demonstrate a good correlation between the two endpoints whereas with HX118 there appears to be greater cell kill for a given level of growth delay. This may be because HX118 is efficient in the repair of potentially lethal damage (PLD). The results support the view that extrinsic factors such as three dimensional contact, hypoxia and repair of PLD can be important and together with the intrinsic cell radiosensitivity will determine the radiation response of tumours. (author)

  11. An Unusual Presentation of Desmoplastic Small Round Cell Tumour of the Abdomen: Morphological, Immunohistochemical, Ultrastructural, and Molecular Studies

    Directory of Open Access Journals (Sweden)

    Preethika Angunawela

    2011-01-01

    Full Text Available Desmoplastic small round cell tumour (DSRCT is an aggressive and a rare neoplasm. We report on a 34-year-old male who had abdominal discomfort with a large intraperitoneal mass. Histological examination of the tumour biopsy revealed sheets of small round cells. The cells were positive with vimentin and desmin (with occasional dot positivity and negative for WT1 and CD 99 with immunohistochemistry. Cytogenetics showed a translocation disrupting the EWSR 1 gene on 22 q 12 consistent with DSRCT. Electron microscopic examination showed sparse cytoplasmic organelles. The patient succumbed 34 months from disease presentation after multiple chemotherapies and thereafter radiotherapy. In summary, our case exemplifies that it is crucial to combine clinical, histological, and molecular aspects in diagnosing DSRCT especially when characteristic dot positivity with desmin is weak along with deficient marking of WT1 and CD99 by immunohistochemistry. Histology was also less clear than published examples of this entity with a poor desmoplastic response. A multidisciplinary approach including early referral to specialised centres is recommended in these cases as tertiary referral centres will be required to substantiate the diagnosis.

  12. The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?

    Science.gov (United States)

    Boussabbeh, Manel; Ben Salem, Intidhar; Rjiba-Touati, Karima; Bouyahya, Chedy; Neffati, Fadwa; Najjar, Mohamed Fadhel; Bacha, Hassen; Abid-Essefi, Salwa

    2016-05-01

    Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models. PMID:26619846

  13. The presence of elafin, SLPI, IL1-RA and STNFα RI in head and neck squamous cell carcinomas and their relation to the degree of tumour differentiation

    Directory of Open Access Journals (Sweden)

    U. Westin

    2002-01-01

    Full Text Available Biopsy samples of head and neck carcinomas were investigated with regard to elafin, secretory leukocyte protease inhibitor (SLPI, interleukin 1-receptor antagonist [(IL1-RA] and soluble tumour necrosis factor α receptor antagonist (STNFα RI. SLPI and elafin are serine protease inhibitors produced in the serous cells of the upper respiratory airways and in the keratinocytes, respectively. We have now found the presence of elafin and SLPI in squamous cell carcinomas of the upper respiratory tract (tonsillar, hypopharyngeal, tongue, mouth floor, gingival and laryngeal cancer. Significantly higher amounts of SLPI and elafin are present in well-differentiated and moderately differentiated tumours than in poorly differentiated tumours (p<0.0001 and p<0.0015. Tumour necrosis factor-α and IL-1β have been shown to stimulate the production of SLPI and elafin. Since these cytokines can both be difficult to detect, we chose to study their inhibitors, STNF α RI and IL1-RA, instead. IL1-RA was expressed in highly differentiated tumours as well as in poorly differentiated ones. No significant difference was seen between the groups. STNF α RI was only found in very small amounts, sparsely distributed in the tumours, and was not related to the degree of differentiation.

  14. Mouse Model of Devil Facial Tumour Disease establishes that an effective immune response can be generated against the cancer cells

    Directory of Open Access Journals (Sweden)

    Terry L Pinfold

    2014-05-01

    Full Text Available The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD. DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.

  15. Garcinol inhibits tumour cell proliferation, angiogenesis, cell cycle progression and induces apoptosis via NF-κB inhibition in oral cancer.

    Science.gov (United States)

    Aggarwal, Sadhna; Das, Satya N

    2016-06-01

    Garcinol, a polyisoprenylated benzophenone is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Its ability to inhibit tumour growth has been demonstrated in certain cancers. In this study, we evaluated the potential anti-tumour effects of garcinol on oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines (SCC-4, SCC-9 and SCC-25) were treated with garcinol for 48 h and its effect on growth and proliferation, clonogenic survival, cell cycle and apoptosis was studied by MTT, clonogenic assay, propidium iodide (PI) staining and annexin-V binding assay, respectively. The alteration in expression of NF-κB and COX-2 was studied by western blot analysis and that of VEGF by ELISA. Garcinol treatment significantly (p < 0.001) inhibited the growth and proliferation and colony formation of OSCC cells with a concomitant induction of apoptosis and cell cycle arrest. It did not show toxic effect on normal cells. It significantly (p < 0.05) reduced the expression of NK-κB and COX-2 expression in treated cells as compared to untreated controls besides inhibiting VEGF expression. It appears that garcinol exerts anti-proliferative, pro-apoptotic, cell-cycle regulatory and anti-angiogenic effects on oral cancer cells through inhibition of NF-κB and COX-2. Thus, garcinol may be developed as a potential chemopreventive and/or chemotherapeutic agent for treatment of oral squamous cell carcinoma. PMID:26662963

  16. Four Cases of Chylous Ascites following Robotic Gynecologic Oncological Surgery

    Directory of Open Access Journals (Sweden)

    Ahmet Göçmen

    2014-01-01

    Full Text Available Chylous ascites is an uncommon form of ascites characterized by milky-appearing fluid caused by blocked or disrupted lymph flow through chyle-transporting vessels. The most common causes of chylous ascites are therapeutic interventions and trauma. In this report, we present four cases of chylous ascites following robot-assisted surgery for endometrial staging and the treatment strategies that we used. After retroperitoneal lymph node dissection, leaving a drain is very useful in diagnosing chylous ascites and observing its resolution; furthermore, the use of octreotide in conjunction with TPN appears to be an efficient treatment modality for chylous ascites and should be considered before any invasive intervention.

  17. A laser-based technology for fabricating a soda-lime glass based microfluidic device for circulating tumour cell capture.

    Science.gov (United States)

    Nieto, Daniel; Couceiro, Ramiro; Aymerich, Maria; Lopez-Lopez, Rafael; Abal, Miguel; Flores-Arias, María Teresa

    2015-10-01

    We developed a laser-based technique for fabricating microfluidic microchips on soda-lime glass substrates. The proposed methodology combines a laser direct writing, as a manufacturing tool for the fabrication of the microfluidics structures, followed by a post-thermal treatment with a CO2 laser. This treatment will allow reshaping and improving the morphological (roughness) and optical qualities (transparency) of the generated microfluidics structures. The use of lasers commonly implemented for material processing makes this technique highly competitive when compared with other glass microstructuring approaches. The manufactured chips were tested with tumour cells (Hec 1A) after being functionalized with an epithelial cell adhesion molecule (EpCAM) antibody coating. Cells were successfully arrested on the pillars after being flown through the device giving our technology a translational application in the field of cancer research. PMID:26218523

  18. Radiosensitivity in vitro of clonogenic and non-clonogenic glioblastoma cells obtained from a human brain tumour

    Energy Technology Data Exchange (ETDEWEB)

    Buronfosse, A.; Thomas, C.P.; Ginestet, C.; Dore, J.F. [Centre de Lutte Contre le Cancer Leon-Berard, 69 - Lyon (France)

    1994-11-01

    Cells obtained from a human glioblastoma (G5) were characterized and used to develop an assay measuring their radiosensitivity in vitro. Surviving fractions were estimated 12 days after irradiation by image analysis of the total surface occupied by the cells. This report evaluates 4 experimental factors which may influence the radiosensitivity in vitro of G5 cells: passage number, delay between plating and irradiation, cell density and clonal heterogeneity. The radiosensitivity of the G5 cell line was found to be passage-independent at least between passages 12 and 75. Experimental conditions influence the radiosensitivity as surviving fraction at 2 Gy (SF2) range from 90% (5 000 cells/well, irradiation 72 h after seeding) to 49% (2 500 cells per well, irradiation 24 h after seeding). The heterogeneity of the radiosensitivity is large at the clonal level as SF2 of six clones isolated from the G5 line were 45%, 50%, 72%, 74%, 79% and 84%. Finally, when G5 cells were irradiated at low cell density and at the beginning of the growth phase, the radiosensitivity measured with this assay is comparable to that obtained with a standard colony assay. We propose that this assay may be useful to determine the intrinsic radiosensitivity of cells obtained from human tumours. (authors). 24 refs., 8 figs., 2 tabs.

  19. The cancer process as a type of immunocomplex hypersensibility involving C3b, natural killer cytotoxicity and antibody-dependent cell cytotoxicity: proposals for tumour immunotherapy and vaccine.

    Science.gov (United States)

    Manzo, G

    1998-05-01

    I have previously assumed that stem tumour cells are 'para-embryonal cells' (PECs) poor or missing in major histocompatibility complex (MHC) antigens. PECs might induce adjoining differentiated hyperplastic cells to also express tumoral phenotype and properties, thus transforming them into 'differentiated para-embryonal cells' (DPECs), MHC-endowed. In such a way, PECs, MHC-lacking, would be automatically surrounded by DPECs, MHC-endowed: this tumour organization was experimentally found by Cordon-Cardo et al in a variety of cancers. Now, I suggest that such a tumour histology might preferentially induce an anti-DPEC T cell immune response which, sparing PECs, might release increasing amounts of DPEC antigens in the peritumour site. DPEC antigens might increase synthesis of specific antibodies and subsequent immunocomplex formation at the peritumour site. Here, abundant immunocomplexes might react through their Fc pieces with CD16 receptors of antibody-dependent cell cytotoxicity (ADCC)-endowed immune cells (natural killer (NK) cells, macrophages, polymorphonuclear cells). These cells would thus be stimulated to secrete their lytic factors before and without their coming into contact with target tumour cells. On the other hand, abundant immunocomplexes at the peritumour site might massively activate the complement system, thus generating large amounts of C3b. C3b might react with CD11b receptors of NK cells, stimulating them to also secrete their lytic factors in an ectopic way at the peritumour site, thus impairing NK cytotoxicity. In such a way, in the absence of ADCC and NK cytotoxicity, a tumour cell enhancement might easily occur. In the light of these ideas, a strategy for antitumour immunotherapy and vaccine is then proposed. PMID:9681920

  20. Genetic Modification of Cancer Cells Using Non-Viral, Episomal S/MAR Vectors for In Vivo Tumour Modelling

    OpenAIRE

    Orestis Argyros; Suet Ping Wong; Kate Gowers; Richard Paul Harbottle

    2012-01-01

    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 genotoxi...

  1. The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

    Directory of Open Access Journals (Sweden)

    Delbé Jean

    2011-05-01

    Full Text Available Abstract Background Heparin affin regulatory peptide (HARP, also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136 was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit in vitro and in vivo the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop. Methods A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. In vitro, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. In vivo, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. In vivo anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay. Results Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. In vitro, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an in vivo Matrigel™ plug assay in mice Conclusions Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on in vitro and in vivo growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP

  2. The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

    International Nuclear Information System (INIS)

    Heparin affin regulatory peptide (HARP), also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136) was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit in vitro and in vivo the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop. A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. In vitro, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. In vivo, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day) for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. In vivo anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay. Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. In vitro, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an in vivo Matrigel™ plug assay in mice Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on in vitro and in vivo growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP receptors (ALK, RPTPβ/ζ, nucleolin). In vivo, the P111

  3. Feasibility study of FDG PET/CT-derived primary tumour glycolysis as a prognostic indicator of survival in patients with non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Aim: To assess the feasibility and prognostic value of measuring total lesion glycolysis of the primary tumour (TLGprimary) using combined 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in patients with proven or suspected non-small-cell lung cancer (NSCLC) in the routine diagnostic setting. Materials and methods: At the All wales Research and Diagnostic Positron Emission Tomography Centre in Cardiff (PETIC), in the calendar year 2011, 288 consecutive patients were identified with a single pulmonary mass in whom NSCLC was confirmed or clinically diagnosed following multidisciplinary team review. In a retrospective analysis, for each patient the PET-derived volume of the primary tumour and SUVMEAN was calculated using adaptive thresholds of 40% and 50% of the SUVMAX of the primary tumour. The TLGprimary (calculated by volume x SUVMEAN) was calculated at these two thresholds and was used to predict survival in a multivariate analysis with TNM (tumour, node, metastasis) stage, age, sex, and SUVMAX. The primary endpoint was overall survival over a minimum follow-up of at least 7 months. Results: In virtually every case, the primary tumour could be measured using the automated software with minimal use of manual adjustments. In multivariate analysis, TNM clinical stage, log(TLGprimary) and sex were independent predictors of overall survival. Conclusion: Measurements of primary tumour total lesion glycolysis are simple to perform and provide additional prognostic information over and above that provided by TNM staging

  4. Whole tumour quantitative measurement of first-pass perfusion of oesophageal squamous cell carcinoma using 64-row multidetector computed tomography: Correlation with microvessel density

    Energy Technology Data Exchange (ETDEWEB)

    Chen Tianwu, E-mail: twchenscu@yahoo.com.cn [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Sichuan Province Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 63 Wen Hua Lu, Nanchong, Sichuan 637007 (China); Yang Zhigang, E-mail: yangzg6666@yahoo.com.cn [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Wang Qiling, E-mail: xiaohongmao99@126.com [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Li Yuan, E-mail: dr.liyuan@163.com [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Qian Lingling, E-mail: moneylinglingch1999@126.com [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Chen Huijiao, E-mail: joan-ch@sohu.com [Department of Pathology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China)

    2011-08-15

    Purpose: To assess correlations between whole tumour first-pass perfusion parameters obtained with 64-row multidetector computed tomography (MDCT), and microvessel density (MVD) in oesophageal squamous cell carcinoma. Materials and Methods: Thirty-one consecutive patients with surgically confirmed oesophageal squamous cell carcinomas were enrolled into our study. All the patients underwent whole tumour first-pass perfusion scan with 64-row MDCT. Perfusion parameters, including perfusion (PF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Postoperative tumour specimens were assessed for MVD. Pearson correlation coefficient tests were performed to determine correlations between each perfusion parameter and MVD. Results: Mean values for PF, PED, BV and TTP of the whole tumour were 28.85 {+-} 20.29 ml/min/ml, 23.16 {+-} 8.09 HU, 12.13 {+-} 5.21 ml/100 g, and 35.05 {+-} 13.85 s, respectively. Mean MVD in whole tumour at magnification (x200) was 15.75 {+-} 4.34 microvessel/tumour sample (vessels/0.723 mm{sup 2}). PED and BV were correlated with MVD (r = 0.651 and r = 0.977, respectively, all p < 0.05). However, PF and TTP were not correlated with MVD (r = 0.070 and r = 0.100, respectively, all p > 0.05). Conclusion: The BV value of first-pass perfusion CT could reflect MVD in oesophageal squamous cell carcinoma, and can be an indicator for evaluating the tumour angiogenesis.

  5. Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: Role of reactive oxygen species and glutathione

    Indian Academy of Sciences (India)

    B V V Pardhasaradhi; Madhurima Reddy; A Mubarak Ali; A Leela Kumari; Ashok Khar

    2005-03-01

    Annonaceous acetogenins are a new class of compounds that have been reported to have potent pesticidal, parasiticidal, anti-microbial, cell growth inhibitory activities. In this study, organic and aqueous extracts from the defatted seeds of Annona squamosa (custard apple) were tested on different human tumour cell lines for antitumoural activity. While organic and aqueous extracts induced apoptosis in MCF-7 and K-562 cells, they failed to do so in COLO-205 cells. Treatment of MCF-7 and K-562 cells with organic and aqueous extracts resulted in nuclear condensation, DNA fragmentation, induction of reactive oxygen species (ROS) generation and reduced intracellular glutathione levels. In addition downregulation of Bcl-2 and PS externalization by Annexin-V staining suggested induction of apoptosis in MCF-7 and K-562 cells by both the extracts through oxidative stress. On the contrary, COLO-205 cells showed only PS externalization but no change in ROS and glutathione levels. These observations suggest that the induction of apoptosis by A. squamosa extracts can be selective for certain types of cancerous cells.

  6. Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.

    Science.gov (United States)

    Vlková, Veronika; Štěpánek, Ivan; Hrušková, Veronika; Šenigl, Filip; Mayerová, Veronika; Šrámek, Martin; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Hejhal, Tomáš; Dérian, Nicolas; Klatzmann, David; Six, Adrien; Reiniš, Milan

    2014-08-30

    Downregulation of MHC class I expression on tumour cells, a common mechanism by which tumour cells can escape from specific immune responses, can be associated with coordinated silencing of antigen-presenting machinery genes. The expression of these genes can be restored by IFNγ. In this study we documented association of DNA demethylation of selected antigen-presenting machinery genes located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNγ treatment with MHC class I upregulation on tumour cells in several MHC class I-deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15). Our data also documented higher methylation levels in these genes in TC-1/A9 cells, as compared to their parental MHC class I-positive TC-1 cells. IFNγ-mediated DNA demethylation was relatively fast in comparison with demethylation induced by DNA methyltransferase inhibitor 5-azacytidine, and associated with increased histone H3 acetylation in the promoter regions of APM genes. Comparative transcriptome analysis in distinct MHC class I-deficient cell lines upon their treatment with either IFNγ or epigenetic agents revealed that a set of genes, significantly enriched for the antigen presentation pathway, was regulated in the same manner. Our data demonstrate that IFNγ acts as an epigenetic modifier when upregulating the expression of antigen-presenting machinery genes.

  7. Solitary fibrous tumour of the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Mordani, J.P. [City General Hospital, Stoke-on-Trent (United Kingdom). Dept. of Radiology; Haq, I.U. [North Staffordshire Royal Infirmary, Stoke-on-Trent (United Kingdom). Dept. of Neuroradiology; Singh, J. [North Staffordshire Royal Infirmary, Stoke-on-Trent (United Kingdom). Dept. of Neurosurgery

    2000-09-01

    We report an intramedullary primary solitary fibrous tumour of the cervical spinal cord in a 33-year-old man. The tumour predominantly consisted of monomorphic spindle cells with a storiform pattern. MRI demonstrated an inhomogeneously enhancing cervical intramedullary tumour. The patient was well without recurrence 18 months after surgery. (orig.)

  8. Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGF-1 and/or CPT-11

    Indian Academy of Sciences (India)

    Roman Paduch; Joanna Jakubowicz-Gil; Martyna Kandefer-Szerszeń

    2009-12-01

    We studied the expression of inducible heat shock protein (HSP27, HSP72) and multidrug-resistance protein (MRP) in co-cultures of human colon carcinoma cell spheroids obtained from different grades of tumour with normal human colon epithelium, myofibroblast and endothelial cell monolayers. We also measured the influence of recombinant human transforming growth factor 1 (rhTGF-1) and camptothecin (CPT-11), added as single agents or in combination, on the levels of the HSPs, MRP, interleukin (IL)-6 and nitric oxide (NO). An immunoblotting analysis with densitometry showed that rhTGF-1 and/or CPT-11 increased HSP27, HSP72 and MRP expression in tumour cells and myofibroblasts, as well as in co-cultures compared with appropriate controls. By contrast, in colonic epithelium, inhibition of HSPs and MRP was comparable with that of the control. In endothelial cells, HSP72 was undetectable. Direct interaction of colon tumour spheroids with normal myofibroblasts caused a significant, tumour-grade dependent increase in IL-6 production. Production of IL-6 was significantly lowered by rhTGF-1 and/or CPT-11. Tumour cell spheroids cultivated alone produced larger amounts of NO than normal cells. In co-culture, the level of the radical decreased compared with the sum of NO produced by the monocultures of the two types of cells. rhTGF-1 and/or CPT-11 decreased NO production both in tumour and normal cell monocultures and their co-cultures. In conclusion, direct interactions between tumour and normal cells influence the expression of HSP27, HSP72 and MRP, and alter IL-6 and NO production. rhTGF-1 and/or CPT-11 may potentate resistance to chemotherapy by increasing HSP and MRP expression but, on the other hand, they may limit tumour cell spread by decreasing the level of some soluble mediators of inflammation (IL-6 and NO).

  9. Lymphomas and chylous ascites: review of the literature.

    Science.gov (United States)

    Almakdisi, Tony; Massoud, Samuel; Makdisi, George

    2005-09-01

    Chylous ascites is a rare and challenging clinical condition that occurs as a result of disruption of the abdominal lymphatics. We include a review of the literature describing the etiology, diagnosis, and therapy of chylous ascites. PMID:16177287

  10. Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids.

    OpenAIRE

    Sakaguchi, M; Rowley, S; Kane, N; Imray, C.; Davies, A; Jones, C; Newbold, M.; Keighley, M R; Baker, P.; Neoptolemos, J P

    1990-01-01

    Seventy-five nude mice received subcutaneous inoculation with 1 X 10(7) cells of the human colonic cancer cell lines COLO-320 or HT-29. Tumour growth was assessed over 4 weeks in animals given one of three iso-caloric diets; standard diet, high saturated fat (20% coconut) diet and high n-3 fat (20% Maxepa fish oil) diet. The n-3 diet produced significant tumour growth reduction compared to the other diets for COLO-320 at 3 to 4 weeks (P less than 0.05 at least) and similarly for HT-29 at 4 we...

  11. Viability and proliferation of L929, tumour and hybridoma cells in the culture media containing sericin protein as a supplement or serum substitute.

    Science.gov (United States)

    Cao, Ting-Ting; Zhang, Yu-Qing

    2015-09-01

    Cell cultures often require the addition of animal serum and other supplements. In this study, silk sericin, a bioactive protein, recovered from the waste of silk floss production was hydrolysed into three pepsin-degraded sericin peptides with different ranges of molecular mass. Normal animal cells, tumour cells and hybridoma cells were cultured systematically in FBS culture media containing sericin as a supplement or serum substitute. The culture test and microscopic observation of L929 cells showed that the smaller molecular weight of the degraded sericin is most suitable for cell culture. The cell culture results showed that with the degradation of sericin, for normal mouse fibroblast L929 cells, addition of 0.75 % sericin into FBS culture medium yields cell viability that is superior to FBS culture medium alone. When all serum was replaced by sericin, cell viability in the sericin medium could reach about one half of that in FBS medium. When in a medium containing a mixture of FBS: sericin (6:4, v/v), the cell culture effect is about 80 %. For the cultures of four tumour and one hybridoma cells, regardless of the molecular weight range, these degraded sericin peptides could substitute all serum in FBS media. The cell viability and proliferation of these tumour and hybridoma cells are equivalent or superior to that in FBS medium. In other words, cell viability and proliferation of these tumour and hybridoma cells in sericin media are more preferable to serum media. The mechanism of the sericin protein to promote cell growth and proliferation will be further investigated later. PMID:25895088

  12. Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo.

    Science.gov (United States)

    Brozovic, Gordana; Orsolic, Nada; Knezevic, Fabijan; Horvat Knezevic, Anica; Benkovic, Vesna; Sakic, Katarina; Hrgovic, Zlatko; Bendelja, Kreso; Fassbender, Walter J

    2009-06-01

    In this study, DNA damage in tumour cells, as well as irreversible cell damage leading to apoptosis induced in vivo by the combined application of cisplatin and inhalation anaesthetics, was investigated. The genotoxicity of anaesthetics on Ehrlich ascites tumour (EAT) cells of mice, alone or in combined application with cisplatin, was estimated by using the alkaline comet assay. The percentage of EAT cell apoptosis was quantified by flow cytometry. Groups of EAT-bearing mice were (i) treated intraperitoneally with cisplatin, (ii) exposed to repeated anaesthesia with inhalation anaesthetic, and (iii) subjected to combined treatment of exposure to anaesthetics after cisplatin for 3 days. Sevoflurane, halothane and isoflurane caused strong genotoxic effects on tumour cells in vivo. The tested anaesthetics alone showed no direct effect on programmed cell death although sevoflurane and especially halothane decreased the number of living EAT cells in peritoneal cavity lavage. Repeated anaesthesia with isoflurane had stimulatory effects on EAT cell proliferation and inhibited tumour cell apoptosis (6.11%), compared to the control group (10.26%). Cisplatin caused massive apoptosis of EAT cells (41.14%) and decreased the number of living EAT cells in the peritoneal cavity. Combined cisplatin and isoflurane treatment additionally increased EAT cell apoptosis to 51.32%. Combined treatment of mice with cisplatin and all anaesthetics increased the number of living tumour cells in the peritoneal cavity compared to cisplatin treatment of mice alone. These results suggest that the inhalation of anaesthetics may protect tumour cells from the cisplatin-induced genotoxic and cytotoxic effects.

  13. Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

    International Nuclear Information System (INIS)

    Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future

  14. Extensive loculated ascites in hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Saranya Buppajarntham

    2014-01-01

    Full Text Available Context: Amyloidosis is a disease of extracellular deposition of misfolded proteinaceous subunits, which could be systemic or localized disease. Though hepatic amyloidosis was not uncommon in autopsy series, most cases of hepatic amyloidosis were asymptomatic. Ascites, jaundice, portal hypertension, and gastrointestinal bleeding from esophageal varices were reported in literature. Case report: A 42-year-old man with end-stage renal disease on hemodialysis and recent small bowel obstruction presented with chronic abdominal pain. Computed tomography of abdomen and pelvis showed extensive loculated ascites and multiple small bowel loops tethered to adhesions and hepatomegaly. Finally, hepatic venography and liver biopsy confirmed hepatic amyloidosis with portal hypertension. The patient was waiting for liver transplant for definite treatment. Conclusion: We report a rare case of hepatic amyloidosis with prior small bowel obstruction presented with extensive loculated ascites and multiple small bowel loops tethered to adhesions.

  15. CD4+ and CD8+ T cells can act separately in tumour rejection after immunization with murine pneumotropic virus chimeric Her2/neu virus-like particles.

    Directory of Open Access Journals (Sweden)

    Kalle Andreasson

    Full Text Available BACKGROUND: Immunization with murine pneumotropic virus virus-like particles carrying Her2/neu (Her2MPtVLPs prevents tumour outgrowth in mice when given prophylactically, and therapeutically if combined with the adjuvant CpG. We investigated which components of the immune system are involved in tumour rejection, and whether long-term immunological memory can be obtained. METHODOLOGY AND RESULTS: During the effector phase in BALB/c mice, only depletion of CD4+ and CD8+ in combination, with or without NK cells, completely abrogated tumour protection. Depletion of single CD4+, CD8+ or NK cell populations only had minor effects. During the immunization/induction phase, combined depletion of CD4+ and CD8+ cells abolished protection, while depletion of each individual subset had no or negligible effect. When tumour rejection was studied in knock-out mice with a C57Bl/6 background, protection was lost in CD4-/-CD8-/- and CD4-/-, but not in CD8-/- mice. In contrast, when normal C57Bl/6 mice were depleted of different cell types, protection was lost irrespective of whether only CD4+, only CD8+, or CD4+ and CD8+ cells in combination were eradicated. No anti-Her2/neu antibodies were detected but a Her2/neu-specific IFNgamma response was seen. Studies of long-term memory showed that BALB/c mice could be protected against tumour development when immunized together with CpG as long as ten weeks before challenge. CONCLUSION: Her2MPtVLP immunization is efficient in stimulating several compartments of the immune system, and induces an efficient immune response including long-term memory. In addition, when depleting mice of isolated cellular compartments, tumour protection is not as efficiently abolished as when depleting several immune compartments together.

  16. Pseudomembranous colitis: an unusual cause of neutrocytic ascites.

    Science.gov (United States)

    Spahr, L; de Saussure, P; Felley, C; Pugin, J; Hadengue, A

    1999-07-01

    Severe cases of pseudomembranous colitis (PMC) may be associated with intraperitoneal fluid accumulation. However, the characteristics of the liquid are seldom described. Specifically, neutrocytic ascites has only been reported once. We report a case of a severe PMC complicated by a highly neutrocytic ascites which remained culture-negative. We discuss the possible mechanisms leading to ascites formation in this condition and review ascitic fluid characteristics in patients with PMC. PMID:10445802

  17. Treatment of ascites and spontaneous bacterial peritonitis - Part I

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Grønbæk, Henning; Aagaard, Niels Kristian;

    2012-01-01

    National guidelines for treatment of ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hyponatremia have been approved by the Danish Society of Gastroenterology and Hepatology. Ascites develops in approximately 60% of patients with cirrhosis during a 10 year period and is freq......National guidelines for treatment of ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hyponatremia have been approved by the Danish Society of Gastroenterology and Hepatology. Ascites develops in approximately 60% of patients with cirrhosis during a 10 year period...

  18. Application of the revised Tumour Node Metastasis (TNM) staging system of clear cell renal cell carcinoma in eastern China: advantages and limitations

    Institute of Scientific and Technical Information of China (English)

    Chao Qin; Li-Jiang Sun; Li Cui; Qiang Cao; Jian Zhu; Pu Li; Gui-Ming Zhang

    2013-01-01

    This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients.A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled.All of the patients had pathologically confirmed clear cell RCC (ccRCC).All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review,and survival data were collected.Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery.Continuous variables,such as age and tumour diameter,were calculated as mean values and standard deviations (s.d.) or as median values.Survival was calculated by the Kaplan-Meier method,and the log-rank test assessed differences between groups.Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system.Therefore,the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients.However,when using the revised 2010 staging system,we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup,and their survival data were not significantly different from those of patients with T2b tumours.In addition,T2 subclassification failed to independently predict survival in RCC patients.

  19. Lymphography in chylothorax and chylous ascites

    Energy Technology Data Exchange (ETDEWEB)

    Rabkin, I.Kh.; Lein, A.P. (Akademiya Meditsinskikh Nauk SSSR, Moscow)

    Sixteen lymphographic studies were made in patients with chylothorax and chylous ascites, which were spontaneous in 14 cases. Disseminated and limited lymphatic system lesions were revealed. Abundant lesions were mostly presented by multiple cysts and lymphangiectasia. Meanwhile solitary cysts, lymphangiomas, wall defects were detected in limited lesions. Lymphographic semiotics for chylothorax and chylous ascites has been developed. Direct signs of damage to the lymph vessels are classified with the most valuable symptoms: radiographic agent extravasation, the contrast substance congestion in the lesion area, its concentration in the pleural or abdominal cavities.

  20. Chylous Ascites after Abdominal Aortic Aneurysm Repair.

    Science.gov (United States)

    Ohki, Shinichi; Kurumisawa, Soki; Misawa, Yoshio

    2016-01-01

    A 73-year-old man was transferred for treatment of abdominal aortic aneurysm. He had no history of abdominal surgeries. Grafting between the infra-renal abdominal aorta and the bilateral common iliac arteries was performed. Proximal and distal cross clamps were applied for grafting. He developed chylous ascites on the 5th post-operative day, 2 days after initiation of oral intake. Fortunately, he responded to treatment with total parenteral hyper-alimentation for 10 days, followed by a low-fat diet. There was no recurrence of ascites. PMID:27087873