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Sample records for ascites tumor cells

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

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    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...

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

    Science.gov (United States)

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

    1990-11-01

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

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

    International Nuclear Information System (INIS)

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

  4. 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.

  5. 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 ...

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

    Science.gov (United States)

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

    2015-05-01

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

  7. 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

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

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hoffmann, Else Kay

    1994-01-01

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

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  11. 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

  12. 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

  13. 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...

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

    DEFF Research Database (Denmark)

    Hoffmann, Else K; Pedersen, Stine F

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    1980-08-01

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

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

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

    2009-07-01

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

  18. 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)

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

    International Nuclear Information System (INIS)

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

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

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    Wintzell My

    2012-08-01

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

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

    International Nuclear Information System (INIS)

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

  2. 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...

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

    Science.gov (United States)

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

    1990-09-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  7. 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.

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

    Science.gov (United States)

    Ookhtens, M; Baker, N

    1983-01-01

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

  9. 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...

  10. Renal cell carcinoma presenting with malignant ascites

    OpenAIRE

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  14. 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...

  15. Evolution of sarcoma 180 (ascitic tumor) in mice infected with Schistosoma mansoni

    OpenAIRE

    Fausto Edmundo Lima Pereira; Pedro Raso; Paulo Marcos Zech Coelho

    1986-01-01

    Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation) started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was short...

  16. Anti-Tumor Activity of Four Ayurvedic Herbs in Dalton Lymphoma Ascites Bearing Mice and Their Short-Term In Vitro Cytotoxicity on DLA-Cell-Line

    OpenAIRE

    Adhvaryu, Meghna R; Reddy, Narshimha; Parabia, Minoo H

    2008-01-01

    The anti-tumor activity and chemopreventive potential of four Ayurvedic herbs viz. Curcuma longa L., Ocimum sanctum L., Tinospora cordifolia (Wild) Miers ex Hook.f & Thomas and Zizyphus mauritiana Lam. were evaluated using Dalton Lymphoma ascites (DLA) tumor model in Swiss Albino mice. The outcome was assessed using survival time, peritoneal ascitic fluid (Tumor volume) and hematological indices as parameters. Animals were divided into five groups (n = 6) viz. one DLA control and four Herb + ...

  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

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

  18. 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

  19. 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.

  20. 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

  1. 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.)

  2. Immune mechanisms in Ehrlich ascites tumor growth in mice

    International Nuclear Information System (INIS)

    Normal mice immunised with irradiated Ehrlich ascites tumor (EAT) cells rejected EAT challenge given 2 weeks later but T-cell-deficient thymectomised lethally irradiated, and bone-marrow-reconstituted (TIR) mice succumbed. However, when TIR mice were injected i.v. with thymus, lymph node, or spleen cells from normalsyngetic donors immediately following i.p. injection of irradiated EAT cells, they rejected the subsequent tumor challenge. This induction of immunity in TIR mice was shown to be T-cell dependent. Spleen cells from EAT- bearing mice given immediately after irradiated tumor cells were also able to promote rejection of EAT challenge in TIR mice. Spleen cells from EAT-immune mice inhibited EAT growth when admixed with tumor cells prior to i.p. injection into normal recipients, but had no effect on progressive tumor growth when given i.v. immediately after i.p. tumor injection. Immune serum inhibited i.p. EAT growth when given either i.p. or i.v. Whereas inhibition of EAT growth by admixed spleen cells was shown to be T-cell independent. The data indicate that T lymphocytes are required only in the induction phase of the immune reponse of mice against EAT, while the efferent phase of the response is accomplished by serum antibodies, perhaps through an interaction with host macrophages. (author)

  3. Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.

    Science.gov (United States)

    Nascimento, Flávia R F; Cruz, Gustavo V B; Pereira, Paulo Vitor S; Maciel, Márcia C G; Silva, Lucilene A; Azevedo, Ana Paula S; Barroqueiro, Elizabeth S B; Guerra, Rosane N M

    2006-04-25

    The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides. PMID:16307762

  4. Radiotherapeutic response of Ehrlich Ascites tumor cells perfused in agarose gel threads and implanted in mice. A 31P MR spectroscopy study

    International Nuclear Information System (INIS)

    Aim: In order to obtain better understanding of radiation-induced alterations in intracellular metabolism, a dynamic and noninvasive experimental model system is required. A serial study in cultured tumor cell line followed by verification in the in vivo samples may be of considerable value for non-invasive prediction and/or detection of tumor response to therapy. The present study was undertaken to evaluate the radiation response of perfused Ehrlich ascites tumors cells (EATC) immobilized in agarose gel matrix to that observed in mouse bearing EATC tumor, in order to identify biomarkers of radiation response. Materials and Methods: Perfused EAT cells, entrapped in agarose gel threads were irradiated in the perfusion assembly outside the magnet with fast electrons (6 Gy, 1 Gy/min) using 30 MeV Betatron. Solid EATC tumors implanted subcutaneously onto right hand limb of Swiss-albino strain 'A' mice, were focally irradiated using 60Co teletherapy (10 Gy, 0.4 Gy/min). Metabolites changes were monitored by 31P MR spectroscopic techniques. Results: A post-irradiation decrease in the levels of ATP and ADP along with an increase in inorganic phosphate and glycerophosphocholine levels was observed. The ratios of β-phosphate of ATP to inorganic phosphate (β-ATP-Pi), and phosphocholine to glycerophosphocholine (PC/GPC), declined during 1-5 hours following irradiation, in perfused EAT cells and in the solid tumors implanted in mice. Conclusion: Perfused cells could be used as a simple model of tumor for prediction of clinical radiotherapeutic response. The present study demonstrates that radiation damage may be occurring both at the DNA protein as well as the membrane lipid levels. Therefore, the bioenergetics and phospholipid profiles of tumor cells could be used as complimentary, reliable and sensitive indirect indicators for devising predictive assays for assessment and monitoring of radiation response, which will also facilitate the individualization and optimization of

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

    Directory of Open Access Journals (Sweden)

    Watanabe,Sadahiro

    1986-12-01

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

  6. Molecular mechanisms of the killing effects on Ehrlich ascites tumor cells by sono-chemical-activated protoporphyrin Ⅸ

    OpenAIRE

    LIU Quan-Hong, XIAO Li-Na; Li, Xiao-ying; Wang, Pan; Wang, Xiao-Bing; Wang, Yu; LI Chen-Di

    2008-01-01

    We studied the Ehrlich ascetic tumor (EAT) cell line killing effects by ultrasound activating protoporphyrin Ⅸ (PPⅨ) and its mechamism. The cellular uptake and subcellular localization of protoporphyrin Ⅸ were estimated by fluorescence photometer and laser scanning confocal microscopy (LSCM) respectively. The trypan blue exclusion method was used to analyze the relative viability of EAT cells after ultrasonically activated protoporphyrin Ⅸ. Changes of ultra-microstructure of the treated cell...

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

    International Nuclear Information System (INIS)

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

  8. Co-Encapsulation of Doxorubicin With Galactoxyloglucan Nanoparticles for Intracellular Tumor-Targeted Delivery in Murine Ascites and Solid Tumors

    Directory of Open Access Journals (Sweden)

    Manu M. Joseph

    2014-10-01

    Full Text Available Doxorubicin (Dox treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001, isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications.

  9. Molecular mechanisms of the killing effects on Ehrlich ascites tumor cells by sono-chemical-activated protoporphyrin Ⅸ

    Directory of Open Access Journals (Sweden)

    LIU Quan-Hong, XIAO Li-Na

    2008-10-01

    Full Text Available We studied the Ehrlich ascetic tumor (EAT cell line killing effects by ultrasound activating protoporphyrin Ⅸ (PPⅨ and its mechamism. The cellular uptake and subcellular localization of protoporphyrin Ⅸ were estimated by fluorescence photometer and laser scanning confocal microscopy (LSCM respectively. The trypan blue exclusion method was used to analyze the relative viability of EAT cells after ultrasonically activated protoporphyrin Ⅸ. Changes of ultra-microstructure of the treated cells were examined by transmission electron microscopy.Mitochondrial membrane potential(MMP, intracellular reactive oxygen species (ROS levels, and the level of lipid peroxidation were determined by Rhodamine 123, 2′,7′- dichlorodihydrofluorescin diacetate (DCFH-DA and thiobarbituric acid reaction method respectively. Results showed that there is a selective uptake and retention of the PPⅨ in tumor cells. CLSM revealed that PPⅨ localize mainly in the mitochondria. In the ultrasound plus PPⅨ group, the survival rate of cells was significantly lower. The ultra-microstructural damage of treated cells was the most remarkable, the loss of mitochondria membrane potential was the most noticeable, levels of ROS and lipid peroxides were remarkably increased. These results indicate that there is significant synergistic killing effect with ultrasound activating PPⅨ. The decreased mitochondria membrane potential and the increased level of lipid peroxidation in the ultrasound plus PPⅨ group may be associated with reactive oxygen species. In summary, reactive oxygen species might be involved in mediating the killing effect of EAT cells in SDT [Acta Zoologica Sinica 54(5: 846– 854, 2008

  10. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis.

    Directory of Open Access Journals (Sweden)

    Richard B Bankert

    Full Text Available Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγ(null (NSG mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  12. 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.

  13. 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

  14. Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

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    Fausto Edmundo Lima Pereira

    1986-03-01

    Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

  15. Chylous Ascites in a Patient with Inflammatory Myofibroblastic Tumor

    Directory of Open Access Journals (Sweden)

    Sascha Dietrich

    2009-08-01

    Full Text Available Background: We present the case of a 64-year-old patient who presented to his primary care physician with fatigue, worsening shortness of breath, abdominal discomfort and a rapidly growing abdominal girth, although he had lost 5 kg of weight within 3 months. He had a history of untreated hypertension, compensated renal insufficiency and COPD. Despite weight loss and fatigue, the patient did not experience any other constitutional symptoms such as fever, night sweats or loss of appetite. Investigations: Physical examination, blood tests, CT scan of the abdomen, MRI scan of the abdomen, fine needle biopsy, excisional biopsy, Video Capsule Endoscopy, histology, PET scan. Diagnosis: Inflammatory myofibroblastic tumor, chylous ascites, chyloperitoneum. Management: Systemic chemotherapy, total parenteral nutrition and octreotide therapy. Conclusion: We describe the case of a patient in whom two extremely rare phenomena are present in combination: the diagnosis of an inflammatory myofibroblastic tumor and chylous ascites. While the tumor could be stabilized by different regimens of chemotherapy, the chyloperitoneum was treated with parenteral nutrition and subcutaneous octreotide injections, which resulted in a significant reduction of the amount of chylous ascites drained during regular paracentesis.

  16. 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 ...

  17. 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...

  18. 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.

  19. 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.

  20. Immunomodulatory and anti-tumor effects of Nigella glandulifera freyn and sint seeds on ehrlich ascites carcinoma in mouse model

    Directory of Open Access Journals (Sweden)

    Ainiwaer Aikemu

    2013-01-01

    Full Text Available Aim : This study investigated the immunomodulatory and anti-tumor effects of Nigella glandulifera Freyn and Sint seeds (NGS on Ehrlich ascites carcinoma in a mouse model. Materials and Methods : Kunming mice with transplanted Ehrlich ascites tumor cells (EAC were treated with NGS by oral administration. On the 11 th day after the EAC implant, mouse thymus, liver, spleen and kidney tumors were removed for histopathological analysis. Blood samples were taken for hematological and biochemical analyses. Results : The results indicate that NGS treatment leads to an increase in TNF-α, IL-1β, and IL-2 blood serum levels. Absence of viable EAC and presence of necrotic cells were observed in the tumor tissue of the NGS-treated animals. Conclusions : The study results indicated that a water extract of NGS had the highest anti-tumor effect. Moreover, NGS treatment also showed an increase in the immune system activity.

  1. The proton stoichiometry of electron transport in Ehrlich ascites tumor mitochondria.

    Science.gov (United States)

    Villalobo, A; Lehninger, A L

    1979-06-10

    Initial rate measurements of the stoichiometric relationships between H+ ejection, K+ and Ca2+ uptake, and electron transport were carried out on mitochondria from Ehrlich ascites tumor cells grown in mice. With succinate as substrate and N-ethylmaleimide to prevent interfering H+ reuptake via the phosphate carrier, close to 8 H+ were ejected per oxygen atom reduced (H+/O ejection ratio = 8.0); with the NAD-linked substrates pyruvate or pyruvate + malate, the H+/O ejection ratio was close to 12. The average H+/site ratio (H+ ejected/2e-/energy-conserving site) was thus close to 4. The simultaneous uptake of charge-compensating cations, either K+ (in the presence of valinomycin) or Ca2+, was also measured, yielding average K+/site uptake ratios of very close to 4 and Ca2+/site ratios close to 2. It was also demonstrated that each calcium ion enters the respiring tumor mitochondria carrying two positive electric charges. These stoichiometric data observed in mitochondria from Ehrlich ascites tumor cells thus are in complete agreement with similar data on normal rat liver and rat heart mitochondria and suggest that the H+/site ratio of mitochondrial electron transport may be 4 generally. It was also observed that the rate of deltaH+ back-decay in anaerobic tumor mitochondria following oxygen pulses is some 6- to 8-fold greater than in rat liver mitochondria tested at equal amounts of mitochondrial protein. PMID:35536

  2. Antitumorigenic Potential of Diallyl Sulfide in Ehrlich Ascites Tumor Bearing Mice

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To study the effects of diallyl sulfide (DAS), an organosulfur compound present in garlic (Allium sativum),on the life span ofehrlich ascites (EA) tumor bearing Swiss albino mice, cytotoxicity and angiogenesis. Methods EA tumor cells were maintained by serial transplantation in peritoneal cavity of male Swiss albino mice. EA tumor cells were inoculated at concentrations of 1 × 106EA cells, 2.5 × l06EAcells and 5 × 106 EA cells. DAS was given in 0.2 mi normal saline i. p., daily for seven days followed one hour later by inoculation with EA cells in respective groups. Results The results revealed that administration of DAS increased the life span of EA tumor bearing animals by more than 25 percent. A significant dose dependant cytotoxic response of DAS was also observed on EA tumor cells. DAS was also found to inhibit the angiogenesis in EA tumor bearing mice in a dose dependent manner. Conclusion It is suggested that DAS may exert its anticarcinogenic effects by more than one mechanism and is a useful chemopreventive and chemotherapeutic agent.

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

    International Nuclear Information System (INIS)

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

  4. Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Fausto Edmundo Lima Pereira

    1986-03-01

    Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.Camundongos infectados com 60 cercárias de Schistosoma mansoni tomaram-se mais resistentes ao sarcoma 180 na forma de tumor ascítico. A inoculação das células tumorais foi feita no 50º dia de infecção e a evolução do tumor foi acompanhada através dapesagem dos animais com intervalos de 48 horas. Nos camundongos infectados o ganho de peso (formação da ascite começou mais tarde e foi menor do que nos controles não infectados. Também o número de células tumorais na cavidade peritoneal 72 horas após a implantação do tumor foi menor no grupo infectado. Este aumento de resistência a um tumor transplantávelpossivelmente está relacionado ao efeito de endotoxinas sobre a atividade tumoricida dos macrofagos ativados pela infecção. A imunossupressão induzida pela infecção favorece a proliferação de bactérias da flora endógena aumentando a quantidade de endotoxinas absorvidas pelo intestino.

  5. EFFECT OF Crotalus durissus terrificus (LAURENTI, 1768 VENOM ON THE EVOLUTION OF EHRLICH ASCITES TUMOR

    Directory of Open Access Journals (Sweden)

    R. J. DA SILVA

    1997-01-01

    Full Text Available The effect of Crotalus durissus terrificus (LAURENTI, 1768 venom on the evolution of Ehrlich ascites tumor cells was evaluated. Thus, 30-day-old male mice of the Swiss strain were inoculated intraperitoneally with 1x10 tumor cells. Then, 7 groups of animals were formed: 3 control groups (physiological, venom and tumor and 4 experimental groups that received different doses of venom. The experimental groups received 5 intraperitoneal venom injections on the 1 , 4 , 7 , 10 and 13 days after tumor implantation. On the 14 day, 5 animals from each one of the groups were sacrificed, and the variables such as the total and differential counts of cells in the peritoneal cavity and functional state of peritoneal macrophages by macrophage spreading were evaluated. The other 5 remaining animals were kept in the laboratory for 60 days for observation of their survival percentage. The results obtained were statistically analyzed by the Kruskal-Wallis test at 5% significance level. It was observed that Crotalus durissus terrificus venom increases survival time of mice, but does not increase mortality percentage. This venom also increases the percentage of macrophage spreading. We suggest that snake venoms can cause inhibition of tumor growth by activating the inflammatory reaction, mainly the macrophages, stimulating the production of TNF- , IL-1, IL-6 and IL-8. These cytokines may act on tumor cells by different mechanisms, inducing its complete elimination.

  6. 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 ...

  7. Clinical value of detection of malignant ascites and thoracic exudate by means of six tumor-markers

    International Nuclear Information System (INIS)

    Objective: To study the clinical value of six potential tumor markers including serums CA125, CYFRA21-1, CA-50, CA15-3, HCG, β-HCG. These were determined in effusions of malignant ascites and hydrothorax of 170 patients, with cellular examination as control. Methods: Using IRMA. Results: The data of our experiments revealed that of all six tumor-markers, CA125 was the highest in positive rate as well as concordance rate with cytology examination. In or- der CA125, CA-50, CA15-3, CYFRA21-1, β-HCG. It was valuable to point out that the specificity of HCG and β-HCG was very strong and there was no false positivity had yet been found with them. Though their positivity was not so high as that of CA125. Have to higher specificity of detection of malignant ascites by CYFRA21-1. Conclusions: It suggested that + CYFRA21-1 should be the preferred choice in diagnosing malignant hydrothorax next + CA-50,CYFRA21-1 +CA-50; for malignant ascites as well, CA125 + β-HCG determination is just as good, next CA125 + CYFRA21-1. We believe that when a clear diagnosis of a primary focus of cancer is made clinically, or a malignant ascites or thoracic exudate come highly under suspicion, the diagnosis of malignancy of the ascites or thoracic exudate can be established even though the exfoliative cells, provided the detection by tumor-markers, it has got one of the following results: the roles of tumor-markers determination in malignant serous effusions, two of CA125, CYFRA21-1. CA15-3 and CA-50 markers are positive; anyone of the above markers plus HCG or β-HCG positivity; both HCG and β-HCG or CA15-3 are positive. (author)

  8. Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma

    OpenAIRE

    Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2011-01-01

    Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On...

  9. 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...

  10. The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line.

    Science.gov (United States)

    Elsherbiny, Nehal M; Younis, Nahla N; Shaheen, Mohamed A; Elseweidy, Mohamed M

    2016-09-01

    Despite the remarkable anti-tumor activity of doxorubicin (DOX), its clinical application is limited due to multiple organ toxicities. Products with less side effects are therefore highly requested. The current study investigated the anti-cancer activities of vanillin against breast cancer and possible synergistic potentiation of DOX chemotherapeutic effects by vanillin. Vanillin (100mg/kg), DOX (2mg/kg) and their combination were administered i.p. to solid Ehrlich tumor-bearing mice for 21days. MCF-7 human breast cancer cell line was treated with vanillin (1 and 2mM), DOX (100μM) or their combination. Protection against DOX-induced nephrotoxicity was studied in rats that received vanillin (100mg/kg, ip) for 10days with a single dose of DOX (15mg/kg) on day 6. Vanillin exerted anticancer effects comparable to DOX and synergesticlly potentiated DOX anticancer effects both in-vivo and in-vitro. The anticancer potency of vanillin in-vivo was mediated via apoptosis and antioxidant capacity. It also offered an in-vitro growth inhibitory effect and cytotoxicity mediated by apoptosis (increased caspase-9 and Bax:Bcl-2 ratio) along with anti-metasasis effect. Vanillin protected against DOX-induced nephrotoxicity in rats. In conclusion, vanillin can be a potential lead molecule for the development of non-toxic agents for the treatment of breast cancer either alone or combined with DOX. PMID:27493101

  11. The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

    Science.gov (United States)

    Silveira-Lacerda, Elisângela de Paula; Vilanova-Costa, Cesar Augusto Sam Tiago; Hamaguchi, Amélia; Pavanin, Luiz Alfredo; Goulart, Luiz Ricardo; Homsi-Brandenburgo, Maria Inês; Dos Santos, Wagner Batista; Soares, Andreimar Martins; Nomizo, Auro

    2010-06-01

    The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency. PMID:19727575

  12. (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)

  13. 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.

  14. Inhibition of subcutaneous growth of Ehrlich Ascites Carcinoma (EAC) tumor by post-immunization with EAC-cell gangliosides and its anti-idiotype antibody in relation to tumor angiogenesis, apoptosis, cell cycle and infiltration of CD4+, CD8+ lymphocytes, NK cells, suppressor cells and APC-cells in tumor

    International Nuclear Information System (INIS)

    Both EAC-tumor associated gangliosides and its anti-idiotype antibody inhibited growth of this tumor significantly. Immuno-histological studies with von Willebrand Factor (vWF) antibody indicated that tumor angiogenesis as determined by expression of vWF decreased in tumors of mice, post-immunized with EAC-cell gangliosides as well as its anti-idiotype antibody. Infiltration of various immune cells of the host in the tumor correlated to some extent with tumor-growth inhibition. Apoptosis study using AnnexinV-FITC and propidium iodide indicated that tumor growth inhibition in mice post-immunized with EAC-gangliosides and its anti-idiotype antibody were due to enhanced apoptosis and cell death. Cell cycle analysis by FACS indicated that EAC-cell associated gangliosides and its anti-idiotype antibody were acting both at the M2 i.e. S and M3 i.e. G2/M phases of the cell cycle to arrest tumor growth. (author)

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

    Directory of Open Access Journals (Sweden)

    Hirotsugu Hashimoto, MD

    2015-09-01

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

  16. Action of the antitumor and antispermatogenic agent lonidamine on electron transport in Ehrlich ascites tumor mitochondria.

    Science.gov (United States)

    Floridi, A; Lehninger, A L

    1983-10-01

    The effect of lonidamine, an antispermatogenic and antitumor drug, on the oxygen consumption, ATPase activity, and redox state of the electron carriers of Ehrlich ascites tumor mitochondria has been studied. Lonidamine inhibits ADP- and uncoupler-stimulated respiration on various NAD- and FAD-linked substrates, but does not affect state 4 respiration. Experiments to determine its site of action showed that lonidamine does not significantly inhibit electron flow through cytochrome oxidase. Electron flow through site 2, the ubiquinone-cytochrome b-cytochrome c1 complex, also was unaffected by lonidamine, which failed to inhibit the oxidation of duroquinol. Moreover, inhibition of electron flow through site 2 was also excluded because of the inability of the N,N,N',N'-tetramethyl-p-phenylenediamine bypass to relieve the lonidamine inhibition of the oxidation of pyruvate + malate. The F0F1ATPase activity and vectorial H+ ejection are also unaffected by lonidamine. The inhibition of succinate oxidation by lonidamine was found to take place at a point between succinate and iron-sulfur center S3. Spectroscopic experiments demonstrated that lonidamine inhibits the reduction of mitochondrial NAD+ by pyruvate + malate and other NAD-linked substrates in the transition from state 1 to state 4. However, lonidamine does not inhibit reduction of added NAD+ by submitochondrial vesicles or by soluble purified NAD-linked dehydrogenases. These observations, together with other evidence, suggest that electron transport in tumor mitochondria is inhibited by lonidamine at the dehydrogenase-coenzyme level, particularly when the electron carriers are in a relatively oxidized state and/or when the inner membrane-matrix compartment is in the condensed state. The action of lonidamine in several respects resembles the selective inhibition of electron transport in tumor cells produced by cytotoxic macrophages (D. L. Granger and A. L. Lehninger (1982) J. Cell Biol. 95, 527). PMID:6227286

  17. Analysis of the inhibitory effects of VP-16-213 (etoposide) and podophyllotoxin on thymidine transport and metabolism in Ehrlich ascites tumor cells in vitro

    International Nuclear Information System (INIS)

    Uptake of 3H after exposure of cells to [3H]-thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, primarily thymidine triphosphate, within the cell. The high rate of thymidine transport relative to thymidine metabolism to the triphosphate within the cell decreases as the extracellular nucleoside concentration is reduced due to a much greater decrease in membrane transport than the subsequent metabolic step. Hence, as extracellular thymidine is decreased, transport becomes increasingly rate limiting to metabolism within the cell. VP-16-213 (etoposide) or podophyllotoxin inhibits the initial uptake rate for thymidine and, as a consequence, inhibits the intracellular formation of thymidine triphosphate. When extracellular thymidine is high, inhibitory effects on transport are transient, and the net rate of thymidine triphosphate accumulation within drug-treated cells rapidly approaches a velocity comparable to that of control cells, indicating no direct VP-16-213 or podophyllotoxin effect on nucleoside and nucleotide phosphorylation. When extracellular thymidine is reduced so that transport is rate limiting to metabolism, the duration of the inhibitory effects of VP-16-213 on thymidine triphosphate formation is prolonged. A secondary effect of VP-16-213 becomes manifest beyond 10 min of incubation with [3H]thymidine with the virtual complete cessation of thymidine incorporation into the acid precipitate without any change in the thymidine triphosphate level. This late effect is not observed with podophyllotoxin and indicates a direct effect of VP-16-213 on DNA synthesis that is distinct from the earlier inhibitory effect on thymidine phosphorylation, which is secondary to membrane transport

  18. 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

  19. 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.

  20. Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

    Science.gov (United States)

    Koga, Y; Naraparaju, V R; Yamamoto, N

    1999-01-01

    Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor. PMID:9893164

  1. Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor.

    Science.gov (United States)

    Yamamoto, N; Naraparaju, V R

    1997-06-01

    Vitamin D3-binding protein (DBP; human DBP is known as Gc protein) is the precursor of macrophage activating factor (MAF). Treatment of mouse DBP with immobilized beta-galactosidase or treatment of human Gc protein with immobilized beta-galactosidase and sialidase generated a remarkably potent MAF, termed DBPMAF or GcMAF, respectively. The domain of Gc protein responsible for macrophage activation was cloned and enzymatically converted to the cloned MAF, designated CdMAF. In Ehrlich ascites tumor-bearing mice, tumor-specific serum alpha-N-acetylgalactosaminidase (NaGalase) activity increased linearly with time as the transplanted tumor cells grew in the peritoneal cavity. Therapeutic effects of DBPMAF, GcMAF, and CdMAF on mice bearing Ehrlich ascites tumor were assessed by survival time, the total tumor cell count in the peritoneal cavity, and serum NaGalase activity. Mice that received a single administration of DBPMAF or GcMAF (100 pg/mouse) on the same day after transplantation of tumor (1 x 10(5) cells) showed a mean survival time of 35 +/- 4 days, whereas tumor-bearing controls had a mean survival time of 16 +/- 2 days. When mice received the second DBPMAF or GcMAF administration at day 4, they survived more than 50 days. Mice that received two DBPMAF administrations, at days 4 and 8 after transplantation of 1 x 10(5) tumor cells, survived up to 32 +/- 4 days. At day 4 posttransplantation, the total tumor cell count in the peritoneal cavity was approximately 5 x 10(5) cells. Mice that received two DBPMAF administrations, at days 0 and 4 after transplantation of 5 x 10(5) tumor cells, also survived up to 32 +/- 4 days, while control mice that received the 5 x 10(5) ascites tumor cells only survived for 14 +/- 2 days. Four DBPMAF, GcMAF, or CdMAF administrations to mice transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals showed an extended survival of at least 90 days and an insignificantly low serum NaGalase level between days 30 and 90

  2. Monovalent ions control proliferation of Ehrlich Lettre ascites cells

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  3. 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.

  4. 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

  5. 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

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

    OpenAIRE

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pradeep Rajkumar

    2012-06-01

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

  8. Antitumor and apoptosis promoting properties of atorvastatin, an inhibitor of HMG-CoA reductase, against Dalton's Lymphoma Ascites tumor in mice.

    Science.gov (United States)

    Ajith, Thekkoottuparambil Ananthanarayanan; Anu, Vijayan; Riji, Thomas

    2008-01-01

    Epidemiological and experimental data indicate that high body fat or high dietary fat can be ascribed to the induction of human cancers. Increased level of products of lipid peroxidation and cholesterol-enriched lipid domains in the plasma membrane can favorthe malignant transformation of cells. An effective chemopreventive agent with hypolipaedemic effect will be worthwhile to intervene early in the process of carcinogenesis to eliminate the pre-malignant cells. Apoptotic promoting and antitumor activities of a HMG-Co A reductase inhibitor, atorvatstain were investigated. The antitumor activity was evaluated using Daltons' Lymphoma Ascites (DLA) cell line transplanted ascites tumor model in mice. Proapoptotic activity was evaluated in DLA cell line induced ascites animals after the treatment of atorvastatin (4 and 16 mg/kg, i.p). Apoptosis was analyzed morphologically by staining with giemsa and biochemically by observing the laddering of DNA in agarose gel electrophoresis. In vitro short term cytotoxic activity of atorvatstain was studied by trypan blue dye exclusion method. Doxorubicin was used as the reference standard. Atorvastatin significantly (P growth at 16 mg/kg body wt (i.p). The percent increase in life span (%ILS) in the 16 mg/kg treated group was 41.1%. Single dose of atorvastatin (16 mg/kg body wt) was also effective to promote the apoptosis of DLA cells in the ascites tumor bearing mice that was evident from the multiple fragmentation of DNA in agarose gel electrophoresis. Further the morphological analysis of DLA cells aspirated from the atorvastatin treated ascites tumor bearing animals showed 36.34 +/- 6.78% apoptotic cells compared to the control animals (10.50 +/- 3.53%). Concentration of atorvastatin required for the 50% of the cytotoxicity was 30 +/- 2 microg/ml. Results of the study concluded that the antitumor activity of atorvastatin may be due to its proapoptotic and cytotoxic activities. These pleiotropic activities of the hypolipedaemic

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

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    Tulika Mishra

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

  11. 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

  12. Tumor inhibitory activity of methanolic and ethyl acetate soluble extracts of Thuja occidentalis L. on mice bearing Ehrlich ascites carcinoma.

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    Archana M Navale

    2014-06-01

    Full Text Available Thuja occidentalis (Cupressaceae is an ornamental plant of European origin. It has been used in folk medicine for the treatment of cancer. Mice bearing Ehrlich Ascites Carcinoma (EAC mice were treated with methanolic extract (165 mg/kg, ethyl acetate soluble fraction (30 mg/kg and combination of both extracts of TO. Inhibition of tumor growth, increase in survival time of animal with treatment, and hematological parameters were determined. Both methanolic and ethyl acetate soluble fractions of TO exerted tumor growth inhibitory activity in mice bearing EAC. Combination treatment of two extracts showed more pronounced effect. In conclusion, Methanolic and ethyl acetate soluble extracts of TO exhibit anticancer activity against Ehrlich ascites carcinoma in mice. Thus, it has anticancer potential and should be further evaluated in higher models.

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

    International Nuclear Information System (INIS)

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

  14. 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.

  15. 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...

  16. 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

  17. 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

  18. Dynamics of Ca2+i and pHi in Ehrlich ascites tumor cells after Ca2+-mobilizing agonists or exposure to hypertonic solution

    DEFF Research Database (Denmark)

    Pedersen, Stine F.; Jørgensen, Nanna K.; Hoffmann, Else Kay

    1998-01-01

    known to elicit transient cell shrinkage in these cells, evoked a transient intracellular acidification, followed by an alkalinization. The latter was due to activation of a Na+/H+ exchanger and was inhibited under conditions preventing agonist-induced cell shrinkage without preventing the increase in...... [Ca2+]i. In contrast, a smaller, slower increase in [Ca2+]i elicited by thapsigargin did not cause cell shrinkage, and did not activate the Na+/H+ exchanger. Exposure to hypertonic solution was not associated with an increase in [Ca2+]i, but elicited an intracellular alkalinization similar to that...... induced by thrombin or bradykinin, via activation of the Na+/H+ exchanger. Thus, activation of the exchanger by the Ca2+-mobilizing agonists is suggested to be secondary to the cell shrinkage induced by these compounds. NH4Cl-induced intracellular alkalinization resulted in an increase in [Ca2+]i...

  19. Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110-kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells

    DEFF Research Database (Denmark)

    Schneider, H R; Reichert, G H; Issinger, O G

    1986-01-01

    mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (cAMP- and cGMP-dependent protein kinases) only show a basal level of enzyme...

  20. 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)

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

    DEFF Research Database (Denmark)

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

    1991-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. Metaphyseal giant cell tumor

    International Nuclear Information System (INIS)

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed. (Author)

  4. Metaphyseal giant cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L.F.; Hemais, P.M.P.G.; Aymore, I.L.; Carmo, M.C.R. do; Cunha, M.E.P.R. da; Resende, C.M.C.

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed.

  5. Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice.

    Science.gov (United States)

    Guo, Huizhen; Zhang, Zhenbiao; Su, Zuqing; Sun, Chaoyue; Zhang, Xie; Zhao, Xiaoning; Lai, Xiaoping; Su, Ziren; Li, Yucui; Zhan, Janis Yaxian

    2016-04-01

    Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL-1β, TNF- α, IL-6 and TGF-β1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-β, α-SMA, p-Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM. PMID:26874212

  6. Nonislet Cell Tumor Hypoglycemia

    OpenAIRE

    Johnson Thomas; Salini C. Kumar

    2013-01-01

    Nonislet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia. It is characterized by increased glucose utilization by tissues mediated by a tumor resulting in hypoglycemia. NICTH is usually seen in large mesenchymal tumors including tumors involving the GI tract. Here we will discuss a case, its pathophysiology, and recent advances in the management of NICTH. Our patient was diagnosed with poorly differentiated squamous cell carcinoma of esophagus. He continued to be hypoglycemic ...

  7. 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

  8. 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)

  9. 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.

  10. 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

  11. Olfactory ensheathing cell tumor

    Directory of Open Access Journals (Sweden)

    Ippili Kaushal

    2009-01-01

    Full Text Available Olfactory ensheathing cells (OECs are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

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

    International Nuclear Information System (INIS)

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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Canine mast cell tumors.

    Science.gov (United States)

    Macy, D W

    1985-07-01

    Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession. PMID:3929444

  18. 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...

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

    Directory of Open Access Journals (Sweden)

    Piché Alain

    2011-05-01

    Full Text Available Abstract Background The acellular fraction of epithelial ovarian cancer (EOC ascites promotes de novo resistance of tumor cells and thus supports the idea that tumor cells may survive in the surrounding protective microenvironment contributing to disease recurrence. Levels of the pro-inflammatory cytokines IL-6 and IL-8 are elevated in EOC ascites suggesting that they could play a role in tumor progression. Methods We measured IL-6 and IL-8 levels in the ascites of 39 patients with newly diagnosed EOC. Commercially available enzyme-linked immunosorbent assay (ELISA was used to determine IL-6 and IL-8 ascites levels. Ascites cytokine levels were correlated with clinicopathological parameters and progression-free survival. Results Mean ascites levels for IL-6 and IL-8 were 6419 pg/ml (SEM: 1409 pg/ml and 1408 pg/ml (SEM: 437 pg/ml respectively. The levels of IL-6 and IL-8 in ascites were significantly lower in patients that have received prior chemotherapy before the surgery (Mann-Whitney U test, P = 0.037 for IL-6 and P = 0.008 for IL-8. Univariate analysis revealed that high IL-6 ascites levels (P = 0.021, serum CA125 levels (P = 0.04 and stage IV (P = 0.009 were significantly correlated with shorter progression-free survival. Including these variables in a multivariate analysis revealed that elevated IL-6 levels (P = 0.033 was an independent predictor of shorter progression-free survival. Conclusion Elevated IL-6, but not IL-8, ascites level is an independent predictor of shorter progression-free survival.

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

    International Nuclear Information System (INIS)

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

  1. Brain tumor stem cells.

    Science.gov (United States)

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies. PMID:20370314

  2. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Eichler, D C; Tatar, T F

    1980-06-24

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

  5. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate

    OpenAIRE

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B.; Fuxe, Jonas; Shoshan, Maria

    2012-01-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility...

  6. Radiologic findings of granulosa cell tumor of the ovary

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jung Eun; Kim, Kie Hwan; Yoo, Ji Young; Lee, Eun Chun; Lee, Tae Hyun; Chin, Soo Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-08-01

    To evaluate the radiologic findings of granulosa cell tumor of the ovary. Fourteen cases(fifteen tumors) of pathologically confirmed ovarian granulosa cell tumor were retrospectively analyzed on the basis of CT(n=10), MR imaging(n=4), and ultrasound(n=7) findings. The patients' mean age was 44.3(range, 5-71)years. The mean diameter of the tumors was 12.1(range, 5-26.5)cm. Thirteen cases were unilateral, and one was bilateral. Eleven tumors(ten cases) were mainly solid and eight of these had focal cystic components. Multilocular cysts accounted for three cases, and in two of these, mural nodules were present. One case was a unilocular cyst with no mural nodule. Ten cases were well demarcated. All the solid tumors were enhanced on postcontrast CT and MR imaging. Endometrial thickening was seen in five cases, ascites in six, and peritoneal implants or omental fat infiltration in five. One was associated with lymph node metastasis. All the postmenopausal patients had solid tumors, whereas 66.7%(4 of 6 cases) of young adults and children had cystic tumors. Granulosa cell tumors of the ovary were solid or cystic;the former were more common. There were no characteristic findings which permitted definitive differentiation from other ovarian tumors.

  7. Radiologic findings of granulosa cell tumor of the ovary

    International Nuclear Information System (INIS)

    To evaluate the radiologic findings of granulosa cell tumor of the ovary. Fourteen cases(fifteen tumors) of pathologically confirmed ovarian granulosa cell tumor were retrospectively analyzed on the basis of CT(n=10), MR imaging(n=4), and ultrasound(n=7) findings. The patients' mean age was 44.3(range, 5-71)years. The mean diameter of the tumors was 12.1(range, 5-26.5)cm. Thirteen cases were unilateral, and one was bilateral. Eleven tumors(ten cases) were mainly solid and eight of these had focal cystic components. Multilocular cysts accounted for three cases, and in two of these, mural nodules were present. One case was a unilocular cyst with no mural nodule. Ten cases were well demarcated. All the solid tumors were enhanced on postcontrast CT and MR imaging. Endometrial thickening was seen in five cases, ascites in six, and peritoneal implants or omental fat infiltration in five. One was associated with lymph node metastasis. All the postmenopausal patients had solid tumors, whereas 66.7%(4 of 6 cases) of young adults and children had cystic tumors. Granulosa cell tumors of the ovary were solid or cystic;the former were more common. There were no characteristic findings which permitted definitive differentiation from other ovarian tumors

  8. Clinical and Radiologic Signs of Relapsed Ovarian Germ Cell Tumor: Tissue Is the Issue

    Directory of Open Access Journals (Sweden)

    M. Y. V. Homs

    2013-01-01

    Full Text Available Malignant ovarian germ cell tumor is a rare disease, but with current treatment strategies including surgery and platinum based chemotherapy survival is excellent. After treatment, intensive followup is indicated to encounter tumor relapse at an early stage. This case describes a 22-year-old female with a history of common variable immune deficiency (CVID who underwent a resection of a large ovarian germ cell tumor followed by 4 cycles of cisplatin and etoposide resulting in clinical complete remission. During followup, she developed a mass at the umbilicus and ascites. Initially, the cytology of the ascites was interpreted as tumor positive, suspicious of relapse of the disease, but tumor markers remained negative. However, during laparoscopy it turned out to be a mature teratoma, which can develop after chemotherapy, the so called growing teratoma syndrome. In retrospect, the ascites was false positive. This case shows that current diagnostic tools are not sufficient to distinguish between vital tumor and mature teratoma and can be misleading. Tumor biopsy and/or laparoscopic inspection are therefore indicated.

  9. Tumor heterogeneity and circulating tumor cells.

    Science.gov (United States)

    Zhang, Chufeng; Guan, Yan; Sun, Yulan; Ai, Dan; Guo, Qisen

    2016-05-01

    In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs. PMID:26902424

  10. Optimization of monoclonal antibody production in mouse ascites by single whole-body irradiation

    International Nuclear Information System (INIS)

    Hybridoma cells injected intraperitoneally into mice induce formation of ascites tumors producing ascites fluid with high levels of monoclonal antibodies. Several parameters affect the growth of the immunoglobulin-producing tumors in vivo. In 10 different hybridomas the average ascites tumor formation rate could be increased from 32% (n = 338 mice) to 77% (n = 112 mice) by only one whole-body irradiation of paraffin-pretreated Balb/c mice. Production of monoclonal antibodies was better in males because of the significantly (p < 0.01) increased volume of ascites fluid. From the increased tumor formation rate in irradiated mice it is suggested that in non-irradiated recipients the tumor growth rate was lowered by immunological reactions against hybridoma cells provoked by cell surface neoantigens revealed by cell fusion and/or tumor-associated antigens of the myeloma parent cells as well as by altered antigen pattern caused by possible mutations in the myeloma cell line and/or Balb/c/K strain. (author)

  11. Intracranial germ cell tumor

    OpenAIRE

    Kreutz, J; Rausin, L.; Weerts, E; Tebache, M; Born, J; Hoyoux, C

    2010-01-01

    Germ cell tumours represent about 3 to 8% of pediatric brain tumours. Occurrence of diabetes insipidus is common in the case of suprasellar germ cell tumors. The diagnosis may be advanced by MRI owing to the location and relatively univocal characteristics of the lesion signal. The existence of a bifocal mass developed in both suprasellar region and pineal zone is highly suggestive of a germinoma. The most important notion is to recognize that at the time of diabetes insipidus diagnosis in a ...

  12. Familial germ cell tumor

    OpenAIRE

    Sanju Cyriac; Rejeev Rajendranath; A. Robert Louis; Sagar, T. G.

    2012-01-01

    Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presenc...

  13. Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

    Directory of Open Access Journals (Sweden)

    Amal I. Hassan

    2014-04-01

    Full Text Available Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ irradiation on nuclear factor, erythroid 2 (NFE2, P53, stromelysin-1 (matrix metalloproteinase-3 (MMP3, BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5 Gy. Sixty-four female mice, weighing 20–25 g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B, the animals were exposed to a single dose of 0.5 Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5 Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96 h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96 h of γ irradiation (IIB. On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96 h of γ irradiation (IIB. As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group when compared to control mice (1st group. Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter

  14. Efeito da solução aquosa de fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich: estudo experimental in vitro Effects of watery solution of phenol, acetic acid and glycerin in Ehrlich mouse ascites tumor: experimental study in vitro

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2004-01-01

    Full Text Available OBJETIVO: Verificar o efeito da solução composta por fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich. MÉTODOS: Após a coleta do líquido ascítico de três camundongos procedeu-se a incubação, a 37° C, do mesmo com diferentes doses da solução teste (0,50, 0,25, 0,10 e 0,05 ml e com solução salina (0,50 ml como controle; estudou-se a viabilidade celular pela técnica de exclusão do azul tripan. RESULTADOS: Observou-se que ao final de 15 minutos todas as células tumorais encontravam-se inviáveis com as diferentes doses da solução teste. CONCLUSÃO: A solução proposta, causa, in vitro, a morte das células tumorais ao foral de 15 minutos.PURPOSE: To evaluate the effects of phenol, acetic and glycerin solution in Ehrlich ascites tumor. METHODS: After the ascites liquid of three mice was collected, the incubation of these cells took place at 37 degrees Celsius with saline solution (0,50mL and different solution dosages (0,25mL, 0,10mL e 0,05mL. RESULTS: After 15 minutes all tumors cells were dead regardless of the dosage. Whereas in the control group the tumor cells were alive. CONCLUSION: This solution destroys the tumor cells in vitro after 15 minutes.

  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. Familial germ cell tumor

    Directory of Open Access Journals (Sweden)

    Sanju Cyriac

    2012-01-01

    Full Text Available Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile.

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

    Science.gov (United States)

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

    2007-12-01

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

  18. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders;

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by...... stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes...

  19. 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...

  20. A Case of Congenital Malignant Spinal Cord Glioma as a Cause of Congenital Ascites in a Neonate.

    Science.gov (United States)

    Karber, Bianca; Omesi, Lenore; Chang, Sunny; Handel, Andrew; Hegedus, Monica; Maduekwe, Echezona

    2016-01-01

    Congenital ascites is rare, but when it occurs, urinary ascites secondary to posterior urethral valve obstruction is the most common, and tumors are the least. Among the tumors in the pediatric population, the central nervous system tumors are common, but spinal cord tumors are rare. We describe a very rare case of congenital malignant spinal cord glioma presenting as isolated congenital ascites secondary to neurogenic bladder. A female infant was diagnosed sonographically with isolated congenital ascites at 40 weeks' gestational age, with uneventful development prior to 40 weeks' gestational age. Magnetic resonance imaging of the spine done within the first week of life identified a lobulated spinal mass with heterogeneous enhancement within the conus medullaris. Spinal fluid analysis showed evidence of small round blue cells and the pathology from the excision biopsy of the mass confirmed a WHO grade III or IV malignant glioma. The postoperative course was uneventful with resolution of the ascites and spontaneous micturition. The patient was discharged home without an indwelling urinary catheter. We report the first documented case of a newborn infant with isolated congenital ascites from neurogenic bladder secondary to a spinal cord glioma. PMID:27597917

  1. 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

  2. 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.

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

    International Nuclear Information System (INIS)

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

  4. Secondary specific immune response in vitro to MSV tumor cells.

    Science.gov (United States)

    Senik, A; Hebrero, F P; Levy, J P

    1975-12-15

    The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3-day in vitro culture, have been studied with a murine sarcoma virus (MSV)-induced tumor. The 3H-thymidine incorporation of lymphoma cells growing in suspension, and the radioactive-chromium release of freshly sampled lymphoma cells regularly added to the culture, have been compared to determine the part played by immune lymphoid cells in cytolysis and cytostasis of the tumor-cell population. The cytolytic activity increases in the culture from day 0 to day 3. It is due, predominantly, to T-cells, and remains specific to antigens shared by MSV tumors and related lymphomas. This activity would be difficult to detect unless freshly sampled ascitic cells were used as targets, since the lymphoma cells spontaneously lose a part of their sensitivity to immune cytolysis during in vitro culture. The method used in the present experiments is a secondary chromium release test (SCRT), which measures the invitro secondary stimulation of cytotoxic T-lymphocytes (CTL) by tumor cells. In the absence of stimulatory cells, the CTL activity would have rapidly fallen in vitro. The cytostatic activity also increases during the 3 days in vitro, in parallel to the cytolytic activity: it is due to non-T-cells and remains mainly non-specific. The significance of these data for the interpretation of invitro demonstrated cell-mediated anti-tumor immune reactions is briefly discussed, as well as their relevance in the in vivo role of immune CTL. PMID:53210

  5. Mast cell tumors: clinical management

    International Nuclear Information System (INIS)

    Mast cell tumors are commonly diagnosed in small animal practice; however, appropriate treatment and prognosis remain controversial. These tumors are considered malignant in dogs but generally are benign in cats. Mast cell tumors are associated with various clinical signs that are related to the release of biologic mediators from the granules of the neoplastic cells, and these signs may be the primary presenting complaint. Clinical staging as well as histopathologic grading are important in determining the treatment of choice and prognosis. Treatment consists of several options, including surgery, radiation therapy, and chemotherapy. This article summarizes the available information regarding diagnosis, treatment, and prognosis of mast cell tumors and makes recommendations for therapy

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

    International Nuclear Information System (INIS)

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

  7. Desmoplastic Small Round Cell Tumor of Stomach

    Directory of Open Access Journals (Sweden)

    Ahmed Abu-Zaid

    2013-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is an extremely uncommon, highly aggressive, and malignant mesenchymal neoplasm of undetermined histogenesis. Less than 200 case reports have been documented in literature so far. Herein, we report a 26-year-old otherwise healthy female patient who presented with a 1-month history of epigastric pain. On physical examination, a palpable, slightly mobile, and tender epigastric mass was detected. All laboratory tests were normal. A chest, abdominal, and pelvic contrast-enhanced computed tomography (CT scans showed a 3.8 × 7.2 × 8.7 cm ill-defined mass, involving gastric fundus and extending into gastric cardia and lower gastroesophageal junction. It was associated with multiple enlarged gastrohepatic lymph nodes; the largest measured 1.2 cm. There was no evidence of ascites or retroperitoneal or mesenteric lymphatic metastases. Patient underwent total gastrectomy with D2 lymphadenectomy, splenectomy, and antecolic Roux-en-Y esophagojejunal anastomosis. Histopathological examination revealed coexpression of mesenchymal, epithelial, and neural markers. The characteristic chromosomal translocation (t(11; 22(p13; q12 was demonstrated on fluorescence in situ hybridization (FISH technique. Diagnosis of DSRCT of stomach was confirmed. Patient received no postoperative radiotherapy or chemotherapy. A postoperative 3-month followup failed to show any recurrence. In addition, a literature review on DSRCT is included.

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

    OpenAIRE

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

    1992-01-01

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

  9. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomioka, Yukiko, E-mail: ytomi@muses.tottori-u.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Morimatsu, Masami, E-mail: mmorimat@vetmed.hokudai.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Nishijima, Ken-ichi, E-mail: nishijma@nubio.nagoya-u.ac.jp [Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Usui, Tatsufumi, E-mail: usutatsu@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Yamamoto, Sayo, E-mail: ysayo@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Suyama, Haruka, E-mail: sharuka@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ozaki, Kinuyo, E-mail: k-ozaki@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ito, Toshihiro, E-mail: toshiito@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); and others

    2014-07-18

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.

  10. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    International Nuclear Information System (INIS)

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation

  11. 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

  12. 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)

  13. Infantile pericardial round cell tumor

    International Nuclear Information System (INIS)

    Cardiac malignancies presenting in infancy are rare. Desmoplastic small round cell tumor (DSRCT) is a rare occurrence in this age group. No case of intrapericardial DSRCT has been reported in the literature in infants

  14. Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.

    Science.gov (United States)

    Greenhouse, W V; Lehninger, A L

    1977-11-01

    Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle. PMID:198130

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

    OpenAIRE

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

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

  18. [Ovarian germ cell tumors in girls].

    Science.gov (United States)

    Nechushkina, I V; Karseladze, A I

    2015-01-01

    Morphological structure of tumor influences on the clinical course of the disease in children with germ cell tumors. Patients with ovarian dysgerminoma at the time of diagnosis are significantly older than patients with immature teratoma and yolk sac tumor. Immature teratoma and mixed germ cell tumors are significantly larger compared to other germ cell tumors. Yolk sac tumor and embryonal carcinoma are the most common cause of emergency surgical interventions and are accompanied by rupture of tumor capsule. PMID:26087605

  19. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available BACKGROUND: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. CONCLUSION/SIGNIFICANCE: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  20. 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.

  1. Desmoplastic small round cell tumor: a case report and review of the literature; Tumor desmoplastico de pequenas celulas: relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Luiz Gustavo Teixeira [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Medicina Interna; Isberner, Rony Klaus [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Radiologia]. E-mail: ronyklaus@terra.com.br; Scolaro, Bruno Lorenzo [Universidade do Vale do Itajai, SC (Brazil). Curso de Medicina]. E-mail: brunoscolaro@yahoo.com.br; Sezerino, Daniel Oseias [Universidade do Vale do Itajai, SC (Brazil). Curso de Medicina. Disciplina de Anatomia Patologica; Almeida, Daniel da Silva [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Radiologia e Diagnostico por Imagem

    2006-10-15

    Desmoplastic small round cell tumor is a rare and highly aggressive neoplasm that predominantly occurs in young adult males. Pain and abdominal distention are frequent, ascites could be observed. His histogenesis is uncertain and the most common location is the peritoneal cavity. This tumor is characterized by presenting a distinct morphology and polyphenotypic differentiation. We present in this report the case of an adolescent admitted in the service of Internal Medicine and Radiology of the Hospital and Maternity Marieta Konder Bornhausen, Itajai, SC, Brazil, in year 2005. (author)

  2. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  3. Cancer stem cells and brain tumors

    OpenAIRE

    Pérez Castillo, Ana; Aguilar Morante, Diana; Morales-García, José A.; Dorado, Jorge

    2008-01-01

    Besides the role of normal stem cells in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Most current research on human tumors is focused on molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and, more recently, in solid tumors suggests that the tumor cell population is heterogeneous. In recent years, several groups have described the existence of a cancer stem cell population in different brain tumors. These neural cancer stem ...

  4. 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.

  5. 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...

  6. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    Science.gov (United States)

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  7. Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

    Science.gov (United States)

    He, Y; Wu, A C; Harrington, B S; Davies, C M; Wallace, S J; Adams, M N; Palmer, J S; Roche, D K; Hollier, B G; Westbrook, T F; Hamidi, H; Konecny, G E; Winterhoff, B; Chetty, N P; Crandon, A J; Oliveira, N B; Shannon, C M; Tinker, A V; Gilks, C B; Coward, J I; Lumley, J W; Perrin, L C; Armes, J E; Hooper, J D

    2016-01-28

    Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC

  8. 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.

  9. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  10. 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.

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

    International Nuclear Information System (INIS)

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

  12. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  13. Influence of gold nanoparticle tagged snake venom protein toxin NKCT1 on Ehrlich ascites carcinoma (EAC) and EAC induced solid tumor bearing male albino mice.

    Science.gov (United States)

    Bhowmik, Tanmoy; Saha, Partha Pratim; DasGupta, Anjan Kumar; Gomes, Antony

    2014-01-01

    Earlier the conjugation of gold nanoparticle (GNP) and snake venom protein toxin NKCT1 was reported and primary characterization was performed. In the present communication, further characterizations of GNP-NKCT1 were done with SEM, EDS, XRD and Raman spectra for its physio-chemical nature and bonding. SEM showed the formation of gold nanoparticles, whereas EDS and XRD confirmed 60-90% gold nanoparticles in the solution. Raman shift corresponding to (C=O), (N-H), (C-N) confirmed the proper conjugation of GNP with NKCT1. GNP-NKCT1 showed anticancer effect both in vivo and in vitro in EAC cell and antitumor effect in EAC induced mice. In in vivo studies, GNPNKCT1 increased MST 108.30% and decreased viable EAC cell count 51.39%. Fluorescent micrograph showed signs of apoptosis (membrane blebbing, membrane disruption). Decreased level of IL-10 and low incorporation of BrdU showed decreased proliferation of EAC induced by GNP-NKCT1. With upregulation of Bax, down regulation of Bcl2 and increased expression of caspase 3/9, it was confirmed that GNP-NKCT1 induced caspase dependent apoptosis pathway in EAC cell. In in vitro studies, GNP-NKCT1 increased the late apoptotic stage of cell and arrested cell cycle division at G0/G1 state. GNP-NKCT1 also decreased the tumor volume and tumor weight in EAC induced tumor in male albino mice. It inhibited angiogenesis, which was confirmed by lower percentage of expression of VEGF. This study indicated the capability of gold nanoparticles which enhanced the tumor uptake of NKCT1 and also suggested that GNP-NKCT1 might be a good source for anti-carcinoma and anti-tumor agents. PMID:24827982

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

    Energy Technology Data Exchange (ETDEWEB)

    Polverelli, M.; Teoule, R.

    1972-09-01

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

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

    DEFF Research Database (Denmark)

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

    1981-01-01

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

  16. Aberrant 3H in Ehrlich mouse ascites tumor cell nucleotides after in vivo labeling with myo-[2-3H]- and L -myo-[1-3H]inositol: implications for measuring inositol phosphate signaling

    DEFF Research Database (Denmark)

    Christensen, Søren C.; Jensen, Annelie Kolbjørn; Simonsen, L.O.

    2003-01-01

    After in vivo radiolabeling of Ehrlich cells for 24 h with conventional myo-[2-3H]inositol we previously demonstrated an aberrant 3H-labeling of ATP that interfered in the HPLC analysis of inositol trisphosphates. This aberrant 3H-labeling was accounted for by the extensive kidney catabolism of m......]Inositol appears nevertheless to be a preferable alternative to myo-[2-3H]inositol for tracing the intact myo-inositol molecule after in vivo labeling, with minimized interference from aberrant 3H-labeling of nucleotides....

  17. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  19. Brain tumor stem cell dancing

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2014-09-01

    Full Text Available Background. Issues regarding cancer stem cell (CSC movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".

  20. Autophagy sensitivity of neuroendocrine lung tumor cells

    OpenAIRE

    HONG, SEUNG-KEUN; Kim, Jin-Hwan; Starenki, Dmytro; Park, Jong-In

    2013-01-01

    Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective treatments are available to cure NE lung tumors, demanding identification of biological features specific to these tumors. Here, we report that autophagy has an important role for NE lung tumor cell proliferation and survival. We found that the expression levels of...

  1. Within tumors, interactions between T cells and tumor cells are impeded by the extracellular matrix

    OpenAIRE

    Salmon, Hélène; Donnadieu, Emmanuel

    2012-01-01

    In principle, T cells can recognize and kill cancer cells. However, tumors have the ability to escape T cell attack. By imaging the dynamic behavior of T cells in human lung tumor explants, we have recently established the importance of the extracellular matrix in limiting access of T cells to tumor cells.

  2. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs−/−) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  3. Atypical extragonadal germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mainak Deb

    2012-01-01

    Full Text Available Aim: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT with a subset analysis of those with atypical features. Materials and Methods: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. Results: Fifteen children aged 7 days to 15 years (median, 1.5 years were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1, anterior neck-thyroid gland (1, mediastinum (4, abdominothoracic extending through the esophageal hiatus (1, retroperitoneal (4 and sacrococcygeal (4. On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years, 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. Conclusions: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

  4. 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

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

    DEFF Research Database (Denmark)

    Litman, Thomas; Pedersen, Stine F.; Kramhøft, Birte;

    1998-01-01

    Multidrug resistance; P-glycoprotein; Intracellular pH; acidification; glucose; Na*O+/H*O+ exchanger; H*O+ efflux......Multidrug resistance; P-glycoprotein; Intracellular pH; acidification; glucose; Na*O+/H*O+ exchanger; H*O+ efflux...

  6. Inhibition of tumor cells multidrug resistance by cucumarioside A2-2, frondoside A and their complexes with cholesterol.

    Science.gov (United States)

    Menchinskaya, Ekaterina S; Aminin, Dmitry L; Avilov, Sergey A; Silchenko, Aleksandra S; Andryjashchenko, Pelageya V; Kalinin, Vladimir I; Stonik, Valentin A

    2013-10-01

    In non-cytotoxic concentrations, frondoside A (1) from the sea cucumber Cucumaria okhotensis and cucumarioside A2-2 (2) from C. japonica, as well as their complexes with cholesterol block the activity of membrane transport P-glycoprotein in cells of the ascite form of mouse Ehrlich carcinoma. They prevent in this way an efflux of fluorescent probe Calcein from the cells. Since the blocking of P-glycoprotein activity results in decrease of multidrug resistance, these glycosides and their complexes with cholesterol may be considered as potential inhibitors of multidrug resistance of tumor cells. PMID:24354179

  7. [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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  9. NK cells in the tumor microenvironment

    DEFF Research Database (Denmark)

    Larsen, Stine K; Gao, Yanhua; Basse, Per H

    2014-01-01

    The presence of natural killer (NK) cells in the tumor microenvironment correlates with outcome in a variety of cancers. However, the role of intratumoral NK cells is unclear. Preclinical studies have shown that, while NK cells efficiently kill circulating tumor cells of almost any origin, they...

  10. Interaction of tumor cells with the microenvironment

    Directory of Open Access Journals (Sweden)

    Lehnert Hendrik

    2011-09-01

    Full Text Available Abstract Recent advances in tumor biology have revealed that a detailed analysis of the complex interactions of tumor cells with their adjacent microenvironment (tumor stroma is mandatory in order to understand the various mechanisms involved in tumor growth and the development of metastasis. The mutual interactions between tumor cells and cellular and non-cellular components (extracellular matrix = ECM of the tumor microenvironment will eventually lead to a loss of tissue homeostasis and promote tumor development and progression. Thus, interactions of genetically altered tumor cells and the ECM on the one hand and reactive non-neoplastic cells on the other hand essentially control most aspects of tumorigenesis such as epithelial-mesenchymal-transition (EMT, migration, invasion (i.e. migration through connective tissue, metastasis formation, neovascularisation, apoptosis and chemotherapeutic drug resistance. In this mini-review we will focus on these issues that were recently raised by two review articles in CCS.

  11. Granular cell tumor: An uncommon benign neoplasm

    Directory of Open Access Journals (Sweden)

    Tirthankar Gayen

    2015-01-01

    Full Text Available Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

  12. Giant cell tumor of the mandible

    OpenAIRE

    Giri, G V V; Gheena Sukumaran; Ravindran, C.; Malathi Narasimman

    2015-01-01

    Giant cell tumor (GCT) of bone is a distinctive neoplasm characterized by abundance of multinucleated giant cells scattered throughout the stroma of mononuclear cells. Its importance lies in recognizing and differentiating the characteristic histology, which at times may mimic several other bone tumors and endocrine disorders ranging from locally aggressive giant cell granulomas to hyperparathyroidism to malignant tumors. The jaw bones account for less than 1% of the lesion.In a literature se...

  13. Granular Cell Tumor: An Uncommon Benign Neoplasm

    OpenAIRE

    Tirthankar Gayen; Anupam Das; Kaushik Shome; Debabrata Bandyopadhyay; Dipti Das; Abanti Saha

    2015-01-01

    Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

  14. Evaluation and treatment of malignant ascites secondary to gastric cancer.

    Science.gov (United States)

    Maeda, Hiromichi; Kobayashi, Michiya; Sakamoto, Junichi

    2015-10-21

    Malignant ascites affects approximately 10% of patients with gastric cancer (GC), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in GC patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points (named "five-point method") on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, "Clinical Benefit Response in GC (CBR-GC)", was recently introduced to measure the efficacy of chemotherapy for malignant ascites of GC. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for GC patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a

  15. Immunotherapy with BCG cell wall plus irradiated tumor cells

    International Nuclear Information System (INIS)

    Two different fibrosarcomas (MCB-I, MCB-II) were induced by methylcholcholanthrene in syngeneic Balb/C mice were used. The tumor cells irradiated with 5,000 to 30,000 rads did not growth in mice on 30 days after inoculation. The viable tumor cells were challenged intradermally to mice on 7 days after inoculation of the tumor cells irradiated with 5,000 to 30,000 rads. The challenged tumor cells were all rejected at 30 days after inoculation. Mice were challenged with 5 x 105 viable tumor cells on 7 days after inoculation of 103 to 108 irradiated tumor cells. Mice pretreated with 105 or 106 irradiated tumor cells rejected the tumor cells completely. The viable tumor cells were challenged to mice on 7 days after inoculation of BCG-CW emulsion plus 106 irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 106 irradiated tumor cells. Optimal dosage of BCG-CW emulsion was 50 or 100 mu g. BCG-CW emulsion plus irradiated tumor cells were injected subcutaneously to the mice after tumor cells inoculation. Three injections of the vaccine significantly suppressed the tumor outgrowth, but not one or two injections in no-treated mice. However, in the mice pretreated with BCG-CW emulsion, the tumor growth was significantly suppressed by one or two injections of the vaccine. Especially, the three injections of the vaccine significantly suppressed the tumor growth and the 25% of the mice were completely cured. The effect of the vaccine was almost the same grade by contralateral or ipsilateral treatment. The irradiated MCB-II tumor cells plus BCG-CW emulsion were not effective to the MCB-1 tumor bearing mice, suggesting the anti-tumor effect of this vaccine was immunologically specific

  16. Immunotherapy with BCG cell wall plus irradiated tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizukuro, Tomoyuki (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-04-01

    Two different fibrosarcomas (MCB-I, MCB-II) were induced by methylcholcholanthrene in syngeneic Balb/C mice were used. The tumor cells irradiated with 5,000 to 30,000 rads did not growth in mice on 30 days after inoculation. The viable tumor cells were challenged intradermally to mice on 7 days after inoculation of the tumor cells irradiated with 5,000 to 30,000 rads. The challenged tumor cells were all rejected at 30 days after inoculation. Mice were challenged with 5 x 10/sup 5/ viable tumor cells on 7 days after inoculation of 10/sup 3/ to 10/sup 8/ irradiated tumor cells. Mice pretreated with 10/sup 5/ or 10/sup 6/ irradiated tumor cells rejected the tumor cells completely. The viable tumor cells were challenged to mice on 7 days after inoculation of BCG-CW emulsion plus 10/sup 6/ irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 10/sup 6/ irradiated tumor cells. Optimal dosage of BCG-CW emulsion was 50 or 100 mu g. BCG-CW emulsion plus irradiated tumor cells were injected subcutaneously to the mice after tumor cells inoculation. Three injections of the vaccine significantly suppressed the tumor outgrowth, but not one or two injections in no-treated mice. However, in the mice pretreated with BCG-CW emulsion, the tumor growth was significantly suppressed by one or two injections of the vaccine. Especially, the three injections of the vaccine significantly suppressed the tumor growth and the 25% of the mice were completely cured. The effect of the vaccine was almost the same grade by contralateral or ipsilateral treatment. The irradiated MCB-II tumor cells plus BCG-CW emulsion were not effective to the MCB-1 tumor bearing mice, suggesting the anti-tumor effect of this vaccine was immunologically specific.

  17. Harnessing Dendritic Cells for Tumor Antigen Presentation

    International Nuclear Information System (INIS)

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8+ and CD4+ T cells; the in vitro loading of DCs with tumor antigens

  18. 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

  19. 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.

  20. Cancer Stem Cells and Pediatric Solid Tumors

    International Nuclear Information System (INIS)

    Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC

  1. Altered tumor cell glycosylation promotes metastasis

    Directory of Open Access Journals (Sweden)

    LuborBorsig

    2014-02-01

    Full Text Available Malignant transformation of cells is associated with aberrant glycosylation presented on the cell-surface. Commonly observed changes in glycan structures during malignancy encompasses aberrant expression and glycosylation of mucins; abnormal branching of N-glycans; and increased presence of sialic acid on proteins and glycolipids. Accumulating evidence supports the notion that the presence of certain glycan structures correlates with cancer progression by affecting tumor cell invasiveness, ability to disseminate through the blood circulation and to metastasize in distant organs. During metastasis tumor cell-derived glycans enable binding to cells in their microenvironment including endothelium and blood constituents through glycan-binding receptors - lectins. In this review we will discuss current concepts how tumor cell-derived glycans contribute to metastasis with the focus on three types of lectins: siglecs, galectins and selectins. Siglecs are present on virtually all hematopoetic cells and usually negatively regulate immune responses. Galectins are mostly expressed by tumor cells and support tumor cell survival. Selectins are vascular adhesion receptors that promote tumor cell dissemination. All lectins facilitate interactions within the tumor microenvironment and thereby promote cancer progression. The identification of mechanisms how tumor glycans contribute to metastasis may help to improve diagnosis, prognosis and aid to develop clinical strategies to prevent metastasis.

  2. Experimental study of electrochemotherapy on implanted liver tumor cells apoptosis of rats

    International Nuclear Information System (INIS)

    Objective: To compare the effects of electrochemotherapy (EChT) on implanted liver tumor cells apoptosis of rats. Methods: Immediate cancerous ascites injection method was used for the formation of rats liver tumor model and then followed by rats liver tumor treatment with EChT. Tumor size, necrosis and apoptosis indexes were observed after one week by imaging or pathologic method. The results were compared with those of control group. Results: Before EChT, rats liver tumor volume appeared as (100 ± 6) mm3 and turned to be (125 ± 10) mm3 one week after EChT, which were significantly smaller than those of the control group [(190 ± 11) mm3], P<0.05. Apoptosis indexes were 9.625 ± 1.172 and 3.523 ± 0.894 in EChT group and control group respectively (P<0.01). Tumor necrosis in EChT group increased significantly than those of the control group. Conclusions: The growth of rats liver tumor is obviously inhibited through inducing apoptosis and promoting necrosis by EChT

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

    Science.gov (United States)

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

    1988-02-01

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

  4. Tumor-Related Methylated Cell-Free DNA and Circulating Tumor Cells in Melanoma

    OpenAIRE

    Salvianti, Francesca; Orlando, Claudio; Massi, Daniela; DE GIORGI, VINCENZO; Grazzini, Marta; Pazzagli, Mario; Pinzani, Pamela

    2016-01-01

    Solid tumor release into the circulation cell-free DNA (cfDNA) and circulating tumor cells (CTCs) which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma. The aim of the pres...

  5. Toxic effect of C60 fullerene-doxorubicin complex towards tumor and normal cells in vitro

    Directory of Open Access Journals (Sweden)

    Prylutska S. V.

    2014-09-01

    Full Text Available Creation of new nanostructures possessing high antitumor activity is an important problem of modern biotechnology. Aim. To evaluate cytotoxicity of created complex of pristine C60 fullerene with the anthracycline antibiotic doxorubicin (Dox, as well as of free C60 fullerene and Dox, towards different cell types – tumor, normal immunocompetent and hepatocytes. Methods. Measurement of size distribution for particles in C60 + Dox mixture was performed by a dynamic light scattering (DLS technique. Toxic effect of C60 + Dox complex in vitro towards tumor and normal cells was studied using the MTT assay. Results. DLS experiment demonstrated that the main fraction of the particles in C60 + Dox mixture had a diameter in the range of about 132 nm. The toxic effect of C60 + Dox complex towards normal (lymphocytes, macrophages, hepatocytes and tumor (Ehrlich ascites carcinoma, leukemia L1210, Lewis lung carcinoma cells was decreased by ~10–16 % and ~7–9 %, accordingly, compared with the same effect of free Dox. Conclusions. The created C60 + Dox composite may be considered as a new pharmacological agent that kills effectively tumor cells in vitro and simultaneously prevents a toxic effect of the free form of Dox on normal cells.

  6. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  7. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

    Science.gov (United States)

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

    2012-12-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations. PMID:22954696

  8. Ascites: Pathogenesis and therapeutic principles

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens; Bendtsen, Flemming

    2009-01-01

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

  9. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  10. Giant cell tumor of the mandible

    Directory of Open Access Journals (Sweden)

    G V V Giri

    2015-01-01

    Full Text Available Giant cell tumor (GCT of bone is a distinctive neoplasm characterized by abundance of multinucleated giant cells scattered throughout the stroma of mononuclear cells. Its importance lies in recognizing and differentiating the characteristic histology, which at times may mimic several other bone tumors and endocrine disorders ranging from locally aggressive giant cell granulomas to hyperparathyroidism to malignant tumors. The jaw bones account for less than 1% of the lesion.In a literature search, we found only five cases of GCT of jaw bones based on the new criteria. We present a rare case of GCT of the mandible which occurred in a 12-year-old female.

  11. 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.

  12. 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)

  13. 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.

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

    International Nuclear Information System (INIS)

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

  15. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  16. Effusion cytomorphology of small round cell tumors

    OpenAIRE

    Katsuhide Ikeda; Koji Tsuta

    2016-01-01

    Background: Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT neoplastic cells in the effusion fluid is very rare. We reported the cytomorphological findings of SRCTs in effusion cytology, and performed statistical and mathematical analyses for a purpose to distinguish SRCTs. Materials and Methods: We analyzed the cytologic findings of effusion samples from 40 SRCT cases and...

  17. 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.

  18. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  19. 103Ru for tumor scanning, 2

    International Nuclear Information System (INIS)

    The mechanism of 103Ru-uptake in tumors was investigated through the incubation of rat ascites hepatoma cells (AH-130) in vitro with various concentrations of Ru-chloride containing 103Ru-chloride as a tracer. Quantitative analysis of Ru binding to the cells indicated that ascites hepatoma cells contained high- and low-affinity binding sites for Ru. When ascites hepatoma cells were incubated with Ru after incubation with a low concentration of papain, most of the Ru was not bound to the cells but was found in the medium containing solubilized glycoproteins. However Ru bound mainly to washed cells after the incubation with papain. About 65% of the Ru bound to ascites hepatoma cells was liberated by the papain treatment, and about 45% of the liberated Ru was precipitated by cetyltrimethylammonium bromide, indicating that Ru bound tightly to glycopeptides. These results suggest that the tumor affinity of 103Ru is related to specific binding to glycopeptides on the tumor cell surface. (author)

  20. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  1. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  2. Helical CT of the islet cell tumors

    International Nuclear Information System (INIS)

    The rapid sequential table incremental dynamic CT (RSS) and the helical CT were performed for 48 nodules from 44 cases of islet cell tumors (26 cases of functioning tumors and 22 of non-functioning tumors). The difference of the detectability of these modalities, and the detectability of metastasis to liver and lymph nodes were examined. Forty-five of 48 nodules (94%) could be diagnosed. Tumors of 35 nodules (73%) were cleared in arterial dominant phase, and tumors of 16 nodules (33%) in equilibrium phase. The arterial phase of the helical CT was useful to detect small tumors including the metastasis to the liver. However, to obtain the good tumor image, the timing to obtain images of arterial phase remains unsolved. In this examinations, also RSS showed high detectability. For the present, the helical CT is more useful in the point of good 3D-images than the diagnostic accuracy for islet cell tumors. This display method in detecting islet cell tumors, the parenchyma of pancreas and surrounding vessels is useful to understand the three dimensional structure at selecting the surgical method. (K.H.)

  3. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  4. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar;

    2011-01-01

    ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 appears to be dispensable for its tumor-promoting effect. Interestingly, we demonstrate that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found that...... tumor progression, but that ADAM12 expression by tumor cells is necessary for tumor progression in these mice. This finding is consistent with our observation that in human breast carcinoma ADAM12 is almost exclusively located in tumor cells and only rarely seen in the tumor-associated stroma. We...

  5. Characterization of cell suspensions from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.

    1985-07-10

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs.

  6. [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

  7. General Information about Extragonadal Germ Cell Tumors

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  8. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  9. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  10. [Benign and malignant granular cell tumors. An immunohistochemical classification of tumor cells].

    Science.gov (United States)

    Kuhn, A; Mahrle, G; Steigleder, G K

    1987-06-15

    Eight benign and three malignant granular cell tumors were characterized by means of antibodies and antisera against keratin, desmin, epithelial membrane antigen, factor VIII-related protein, lysozyme, myelin basic protein, myoglobin, neurone-specific enolase, S 100 protein, myelin-associated protein (Leu 7), glial fibrillary acidic protein, vimentin, and neurofilament. All benign granular cell tumours showed positive staining of the tumor cells to antibodies against vimentin, S 100 protein, and neurone-specific enolase; myelin-associated protein (Leu 7), in contrast, was only detectable in a few tumor sections. Histogenetically the granular cells may be classified as Schwann's cells which lost their expression of laminin. The three malignant granular cell tumors showed a staining pattern significantly different from that of the benign tumours. Thus, only neurone-specific enolase was detectable in all the tumors, whereas S 100 protein and vimentin could not be demonstrated but in one and two, resp., out of three tumors. PMID:3303714

  11. Next generation sequencing of disseminated tumor cells

    Directory of Open Access Journals (Sweden)

    ElenKristineMøller

    2013-12-01

    Full Text Available Disseminated tumor cells (DTCs detected in the bone marrow have been shown as an independent prognostic factor for women with breast cancer. However, the mechanisms behind the tumor cell dissemination are still unclear and more detailed knowledge is needed to fully understand why some cells remain dormant and others metastasize. Sequencing of single cells has opened for the possibility to dissect the genetic content of subclones of a primary tumor, as well as DTCs. Previous studies of genetic changes in DTCs have employed single-cell array comparative genomic hybridization which provides information about larger aberrations. To date, next generation sequencing provides the possibility to discover new, smaller and copy neutral genetic changes. In this study, we performed whole genome amplification and subsequently next generation sequencing to analyze DTCs from two breast cancer patients. We compared copy number profiles of the DTCs and the corresponding primary tumor generated from sequencing and SNP-CGH data, respectively. While one tumor revealed mostly whole arm gains and losses, the other had more complex alterations, as well as subclonal amplification and deletions. Whole arm gains or losses in the primary tumor were in general also observed in the corresponding DTC. Both primary tumors showed amplification of chromosome 1q and deletion of parts of chromosome 16q, which was recaptured in the corresponding DTCs. Interestingly, clear differences were also observed, indicating that the DTC underwent further evolution at the copy number level. This study provides a proof-of-principle for sequencing of DTCs and correlation with primary copy number profiles. The analyses allow insight into tumor cell dissemination and show ongoing copy number evolution in DTCs compared to the primary tumors.

  12. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  13. Establishment of a hamster lymphoma cell line

    Directory of Open Access Journals (Sweden)

    Abe,Shinji

    1974-08-01

    Full Text Available The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

  14. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

    Directory of Open Access Journals (Sweden)

    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  15. Osteoclastic giant cell tumor of the pancreas: an immunohistochemical study

    DEFF Research Database (Denmark)

    Dizon, M A; Multhaupt, H A; Paskin, D L;

    1996-01-01

    A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor.......A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor....

  16. Interaction of sarcolysine with β-adrenergic receptors of tumor cells

    International Nuclear Information System (INIS)

    The sites of specific binding of [L-3H]dihydroalprenolol ([3H]DHA), possessing the properties of β-adrenergic receptors, coupled with adenylate cyclase, were detected by methods of competitive displacement and binding of β-adrenoblockers: [3H]-DHA and L-propranolol on the surface of ascites sarcoma 37 cells. Specific binding of the ligand occurs rapidly and with saturation. The total number of binding sites in the case of total saturation is (30-40) x 103 per cell. An analysis of the results by the Scatchard method permitted the detection of two types of β-adrenoreceptors with high (K/sub d/ = 0.9-1.0 mM) and low (K/sub d/ = 15-20 nM) affinity for [3H]DHA. The number of receptors of the first type is (5.0-7.5) x 103, and of the second (20-30) x 103 per cell. Sarcolysine in 1-10 μM concentrations is capable of displacing [3H]DHA bound to the β-adrenoreceptors, competing with it for common binding sites, and, like isoproterenol, inducing a brief increase in the content of cAMP in the tumor cells. Since sarcolysine noncompetitively inhibits cAMP phosphodiesterase of the plasma membranes of ascites sarcoma 37 cells in the same concentration range (2.5-25 μM), a possible functional association between the β-adrenoreceptors, adenylate cyclase, and the membrane cAMP phosphodiesterase and the participation of this complex in the antitumor effect of the cytostatic are suggested

  17. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1 cell cycle arrest in EAC cells.

    Science.gov (United States)

    Fukumasu, Heidge; Latorre, Andreia Oliveira; Zaidan-Dagli, Maria Lucia

    2011-01-01

    The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant. PMID:20564499

  18. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  19. Apoptin: specific killer of tumor cells?

    Science.gov (United States)

    Tavassoli, M; Guelen, L; Luxon, B A; Gäken, J

    2005-08-01

    In the early 1990s it was discovered that the VP3/Apoptin protein encoded by the Chicken Anemia virus (CAV) possesses an inherent ability to specifically kill cancer cells. Apoptin was found to be located in the cytoplasm of normal cells while in tumor cells it was localized mainly in the nucleus.(1) These differences in the localization pattern were suggested to be the main mechanism by which normal cells show resistance to Apoptin-mediated cell killing. Although the mechanism of action of Apoptin is presently unknown, it seems to function by the induction of programmed cell death (PCD) after translocation from the cytoplasm to the nucleus and arresting the cell cycle at G2/M, possibly by interfering with the cyclosome.(2) In addition, cancer specific phosphorylation of Threonine residue 108 has been suggested to be important for Apoptin's function to kill tumor cells.(3) In contrast to the large number of publications reporting that nuclear localization, induction of PCD and phosphorylation of Apoptin is restricted to cancer cells, several recent studies have shown that Apoptin has the ability to migrate to the nucleus and induce PCD in some of the normal cell lines tested. There is evidence that high protein expression levels as well as the cellular growth rate may influence Apoptin's ability to specifically kill tumor cells. Thus far both in vitro and in vivo studies indicate that Apoptin is a powerful apoptosis inducing protein with a promising prospective utility in cancer therapy. However, here we show that several recent findings contradict some of the earlier results on the tumor specificity of Apoptin, thus creating some controversy in the field. The aim of this article is to review the available data, some published and some unpublished, which either agree or contradict the reported "black and white" tumor cell specificity of Apoptin. Understanding what factors appear to influence its function should help to develop Apoptin into a potent anti

  20. Radiation therapy for intracranial germ cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Wakako; Takizawa, Yoshikazu; Yoshida, Hiroshi; Aruga, Moriyo; Arimizu, Noboru (Chiba Univ. (Japan). School of Medicine); Itami, Jun

    1993-05-01

    From 1974 through 1988, 27 patients with intracranial germ cell tumor underwent radiotherapy in Chiba University Hospital. Radiation field encompassed the whole neuroaxis in 19 patients, the local area in 5, and the whole brain in 3. Overall 5-year survival rate of all 27 patients was 88.9%. There was no significant difference in 5-year overall survival rate between the patients who were treated by the neuroaxis radiation and by the more limited fields. The most significant prognostic factor was pathology of the tumors. Germinoma and histology-unknown tumors which showed good response to irradiation have more favorable prognosis than embryonal carcinoma and choriocarcinoma. From our data, three possibilities emerged: (1) some germinomas might be controlled by localized radiation; (2) optimal dose might be 45[approx]50 Gy; (3) if histology-unknown tumor has good response to radiation at 20 Gy, the tumor can be treated by the same way as germinoma. (author).

  1. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies. PMID:26482724

  2. Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells.

    Science.gov (United States)

    Chi, Lianhua; Na, Moon-Hee; Jung, Hyun-Kyung; Vadevoo, Sri Murugan Poongkavithai; Kim, Cheong-Wun; Padmanaban, Guruprasath; Park, Tae-In; Park, Jae-Yong; Hwang, Ilseon; Park, Keon Uk; Liang, Frank; Lu, Maggie; Park, Jiho; Kim, In-San; Lee, Byung-Heon

    2015-07-10

    A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to lung tumor. IL4RPep-1 preferentially bound to H226 lung tumor cells which express higher levers of IL-4R compared to H460 lung tumor cells which express less IL-4R. Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were the key binding determinants. IL4RPep-1-labeled liposomes containing doxorubicin were more efficiently internalized in H226 cells and effectively delivered doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence imaging of nude mice subcutaneously xenotransplanted with H226 tumor cells indicated that IL4RPep-1-labeled liposomes accumulate more efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes. Interestingly, expression of IL-4R was high in vascular endothelial cells of tumor, while little was detected in vascular endothelial cells of control organs including the liver. IL-4R expression in cultured human vascular endothelial cells was also up-regulated when activated by a pro-inflammatory cytokine tumor necrosis factor-α. Moreover, the up-regulation of IL-4R expression was observed in primary human lung cancer tissues. These results indicate that IL-4R-targeting nanocarriers may be a useful strategy to enhance drug delivery through the recognition of IL-4R in both tumor cells and tumor endothelial cells. PMID:25979323

  3. Desmoplastic small round cell tumor with sphere-like clusters mimicking adenocarcinoma.

    Science.gov (United States)

    Hattori, Yukinori; Yoshida, Akihiko; Sasaki, Naoshi; Shibuki, Yasuo; Tamura, Kenji; Tsuta, Koji

    2015-03-01

    Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere-like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients. PMID:24819999

  4. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    Science.gov (United States)

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

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

    Science.gov (United States)

    Wang, Yongwei; Guo, Yuming; Ning, Dong; Peng, Yunzhi; Cai, Hong; Tan, Jianzhuang; Yang, Ying; Liu, Dan

    2012-01-01

    Ascites syndrome is still a problem for chicken industry in various parts of the world. Despite the intensive investigations of this syndrome for many years, its pathogenesis remains unclear. The objective of this study was to analyze the difference in hepatic proteomics between ascites and healthy broilers by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Changes of biochemical parameters of liver and blood were also determined. The results indicated that red blood cell counts (RBC), hematocrit (HCT) and haemoglobin (HGB) of ascites broilers were significantly greater than healthy broilers. Hepatic malondialdehyde (MDA) level of ascites broilers was significantly increased, and the activity of total superoxide dismutase (T-SOD) was significantly decreased. Hepatic lactic acid (LD) level of ascitic broilers were significantly lower than healthy ones. Serum glucose and cholesterol level of ascites broilers were significantly increased, and serum globulin level was significantly decreased in ascites broilers. There was no significant difference in triglyceride (TG) and blood urea nitrogen (BUN) level. The activity of liver hexokinase (HK) and succinodehydrogenase (SDH) in ascites broilers was significantly decreased, and there was no significant difference in the activity of liver pyruvate kinase (PK) and Na+-K+-ATPase. The hepatic proteomics analysis showed that 18 proteins expression difference were identified between ascites and healthy broilers. These proteins were mainly involved in: 1) cytoskeleton; 2) glucose, lipids and amino acid metabolism; 3) cell secretion; 4) cell apoptosis; 5) signal transduction; 6) immune and inflammatory response; and 7) cellular redox homeostasis. Mitochondrial isoform phosphoenolpyruvate carboxykinase (M-PEPCK) mainly participates in gluconeogenesis of chicken liver. In conclusion, liver oxidative damage was significantly aggravated, but

  6. Giant cell tumor of the rib

    International Nuclear Information System (INIS)

    A 27-year-old woman with a giant cell tumor of the rib with a cystic-hemorrhagic appearance underwent surgery consisting of en bloc resection and reconstruction of the thoracic wall with Marlex mesh, reinforced with two titanium plates. When possible this type of tumor requires resection, instead of radiotherapy, since the majority of cases of malignant transformation are linked to prior radiation therapy. (orig.)

  7. Tumor cure and tumor cell survival kinetics after photoradiation treatment in vivo in two experimental mouse tumor systems

    International Nuclear Information System (INIS)

    To study the question whether tumor destruction by photoradiation therapy (PRT) in vivo is due to direct tumor cell kill or whether it is a consequence of damage to the tumor support structures, the authors have used the EMT-6 and RIF in vivo-in vitro tumor systems, which allow colony formation survival assay of tumor cells treated with PRT in vivo. The EMT-6 tumor showed no significant reduction in tumor cell clonogenicity at the completion of PRT at doses which are curative to the tumor. However, when the tumors were allowed to remain in situ for varying lengths of time (1-24 h) after PRT, tumor cell death occurred rapidly and progressively. Very similar tumor cell survival kinetics were found in RIF tumors, although cure of these tumors by PRT is rare. The pattern of tumor cell death following PRT in vivo closely matches that of tumors deprived of oxygen, implying that one of the major factors leading to tumor destruction by PRT may be the shut-down of tumor vasculature, which has been shown to be one of the initial effects of PRT

  8. The Human Cell Surfaceome of Breast Tumors

    Directory of Open Access Journals (Sweden)

    Júlia Pinheiro Chagas da Cunha

    2013-01-01

    Full Text Available Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors.

  9. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  10. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    Directory of Open Access Journals (Sweden)

    Philip G.R. Schmalz

    2011-02-01

    Full Text Available Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed.

  11. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    OpenAIRE

    Schmalz, Philip G.R.; Park, John K.; Shen, Michael J.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects o...

  12. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  13. 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...

  14. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    Science.gov (United States)

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  15. Risk assessment of thyroid follicular cell tumors.

    OpenAIRE

    Hill, R. N.; Crisp, T M; Hurley, P M; Rosenthal, S L; Singh, D. V.

    1998-01-01

    Thyroid follicular cell tumors arise in rodents from mutations, perturbations of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1)...

  16. Isolation of Circulating Tumor Cells by Dielectrophoresis

    OpenAIRE

    Gascoyne, Peter R.C.; Sangjo Shim

    2014-01-01

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim...

  17. Altered tumor cell glycosylation promotes metastasis

    OpenAIRE

    LuborBorsig

    2014-01-01

    Malignant transformation of cells is associated with aberrant glycosylation presented on the cell-surface. Commonly observed changes in glycan structures during malignancy encompasses aberrant expression and glycosylation of mucins; abnormal branching of N-glycans; and increased presence of sialic acid on proteins and glycolipids. Accumulating evidence supports the notion that the presence of certain glycan structures correlates with cancer progression by affecting tumor cell invasiveness, ab...

  18. Tumor-associated macrophages promote tumor cell proliferation in nasopharyngeal NK/T-cell lymphoma

    OpenAIRE

    Liu, Yixiong; Fan, Linni; Wang, Yingmei; Li, Peifeng; Zhu, Jin; Wang, Lu; Zhang, Weichen; Zhang, Yuehua; Huang, Gaosheng

    2014-01-01

    Objective: To explore the relationship between the number of tumor-associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T-cell lymphoma. Methods: Immunohistochemistry was used to reconfirm the diagnosis of nasal NK/T-cell lymphoma and detect the numbers of TAMs and the ki-67 label index of the tumor cells in all 31 cases. In addition, 12 cases of inflammatory cases were collected as c...

  19. Generation of hydroxyl radicals during ascites experimentally induced in broilers.

    Science.gov (United States)

    Arab, H A; Jamshidi, R; Rassouli, A; Shams, G; Hassanzadeh, M H

    2006-04-01

    Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the most important features of the ascites syndrome in broiler chickens. However, the mechanism of cell injury causing the pathogenesis of the syndrome is not clearly understood. Our study aimed to examine the generation of hydroxyl radicals (OH*) in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens were purchased from a local hatchery and reared in an open poultry house for 46 d. They were divided at random into three groups and ascites was induced in two groups by exposing them to low temperature or administration of triiodothyronine (T(3)). The third group served as control and was reared normally. Haematological, biochemical and pathological tests were used to determine the incidence of ascites: including total red blood cell (RBC), packed cell volume (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and ratio of right ventricular weight to total ventricular weight (RV/TV). A salicylate hydroxylation method was used to examine the generation of hydroxyl radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites, 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to detect the generation of OH*. An ascites syndrome was observed in T(3) and low-temperature treated groups, as shown by necropsy changes and increases in f RBC, PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were increased in groups experiencing ascites compared to control group. It is suggested that reactive oxygen species that is OH* ions, may be involved in the pathogenesis of the ascites syndrome in broiler chickens. PMID:16641033

  20. 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

  1. 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.

  2. Prognostic significance of new onset ascites in patients with pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Luzardo German

    2006-03-01

    Full Text Available Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm. All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

  3. Granular cell tumor of the esophagus.

    Science.gov (United States)

    Patel, R M; DeSota-LaPaix, F; Sika, J V; Mallaiah, L R; Purow, E

    1981-12-01

    Two cases of granular cell tumor of the esophagus are reported and the main features of the previously reported cases are summarized. Dysphagia and substernal discomfort or pain are the most common symptoms seen and are likely to occur with lesions greater than 1 cm. in diameter. The diagnosis should be considered in adult females with an intramural mass of the esophagus. The cell of origin is still disputed. The treatment of choice, when the patient is symptomatic or the lesion greater than 1 cm. in size, is local resection. The tumor, when incidentally discovered in an asymptomatic patient, may safely be followed endoscopically. PMID:6277183

  4. Tumor-to-Tumor Metastasis to Chromophobe Renal Cell Carcinoma: A First Report

    OpenAIRE

    Hiromitsu Mimata; Fuminori Sato; Tomoko Kan; Toshitaka Shin

    2011-01-01

    Tumor-to-tumor metastasis is a rare phenomenon. From our review of the international literature, around 150 cases have been reported since it was first documented by Campbel in 1868. Renal clear cell carcinoma is well known to be the most common recipient of tumor-to-tumor metastasis in all tumors. However, renal chromophobe cell carcinoma has not been reported to be a recipient. Here, we report a first case of colorectal carcinoma metastatic to chromophobe renal cell carcinoma.

  5. Granular Cell Tumor of Brachial Plexus Mimicking Nerve Sheath Tumor: A Case Report

    OpenAIRE

    Kim, Young-Im; Lee, Chul-kyu; Cho, Ki Hong; Kim, Sang-Hyun

    2012-01-01

    Primary tumors of the brachial plexus region are rare and granular cell tumors arising from the brachial plexus region is an extremely rare disease. We present a case of granular cell tumor arising from of the brachial plexus which appeared to be a usual presentation of nerve sheath tumor before the pathological confirmation. We report a granular cell tumor of the brachial plexus with literature review. Total resection is important for good clinical outcome and prognosis in the treatment of g...

  6. Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy

    OpenAIRE

    Ye, Jian; Peng, Guangyong

    2015-01-01

    Understanding molecular mechanisms involved in creating and sustaining the tumor suppressive microenvironment is critical for the development of novel antitumor therapeutic strategies. We have identified the induction of T cell senescence as a novel mechanism utilized by human tumor cells to induce immune suppression, and provided a new strategy using TLR8 ligands to reverse tumor immunosuppressive effects for tumor immunotherapy.

  7. Apoptin: Specific killer of tumor cells?

    OpenAIRE

    Tavassoli, M; Guelen, L.; Luxon, B. A.; Gäken, J

    2005-01-01

    In the early 1990s it was discovered that the VP3/Apoptin protein encoded by the Chicken Anemia virus (CAV) possesses an inherent ability to specifically kill cancer cells. Apoptin was found to be located in the cytoplasm of normal cells while in tumor cells it was localized mainly in the nucleus.1 These differences in the localization pattern were suggested to be the main mechanism by which normal cells show resistance to Apoptin-mediated cell killing. Although the mechanism of action of Apo...

  8. Ovarian Germ Cell Tumors Treatment

    Science.gov (United States)

    ... c) cancer cells are found in the pelvic peritoneum. In stage I , cancer is found in one ... in the abdomen ) or in washings of the peritoneum ( tissue lining the peritoneal cavity). Stage II Enlarge ...

  9. Chemotherapy of WAP-T mouse mammary carcinomas aggravates tumor phenotype and enhances tumor cell dissemination.

    Science.gov (United States)

    Jannasch, Katharina; Wegwitz, Florian; Lenfert, Eva; Maenz, Claudia; Deppert, Wolfgang; Alves, Frauke

    2015-07-01

    In this study, the effects of the standard chemotherapy, cyclophosphamide/adriamycin/5-fluorouracil (CAF) on tumor growth, dissemination and recurrence after orthotopic implantation of murine G-2 cells were analyzed in the syngeneic immunocompetent whey acidic protein-T mouse model (Wegwitz et al., PLoS One 2010; 5:e12103; Schulze-Garg et al., Oncogene 2000; 19:1028-37). Single-dose CAF treatment reduced tumor size significantly, but was not able to eradicate all tumor cells, as recurrent tumor growth was observed 4 weeks after CAF treatment. Nine days after CAF treatment, residual tumors showed features of regressive alterations and were composed of mesenchymal-like tumor cells, infiltrating immune cells and some tumor-associated fibroblasts with an intense deposition of collagen. Recurrent tumors were characterized by coagulative necrosis and less tumor cell differentiation compared with untreated tumors, suggesting a more aggressive tumor phenotype. In support, tumor cell dissemination was strongly enhanced in mice that had developed recurrent tumors in comparison with untreated controls, although only few disseminated tumor cells could be detected in various organs 9 days after CAF application. In vitro experiments revealed that CAF treatment of G-2 cells eliminates the vast majority of epithelial tumor cells, whereas tumor cells with a mesenchymal phenotype survive. These results together with the in vivo findings suggest that tumor cells that underwent epithelial-mesenchymal transition and/or exhibit stem-cell-like properties are difficult to eliminate using one round of CAF chemotherapy. The model system described here provides a valuable tool for the characterization of the effects of chemotherapeutic regimens on recurrent tumor growth and on tumor cell dissemination, thereby enabling the development and preclinical evaluation of novel therapeutic strategies to target mammary carcinomas. PMID:25449528

  10. Management of nonfunctioning islet cell tumors

    Institute of Scientific and Technical Information of China (English)

    Han Liang; Pu Wang; Xiao-Na Wang; Jia-Cang Wang; Xi-Shan Hao

    2004-01-01

    AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years.METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests.RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twentyeight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%),nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients.Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than :10 cm were positive prognostic factors in females younger than 30years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007.CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are

  11. Peculiarities in the CT findings of germ cell tumors in various tumor localizations

    International Nuclear Information System (INIS)

    The CT findings of 17 germ cell tumors were studied in relation to the locations of the tumor, the pathological diagnoses, and the tumor markers (AFP and HCG). Generally, the CT findings of germ cell tumors depended on the pathological diagnoses more strongly than on the location of the tumors. On plain CT of 7 germ cell tumors in the pineal region, all of them demonstrated heterogeneous findings. Hydrocephalus was seen in 6 cases (86%) and calcification in 6 cases (86%) of the germ cell tumors in the pineal region. Calcification and hydrocephalus that appeared more often than in other regions were characteristic of germ cell tumors of the pineal region. The germ cell tumors in the basal ganglia had a slightly homogenous high density, with small cysts and calcification in most of them on plain CT. On enhanced CT, the tumors were moderately enhanced in all cases located in the basal ganglia. Four cases of germ cell tumors located in the basal ganglia revealed the dilatation of lateral ventricle due to hemispheric atrophy in the tumor side. The germ cell tumors showing an increase in the tumor markers such as AFP and HCG, which were usually malignant germ cell tumors, were strongly enhanced on enhanced CT. (author)

  12. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    Science.gov (United States)

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  13. ROS Induce Cardiomyocyte Apoptosis in Ascitic Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Zhaofang Xi§, Shijin Yang§, Dongyang Liu, Liming Wu, Xiaodong Liu, Jing Zhao and Dingzong Guo*

    2012-10-01

    Full Text Available It is believed that ascitic broilers die of right heart failure caused by pulmonary hypertension, but the underlying mechanisms of right heart failure are unknown. However, recent studies have shown that reactive oxygen species have the ability to damage heart cells. This study aimed to determine the changes of reactive oxygen species in serum and plasma, and the effect of this variation on myocardial cells during broiler ascites. We used hypoxia and a low-temperature method to induce broiler ascites in the fast-growing group. For controls, we treated a slow-growing group of broilers with 70% restricted feeding under the same circumstances as the fast-growing group. The results showed that hypoxia is a more effective and better way to induce broiler ascites than a low-temperature environment and high growth rate. In addition, reactive oxygen species levels were significantly increased in the fast-growing group compared with those in the slow-growing group. This significant increase in reactive oxygen species resulted in myocardial cell apoptosis in the fast-growing group. Our results suggest that cardiomyocyte apoptosis caused by increased reactive oxygen species levels of ascitic broilers is one of the most important reasons for causing heart failure.

  14. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology. PMID:23980681

  15. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  16. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  17. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  19. The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype.

    Science.gov (United States)

    Schultz, Matthew J; Holdbrooks, Andrew T; Chakraborty, Asmi; Grizzle, William E; Landen, Charles N; Buchsbaum, Donald J; Conner, Michael G; Arend, Rebecca C; Yoon, Karina J; Klug, Christopher A; Bullard, Daniel C; Kesterson, Robert A; Oliver, Patsy G; O'Connor, Amber K; Yoder, Bradley K; Bellis, Susan L

    2016-07-01

    The glycosyltransferase ST6Gal-I, which adds α2-6-linked sialic acids to substrate glycoproteins, has been implicated in carcinogenesis; however, the nature of its pathogenic role remains poorly understood. Here we show that ST6Gal-I is upregulated in ovarian and pancreatic carcinomas, enriched in metastatic tumors, and associated with reduced patient survival. Notably, ST6Gal-I upregulation in cancer cells conferred hallmark cancer stem-like cell (CSC) characteristics. Modulating ST6Gal-I expression in pancreatic and ovarian cancer cells directly altered CSC spheroid growth, and clonal variants with high ST6Gal-I activity preferentially survived in CSC culture. Primary ovarian cancer cells from patient ascites or solid tumors sorted for α2-6 sialylation grew as spheroids, while cells lacking α2-6 sialylation remained as single cells and lost viability. ST6Gal-I also promoted resistance to gemcitabine and enabled the formation of stably resistant colonies. Gemcitabine treatment of patient-derived xenograft tumors enriched for ST6Gal-I-expressing cells relative to pair-matched untreated tumors. ST6Gal-I also augmented tumor-initiating potential. In limiting dilution assays, subcutaneous tumor formation was inhibited by ST6Gal-I knockdown, whereas in a chemically induced tumor initiation model, mice with conditional ST6Gal-I overexpression exhibited enhanced tumorigenesis. Finally, we found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug. Collectively, this work highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. Cancer Res; 76(13); 3978-88. ©2016 AACR. PMID:27216178

  20. 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

  1. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André;

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...... still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the...... appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, this approach has now been evaluated in clinical trials, although with limited success. We summarize and discuss the results from the animal studies and first clinical trials. We also present a new approach...

  2. Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor

    OpenAIRE

    Shukun Shen; Wenjun Yang; Zhugang Wang; Xia Lei; Liqun Xu; Yang Wang; Lizhen Wang; Lei Huang; Zhiwei Yu; Xinhong Zhang; Jiang Li; Yan Chen; Xiaoping Zhao; Xuelai Yin; Chenping Zhang

    2011-01-01

    Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44(high) (CD44(hi)) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi) tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a...

  3. Suppression of T cell responses in the tumor microenvironment.

    Science.gov (United States)

    Frey, Alan B

    2015-12-16

    The immune system recognizes protein antigens expressed in transformed cells evidenced by accumulation of antigen-specific T cells in tumor and tumor draining lymph nodes. However, despite demonstrable immune response, cancers grow progressively suggesting that priming of antitumor immunity is insufficiently vigorous or that antitumor immunity is suppressed, or both. Compared to virus infection, antitumor T cells are low abundance that likely contributes to tumor escape and enhancement of priming is a long-sought goal of experimental vaccination therapy. Furthermore, patient treatment with antigen-specific T cells can in some cases overcome deficient priming and cause tumor regression supporting the notion that low numbers of T cells permits tumor outgrowth. However, tumor-induced suppression of antitumor immune response is now recognized as a significant factor contributing to cancer growth and reversal of the inhibitory influences within the tumor microenvironment is a major research objective. Multiple cell types and factors can inhibit T cell functions in tumors and may be grouped in two general classes: T cell intrinsic and T cell extrinsic. T cell intrinsic factors are exemplified by T cell expression of cell surface inhibitory signaling receptors that, after contact with cells expressing a cognate ligand, inactivate proximal T Cell Receptor-mediated signal transduction therein rendering T cells dysfunctional. T cell extrinsic factors are more diverse in nature and are produced by tumors and various non-tumor cells in the tumor microenvironment. These include proteins secreted by tumor or stromal cells, highly reactive soluble oxygen and nitrogen species, cytokines, chemokines, gangliosides, and toxic metabolites. These factors may restrict T cell entrance into the tumor parenchyma, cause inactivation of effector phase T cell functions, or induce T cell apoptosis ultimately causing diminished cancer elimination. Here, we review the contributions of inhibitory

  4. Functional erythropoietin receptors on human tumor cells

    International Nuclear Information System (INIS)

    Erythropoietin (EPO) is the principal regulator of red blood cell survival, growth and maturation and has achieved great clinical utility for the correction of anemia associated with renal failure, cancer and chemotherapy, and stem cell transplantation. EPO increasingly is being recognized as a pleiotrophic growth factor, having actions on nonhematopoietic cells as well. Both EPO and erythropoietin receptor (EPO-R) expression have been associated with cells of the endothelium, retina, central nervous system, gastrointestinal tract and female reproductive system. The role of EPO in these nonhematopoietic sites is not thoroughly understood and in some instances may be site-specific. Promotion of angiogenesis and blood vessel integrity, increased cell proliferation, prevention of apoptosis, and protection against ischemic damage in the presence of hypoxia have all been described as possible functions of EPO in one or more of these cell types. On the other hand, EPO-R also have been identified on a variety of tumor cells (while in some cases not on the adjacent normal tissue), and several reports have suggested a role for EPO in the direct stimulation of cancer cell growth in vivo and in vitro. Among those tumor cells on which we and others have identified functional EPO-R are breast and ovarian cancer cells. Additionally, the work presented here describes the first evidence that transformed prostate epithelial cells, prostate cancer cell lines, and both normal and cancerous prostate tissue express EPO-R. All of the EPO-R bearing prostate cell lines tested underwent a significant dose-dependent proliferative response to EPO, and EPO triggered intracellular signaling in the cells as evidenced by protein phosphorylation. The results implicate EPO in the biology of both normal and malignant prostate cells and suggest the need for careful evaluation of the use of recombinant EPO as a therapeutic agent in prostate cancer

  5. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  6. The biology of circulating tumor cells.

    Science.gov (United States)

    Pantel, K; Speicher, M R

    2016-03-10

    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice. PMID:26050619

  7. Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

    International Nuclear Information System (INIS)

    Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts

  8. Ascite quilosa traumática Traumatic chylous ascites

    Directory of Open Access Journals (Sweden)

    João Baptista de Resende Neto

    2002-02-01

    Full Text Available Chylous ascites is a rare clinical entity. In infancy it is less commom still. The etiology of most of them is usually congenital or idiopathic; trauma is a less frequent cause. It has been implicated in about 10% of all cases 1-5. There have been less than one hundred cases published in the English literature, including 12 in children. We report a pediatric case of chylous ascites as a result of blunt abdominal trauma managed by ligation of the lymphatic leak.

  9. NMR exposure sensitizes tumor cells to apoptosis.

    Science.gov (United States)

    Ghibelli, L; Cerella, C; Cordisco, S; Clavarino, G; Marazzi, S; De Nicola, M; Nuccitelli, S; D'Alessio, M; Magrini, A; Bergamaschi, A; Guerrisi, V; Porfiri, L M

    2006-03-01

    NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3-66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95-102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8-2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies. PMID:16528477

  10. Antiproliferative and antioxidant activity of Aegle marmelos (Linn. leaves in Dalton′s Lymphoma Ascites transplanted mice

    Directory of Open Access Journals (Sweden)

    Vijaya Chockalingam

    2012-01-01

    Full Text Available Objective: The present investigation was performed to evaluate the antiproliferative and antioxidant activity of Aegle marmelos leaves in Dalton′s Lymphoma Ascites (DLA-bearing mice. Materials and Methods: The DLA cells maintained in vivo in Swiss albino mice were used for developing ascitic tumor in mice by intraperitoneal transplantation. The standardized 50% ethanolic extract of A. marmelos leaves (AMEE was administered intraperitoneally in dose levels 200 and 400 mg/kg, after 24 hours of tumor inoculation in mice for two weeks. Results: The AMEE treatment significantly prevented (P<0.001 the increase in body weight due to tumor cell growth and increased the mean survival time of the tumor-bearing mice as compared to the untreated DLA control mice. The treatment of DLA-bearing mice brought down the Alanine Aminotransferase (ALAT, Aspartate Aminotransferase (ASAT, and alkaline phosphatase to normal levels. The extract decreased the levels of hepatic lipid peroxidation and increased the levels of hepatic antioxidants Glutathione, Superoxide Dismutase (SOD, and catalase. All the changes observed with AMEE treatment were dose dependent. Conclusion: The hydroalcoholic extract of A. marmelos exhibits strong antitumor and antioxidant activities in DLA-bearing mice.

  11. MR imaging of intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masayuki; Takashima, Tsutomu; Akakura, Yukari (Kanazawa Univ. (Japan). School of Medicine) (and others)

    1994-04-01

    MRI of 13 patients with intracranial germ cell tumor (GCT) was performed with a 1.5 T superconductive scanner. T1-and T2-weighted images (T1WI and T2WI) and Gd-DTPA-enhanced T1-weighted images (Gd-T1WI) were obtained. On T1WI and T2WI, five germinomas and one teratoma were homogeneously isointense with gray matter. Two germinomas with cystic component exhibited markedly hypointense and hyperintense areas, respectively. Three teratomas were heterogeneous on both sequences due to cystic portion, fat, and hemorrhage. Yolk sac tumor (YST) was isointense on T1WI and heterogeneous on T2WI. On Gd-T1WI, five germinomas and YST were homogeneously enhanced. All but one of the others were heterogeneously enhanced. There were increased AFP in YST and increased HCG in malignant teratoma. Differential diagnosis of GCT may be possible with MRI. However, tumor markers should be taken into consideration. (author).

  12. PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

    DEFF Research Database (Denmark)

    Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick;

    2015-01-01

    serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0......Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared...

  13. 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.

  14. Multifunctional Nucleic Acids for Tumor Cell Treatment

    DEFF Research Database (Denmark)

    Pofahl, Monika; Wengel, Jesper; Mayer, Günter

    2014-01-01

    We report on a multifunctional nucleic acid, termed AptamiR, composed of an aptamer domain and an antimiR domain. This composition mediates cell specific delivery of antimiR molecules for silencing of endogenous micro RNA. The introduced multifunctional molecule preserves cell targeting, anti......-proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor...

  15. Diagnostic value of circulating tumor cells in cerebrospinal fluid

    OpenAIRE

    Ning Mu; Chunhua Ma; Rong Jiang; Yuan Lv; Jinduo Li; Bin Wang; Liwei Sun

    2016-01-01

    To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining–fluorescence in situ hybridization (TM-iFISH).

  16. Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity1

    OpenAIRE

    Liu, Zuqiang; Kim, Jin H.; Falo, Louis D.; You, Zhaoyang

    2009-01-01

    Treg from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4+ T cell activity is comparable to Treg from naïve mice (naïve Treg), only tumor Treg suppress naïve CD8+ T cell activation and DC function. Neither tumor Treg nor naïve Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. This is consistent with the observation that, in this ...

  17. Endothelial cell-derived interleukin-6 regulates tumor growth

    International Nuclear Information System (INIS)

    Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells

  18. Defense mechanisms of normal and tumor cells

    International Nuclear Information System (INIS)

    This paper reviews the protective systems of normal and tumor cells against chemical and radiation injury. The glutathione redox cycle is an important cell defense system that can be compromised by various chemical modifiers. Acute cell injury can involve the glutathione pools of both the cytosol and the mitochondria. Intracellular calcium may have a role in cell death following acute cell injury but extracellular calcium does not seem to initiate the events leading to cell death. Changes in the glutathione redox status affects the distribution of intracellular calcium and the protein thiol-disulfide redox status. Formation of glutathione protein-mixed disulfides is discussed in terms of a possible protective mechanism against oxidative injury. 46 references

  19. Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

    DEFF Research Database (Denmark)

    Poulsen, Kristian Arild; Andersen, E C; Hansen, C F;

    2010-01-01

    Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT...... was further reduced. AVD(1) and AVD(2) were coupled to net loss of Cl(-), K(+), Na(+), and amino acids (ninhydrin-positive substances), whereas during AVD(T), Na(+) and Cl(-) were accumulated. MDR EATC was resistant to cisplatin, showing increased viability and less caspase 3 activation. Compared with...... AVD, primarily via modulation of NaCl movements, contribute to protection against apoptosis in MDR EATC....

  20. Dendritic cells generated from naïve and tumor-bearing mice uniquely restores different leukocyte subpopulations in chemotherapy-treated tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Mohamed Labib Salem

    2016-01-01

    Full Text Available Background: Dendritic cell (DC-based vaccination has shown promising application in tumor immunotherapy. However, it is not clear whether the presence of tumor impacts the efficacy of generation and functionality of DCs. Aim: To compare the phenotype of DCs generated from naïve or tumor bearing mice and their capability to restore leukopenia-associated chemotherapy. Materials and Methods: DCs were generated from bone marrow (BM of naïve or Ehrlich ascites carcinoma (EAC bearing mice. EAC is an undifferentiated breast cancer cell line with the high transplantable capability and rapid proliferation. BM cells were cultured in vitro for 7 days with granulocyte macrophage colony-stimulating factor and interleukin-4 (20 ng/ml each, loaded with different concentrations of EAC cell lysate (0.5, 1, 3 and 5 mg/106 DCs followed by activation with the toll-like receptor 3 ligand poly(I:C. For DC-based vaccination, CD1 mice (n = 5/group were inoculated with an intraperitoneal (i.p. injection of 0.25 × 106 EAC cells to form ascites, treated on day 14 with an i.p. injection of cyclophosphamide (4 mg/mouse and on day 15 with subcutaneous injection of 2 × 106 DCs from control or EAC bearing mice. Injected DCs were loaded with or without EAC lysate followed by i.p. injection of 50 μg/mouse poly(I:C. On day 21, mice were bled and sacrificed for peripheral blood count and spleen and BM cellularity. Results: Yield of DCs generated from naÏve or EAC bearing mice, as well as their phenotype (CD11c+ CD11b+ and activation (CD40 and CD80 with poly(I:C were similar. Loading DCs with 1 mg EAC lysate induced better viability and activation phenotype as compared with the other concentrations. Regardless the source of DCs, DCs vaccination restored the total numbers of leukocytes in blood but not in the spleen and BM. The effect on peripheral blood leukocytes was coincided with the restoration of the relative numbers of lymphocytes, monocytes, and granulocytes

  1. Endothelial cell pseudopods and angiogenesis of breast cancer tumors

    OpenAIRE

    Sun LuZhe; Short Nicholas; Cameron Ivan L; Hardman W Elaine

    2005-01-01

    Abstract Background A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm3, it developed a well-vascularized capsule. Histological sections of tumors greater than...

  2. Rare tumors of the gallbladder: Clear cell carcinoma

    OpenAIRE

    Huseyin Eken; Mecdi Gurhan Balci; Sercan Buyukakincak; Arda Isik; Deniz Firat; Orhan Cimen

    2015-01-01

    Introduction: Gallbladder cancer is a rare tumor in the gastrointestinal tract has poor prognosis, low survival and is difficult to diagnose. The most common type of gallbladder cancer is adenocarcinoma, and the incidence of clear cell carcinoma is low. Mostly, it is difficult to determine whether the isolated tumor is a primary tumor in the gallbladder or a metastatic tumor from another region. Before accepting a clear cell carcinoma as a primary gallbladder tumor, the kidneys and other poss...

  3. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    OpenAIRE

    Korkaya, Hasan; Liu, Suling; Wicha, Max S.

    2011-01-01

    Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment — including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells — through networks of cytokines and growth factors. Since these components have a direct...

  4. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive traet

    OpenAIRE

    Liang, Wei; Wang, Hui; Sun, Tie-Mie; Yao, Wen-Qing; Chen, Li-Li; Jin, Yu; Chun-ling LI; Meng, Fan-Juan

    2003-01-01

    AIM: To treat patients with stage I-IV malignant tumors of digestive tract using autologous tumor cell vaccine and NDV (Newcastle disease virus) vaccine, and observe the survival period and curative effect.

  5. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    International Nuclear Information System (INIS)

    Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer

  6. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oakman, Catherine; Pestrin, Marta [‘Sandro Pitigliani’ Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy); Bessi, Silvia; Galardi, Francesca [Translational Research Unit, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [‘Sandro Pitigliani’ Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy)

    2010-06-08

    Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer.

  7. Colon tumor cells grown in NASA Bioreactor

    Science.gov (United States)

    2001-01-01

    These photos compare the results of colon carcinoma cells grown in a NASA Bioreactor flown on the STS-70 Space Shuttle in 1995 flight and ground control experiments. The cells grown in microgravity (left) have aggregated to form masses that are larger and more similar to tissue found in the body than the cells cultured on the ground (right). The principal investigator is Milburn Jessup of the University of Texas M. D. Anderson Cancer Center. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Cell constructs grown in a rotating bioreactor on Earth (left) eventually become too large to stay suspended in the nutrient media. In the microgravity of orbit, the cells stay suspended. Rotation then is needed for gentle stirring to replenish the media around the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: NASA and University of Texas M. D. Anderson Cancer Center.

  8. Tumor Cells Express FcγRl Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

    OpenAIRE

    M. Bud Nelson; Nyhus, Julie K; Oravecz-Wilson, Katherine I; Emilio Barbera-Guillem

    2001-01-01

    High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRl expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, a...

  9. Tumor Cells Express FcγRI Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

    OpenAIRE

    Nelson, M. Bud; Nyhus, Julie K; Oravecz-Wilson, Katherine I; Barbera-Guillem, Emilio

    2001-01-01

    High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRI expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, a...

  10. Giant cell tumor of the spine.

    Science.gov (United States)

    Ozaki, Toshifumi; Liljenqvist, Ulf; Halm, Henry; Hillmann, Axel; Gosheger, Georg; Winkelmann, Winfried

    2002-08-01

    Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion. PMID:12151896

  11. Vertebral bony tumor of giant cells

    International Nuclear Information System (INIS)

    This is a report of a 37 years old, masculine patient, in whom a unique primary bone injury was demonstrated, located at T-11, diagnosed as a giant cells tumor (osteoclastoma). Location is described in the literature as unusual. The clinical presentation of the injury is described, as the initial radiological studies and magnetic resonance images 8 years after surgical treatment, with no neoplasic recurrences. The medical literature of these primary bone injuries and its treatment was also reviewed. Objectives: to present a patient with an unusual extramedullar tumor injury, of primary bone origin, benign, treated surgically and who has a post surgical follow-up of 8 years. Local tumor recurrence and not pulmonary metastasis was demonstrated. The medical literature of this bone pathology that affects the spine in an infrequent manner, was also reviewed, specially the related to medical, surgical and radio-therapeutic treatments. Methodology: the clinical history of the patient is described, who was successfully operated, because the expansive tumor was totally drawn out, without neurological injury; inter operating or post-operating vertebral instability was not observed or diagnosed. The patient was controlled in periodic form, with last medical checkup and of magnetic resonance 8 years after the surgery. The medical publications existing are reviewed

  12. Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment.

    Science.gov (United States)

    Lee, J; Fenton, B M; Koch, C J; Frelinger, J G; Lord, E M

    1998-04-01

    Microenvironmental conditions within solid tumors can have marked effects on the growth of the tumors and their response to therapies. The disorganized growth of tumors and their attendant vascular systems tends to result in areas of the tumors that are deficient in oxygen (hypoxic). Cells within these hypoxic areas are more resistant to conventional therapies such as radiation and chemotherapy. Here, we examine the hypoxic state of EMT6 mouse mammary tumors and the location of host cells within the different areas of the tumors to determine whether such microenvironmental conditions might also affect their ability to be recognized by the immune system. Hypoxia within tumors was quantified by flow cytometry and visualized by immunohistochemistry using a monoclonal antibody (ELK3-51) against cellular adducts of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetam ide (EF5), a nitroimidazole compound that binds selectively to hypoxic cells. Thy-1+ cells, quantified using a monoclonal antibody, were found only in the well-oxygenated areas. The location of these Thy-1+ cells was also examined in EMT6 tumors that had been transfected with the gene for interleukin-2 (IL-2) because these tumors contain greatly increased numbers of host cells. Surprisingly, we found that IL-2-transfected tumors had significantly decreased hypoxia compared to parental tumors. Furthermore, using the fluorescent dye Hoechst 33342, an in vivo marker of perfused vessels, combined with immunochemical staining of PECAM-1 (CD31) as a marker of tumor vasculature, we found increased vascularization in the IL-2-transfected tumors. Thus, expression of IL-2 at the site of tumor growth may enhance tumor immunity not only by inducing the generation of tumor-reactive CTLs but also by allowing increased infiltration of activated T cells into the tumors. PMID:9537251

  13. Induction of myeloid-derived suppressor cells by tumor exosomes

    OpenAIRE

    Xiang, Xiaoyu; Poliakov, Anton; Liu, Cunren; Liu, Yuelong; Deng, Zhong-Bin; wang, Jianhua; Cheng, Ziqiang; Shah, Spandan V.; Wang, Gui-Jun; Zhang, Liming; Grizzle, William E.; Mobley, Jim; Zhang, Huang-Ge

    2009-01-01

    Myeloid-derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T-exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T-exosomes switch the di...

  14. Expression of parafibromin in major renal cell tumors

    OpenAIRE

    Cui, C.; Lal, P; Master, S.; Ma, Y.; Baradet, T.; Bing, Z.

    2012-01-01

    Parafibromin, encoded by HRPT2 gene, is a recently identified tumor suppressor. Complete and partial loss of its expression have been observed in hyperparathyroidism-jaw tumor (HPT-JT), parathyroid carcinoma, breast carcinoma, lung carcinoma, gastric and colorectal carcinoma. However, little has been known about its expression in renal tumors. In order to study the expression of parafibromin in a series of the 4 major renal cell tumors - clear cell renal cell carcinoma (ccRCC), papillary ren...

  15. Astrocytes Directly Influence Tumor Cell Invasion and Metastasis In Vivo

    OpenAIRE

    Wang, Ling; Cossette, Stephanie M.; Rarick, Kevin R.; Gershan, Jill; Michael B Dwinell; Harder, David R.; Ramchandran, Ramani

    2013-01-01

    Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among wh...

  16. Biology and Molecular Markers of Malignant Gonadal Germ Cell Tumors

    OpenAIRE

    Salonen, Jonna

    2009-01-01

    Germ cell tumors occur both in the gonads of both sexes and in extra-gonadal sites during adoles-cence and early adulthood. Malignant ovarian germ cell tumors are rare neoplasms accounting for less than 5% of all cases of ovarian malignancy. In contrast, testicular cancer is the most common malignancy among young males. Most of patients survive the disease. Prognostic factors of gonadal germ cell tumors include histology, clinical stage, size of the primary tumor and residua, and levels of tu...

  17. Abdominal germ cell tumors in children - report of two cases

    International Nuclear Information System (INIS)

    Abdominal germ cell tumors are neoplasms which originate from the primary germ cells. Diagnostic imaging (US, CT and MRI) can detect and localize the tumor as well as show its structure. We present two cases of germ cell tumors which, despite very good imaging in sonography and CT, caused problems in final diagnosis. In a boy, a polycyclic tumor of the liver hilus was detected. In a girl, two tumors in the pelvis and a few others in the retropeperitoneal space were detected. Lymphoma, neuroblastoma and PNET tumors were included in the differential diagnosis. In case of clinical suspicion of abdominal tumor, including germ cell tumors, diagnostics imaging should begin sonography. Replacing CT which is not charged with ionizing radiation with MRI, especially in monitoring of the treatment effects, should be considered. The ultimate diagnosis of the tumor type must be established on the basis of histopathological examination. (author)

  18. 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.

  19. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2016-07-26

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  20. Retention mechanism of hypoxia selective nuclear imaging/radiotherapeutic agent Cu-diacetyl-bis(N{sup 4}-methylthiosemicarbazone) (Cu-ATSM) in tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Obata, Atsushi; Waki, Atsuo; Yonekura, Yoshiharu; Fujibayashi, Yasuhisa [Fukui Medical Univ., Matsuoka (Japan). Biomedical Imaging Research Center; Yoshimi, Eiji; Lewis, J.S.; Oyama, Nobuyuki; Welch, M.J.; Saji, Hideo

    2001-12-01

    The retention mechanism of the novel imaging/radiotherapeutic agent, Cu-diacetyl-bis(N{sup 4}-methylthiosemicarbazone) (Cu-ATSM) in tumor cells was clarified in comparison with that in normal tissue in vitro. With Cu-ATSM and reversed phase HPLC analysis, the reductive metabolism of Cu-ATSM in subcellular fractions obtained from Ehrlich ascites tumor cells was examined. As a reference, mouse brain was used. To determine the contribution of enzymes in the retention mechanisms, and specific inhibitor studies were performed. In subcellular fractions of tumor cells, Cu-ATSM was reduced mainly in the microsome/cytosol fraction rather than in the mitochondria. This finding was completely different from that found in normal brain cells. The reduction process in the microsome/cytosol was heat-sensitive and enhanced by adding exogenous NAD(P)H, an indication of enzymatic reduction of Cu-ATSM in tumor cells. Among the known bioreductive enzymes, NADH-cytochrome b5 reductase and NADPH-cytochrome P450 reductase in microsome played a major role in the reductive retention of Cu-ATSM in tumors. This enzymatic reduction was enhanced by the induction of hypoxia. Radiocopper labeled Cu-ATSM provides useful information for the detection of hypoxia as well as the microsomal bioreductive enzyme expression in tumor. (author)

  1. Retention mechanism of hypoxia selective nuclear imaging/radiotherapeutic agent Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells

    International Nuclear Information System (INIS)

    The retention mechanism of the novel imaging/radiotherapeutic agent, Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells was clarified in comparison with that in normal tissue in vitro. With Cu-ATSM and reversed phase HPLC analysis, the reductive metabolism of Cu-ATSM in subcellular fractions obtained from Ehrlich ascites tumor cells was examined. As a reference, mouse brain was used. To determine the contribution of enzymes in the retention mechanisms, and specific inhibitor studies were performed. In subcellular fractions of tumor cells, Cu-ATSM was reduced mainly in the microsome/cytosol fraction rather than in the mitochondria. This finding was completely different from that found in normal brain cells. The reduction process in the microsome/cytosol was heat-sensitive and enhanced by adding exogenous NAD(P)H, an indication of enzymatic reduction of Cu-ATSM in tumor cells. Among the known bioreductive enzymes, NADH-cytochrome b5 reductase and NADPH-cytochrome P450 reductase in microsome played a major role in the reductive retention of Cu-ATSM in tumors. This enzymatic reduction was enhanced by the induction of hypoxia. Radiocopper labeled Cu-ATSM provides useful information for the detection of hypoxia as well as the microsomal bioreductive enzyme expression in tumor. (author)

  2. Clinical significance of CT-defined minimal ascites in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Dong Kyung Chang; Ji Won Kim; Byung Kwan Kim; Kook Lae Lee; Chi Sung Song; Joon Koo Han; In Sung Song

    2005-01-01

    AIM: To study the clinical significance of minimal ascites,which was only defined by the CT and whose nature was not determined preoperatively, in the relationship with the peritoneal carcinomatosis.METHODS: The medical records and the dynamic CT films of 118 patients with gastric cancer were reviewed.Factors associated with peritoneal carcinomatosis were analyzed in 40 patients who had CT-defined ascites of which the nature was surgically confirmed.RESULTS: Only 12.5-25% of the CT-defined minimal ascites, whose volume was estimated to be less than 50 mL, were associated with peritoneal carcinomatosis.When the estimated CT-defined ascitic volume was 50 mL or more, peritoneal carcinomatosis was identified in 75-100%. When CT-defined lymph node enlargements were not found beyond the regional gastric area,perigastricinvasions were not suspected, and the size of tumor was less than 3 cm, peritoneal carcinomatosis seemed significantly less accompanied at the univariate analysis. However, except for the minimal volume of CTdefined ascites in comparison with the mild or more,other factors were not confirmed multivariately.CONCLUSION: In the patients with gastric cancer, CTdefined minimal ascites alone is rarely associated with peritoneal carcinomatosis, if it does not accompany other signs suggestive of malignant seeding. Therefore,consideration of active curative resection should not be hesitated, if CT-defined minimal ascites is the only delusive sign.

  3. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  4. Tumor Cells Express FcγRl Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

    Directory of Open Access Journals (Sweden)

    M. Bud Nelson

    2001-01-01

    Full Text Available High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRl expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, and sequence analysis. Immune complexes containing shed tumor antigen and anti-shed tumor antigen Ab cross-linked FcγRl-expressing tumor cells, which resulted in an induction of tumor cell proliferation and of shed tumor antigen production. Use of selective tyrosine kinase inhibitors demonstrated that tumor cell proliferation induced by immune complex cross-linking of FcγRl is dependent on the tyrosine kinase signal transduction pathway. A selective inhibitor of phosphatidylinositol-3 kinase also inhibited this induction of tumor cell proliferation. These findings support a role for immune complexes and FcγRl expression by tumor cells in augmentation of tumor growth and a metastatic phenotype.

  5. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Gascoyne, Peter R. C., E-mail: pgascoyn@mdanderson.org [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)

    2014-03-12

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  6. Isolation of Circulating Tumor Cells by Dielectrophoresis

    International Nuclear Information System (INIS)

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies

  7. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Directory of Open Access Journals (Sweden)

    Peter R. C. Gascoyne

    2014-03-01

    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  8. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  9. Circulating Tumor Cells, Enumeration and Beyond

    International Nuclear Information System (INIS)

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology

  10. Circulating Tumor Cells, Enumeration and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Jian-Mei [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Krebs, Matthew [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Ward, Tim; Morris, Karen; Sloane, Robert [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Blackhall, Fiona [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Dive, Caroline, E-mail: cdive@picr.man.ac.uk [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom)

    2010-06-09

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  11. Radiation therapy for intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Shingo; Hayakawa, Kazushige; Tsuchiya, Miwako; Arai, Masahiko; Kazumoto, Tomoko; Niibe, Hideo; Tamura, Masaru

    1988-04-01

    The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1 % for germinomas and 38.1 % for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis iradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.

  12. On the role of calcium in the regulatory volume decrease (RVD) response in Ehrlich mouse ascites tumor cells

    DEFF Research Database (Denmark)

    Jørgensen, Nanna K.; Christensen, Søren; Harbak, Henrik; Brown, Anthony M.; Lambert, Ian Henry; Hoffmann, Else Kay; Simonsen, L.O.

    Fysiologi, volume regulation, phosphoinositidase C, Ins(1,4,5)P*U3, Ca*O2*O+-signaling, K*O+ channels, charybdotoxin, clotrimazole......Fysiologi, volume regulation, phosphoinositidase C, Ins(1,4,5)P*U3, Ca*O2*O+-signaling, K*O+ channels, charybdotoxin, clotrimazole...

  13. Preoperative scintigraphic evaluation of the location of juxtaglomerular cell tumor

    International Nuclear Information System (INIS)

    Juxtaglomerular cell tumor is a rare condition which cannot be correctly diagnosed preoperatively. In the only previously reported case in which scintigraphy has been used, this method failed to detect the tumor. We present a case of juxtaglomerular cell tumor in which renal scintigraphy revealed a well-defined cold area in the hilar region of the left kidney. (orig.)

  14. Hypoxic cell turnover in different solid tumor lines.

    NARCIS (Netherlands)

    Ljungkvist, A.; Bussink, J.; Kaanders, J.H.A.M.; Rijken, P.F.J.W.; Begg, A.C.; Raleigh, J.A.; Kogel, A.J. van der

    2005-01-01

    PURPOSE: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be im

  15. Preclinical experiments for analysis of tumor regression due to negative pions

    International Nuclear Information System (INIS)

    To test the potential therapeutic value of negative pions in comparison with conventional x-rays, cobalt-60 γ rays, and high energy electrons and photons (Betatron), experimental analyses with induced tumors (transplant tumors) after irradiation are to be performed in vivo and in vitro (tumor cell suspensions, cell cultures, spontaneous tumors, carcinoma in ascites form); in addition to tumors primarily of mice, human cell tumors will be used; studies will also be made of cell kinetics with various cell types (normal cells, transformed (malignant) cells, beam-resistant, beam-sensitive types) using cell cultures from Chinese hamsters. An attempt will be made to compare slow- and fast-growing tumors. In a second phase, human tumors in conditioned animals will be tested in situ or as cell cultures. Skin, small intestine, regenerating liver and kidney, together with cell cultures, will serve as normal reaction systems

  16. Tumor-initiating cells are enriched in CD44(hi population in murine salivary gland tumor.

    Directory of Open Access Journals (Sweden)

    Shukun Shen

    Full Text Available Tumor-initiating cells (T-ICs discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1 transgenic mouse model of a salivary gland tumor, we identified CD44(high (CD44(hi tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU, at a lower rate than their CD44(negative (CD44(neg counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25% of the CD44(hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44(hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1×10(4 CD44(neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81-96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation.

  17. Appearance of Tumor Cells in Cyst Fluid of Malignant Ovarian Tumor

    OpenAIRE

    Numa, Fumitaka; Suminami, Yoshinori; Ogata, Hidenobu; Nawata, Shugo; Umayahara, Kenji; Nakamura, Yasuhiko; Sugino, Norihiro; Hiraoka, Fumiko; Ise, Etsuko; TAKAHASHI, MUTSUO; Hirabayashi, Kei; Hiratsuka, Keisuke; Kato, Hiroshi

    2000-01-01

    The significance of spillage of tumor cells into the abdominal cavity by fine needle aspiration or rupture of adnexel masses in case of malignancy is the focus. However, the appearance rate of malignant cells in cyst fluid by fine needle aspiration has been quite variable. We therefore evaluated the appearance rate of malignant cells in the cyst fluid from malignant ovarian tumors. Our study population included 29 women with malignant ovarian tumor who attended two hospitals between November...

  18. Adult Primary Extragonadal Germ Cell Tumors: Report of Three Cases

    OpenAIRE

    Ružić, Boris; Trnski, Davor; Dimanovski, Jordan; Kraus, Ognjen; Tomašković, Igor; Krušlin, Božo

    2004-01-01

    Primary extragonadal germ cell tumors are rare neoplasms affecting young males. They usually present with abdominal retroperitoneal, mediastinal mass with varying symptoms. The rarest among these rare extragonadal germ cell tumors are embryonal cell carcinomas. Three cases of embryonal cell carcinomas are presented to show that the clinical presentation of this treatable tumor in this patient population may be quite unusual and difficult to diagnose. Differentiation between primary extragonad...

  19. Cancer Stem Cells in Brain Tumors and Their Lineage Hierarchy

    OpenAIRE

    Kong, Doo-Sik

    2012-01-01

    Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.

  20. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology. PMID:25178695

  1. Expression of Hyaluronidase by Tumor Cells Induces Angiogenesis in vivo

    Science.gov (United States)

    Liu, Dacai; Pearlman, Eric; Diaconu, Eugenia; Guo, Kun; Mori, Hiroshi; Haqqi, Tariq; Markowitz, Sanford; Willson, James; Sy, Man-Sun

    1996-07-01

    Hyaluronic acid is a proteoglycan present in the extracellular matrix and is important for the maintenance of tissue architecture. Depolymerization of hyaluronic acid may facilitate tumor invasion. In addition, oligosaccharides of hyaluronic acid have been reported to induce angiogenesis. We report here that a hyaluronidase similar to the one on human sperm is expressed by metastatic human melanoma, colon carcinoma, and glioblastoma cell lines and by tumor biopsies from patients with colorectal carcinomas, but not by tissues from normal colon. Moreover, angiogenesis is induced by hyaluronidase+ tumor cells but not hyaluronidase- tumor cells and can be blocked by an inhibitor of hyaluronidase. Tumor cells thus use hyaluronidase as one of the ``molecular saboteurs'' to depolymerize hyaluronic acid to facilitate invasion. As a consequence, breakdown products of hyaluronic acid can further promote tumor establishment by inducing angiogenesis. Hyaluronidase on tumor cells may provide a target for anti-neoplastic drugs.

  2. ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO OTHER GASTROINTESTINAL SPINDLE CELL TUMORS.

    Science.gov (United States)

    Hobbs, Joshua; Sutherland-Smith, James; Penninck, Dominique; Jennings, Samuel; Barber, Lisa; Barton, Bruce

    2015-01-01

    Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of gastrointestinal spindle cell tumor recognized with the increasing use of immunohistochemistry. To our knowledge, no imaging features have been described in immunostochemically confirmed canine GISTs. The objective of this retrospective, cross-sectional study was to describe ultrasonographic features of canine GISTs compared with other spindle cell tumors. Thirty-seven dogs with an ultrasonographically visible gastrointestinal mass and a histopathologic diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining was performed for retrieved tissue samples to further differentiate the tumor type and each sample was interpreted by a single veterinary pathologist. Ultrasonographic features recorded examined included mass echogenicity, homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and loss of wall layering, location, size, vascularity, and evidence of perforation or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were significantly more likely to be associated (P < 0.03) with abdominal effusion than other tumor types. There was overlap between the anatomical locations of all tumors types with the exception of the cecum where all eight tumors identified were GISTs. Besides location, there were no unique ultrasound features of GISTs that would allow distinction from other gastrointestinal spindle cell tumors. Similar to previous studies, GISTs appeared to be the most common spindle cell tumor associated with the cecum in our sample of dogs. The high frequency of abdominal effusion with GIST's was of unknown etiology could possibly have been due to septic peritonitis. PMID:25846814

  3. Granulosa cell tumor of testis: Clinicopathological correlation of a rare tumor

    Directory of Open Access Journals (Sweden)

    Swapnil Ulhas Rane

    2014-01-01

    Full Text Available Background: Granulosa cell tumor of testis is a rare tumor accounting for less than 4% of adult testicular tumors though they account for nearly 30% of childhood testicular tumors. Due to the rarity of these tumors, exact etiology, pathogenesis, prognostic factors and best treatment approach are not well known. The molecular events in pathogenesis of these stromal tumors have begun to unravel and these developments put forth a reasonable and scientific explanation for the association of these tumors with developmental anomalies like undescended testis. However, many questions remain unanswered. Materials and Methods: We performed a retrospective analysis of clinicopathological features of all Granulosa Cell Tumors of testis from our archives in addition to an extensive literature search using PUBMED with the key words "Granulosa Cell Tumor, testis". Results: We found six cases in our archives, two of which were of juvenile type and four of adult type. One out of these six cases presented with metastases. All cases underwent radical orchidectomy. Morphology and immunohistochemistry were classical in all cases and there was no diagnostic dilemma. Literature search revealed 63 cases of testicular Granulosa Cell Tumor in addition to highlighting the similarities in the biology and the dissimilarities in the clinical behavior as compared to ovarian Granulosa Cell Tumor. Conclusion: Testicular Granulosa Cell Tumor is a rare tumor, which although histologically similar to its ovarian counterpart, differs in clinical behavior. Further detailed investigations are needed to reveal the mystery behind the differing clinical behavior despite histological and immunohistochemical similarity between the testicular and ovarian Granulosa Cell Tumors.

  4. Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

    International Nuclear Information System (INIS)

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed. Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Results: Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q

  5. Dendritic-Tumor Fusion Cell-Based Cancer Vaccines

    OpenAIRE

    Shigeo Koido

    2016-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whol...

  6. Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells

    OpenAIRE

    Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-Wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A.; Lo, Chung Mau; Man, Kwan; Sun, Dong

    2016-01-01

    Background Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. Methods We employed laser-induced single-cell fusion technique to fuse the hepatocellular carci...

  7. Astrocytes directly influence tumor cell invasion and metastasis in vivo.

    Directory of Open Access Journals (Sweden)

    Ling Wang

    Full Text Available Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2 (MMP-2 and MMP-9 were partly responsible for the astrocyte media-induced tumor cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and invade in vitro. Further, injection of astrocyte media-conditioned breast cancer cells in mice showed increased invasive activity to the brain and other distant sites. More importantly, blocking the preconditioned tumor cells with broad spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells, in particular to the brain in vivo. Collectively, our data implicate astrocyte-derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration and invasion leading to brain metastasis.

  8. Proteolytic Activity of Human Lymphoid Tumor Cells. Correlation with Tumor Progression

    OpenAIRE

    Angelo Vacca; Domenico Ribatti; Roberto Ria; Antonio Pellegrino; Michele Bruno; Francesca Merchionne; Franco Dammacco

    2000-01-01

    Matrix metalloproteinase (MMP) expression and production are associated with advanced-stage tumor and contribute to tumor progression, invasion and metastases. The current study was designed to determine the expression and production of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by human lymphoid tumor cells. Changes in expression and production were also investigated during tumor progression of multiple myeloma and mycosis fungoides. In situ hybridization analysis revealed that lymphoblas...

  9. Pharmacogenomics of Scopoletin in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Ean-Jeong Seo

    2016-04-01

    Full Text Available Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2. This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.

  10. Tumor infiltrating immune cells in gliomas and meningiomas.

    Science.gov (United States)

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Miranda, David; Ruiz, Laura; Sousa, Pablo; Ciudad, Juana; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2016-03-01

    Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control. PMID:26216710

  11. Optimization of tumor radiotherapy. Pt. 6. Modification of tumor glucose metabolism for increasing the bioavailability of 2-deoxy-D-glucose (2-DG) in a murine tumor model

    International Nuclear Information System (INIS)

    Aim: Differential radiomodification induced by 2-deoxy-D-glucose (2-DG) is proving to be a feasible modality for optimizing tumor radiotherapy. Our earlier work on Ehrlich ascites tumor cells has shown that pretreatment with hematoporphyrin derivatives increases the uptake and phosphorylation of 2-DG. Moreover, the alteration induced in bioenergetic profile was more drastic and less reversible. The promising combination of hematoporphyrin derivatives and 2-DG has been further evaluated in the Ehrlich ascites tumor bearing mice for determining the effects on radiotherapeutic response. Materials and methods: Solid tumors (average volume=0.9±0.1 cm3) implanted in Swiss-albino strain 'A' mice were focally irradiated (10 Gy) using 60Co teletherapy. Drugs were administered intravenously. Tumor bioenergetics was assessed by 31P MR spectroscopy. Results: The uptake and phosphorylation of 2-DG was observed to be increased following pretreatment with hematoporphyrin derivatives. Upon hematoporphyrin derivatives +2-DG treatment followed by irradiation, the intracellular pH reduced and a remarkable increase in glycerophosphorylcholine and inorganic phosphate levels was observed. Conclusion: The present study demonstrates the potential of hematoporphyrin derivative pretreatment in increasing the bioavailability of 2-DG in a mice Ehrlich ascites tumor model. The finding may have interesting clinical implications in the form of increased manifestation of the radiation-induced damage in the case of use of these drugs as a potential adjuvant in radiotherapy of tumors. (orig.)

  12. Chylous ascites af ter pancreatico-duodenectomy

    Institute of Scientific and Technical Information of China (English)

    Mansoor Ahmed Madanur; Narendra Battula; Muhammad Omar Azam; Nigel Heaton; Mohamed Rela

    2007-01-01

    BACKGROUND: Chylous ascites (CA) following pancreatico-duodenectomy (PD) is a rare complication secondary to disruption of the lymphatics during extended retroperitoneal lymph node dissection. The majority of cases do not develop CA, possibly due to patency of the proximal thoracic duct and good collaterals. CA may be due to a consequence of occult obstruction of the proximal thoracic duct by malignant inifltration or tumor embolus. This study was to report the incidence of CA and its outcomes of management. METHODS: A retrospective search of our liver database was performed using the key words "pancreatico-duodenectomy", "chylous ascites" from January 2000 to December 2005. The medical records of CA patients and their management and outcome were reviewed. RESULTS: In 138 patients who had undergone PD in our centre for pancreatic malignancy, 3 were identiifed with CA and managed by abdominal paracentesis. CA resolved in 2 patients with low fat medium chain triglyceride diet alone and 1 patient had total parenteral nutrition (TPN) for persistent CA. Resolution of CA occurred in these 3 patients at a median follow-up of 4 weeks (range 4-12 weeks). Histologically, resected specimen conifrmed pancreatic adenocarcinoma in all the patients. Two patients developed loco-regional recurrences at a median follow up of 8 months (range 6-10 months). And the other was currently disease free at a 10-month follow up. CONCLUSIONS: CA as an uncommon postoperative complication requires frequent paracentesis, prolonged hospital stay, and delayed adjuvant chemotherapy. CA is treated with low fat medium chain triglyceride diet or occasionally TPN is required.

  13. Circulating tumor cells in oral squamous cell carcinoma: An insight

    Directory of Open Access Journals (Sweden)

    B V Prakruthi

    2015-01-01

    Full Text Available Circulating tumor cells (CTCs are those cells present in the blood and have antigenic and/or genetic characteristics of a specific tumor type. CTCs can be detected in the peripheral blood of cancer patients. Various techniques are available for detection of CTCs, which provide evidence for future metastasis. CTCs may provide new insight into the biology of cancer and process of metastasis in oral squamous cell carcinoma (OSCC. The detection of CTCs may represent a new diagnostic tool for predicting the occurrence of metastatic disease in OSCC and endow with the treatment strategies to efficiently treat and prevent cancer metastasis. This review gives an insight into the significance of CTCs and different techniques for detection of CTCs.

  14. In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

    Directory of Open Access Journals (Sweden)

    Mees Soeren T

    2010-04-01

    Full Text Available Abstract Background Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer. Methods Anaesthetized CD rats were mechanically ventilated and 106 human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection. Results After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p Conclusions These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.

  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. TUMOR-RELATED METHYLATED CELL-FREE DNA AND CIRCULATING TUMOR CELLS IN MELANOMA

    Directory of Open Access Journals (Sweden)

    Francesca eSalvianti

    2016-01-01

    Full Text Available Solid tumor release into the circulation cell-free DNA (cfDNA and circulating tumor cells (CTCs which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma.The aim of the present study was to assess the diagnostic performance of a tumor-related methylated cfDNA marker in melanoma patients and to compare this parameter with the presence of CTCs.RASSF1A promoter methylation was quantified in cfDNA by qPCR in a consecutive series of 84 melanoma patients and 68 healthy controls. In a subset of 68 cases, the presence of CTCs was assessed by a filtration method (Isolation by Size of Epithelial Tumor Cells, ISET as well as by an indirect method based on the detection of tyrosinase mRNA by RT-qPCR. The distribution of RASSF1A methylated cfDNA was investigated in cases and controls and the predictive capability of this parameter was assessed by means of the area under the ROC curve (AUC.The percentage of cases with methylated RASSF1A promoter in cfDNA was significantly higher in each class of melanoma patients (in situ, invasive and metastatic than in healthy subjects (Pearson chi-squared test, p<0.001. The concentration of RASSF1A methylated cfDNA in the subjects with a detectable quantity of methylated alleles was significantly higher in melanoma patients than in controls. The biomarker showed a good predictive capability (in terms of AUC in discriminating between melanoma patients and healthy controls. This epigenetic marker associated to cfDNA did not show a significant correlation with the presence of CTCs, but, when the two parameters are jointly considered, we obtain a higher sensitivity of the detection of positive cases in invasive

  17. Tumor-Related Methylated Cell-Free DNA and Circulating Tumor Cells in Melanoma

    Science.gov (United States)

    Salvianti, Francesca; Orlando, Claudio; Massi, Daniela; De Giorgi, Vincenzo; Grazzini, Marta; Pazzagli, Mario; Pinzani, Pamela

    2016-01-01

    Solid tumor release into the circulation cell-free DNA (cfDNA) and circulating tumor cells (CTCs) which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma. The aim of the present study was to assess the diagnostic performance of a tumor-related methylated cfDNA marker in melanoma patients and to compare this parameter with the presence of CTCs. RASSF1A promoter methylation was quantified in cfDNA by qPCR in a consecutive series of 84 melanoma patients and 68 healthy controls. In a subset of 68 cases, the presence of CTCs was assessed by a filtration method (Isolation by Size of Epithelial Tumor Cells, ISET) as well as by an indirect method based on the detection of tyrosinase mRNA by RT-qPCR. The distribution of RASSF1A methylated cfDNA was investigated in cases and controls and the predictive capability of this parameter was assessed by means of the area under the ROC curve (AUC). The percentage of cases with methylated RASSF1A promoter in cfDNA was significantly higher in each class of melanoma patients (in situ, invasive and metastatic) than in healthy subjects (Pearson chi-squared test, p < 0.001). The concentration of RASSF1A methylated cfDNA in the subjects with a detectable quantity of methylated alleles was significantly higher in melanoma patients than in controls. The biomarker showed a good predictive capability (in terms of AUC) in discriminating between melanoma patients and healthy controls. This epigenetic marker associated to cfDNA did not show a significant correlation with the presence of CTCs, but, when the two parameters are jointly considered, we obtain a higher sensitivity of the detection of positive cases in invasive and

  18. Detection and Characterization of Circulating Tumor Cells

    Science.gov (United States)

    Bruce, Richard

    2009-03-01

    Circulating tumor cells (CTCs) occur in blood below the concentration of 1 cell in a hundred thousand white blood cells and can provide prognostic and diagnostic information about the underlying disease. While numeration of CTCs has provided useful information on progression-free and overall survival, it does not provide guidance of treatment choice. Since CTCs are presumed contain features of the metastatic tissue, characterization of cancer markers on these cells could help selection of treatment. At such low concentrations, reliable location and identification of these cells represents a significant technical challenge. Automated digital microscopy (ADM) provides high levels of sensitivity, but the analysis time is prohibitively long for a clinical assay. Enrichment methods have been developed to reduce sample size but can result in cell loss. A major barrier in reliable enrichment stems from the biological heterogeneity of CTCs, exhibited in a wide range of genetic, biochemical, immunological and biological characteristics. We have developed an approach that uses fiber-optic array scanning technology (FAST) to detect CTCs. Here, laser-printing optics are used to excite 300,000 cells/sec, and fluorescence from immuno-labels is collected in an array of optical fibers that forms a wide collection aperture. The FAST cytometer can locate CTCs at a rate that is 500 times faster than an ADM with comparable sensitivity and improved specificity. With this high scan rate, no enrichment of CTCs is required. The target can be a cytoplasm protein with a very high expression level, which reduces sensitivity to CTC heterogeneity. We use this method to measure expression levels of multiple markers on CTCs to help predict effective cancer treatment.

  19. 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.

  20. The metabolic advantage of tumor cells

    Directory of Open Access Journals (Sweden)

    Schwartz Laurent

    2011-06-01

    Full Text Available Abstract 1- Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors. Other oncogenes alter the PP2A phosphatase brake over these kinases. 2- Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas. Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases. 3- Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase. In addition, demethylated PP2A would no longer dephosphorylate these enzymes. A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination. This pyruvate forms lactate (Warburg effect and NAD+ for glycolysis. Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available. ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis. Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis. 4- The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase 5- IGFBP stops binding the IGF - IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability. 6- An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...

  1. T cell avidity and tumor recognition: implications and therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Roszkowski Jeffrey J

    2005-09-01

    Full Text Available Abstract In the last two decades, great advances have been made studying the immune response to human tumors. The identification of protein antigens from cancer cells and better techniques for eliciting antigen specific T cell responses in vitro and in vivo have led to improved understanding of tumor recognition by T cells. Yet, much remains to be learned about the intricate details of T celltumor cell interactions. Though the strength of interaction between T cell and target is thought to be a key factor influencing the T cell response, investigations of T cell avidity, T cell receptor (TCR affinity for peptide-MHC complex, and the recognition of peptide on antigen presenting targets or tumor cells reveal complex relationships. Coincident with these investigations, therapeutic strategies have been developed to enhance tumor recognition using antigens with altered peptide structures and T cells modified by the introduction of new antigen binding receptor molecules. The profound effects of these strategies on T celltumor interactions and the clinical implications of these effects are of interest to both scientists and clinicians. In recent years, the focus of much of our work has been the avidity and effector characteristics of tumor reactive T cells. Here we review concepts and current results in the field, and the implications of therapeutic strategies using altered antigens and altered effector T cells.

  2. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  3. Cytogenetics of a malignant ovarian germ-cell tumor

    NARCIS (Netherlands)

    van Echten, J; van Doorn, LC; van der Linden, HC; van der Veen, AY; de Jong, B

    1998-01-01

    Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ-cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal st

  4. 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.

  5. Giant Cell Tumor of Tendon Sheath

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    Jan Paul Briët

    2015-01-01

    Full Text Available Background:  Giant cell tumor of tendon sheath (GCTTS is often thought of as a volar finger mass. We hypothesized that GCTTS are equally common on the dorsal and volar aspects of the hand. In addition, we hypothesized that there are no factors associated with the location (volar versus dorsal and largest measured dimension of a GCTTS.  Methods:  A total of 126 patients with a pathological diagnosis of a GCTTS of the hand or finger were reviewed. Basic emographic and GCTTS specific information was obtained. Bivariable analyses were used to assess predicting factors for location (volar or dorsal side and largest measured diameter of a GCTTS.  Results:  Seventy-two tumors (57% were on the volar side of the hand, 47 (37% were dorsal, 6 (4.8% were both dorsal and volar, and one was midaxial (0.79%. The most common site of a GCTTS was the index finger (30%. There were no factors significantly associated with the location (volar or dorsal, n=119 of the GCTTS. There were also no factors significantly associated with a larger diameter of a GCTTS.  Conclusions:  A GCTTS was more frequently seen on the volar aspect of the hand. No significant factors associated with the location or an increased size of a GCTTS were found in this study.

  6. Individual Cell-Based Models of Tumor-Environment Interactions : Multiple Effects of CD97 on Tumor Invasion

    OpenAIRE

    Galle, Joerg; Sittig, Doreen; Hanisch, Isabelle; Wobus, Manja; Wandel, Elke; Loeffler, Markus; Aust, Gabriela

    2006-01-01

    The presence of scattered tumor cells at the invading front of several carcinomas has clinical significance. These cells differ in their protein expression from cells in central tumor regions as recently shown for the EGF-TM7 receptor CD97. To understand the impact of such heterogeneity on tumor invasion, we investigated tumor cells with modified CD97 expression in vitro and in vivo. Applying an individual cell-based computer model approach, we linked specific cell properties of these cells t...

  7. 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

  8. Dissecting Social Cell Biology and Tumors Using Drosophila Genetics

    OpenAIRE

    Pastor-Pareja, José Carlos; Xu, Tian

    2013-01-01

    Cancer was seen for a long time as a strictly cell-autonomous process in which oncogenes and tumor-suppressor mutations drive clonal cell expansions. Research in the past decade, however, paints a more integrative picture of communication and interplay between neighboring cells in tissues. It is increasingly clear as well that tumors, far from being homogenous lumps of cells, consist of different cell types that function together as complex tissue-level communities. The repertoire of interact...

  9. CT and MRI of germ-cell tumors with metastasis or multi-located tumors

    International Nuclear Information System (INIS)

    Twenty-seven cases of germ-cell tumors were examined with a CT scan in our clinic. In the 11 cases of metastasis or multi-localized tumors, the CT findings were studied in connection with the MRI findings. There were 6 cases of germ-cell tumors which had broad infiltrating tumors with multiple lesions on first admission. Their tumor sites were different from that in cases of malignant glioma, being frequently localized in the pineal and/or the suprasellar region, on the wall of the third and/or lateral ventricle, and in the region of the basal ganglia. Five of the cases of germ-cell tumors had metastasis with various patterns connected to a remote area - that is, to spinal cords, to the ventricular wall and basal cistern of the brain stem by CSF dissemination, to a lung by hematogeneous metastasis, and to the peritoneal wall or organs by a V-P shunt. The CT findings of germ-cell tumors were correlated mainly with the results of the histological diagnosis; they were found not to differ with the tumor site. The germinoma in the suprasellar region had less calcification than in the pineal region. Cysts, calcification, and an enlargement of the lateral ventricle on the tumor side were frequently seen in the germinoma of the basal ganglia. On the MRI of 5 cases of germinoma, the T1-weighted image revealed a slightly low or iso signal intensity, while the T2-weighted image showed a high signal intensity. In the case of multiple tumor lesions, some cases demonstrated different CT findings and radiosensitivities for each tumor. The possibility of a multicentric origin for the tumors is thus suggested in some cases of germ-cell tumors. (author)

  10. Evaluation of antitumor activity and antioxidant status of Alternanthera brasiliana against Ehrlich ascites carcinoma in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Pavan Kumar Samudrala

    2015-01-01

    Full Text Available Objective : The main objective of the present study was to explore the antitumor activity of the ethyl acetate extract of the Alternanthera brasiliana (EAAB and its antioxidant status against Ehrlich ascites carcinoma (EAC in Swiss albino mice. Materials and Methods: Based on the preliminary in vitro cytotoxicity studies, EAAB was selected for anti-tumor and antioxidant effects. Anticancer activity of EAAB was evaluated against EAC in Swiss albino mice at the doses of 200 and 400 mg/kg. EAAB was administered for 14 consecutive days after induction of cancer. After 24 h of the last dose and 18 h of fasting, half of the mice were sacrificed and rest were kept alive for assessing any increase in life span. The antitumor effect of EAAB was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological and biochemical parameters of EAC bearing host. Furthermore, the antioxidant and histopathological parameters were evaluated. Results: EAAB treatment has shown significant decrease in tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice in a dose dependent manner. In hematological profile count of RBC, hemoglobin, and WBC were found reverted to normal. EAAB also significantly decreased the levels of lipid peroxidation and significantly increased the levels of GSH, SOD and Catalase. Conclusion: From the above results it may be concluded that EAAB has potent dose dependent antitumor activity and is comparable to that of 5-flourouracil.

  11. Echocardiographic characteristics of chickens with ascites syndrome.

    Science.gov (United States)

    Deng, G; Zhang, Y; Peng, X; Guo, D; Li, C

    2006-12-01

    1. B- and M-mode echocardiography was used to compare cardiac function in broilers with spontaneous ascites syndrome with that of normal chickens. 2. Thirty ascitic chickens and 15 normal chickens aged three, 4, 5, and 6 weeks from the same flock (180 birds in total) were examined. They were restrained gently in a natural standing position, and echocardiographs were obtained from a 7.0-MHz linear transducer placed on the left pectoral apterium. Indices of cardiac structure and functioning were calculated from the echocardiographs, and some were normalised to body weight. Heart rate was also measured. 3. All cardiac structural indices in both ascitic and normal chickens increased with age. Compared with normal chickens, right ventricular diameter at the end of systole in ascitic chickens was greater at 4, 5 and 6 weeks of age. Ventricular septal thickness at the end of both systole and diastole was greater in ascitic chickens at 5 and 6 weeks. Left ventricular free wall thickness at the end of diastole was less in ascitic chickens at 3 weeks. However, all the structural indices decreased with age after normalisation with body weight. 4. The heart rate of ascitic chickens was lower at 4, 5 and 6 weeks. Normalised left ventricular fractional shortening was lower in ascitic chickens at 4, 5 and 6 weeks, as was normalised right ventricular fractional shortening. Incrassation of the ventricular septum (Delta T), which changed little in normal chickens, was less at 4, 5 and 6 weeks in ascitic chickens. Left ventricular fractional shortening, right ventricular fractional shortening and Delta T were all negatively correlated with ascites heart index at all ages. 5. Taken together the results suggest heart failure of both ventricle, but that right ventricular dysfunction is more extensive than left ventricular dysfunction. We suggest that secondary pulmonary hypertension would result in these ascitic chickens due to volume overload. PMID:17190684

  12. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-02-18

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  13. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    Directory of Open Access Journals (Sweden)

    Kalpna Gupta

    2013-02-01

    Full Text Available Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm3 grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve

  14. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    International Nuclear Information System (INIS)

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm3) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the oxygenation

  15. Concomitant presence of anti-tumor effector cells and suppressor cells in the spleen of tumor-bearing mice : the nature of suppressor cells.

    Directory of Open Access Journals (Sweden)

    Hizuta,Akio

    1981-10-01

    Full Text Available In order to investigate the immunological responsiveness of tumor-bearing hosts to tumor cells, splenic suppressor cells from Ehrlich tumor-bearing mice that inhibited anti-tumor effector cell activity were characterized. In vitro cell-mediated cytoxicity and cytostasis assays were performed to test for the existence of anti-tumor immunity. suppressive activity assayed by cell mixture experiments became apparent with decline of anti-tumor immunity and progressive tumor growth. The cells mediating the suppression were found to be nylon wool column adherent T cells and inhibited T cell dependent cytotoxicity rather than non-T cell dependent cytostasis. In vivo cell transfer experiments demonstrated that intravenous injection of suppressor cells to a host already inoculated with tumor cells mixed with antitumor effector cells resulted in significant enhancement of tumor growth. This inhibition of in vivo neutralization assay be suppressor cells was found in not only allogeneic but also syngeneic tumor system. Splenectomy at the time of tumor resection endowed the host with stronger resistance against subsequent reinoculated tumor than sham-splenectomy did, reflected by prolonged survival times. These results suggest that splenectomy combined with surgical removal of the tumor is a useful treatment of clinical malignancies.

  16. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  17. Antitumor efficacy of vaccinia virus-modified tumor cell vaccine

    International Nuclear Information System (INIS)

    The antitumor efficacies of vaccinia virus-modified tumor cell vaccines were examined in murine syngeneic MH134 and X5563 tumor cells. UV-inactivated vaccinia virus was inoculated i.p. into C3H/HeN mice that had received whole body X-irradiation at 150 rads. After 3 weeks, the vaccines were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with various doses of syngeneic MH134 or X5563 viable tumor cells. Four methods were used for preparing tumor cell vaccines: X-ray irradiation; fixation with paraformaldehyde for 1 h or 3 months; and purification of the membrane fraction. All four vaccines were effective, but the former two vaccines were the most effective. A mixture of the membrane fraction of untreated tumor cells and UV-inactivated vaccinia virus also had an antitumor effect. These results indicate that vaccine with the complete cell structure is the most effective. The membrane fraction of UV-inactivated vaccinia virus-absorbed tumor cells was also effective. UV-inactivated vaccinia virus can react with not only intact tumor cells but also the purified membrane fraction of tumor cells and augment antitumor activity

  18. Radiation response of ''clonogenic'' tumor-cell release (CTCR) from NFSA2ALM1 tumors

    International Nuclear Information System (INIS)

    Blocking the release of living tumor-cells from primary tumors would be one way to prevent or control metastatic dissemination. In the past, most tumor-cell-release studies relied on controversial morphological identification of blood-borne tumor cells without assessing clonogenicity. In the present study, a new method for quantification of ''clonogenic'' tumor-cells released into the blood from primary tumors was used. Mice bearing NFSA2ALM1 were irradiated locally with /sup 137/Cs γ-rays followed at designated times by standard 150 Gy thorax irradiation (TXRT) for CTCR assay. The mice were killed 22 hr after TXRT. The lungs were removed and made into cell suspensions by mincing and enzyme digestion. The cell suspensions were plated in 10cm petri dishes in Fischer's medium supplemented with 10% horse serum. Colonies were stained and counted 11 days later. Time course for suppression of CTCR and its dose response relationship for tumor irradiation were determined: CTCR colonies/mouse/22 hr after 10Gy on tumors were 0.8 +- 0.4, 2.3 +- 0.2, 3.2 +- 1.1 for Day 1,2,7, respectively, while unirradiated control showed 25.7 +- 1.5. Dose response relationship curve had a slope of Do=3.8Gy determined at day 1

  19. Effect of cold stress on broilers selected for resistance or susceptibility to ascites syndrome.

    Science.gov (United States)

    Balog, J M; Kidd, B D; Huff, W E; Huff, G R; Rath, N C; Anthony, N B

    2003-09-01

    Genetic selection for an ascites-resistant line of broilers is seen as a permanent solution to the ascites problem. Ascites-resistant and ascites-susceptible lines have been developed using sire family selection based on mortality data taken from siblings reared in a hypobaric chamber (simulated 2,900 m above sea level). The relaxed line is representative of the original commercial pureline stock randomly mated with no artificial selection pressure. The objectives of this study were to evaluate the differences between the lines when reared in floor pens and subjected to an ascites-inducing cold stress. Seven hundred eighty three straight run broilers were reared in floor pens at local elevation (390 m above sea level). Feed and water were available ad libitum. Birds were brooded at 32 C during the first week. The second week birds were maintained at 30 degrees C. Cold stress was applied for the remaining 4 wk at 14 degrees C. Mortalities were necropsied daily to determine cause of death. Birds and feed were weighed weekly. At 6 wk, five birds per pen were bled, and half the survivors in each pen (8 to 15 birds) were killed, necropsied, and scored for ascites. Blood gases, clinical chemistries, and blood cell counts were taken. Liver, spleen, split heart, and lung weights were recorded. Body weights were not different among the resistant, susceptible, and relaxed lines (P Ascites incidence, as measured by mortality and lesion score at necropsy, was higher in the susceptible and relaxed lines when compared to the resistant line; 18.8, 12.7, and 1.6% respectively (P ascites-resistant line was growing as rapidly as the other lines and was as resistant to ascites as it had been under hypobaric conditions. PMID:12967249

  20. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

    Directory of Open Access Journals (Sweden)

    Ganapati V Hegde

    Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

  1. Tumor-specific T cells signal tumor destruction via the lymphotoxin β receptor

    Directory of Open Access Journals (Sweden)

    Fox Bernard A

    2007-03-01

    Full Text Available Abstract Background Previously, we reported that adoptively transferred perforin k/o (PKO, and IFN-γ k/o (GKO, or perforin/IFN-γ double k/o (PKO/GKO effector T cells mediated regression of B16BL6-D5 (D5 pulmonary metastases and showed that TNF receptor signaling played a critical role in mediating tumor regression. In this report we investigated the role of lymphotoxin-α (LT-α as a potential effector molecules of tumor-specific effector T cells. Methods Effector T cells were generated from tumor vaccine-draining lymph node (TVDLN of wt, GKO, LT-α deficient (LKO, or PKO/GKO mice and tested for their ability to mediate regression of D5 pulmonary metastases in the presence or absence of LT-βR-Fc fusion protein or anti-IFN-γ antibody. Chemokine production by D5 tumor cells was determined by ELISA, RT-PCR and Chemotaxis assays. Results Stimulated effector T cells from wt, GKO, or PKO/GKO mice expressed ligands for LT-β receptor (LT-βR. D5 tumor cells were found to constitutively express the LT-βR. Administration of LT-βR-Fc fusion protein completely abrogated the therapeutic efficacy of GKO or PKO/GKO but not wt effector T cells (p Conclusion The contribution of LT-α expression by effector T cells to anti-tumor activity in vivo was not discernable when wt effector T cells were studied. However, the contribution of LT-β R signaling was identified for GKO or PKO/GKO effector T cells. Since LT-α does not directly induce killing of D5 tumor cells in vitro, but does stimulate D5 tumor cells to secrete chemokines, these data suggest a model where LT-α expression by tumor-specific effector T cells interacts via cross-linking of the LT-βR on tumor cells to induce secretion of chemokines that are chemotactic for macrophages. While the contribution of macrophages to tumor elimination in our system requires additional study, this model provides a possible explanation for the infiltration of inate effector cells that is seen coincident with tumor

  2. An Effective Approach for Immunotherapy Using Irradiated Tumor Cells

    International Nuclear Information System (INIS)

    This study has been aimed to investigate the effect of injection of Irradiated Ehrlich tumor cells alone or concurrent with immunomodulator in mice before and after challenge with viable Ehrlich tumor cells for enhancement of immune system. This study includes the estimation of survival, tumor size, lymphocyte count, LDH, MTT, granzyme B, and DNA fragmentation. In order to fulfill the target of this study, a total of 120 female swiss albino mice were used. They were divided into two classes vaccinated (injection of vaccine before challenge) and therapeutic class (injection of vaccine after challenge). Each class was divided into four groups, group (1) mice injected with viable Ehrlich tumor cells (G1), group (2) mice injected with irradiated tumor cells (G2), group (3) mice injected with immunomodulator (G3), and group (4) mice injected with irradiated tumor cells + immunomodulator (G4). Results obtained from this study demonstrated that, the lymphocyte count and granzyme B activity were increased in both the vaccinated and therapeutic classes compared with control group. LDH activity was decreased in all groups of vaccinated class and also in G2 and G4 groups of therapeutic class compared with control group. There was a significant increase in percent apoptosis of tumor cells cultured with spleenocytes of the groups of vaccinated class as compared with control group. Cellular DNA from Ehrlich tumor cell line cultured with spleenocytes of immunized groups was fragmented into discrete bands of approximate multiples of 200 bp. Revealing significant apoptosis in tumor cells due to vaccination. It is concluded that, vaccination with irradiated tumor cells is an effective approach in stimulation of immune system against viable tumor cells.

  3. Effects of caffeine on X-irradiated synchronous, asynchronous and plateau phase mouse ascites cells: the importance of progression through the cell cycle for caffeine enhancement of killing

    International Nuclear Information System (INIS)

    Caffeine potentiated the killing effect of X-rays on exponentially growing cells giving rise to exponential curves (D0=(0.8+-0.05)Gy) at 4mM and 14 hours treatment. Irradiated plateau phase cells were less sensitive. Exponentially growing cells also became less sensitive to the effects of caffeine when they were incubated in the conditioned medium of plateau phase cells(C-medium) in which cell growth was considerably inhibited. Low caffeine concentrations(2mM) enhanced X-ray induced killing of cells irradiated in G1-,G1/S- or S-phase, but more effectively G2-phase cells. High caffeine concentrations (6mM) enhanced killing of cells in all phases of the cell cycle. Incubation of synchronized populations in C-medium during treatment with caffeine (2mM and 6mM) resulted in less potentiation than in cells treated in fresh medium. The expression of X-ray induced potentially lethal damage caused by 6mM caffeine in cells irradiated in various phases resulted in an exponential survival curve with a mean lethal dose of (0.8+-0.05)Gy, but the time of caffeine treatment necessary to reach this curve was different for cells irradiated in different phases. PLD repair, measured as loss of sensitivity to 6mM caffeine (4 hours treatment) was of 1-2 hours duration. (author)

  4. A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor

    Directory of Open Access Journals (Sweden)

    Fatma Dursun

    2015-01-01

    Full Text Available Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex.

  5. A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor

    Science.gov (United States)

    Dursun, Fatma; Su Dur, Şeyma Meliha; Şahin, Ceyhan; Kırmızıbekmez, Heves; Karabulut, Murat Hakan; Yörük, Asım

    2015-01-01

    Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex. PMID:26366315

  6. A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor

    OpenAIRE

    Fatma Dursun; Şeyma Meliha Su Dur; Ceyhan Şahin; Heves Kırmızıbekmez; Murat Hakan Karabulut; Asım Yörük

    2015-01-01

    Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex.

  7. Cell biological mechanisms of multidrug resistance in tumors.

    OpenAIRE

    Simon, S. M.; Schindler, M

    1994-01-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional cha...

  8. Magnetic resonance spectroscopy in tumor cell lines research

    International Nuclear Information System (INIS)

    MRS can be used non-invasively to study the several trace metabolites and energy metabolism in vivo. By quantitatively analyzing the compounds changes we could detect abnormal metabolism in tumor and its surrounding tissue, and estimate tumor infiltration in vivo and vitro. In recent years, MRS has been applied in cell line research and is becoming a promising method. In this article we summarized the applications of MRS in cell lines in studying diagnosis, treatment, and tumor mechanisms. (authors)

  9. Pediatric Germ Cell Tumors; A 10-year Experience

    OpenAIRE

    Khaleghnejad-tabari, Ahmad; Mirshemirani, Alireza; Rouzrokh, Mohsen; Mohajerzadeh, Leily; Khaleghnejad-Tabari, Nasibeh; Hasas-Yeganeh, Shaghayegh

    2014-01-01

    Objective: The aim of this study was to evaluate the outcome of germ cell tumors in patients admitted to our center during a ten year period. Methods: In a retrospective descriptive study, patients with the pathological diagnosis of germ cell tumor (GCT) were included. All records were evaluated and patients followed by personal visit in clinic or phone call. Data regarding age, sex, tumor site, bio-chemical assay, pathology, treatment and outcomes were gathered. For qualitative variables we ...

  10. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-04-15

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  11. 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...

  12. Research Advances on Th17 Cells in Tumor

    Directory of Open Access Journals (Sweden)

    Jiansheng WANG

    2011-11-01

    Full Text Available The Th17 cells, identified recently as a novel CD4+ T cell lineage, are characteristic of their production of IL-17 and distinct from Th1 and Th2 lineages. Their involvement in autoimmune and chronic inflammation diseases has been well observed. Recent evidence suggests that Th17 cells are also involved in tumor immunology. However, it remains unclear that how these cells regulate immune responses to tumor growth. In this review, we summarize the most recent findings about the biologics of the Th17 cells in tumor development with a hope of providing new insights into future development of effective new cancer immunotherapies.

  13. Identifying cancer origin using circulating tumor cells.

    Science.gov (United States)

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih

    2016-04-01

    Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF-1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  14. An unusual mixed germ cell tumor of the testis consisting of rhabdomyosarcoma, mature teratoma and yolk sac tumor

    Institute of Scientific and Technical Information of China (English)

    Eva Lovri(c); Dubravka Bobonj Hi(z)ak; Melita Peri(c) Balja; Tanja Leni(c)ek; Bo(z)o Kru(s)lin

    2010-01-01

    @@ Dear Editor, We recently encountered a rare case of testicular mixed germ cell tumor (MGCT) in a 32-year-old man. The tumor was composed of a combination of a yolk sac tumor, teratoma and rhabdomyosarcomatous somatic type malignancy.

  15. Ovarian hemangioma with elevated CA125 and ascites mimicking ovarian cancer.

    Science.gov (United States)

    Erdemoglu, E; Kamaci, M; Ozen, S; Sahin, H G; Kolusari, A

    2006-01-01

    We report a case of a very rare tumor of the ovary with an unusual presentation; an ovarian hemangioma with massive ascites and elevated CA125. A 57-year-old woman presenting with elevated CA125, massive ascites and a left solid adnexal mass of 60 x 47 mm, with calcification and increased blood flow at Doppler examination, was submitted to laparotomy. Frozen section was inconclusive and a staging procedure which complicated the patient was performed. Pathologic examination revealed cavernous hemangioma which is an extremely rare tumor of the ovary. Although it is very unusual, an ovarian hemangioma may present with ascites and elevated CA125 and the differential diagnosis from ovarian cancer should be considered. PMID:16620071

  16. MOLECULAR AND CYTOGENETIC ANALYSIS OF LUNG TUMOR CELL LINES

    Science.gov (United States)

    We have measured the levels of amplification of oncogenes and tumor marker genes or other genes of interest in nine human lung tumor cell lines in comparison to normal human bronchial epithelial cells or normal blood lymphocytes to test the hypothesis that aberrant amplification ...

  17. Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Raymond, J T; White, M R; Janovitz, E B

    1997-01-01

    In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an adult African hedgehog (Atelerix albiventris) from a zoological park (West Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm subcutaneous mass along the ventrum of the neck. Metastasis to the right submandibular lymph node occurred. PMID:9027702

  18. Intraorbital Granular Cell Tumor Ophthalmologic and Radiologic Findings

    Science.gov (United States)

    de la Vega, Gabriela; Villegas, Victor M; Velazquez, Jose; Barrios, Mirelys; Murray, Timothy G; Elhammady, Mohamed Samy

    2015-01-01

    Granular cell tumor is a rare soft tissue neoplasm that commonly affects the head and neck regions. We describe a case of a granular cell tumor of the orbit including its clinical presentation, histopathology, and magnetic resonance imaging findings. PMID:25963156

  19. Therapeutic attack of hypoxic cells of solid tumors: presidential address.

    Science.gov (United States)

    Sartorelli, A C

    1988-02-15

    Hypoxic cells of solid tumors are relatively resistant to therapeutic assault. Studies have demonstrated that oxygen-deficient tumor cells exist in an environment conducive to reductive reactions making hypoxic cells particularly sensitive to bioreductive alkylating agents. Mitomycin C, the prototype bioreductive alkylating agent available for clinical use, is capable of preferentially killing oxygen-deficient cells both in vitro and in vivo. This phenomenon is at least in part the result of differences in the uptake and metabolism of mitomycin C by hypoxic and oxygenated tumor cells, with the ultimate critical lesion being the cross-linking of DNA by the mitomycin antibiotic. The combination of mitomycin C with X-irradiation, to attack hypoxic and oxygenated tumor cell populations, respectively, has led to enhanced antitumor effects in mice bearing solid tumor implants and in patients with cancer of the head and neck. More efficacious kill of hypoxic tumor cells may be possible by the use of dicoumarol in combination with mitomycin or by the use of the related antibiotic porfiromycin. The findings support the use of an agent with specificity for hypoxic tumor cells in potentially curative regimens for solid tumors. PMID:3123053

  20. Cancer stem cells: a new approach to tumor development

    Directory of Open Access Journals (Sweden)

    Natália Cristina Ciufa Kobayashi

    2015-02-01

    Full Text Available Many theories have been proposed to explain the origins of cancer. Currently, evidences show that not every tumor cell is capable of initiating a tumor. Only a small part of the cancer cells, called cancer stem cells (CSCs, can generate a tumor identical to the original one, when removed from human tumors and transplanted into immunosuppressed mice. The name given to these cells comes from the resemblance to normal stem cells, except for the fact that their ability to divide is infinite. These cells are also affected by their microenvironment. Many of the signaling pathways, such as Wnt, Notch and Hedgehog, are altered in this tumoral subpopulation, which also contributes to abnormal proliferation. Researchers have found several markers for CSCs; however, much remains to be studied, or perhaps a universal marker does not even exist, since they vary among tumor types and even from patient to patient. It was also found that cancer stem cells are resistant to radiotherapy and chemotherapy. This may explain the re-emergence of the disease, since they are not completely eliminated and minimal amounts of CSCs can repopulate a tumor. Once the diagnosis in the early stages greatly increases the chances of curing cancer, identifying CSCs in tumors is a goal for the development of more effective treatments. The objective of this article is to discuss the origin of cancer according to the theory of stem cell cancer, as well as its markers and therapies used for treatment.

  1. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.

    Science.gov (United States)

    Huang, Zhen; Gan, Jingjing; Long, Ziyan; Guo, Guangxing; Shi, Xiafei; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2016-06-01

    Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy. PMID:26994345

  2. Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation.

    Science.gov (United States)

    Tape, Christopher J; Ling, Stephanie; Dimitriadi, Maria; McMahon, Kelly M; Worboys, Jonathan D; Leong, Hui Sun; Norrie, Ida C; Miller, Crispin J; Poulogiannis, George; Lauffenburger, Douglas A; Jørgensen, Claus

    2016-05-01

    Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRAS(G12D) signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRAS(G12D) engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRAS(G12D). Consequently, reciprocal KRAS(G12D) produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRAS(G12D) alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. VIDEO ABSTRACT. PMID:27087446

  3. Entry of diphtheria toxin into cells: possible existence of cellular factor(s) for entry of diphtheria toxin into cells was studied in somatic cell hybrids and hybrid toxins

    OpenAIRE

    1984-01-01

    Ehrlich ascites tumor cells were found to be very insensitive to diphtheria toxin. We formed 37 hybrids from Ehrlich tumor cells and diphtheria toxin-sensitive human fibroblasts. The effects of diphtheria toxin on protein synthesis in those hybrids were examined. The hybrids were divided into three groups on the basis of toxin sensitivity. Group A hybrids were as sensitive to diphtheria toxin as human fibroblasts, Group C were as resistant as Ehrlich tumor cells, and Group B had intermediate ...

  4. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  5. Platelets surrounding primary tumor cells are related to chemoresistance.

    Science.gov (United States)

    Ishikawa, Satoko; Miyashita, Tomoharu; Inokuchi, Masafumi; Hayashi, Hironori; Oyama, Katsunobu; Tajima, Hidehiro; Takamura, Hironori; Ninomiya, Itasu; Ahmed, A Karim; Harman, John W; Fushida, Sachio; Ohta, Tetsuo

    2016-08-01

    Platelets are crucial components of the tumor microenvironment that function to promote tumor progression and metastasis. In the circulation, the interaction between tumor cells and platelets increases invasiveness, protects tumor cells from shear stress and immune surveillance, and facilitates tumor cell extravasation to distant sites. However, the role and presence of platelets in the primary tumor have not been fully determined. Here, we investigated the presence of platelets around breast cancer primary tumor cells and the associations between these cells. We further investigated the associations among platelets, tumor cells, chemoresistance, and epithelial-mesenchymal transition (EMT). We retrospectively analyzed data from 74 patients with human epidermal growth factor receptor 2 (HER2)‑negative breast cancer who underwent biopsies before treatment and subsequent neo-adjuvant chemotherapy. In biopsy specimens, we evaluated the expression of platelet-specific markers and EMT markers using immunohistochemistry. The associations among the expression of platelet‑specific markers in biopsy specimens, EMT, response to neo‑adjuvant chemotherapy, and survival were analyzed. The presence of platelets was observed in 44 out of 74 (59%) primary breast cancer biopsy specimens. Platelet‑positive tumor cells showed EMT‑like morphological changes and EMT marker expression. Primary tumor cells associated with platelets were less responsive to neo‑adjuvant chemotherapy (pCR rate: 10 vs. 50%, respectively; p=0.0001). Platelets were an independent predictor of the response to chemotherapy upon multivariable analysis (pbreast cancer. Platelets surrounding primary tumor cells may represent novel predictors of chemotherapeutic responses. PMID:27349611

  6. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

  7. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    OpenAIRE

    C. M. de Souza; P.A. Auler; D.C. Reis; G.E. Lavalle; Ferreira, E.; G.D. Cassali

    2014-01-01

    Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. ...

  8. Radiation induction of drug resistance in RIF-1 tumors and tumor cells

    International Nuclear Information System (INIS)

    The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

  9. Cryo-ablation improves anti-tumor immunity through recovering tumor educated dendritic cells in tumor-draining lymph nodes

    Directory of Open Access Journals (Sweden)

    He XZ

    2015-03-01

    Full Text Available Xiao-Zheng He,1,2 Qi-Fu Wang,1,2 Shuai Han,3 Hui-Qing Wang,1,2 Yong-Yi Ye,1,2 Zhi-Yuan Zhu,1,2 Shi-Zhong Zhang1,2 1Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China Background: In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3+ and CD4+T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs. Methods: Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition. Results: DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10 and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo

  10. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    Science.gov (United States)

    Jung, Younghun; Kim, Jin Koo; Shiozawa, Yusuke; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Krebsbach, Paul H.; Keller, Evan T.; Pienta, Kenneth J.; Taichman, Russell S.

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumor cells and induces an epithelial to mesenchymal transition, which ultimately promotes metastasis to secondary tumor sites. Our results provide the molecular basis for MSC recruitment into tumors and how this process leads to tumor metastasis. PMID:23653207

  11. Tumor-stem cells interactions by fluorescence imaging

    Science.gov (United States)

    Meleshina, Aleksandra V.; Cherkasova, Elena I.; Sergeeva, Ekaterina; Turchin, Ilya V.; Kiseleva, Ekaterina V.; Dashinimaev, Erdem B.; Shirmanova, Marina V.; Zagaynova, Elena V.

    2013-02-01

    Recently, great deal of interest is investigation the function of the stem cells (SC) in tumors. In this study, we studied «recipient-tumor- fluorescent stem cells » system using the methods of in vivo imaging and laser scanning microscopy (LSM). We used adipose-derived adult stem (ADAS) cells of human lentiviral transfected with the gene of fluorescent protein Turbo FP635. ADAS cells were administrated into nude mice with transplanted tumor HeLa Kyoto (human cervical carcinoma) at different stages of tumor growth (0-8 days) intravenously or into tumor. In vivo imaging was performed on the experimental setup for epi - luminescence bioimaging (IAP RAS, Nizhny Novgorod). The results of the imaging showed localization of fluorophore tagged stem cells in the spleen on day 5-9 after injection. The sensitivity of the technique may be improved by spectral separation autofluorescence and fluorescence of stem cells. We compared the results of in vivo imaging and confocal laser scanning microscopy (LSM 510 META, Carl Zeiss, Germany). Internal organs of the animals and tumor tissue were investigated. It was shown that with i.v. injection of ADAS, bright fluorescent structures with spectral characteristics corresponding to TurboFP635 protein are locally accumulated in the marrow, lungs and tumors of animals. These findings indicate that ADAS cells integrate in the animal body with transplanted tumor and can be identified by fluorescence bioimaging techniques in vivo and ex vivo.

  12. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    Science.gov (United States)

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang

    2015-03-01

    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  13. Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors

    DEFF Research Database (Denmark)

    Li, Qiang; Zhi, Xiaofei; Zhou, Jianping;

    2016-01-01

    BACKGROUND: Circulating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients. RES...

  14. X-ray sensitivity of human tumor cells in vitro

    International Nuclear Information System (INIS)

    Clonally-derived cells from ten human malignant tumors considered radiocurable (breast, neuroblastoma, medulloblastoma) or non-radiocurable (osteosarcoma, hypernephroma, glioblastoma, melanoma) were studied in cell culture and their in vitro x-ray survival curve parameters determined (anti n, D0). There were no significant differences among the tumor cell lines suggesting that survival parameters in vitro do not explain differences in clinical radiocurability. Preliminary investigation with density inhibited human tumor cells indicate that such an approach may yield information regarding inherent cellular differences in radiocurability

  15. Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo.

    Science.gov (United States)

    Franki, Suzanne N; Steward, Kristopher K; Betting, David J; Kafi, Kamran; Yamada, Reiko E; Timmerman, John M

    2008-02-01

    The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of antitumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit antitumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were cocultured with bone marrow-derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs cocultured with mAb-coated tumor cells were protected from tumor challenge (60% long-term survival), whereas DCs loaded with tumor cells alone were much less effective. The opsonized whole tumor cell-DC vaccine elicited significantly better tumor protection than a traditional lymphoma idiotype (Id) protein vaccine, and in combination with chemotherapy could eradicate preexisting tumor. Moreover, the DC vaccine protected animals from both wild-type and Id-negative variant tumor cells, indicating that Id is not a major target of the induced tumor immunity. Protection was critically dependent upon CD8(+) T cells, with lesser contribution by CD4(+) T cells. Importantly, opsonized whole tumor cell-DC vaccination did not result in tissue-specific autoimmunity. Since opsonized whole tumor cell-DC and Id vaccines appear to target distinct tumor antigens, optimal antilymphoma immunity might be achieved by combining these approaches. PMID:17993615

  16. Biological characteristics of side population cells in a self-established human ovarian cancer cell line

    Science.gov (United States)

    WEI, ZHENTONG; LV, SHUANG; WANG, YISHU; SUN, MEIYU; CHI, GUANGFAN; GUO, JUN; SONG, PEIYE; FU, XIAOYU; ZHANG, SONGLING; LI, YULIN

    2016-01-01

    The aim of the present study was to establish an ovarian cancer (OC) cell line from ascites of an ovarian serous cystadenocarcinoma patient and investigate the biological characteristics of its side population (SP) cells. The OC cell line was established by isolating, purifying and subculturing primary cells from ascites of an ovarian serous cystadenocarcinoma patient (stage IIIc; grade 3). SP and non-SP (NSP) cells were isolated by fluorescence-activated cell sorting and cultured in serum-free medium and soft agar to compare the tumorsphere and colony formation capacities. Furthermore, SP and NSP cell tumorigenesis was examined by subcutaneous and intraperitoneal injection of the cells to non-obese diabetic/severe combined immune deficiency (NOD/SCID) mice. Drug resistance to cisplatin was examined by cell counting kit-8. The OC cell line was successfully established from ascites of an ovarian serous cystadenocarcinoma patient, which exhibited properties similar to primary tumors subsequent to >50 passages and >2 years of culture. The SP cell ratio was 0.38% in the OC cell line, and a similar SP cell ratio (0.39%) was observed when sorted SP cells were cultured for 3 weeks. Compared with NSP cells, SP cells exhibited increased abilities in differentiation and tumorsphere and colony formation, in addition to the formation of xenografted tumors and ascites and metastasis of the tumors in NOD/SCID mice, even at low cell numbers (3.0×103 cells). The xenografted tumors demonstrated histological features similar to primary tumors and expressed the ovarian serous cystadenocarcinoma marker CA125. In addition, SP cells demonstrated a significantly stronger drug resistance to cisplatin compared with NSP and unsorted cells, while treatment with verapamil, an inhibitor of ATP-binding cassette transporters, potently abrogated SP cell drug resistance. In conclusion, the present study verified SP cells from an established OC cell line and characterized the cells with self

  17. Numerical model of dog mast cell tumor treated by electrochemotherapy.

    Science.gov (United States)

    Suzuki, Daniela O H; Anselmo, Jânio; de Oliveira, Krishna D; Freytag, Jennifer O; Rangel, Marcelo M M; Marques, Jefferson L B; Ramos, Airton

    2015-02-01

    Electrochemotherapy is a combination of high electric field and anticancer drugs. The treatment basis is electroporation or electropermeabilization of the cell membrane. Electroporation is a threshold phenomenon and, for efficient treatment, an adequate local distribution of electric field within the treated tissue is important. When this local electric field is not enough, there is a regrown tumor cell; however, if it is stronger than necessary, permanent damage to the tissue occurs. In the treatment of dogs, electrochemotherapy is not yet an established treatment for mast cell tumor in veterinary medicine, although there are studies showing evidence of its effectiveness. In this study, we examined electrochemotherapy of dog mast cell tumor with numerical simulation of local electric field distribution. The experimental result was used to validate the numerical models. The effect of tumor position and tissue thickness (tumor in different parts of dog body) was investigated using plate electrodes. Our results demonstrated that the electrochemotherapy is efficient and flexible, and even when the tumor extends into the subcutis, the treatment with plate electrode eliminated the tumor cells. This result suggests that electrochemotherapy is a suitable method to treat mast cell tumors in dog. PMID:25041415

  18. Efficient construct of a large and functional scFv yeast display library derived from the ascites B cells of ovarian cancer patients by three-fragment transformation-associated recombination.

    Science.gov (United States)

    Yuan, Xiaopeng; Chen, Xiang; Yang, Mingjuan; Hu, Jia; Yang, Wei; Chen, Tingtao; Wang, Qirui; Zhang, Xuhua; Lin, Ruihe; Zhao, Aizhi

    2016-05-01

    Over the past decade, yeast display technology has emerged as a powerful tool for the isolation of high-affinity immunoglobulin fragments with potential utility as clinical diagnostic and therapeutic reagents. Despite significant refinement of the various methodologies underpinning library construction and selections, certain aspects remain challenging and process limiting. We have sought to significantly improve the robustness of the single-chain Fv (scFv) library construction step by overcoming the technical inefficiencies frequently encountered during the PCR-mediated assembly of scFvs from the discrete heavy and light V-domain repertoires. Using a novel primer set designed to provide maximum amplification coverage of the known germ-line V-domain repertoire, we have exploited the potential of the in vivo homologous gap-repair apparatus of Saccharomyces cerevisiae to assemble intact scFvs directly from co-transformed PBMC-derived VH, VL, and linearized vector component fragments. We have successfully applied this three-fragment assembly strategy to construct a large (>10(9)) scFv yeast display library from the ascites immune repertoire of ovarian cancer patients and validated the approach by applying FACS-based sorting to readily isolate scFvs that recognize various tumor marker antigens (TMAs). It is expected that this simplified construction method may find general utility, both for de novo scFv library construction and for subsequent combinatorial affinity maturation manipulations that require more than two fragments. PMID:26782745

  19. Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

    Science.gov (United States)

    Wang, Ying; Zhou, Feng; Qian, Zhida; Qing, Jiale; Zhao, Mengdam; Huang, Lili

    2014-11-01

    We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors. PMID:25518772

  20. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. PMID:23207444

  1. Drosera indica L: Potential effect on liver enzyme, lipid profile and hormone change in DaltonAND#8217;s lymphoma ascites (DLA) bearing mice

    OpenAIRE

    Raju Asirvatham; Arockiasamy Josphin Maria Christina

    2012-01-01

    Abstract Aim: In this study, the ethanol and aqueous extracts of Drosera indica L were prepared and cancer induced liver enzyme, lipid profile and hormone changes were studied in mice using the Dalton and #8217;s lymphoma ascites (DLA) cells. Method: Animals were divided into seven groups as the normal control, DLA control, standard (5FU) and the ethanol and aqueous extracts (250 and 500mg/kg each) of D. indica L + DLA (four groups) were given the respective treatments 24 h after tumor...

  2. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

    Science.gov (United States)

    Cardoso, Ana Carolina Ferreira; Andrade, Luciana Nogueira de Sousa; Bustos, Silvina Odete; Chammas, Roger

    2016-01-01

    Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular

  3. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments.

    Science.gov (United States)

    Cardoso, Ana Carolina Ferreira; Andrade, Luciana Nogueira de Sousa; Bustos, Silvina Odete; Chammas, Roger

    2016-01-01

    Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular

  4. Endothelial cell pseudopods and angiogenesis of breast cancer tumors

    Directory of Open Access Journals (Sweden)

    Sun LuZhe

    2005-05-01

    Full Text Available Abstract Background A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse. Once the tumor grew to 35 mm3, it developed a well-vascularized capsule. Histological sections of tumors greater than 35 mm3 were stained with PAS, with CD-31 antibody (an endothelial cell maker, or with hypoxia inducible factor 1α antibody (HIF. The extent of blood vessel and endothelial cell pseudopod volume density was measured by ocular grid intercept counting in the PAS stained slides. Results The tumor area within 100–150 μm of the well-vascularized capsule had few blood vessels and only occasional endothelial cell pseudopods, whereas the area greater than 150 μm from the capsule had more blood vessels, capillaries, and a three-fold increase in volume density of pseudopods sprouting from the capillary endothelial cells. This subcortical region, rich in pseudopods, some of which were observed to have vacuoles/lumens, was strongly positive for presence of HIF. In some larger tumors, pseudopods were observed to insinuate for mm distances through hypoxic regions of the tumor. Conclusion The positive correlation between presence of HIF and the increased extent of pseudopods suggests volume density measure of the latter as a quantifiable marker of tumor hypoxia. Apparently, hypoxic regions of the tumor produce HIF leading to production of vascular endothelial growth factors that stimulate sprouting of capillary endothelial cells and formation of endothelial cell pseudopods.

  5. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available BACKGROUND: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet. CONCLUSIONS/SIGNIFICANCE: These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  6. NKT cells as an ideal anti-tumor immunotherapeutic

    Directory of Open Access Journals (Sweden)

    Shin-ichiro eFujii

    2013-12-01

    Full Text Available Human NKT cells are characterized by their expression of an invariant T cell antigen receptor (TCR  chain variable region encoded by a V24J18 rearrangement. These NKT cells recognize -galactosylceramide (-GalCer in conjunction with the MHC class-I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of -GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN- production had significantly prolonged median survival times (MST of 29.3 Mo with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 wks after the combination therapy of -GalCer-DCs and activated NKT cells.We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and -GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even one year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN- in vitro and in vivo

  7. Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis

    International Nuclear Information System (INIS)

    The Duffy antigen receptor for chemokines (DARC) is known to be a promiscuous chemokine receptor that binds a variety of CXC and CC chemokines in the absence of any detectable signal transduction events. Within the CXC group of chemokines, DARC binds the angiogenic CXC chemokines including IL-8 (CXCL8), GROα (CXCL1) and ENA-78 (CXCL5), all of which have previously been shown to be important in non-small cell lung carcinoma (NSCLC) tumor growth. We hypothesized that overexpression of DARC by a NSCLC tumor cell line would result in the binding of the angiogenic ELR+ CXC chemokines by the tumor cells themselves, and thus interfere with the stimulation of endothelial cells and induction of angiogenesis by the tumor cell-derived angiogenic chemokines. NSCLC tumor cells that constitutively expressed DARC were generated and their growth characteristics were compared to control transfected cells in vitro and in vivo in SCID animals. We found that tumors derived from DARC-expressing cells were significantly larger in size than tumors derived from control-transfected cells. However, upon histological examination we found that DARC-expressing tumors had significantly more necrosis and decreased tumor cellularity, as compared to control tumors. Expression of DARC by NSCLC cells was also associated with a decrease in tumor-associated vasculature and a reduction in metastatic potential. The expression of DARC in the context of NSCLC tumors may act as a chemokine decoy receptor and interferes with normal tumor growth and chemokine-induced tumor neovascularization

  8. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds. PMID:26742746

  9. Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity

    OpenAIRE

    Ganapati V. Hegde; Cecile de la Cruz; Jeffrey Eastham-Anderson; Yanyan Zheng; E Alejandro Sweet-Cordero; Jackson, Erica L.

    2012-01-01

    Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the orig...

  10. Identification and Characterization of Tumor Initiating Cells in Various Mouse Mammary Tumor Models

    OpenAIRE

    Ishibashi, Tomoko

    2016-01-01

    Breast cancer is not a single disease as it can be classified into different subtypes according to cellular composition, morphology, proliferative index, genetic lesions and therapeutic responses. The molecular and cellular mechanisms underpinning tumor heterogeneity remain a central question in the cancer biology field. To explain the multitude of breast cancer phenotypes, it has been proposed that tumor-initiating cells (TICs) might originate from different cells within the mammary lineage....

  11. Circulating Tumor Cell Composition in Renal Cell Carcinoma

    Science.gov (United States)

    Bublitz, Kira; Lazaridis, Lazaros; Goergens, André; Giebel, Bernd; Schuler, Martin; Hoffmann, Andreas-Claudius

    2016-01-01

    Purpose Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a “liquid biopsy” in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies. Experimental Design Peripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis. Results We detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC. Conclusions Patients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted. PMID:27101285

  12.  An Uncommon Presentation of Giant Cell Tumor

    Directory of Open Access Journals (Sweden)

    Gopal Malhotra

    2011-09-01

    Full Text Available  Giant Cell Tumors commonly occur at the ends of long bones. However in rare cases, they can occur in the bones of the hands and feet. Tumors in these locations occur in younger patients; in addition, these tumors are more commonly multifocal and are associated with a higher risk for local recurrence than tumors at the ends of long bones. Since lesions in the small bones may be multifocal, a patient with a giant cell tumor of the small bones should undergo a skeletal survey to exclude similar lesions elsewhere. Primary surgical treatment ranges from curettage or excision with or without bone grafting to amputation. The success of surgical treatment depends on the completeness with which the tumor was removed. We are presenting a case report of a 34 year old female, who presented with a swelling in the right hand, following trauma. X-ray of the hand showed an osteolytic expansile lesion at the base of the 1st metacarpal bone. The lesion was initially curetted and then treated by local resection with bone grafting. Histological examination revealed a typical benign giant cell tumor composed of closely packed stromal cells with a variable admixture of giant cells. Follow up at the end of one year did not reveal any recurrence of the tumor.

  13. Short Telomeres Initiate Telomere Recombination in Primary and Tumor Cells

    OpenAIRE

    Morrish, Tammy A.; Greider, Carol W

    2009-01-01

    Human tumors that lack telomerase maintain telomeres by alternative lengthening mechanisms. Tumors can also form in telomerase-deficient mice; however, the genetic mechanism responsible for tumor growth without telomerase is unknown. In yeast, several different recombination pathways maintain telomeres in the absence of telomerase-some result in telomere maintenance with minimal effects on telomere length. To examine non-telomerase mechanisms for telomere maintenance in mammalian cells, we us...

  14. Significance of DNA quantification in testicular germ cell tumors.

    Science.gov (United States)

    Codesal, J; Paniagua, R; Regadera, J; Fachal, C; Nistal, M

    1991-01-01

    A cytophotometric quantification of DNA in tumor cells was performed in histological sections of orchidectomy specimens from 36 men with testicular germ cell tumors (TGCT), 7 of them showing more than one tumor type. Among the variants of seminoma (classic and spermatocytic) the lowest DNA content were in spermatocytic seminoma. With respect to non-seminomatous tumors (yolk sac tumor, embryonal carcinoma, teratoma, and choriocarcinoma), choriocarcinomas showed the highest DNA content, and the lowest value was found in teratomas. No significant differences were found between the average DNA content of seminomas (all types) and non-seminomatous tumors (all types). Both embryonal carcinoma and yolk sac tumor showed similar DNA content when they were the sole tumor and when they were found associated with other tumors. In this study, except for the 4 cases of teratoma and the case of spermatocytic seminoma, all TGCT examined did not show modal values of DNA content in the diploid range. Such an elevated frequency of aneuploidism in these tumors may be helpful for their diagnosis. PMID:1666273

  15. Giant cell tumor of the distal ulna: a case report

    Directory of Open Access Journals (Sweden)

    Vanni Daniele

    2012-06-01

    Full Text Available Abstract Introduction Several cases of long bone giant cell tumor have been reported in the literature. We report the case of a patient with a giant cell tumor in the distal ulna. This is very unusual, with a reported incidence of 0.45 to 6%. Case presentation A 17-year-old Colombian man presented with a painful swelling of the left wrist. After performing an instrumental examination, a diagnosis of distal ulna giant cell tumor was made. The tumor was treated with an intralesional curettage, phenol application and bone grafting. Conclusions This tumor may have a good prognosis if it is diagnosed early and radically treated. It is important to be aware of atypical cancer localizations in order to perform a proper diagnosis.

  16. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  17. Metachronous bilateral testicular germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    James Francis

    2009-01-01

    Full Text Available Metachronous bilateral testicular germ cell tumors is a rare known problem. However, no report of metachronus bilateralism was identified in the PubMed database published from India so far, where testicular cancer is relatively rare. We report the cases of two gentlemen. One had stage 1 nonseminomatous germ cell tumor (NSGCT at the age of 32 in 1990 and developed marker relapse on surveillance and had chemotherapy using cisplatin and etoposide for four cycles. He developed contralateral seminoma in the testis 13 years later. Another patient had left orchidectomy in 2003 for NSGCT, had adjuvant BEP for two cycles, and developed a contralateral testicular tumor 5 years later, which was also seminoma. As more patients with germ cell tumors are cured with chemotherapy, long-term problems become important. Contralateral testicular tumor is one of them. As it can be very late, many years of continued follow-up examination and patients′ awareness are necessary.

  18. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author)

  19. Th17 cells promote cytotoxic T cell activation in tumor immunity

    OpenAIRE

    Martin-Orozco, Natalia; Muranski, Pawel; Chung, Yeonseok; Yang, Xuexian O.; Yamazaki, Tomohide; Lu, Sijie; Hwu, Patrick; Restifo, Nicholas P; Overwijk, Willem W.; Dong, Chen

    2009-01-01

    Although T helper 17 (Th17) cells have been found in human tumor tissues, their function in cancer immunity is unclear. Here we show that IL-17-deficient mice were more susceptible to the development of lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the donor Th17 cells retained their cytokine expression phenotype and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 but not Th1...

  20. The retinoblastoma tumor suppressor and stem cell biology

    OpenAIRE

    Sage, Julien

    2012-01-01

    Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In this review by Sage, recent studies investigating the role of RB in embryonic stem cells, adult stem cells, and progenitor cells in plants and mammals is ...

  1. A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells

    OpenAIRE

    Chatterjee, Shilpak; Mookerjee, Ananda; Mookerjee Basu, Jayati; Chakraborty, Paramita; Ganguly, Avishek; Adhikary, Arghya; Mukhopadhyay, Debanjan; Ganguli, Sudipta; Banerjee, Rajdeep; Ashraf, Mohammad; Biswas, Jaydip; Das, Pradeep K; Sa, Gourisankar; Chatterjee, Mitali; Das, Tanya

    2009-01-01

    Background At the early stages of carcinogenesis, the induction of tumor specific T cell mediated immunity seems to block the tumor growth and give protective anti-tumor immune response. However, tumor associated macrophages (TAMs) might play an immunosuppressive role and subvert this anti tumor immunity leading to tumor progression and metastasis. Methodology/Principal Findings The Cu (II) complex, (chelate), copper N-(2-hydroxy acetophenone) glycinate (CuNG), synthesized by us, has previous...

  2. Increased calcium deposits and decreased Ca2+-ATPase in right ventricular myocardium of ascitic broiler chickens.

    Science.gov (United States)

    Li, K; Qiao, J; Zhao, L; Dong, S; Ou, D; Wang, J; Wang, H; Xu, T

    2006-11-01

    Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca(2+) and Ca(2+)-ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P ascitic broilers was significantly lower than that of the controls (P ascitic broilers, whereas in the age-matched control broilers, calcium deposits were much less. The Ca(2+)-ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca(2+)-ATPase activity might be the important factors. PMID:17054481

  3. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  4. In vivo imaging of tumor vascular endothelial cells

    Science.gov (United States)

    Zhao, Dawen; Stafford, Jason H.; Zhou, Heling; Thorpe, Philip E.

    2013-02-01

    Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab')2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ~5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 +/- 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.

  5. Functional significance of erythropoietin receptor on tumor cells

    Institute of Scientific and Technical Information of China (English)

    Kodetthoor B Udupa

    2006-01-01

    Erythropoietin (Epo) is the regulator of red blood cell formation. Its receptor (EpoR) is now found in many cells and tissues of the body. EpoR is also shown to occur in tumor cells and Epo enhances the proliferation of these cells through cell signaling. EpoR antagonist can reduce the growth of the tumor in vivo. In view of our current knowledge of Epo, its recombinant forms and receptor,use of Epo in cancer patients to enhance the recovery of hematocrit after chemotherapy treatment has to be carefully evaluated.

  6. Androgen - secreting steroid cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Paras Ratilal Udhreja

    2014-01-01

    Full Text Available Steroid cell tumors (SCTs, not otherwise specified of the ovary are rare subgroup of sex cord tumors, which account for less than 0.1% of all ovarian tumors and also that will present at any age. The majority of these tumors produce steroids with testosterone being the most common. A case of a 28-year-old woman who presented with symptoms of virilization is reported. Although SCTs are generally benign, there is a risk for malignant transformation. Surgery is the most important and hallmark treatment.

  7. General Information About Childhood Central Nervous System Germ Cell Tumors

    Science.gov (United States)

    ... germ cell tumors to form is near the pineal gland and in an area of the brain that ... of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in ...

  8. Treatment Options for Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  9. General Information about Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  10. Forcing Tumor Cells to Present Their Own Tumor Antigens to the Immune System: a Necessary Design for an Efficient Tumor Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    RobertE.Humphreys; GildaG.Hillman; EricyonHofe; MinzhenXu

    2004-01-01

    The general principle for tumor cells to escape from immune surveillance is to prevent tumor antigens from being recognized by the immune system. Many methods have been developed to increase the immunogenecity of the tumor cells. The most efficient methods are able to force tumor cells to present their own tumor antigens to the immune system. Stimulating Th cells by converting tumor cells into MHC class II+/Ii- antigen presenting cells is one of the most efficient technologies. Using antisense methods, we suppress the expression of the Ii protein that normally co-expresses with MHC class II molecules and blocks the antigenic peptide binding site of MHC class II molecules during synthesis in the endoplasmic reticulum. In such tumor cells, the"unprotected" MHC class II molecules pick up endogenous tumor antigenic peptides, which have been transported into the ER for binding to MHC class I molecules. Simultaneous presentation of tumor antigens by both MHC class I and II molecules generates a robust and long-lasting anti-tumor immune response. MHC class II+/Ii- tumor cells are potent tumor cell vaccines and also cure a significant number of animals with renal and prostate tumors. We have developed analogous human gene vectors that are suitable for most patients and cancers.

  11. Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity.

    Science.gov (United States)

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J; Powers, Gordon D; Sato, Takami; Campbell, Kerry S; Sykulev, Yuri

    2014-08-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high antibody concentration, revealing a dose limiting effect. A similar effect was also observed with primary human NK cells. The effect was erased after IFN-γ treatment of tumor cells resulting in upregulation of ICAM-1. Furthermore, killing of the same tumor cells induced by Herceptin antibody was significantly impaired in the presence of CNTO 95Ala-Ala antibody variant that blocks αV integrins but is incapable of binding to CD16. These data suggest that αV integrins on tumor cells could compensate for the loss of ICAM-1 molecules, thereby facilitating ADCC by NK cells. Thus, NK cells could exercise cytolytic activity against ICAM-1 deficient tumor cells in the absence of proinflammatory cytokines, emphasizing the importance of NK cells in tumor-specific immunity at early stages of cancer. PMID:24810893

  12. Response of mouse transplantable tumor to Plumbago Rosea and plumbagin in combination with radiation

    International Nuclear Information System (INIS)

    The anticancer and radiosensibility effects of the alcoholic root extract of the medicinal plant Plumbago rosea and its active component plumbagin were studied on mouse Ehrilich ascites carcinoma, grown intraperitoneally in Swiss mice. Mice were injected i. p. with Plumbago extract (50 or 75 mg/kg) (10) or plumbagin (2.5 mg/kg) (4), (3 mg/kg) (3), (6 mg/kg) (1) starting from 24 h after tumor cell transplantation with or without one abdominal exposure to 7.5 Gy gamma radiation after the first drug dose. Tumor growth and mouse survival were studied for 120 days. Both treatments inhibited tumor growth and increased the life span. Combination with radiation further increased the life span and number of survivors indicating a response modifying effect on Ehrlich ascites tumor in vivo. The purified plumbagin was more toxic than the extract

  13. Response of mouse transplantable tumor to Plumbago Rosea and plumbagin in combination with radiation

    Energy Technology Data Exchange (ETDEWEB)

    Emerson Solomon, F.; Sharada, A.C.; Uma Devi, P. [Kasturba Medical College, Manipal (India)

    1994-12-31

    The anticancer and radiosensibility effects of the alcoholic root extract of the medicinal plant Plumbago rosea and its active component plumbagin were studied on mouse Ehrilich ascites carcinoma, grown intraperitoneally in Swiss mice. Mice were injected i. p. with Plumbago extract (50 or 75 mg/kg) (10) or plumbagin (2.5 mg/kg) (4), (3 mg/kg) (3), (6 mg/kg) (1) starting from 24 h after tumor cell transplantation with or without one abdominal exposure to 7.5 Gy gamma radiation after the first drug dose. Tumor growth and mouse survival were studied for 120 days. Both treatments inhibited tumor growth and increased the life span. Combination with radiation further increased the life span and number of survivors indicating a response modifying effect on Ehrlich ascites tumor in vivo. The purified plumbagin was more toxic than the extract.

  14. agged tumor cells reveal regulatory steps during earliest stages of tumor progression and micrometastasis

    OpenAIRE

    Culp, L A; Lin, W.C.

    1999-01-01

    Histochemical marker genes were used to "tag" mouse fibrosarcoma or human neuroblastoma cells, providing a better understanding of their subsequent progression and metastasis mechanisms in nude mice. Micrometastases in the lung were initiated from clusters of 2-6 cells rather than single cells in most cases; tumor cells were also visualized binding to the endothelium of small blood vessels to initiate these micrometastases. Shortterm, these mechanisms relied ...

  15. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  16. Clear cell carcinoid tumor of the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Tsukada Katsuhiko

    2007-01-01

    Full Text Available Abstract Background Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC tumors in the distal bile duct (DBD to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT and magnetic resonance cholangiopancreaticography (MRCP demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size. The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE, chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct.

  17. Familial primary mediastinal nonseminomatous germ-cell tumors.

    Science.gov (United States)

    Marti, Adina; Culine, Stéphane; Carde, Patrice; Paugam, Bertrand; Fizazi, Karim

    2004-01-01

    In this article, we describe the case of 4 brothers, 2 of which had primary mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had benign mediastinal disease. We discuss the relationship between these diseases of the mediastinum and the thymic microenvironment. Additionally, we suggest that a genetic predisposition for germ-cell tumors (GCT) may be involved since the parents were relatives. PMID:15464924

  18. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    OpenAIRE

    Jung, Younghun; Kim, Jin Koo; SHIOZAWA, YUSUKE; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Paul H Krebsbach

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also kno...

  19. Apoptosis by Direct Current Treatment in Tumor Cells and Tissues

    Science.gov (United States)

    Kim, Hongbae; Sim, Sungbo; Ahn, Saeyoung

    2003-10-01

    Electric field induces cell fusion, electroporation on biological cells, including apoptosis. Apoptosis is expressed in a series of natural enzymatic reactions for the natural elimination of unhealthy, genetically damaged, or otherwise aberrant cells that are not needed or not advantageous to the well-being of the organism. Its markers involve cell shrinkage, activation of intracellular caspase proteases, externalization of phosphatidylserine at the plasma membrane, and fragmentation of DNA. Direct electric fields using direct current have been exploited recently to investigate its effects on tumor cells and tissues, but the mechanism of direct electric fields has not been exhibited clearly other than by electroosmosis or pH changes. Direct electric field induces apoptosis in tumor cells cultured and tumor tissues as indicated by cell shrinkage, DNA fragmentation and tumor suppression. In our experiment that direct electric field was applied to tumor tissues via two needle electrodes inserted into tumor tissue 5mm at distance in parallel, pH changes resulted from electrochemical reaction, exhibiting about pH 9.0, 1.83, 2.0 in the vicinity of cathodic and anodic electrode, and at their mid-point, respectively. DNA fragmentation of tumor tissues destructed by direct electric field was analyzed by Tunel assay by ApopTag technology. As a result of this analysis, it showed that apoptosis in tumor tissue destructed was increased up to 59.1normal(control) tissues, showing 41.1, 31.1cathodic tissues. In vitro cell survival was exhibited that it was decreased with enhancing electric current intensity in the same condition of electrical charge 5C having different time applied. We will show results of apoptosis analyzed by flow cytometry in vitro.

  20. Collective Behavior of Brain Tumor Cells: the Role of Hypoxia

    Science.gov (United States)

    Khain, Evgeniy; Katakowski, Mark; Hopkins, Scott; Szalad, Alexandra; Zheng, Xuguang; Jiang, Feng; Chopp, Michael

    2013-03-01

    We consider emergent collective behavior of a multicellular biological system. Specifically we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. The first set of experiments was performed in a typical wound healing geometry: cells were placed on a substrate, and a scratch was done. In the second set of experiments, cell migration away from a tumor spheroid was investigated. Experiments show a controversy: cells under normal and hypoxic conditions have migrated the same distance in the ``spheroid'' experiment, while in the ``scratch'' experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.

  1. Integrin Receptors on Tumor Cells Facilitate NK cell-mediated Antibody-dependent Cytotoxicity

    OpenAIRE

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J.; Powers, Gordon D.; Sato, Takami; Campbell, Kerry S.; Sykulev, Yuri

    2014-01-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high anti...

  2. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas; Custodio Domingues, Maria Aparecida; Rogatto, Silvia Regina

    2008-01-01

    with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a......Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...... small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected...

  3. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    Science.gov (United States)

    2016-04-07

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  4. Laparotomy for post chemotherapy residue in ovarian germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mathew G

    2006-01-01

    Full Text Available Background : Primary conservative surgery and cisplatin-based chemotherapy have resulted in high cure ratesin malignant ovarian germ cell tumors. A significant proportion of advanced tumors may have post-chemotherapyresidue and it is important to distinguish necrosis or fibrosis without viable tumor from persistent viable tumorand teratoma. Aims : To evaluate the role of laparotomy in assessing the nature of post-chemotherapy residue in ovariangerm cell tumors. Materials and Methods : Eighty-three patients with malignant ovarian germ cell tumors seen at Cancer Institute,Chennai between 1992 and 2002 were studied. Sixty-eight patients completed combination chemotherapywith cisplatin regimes, of whom 35 had radiological residual masses. Twenty-nine out of these 35 patientsunderwent laparotomy to assess the nature of the residue. Results : On laparotomy, three patients had viable tumor, seven immature teratoma, three mature teratomaand 16 only necrosis or fibrosis. None of our patients with dysgerminoma, embryonal carcinoma, absence ofteratoma element in the primary tumor and radiological residue of < 5 cm had viable tumor whereas all patientswith tumors containing teratoma component initially had residual tumor. Absence of viable disease was higherin patients who had normalization of serum markers by two cycles of chemotherapy. Conclusion : Our study suggests that patients with absence of teratoma element initially, radiological residue of< 5 cm and normalization of serum markers after two cycles of chemotherapy do not require surgery to assessthe nature of post-chemotherapy residue. However, laparotomy should be performed in patients with tumorsthat initially contain teratoma element and in those with sluggish tumor marker response after two cycles ofchemotherapy since they have a high chance of having viable postchemotherapy residue.

  5. Frequency and distribution of Notch mutations in tumor cell lines

    International Nuclear Information System (INIS)

    Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context. In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico. Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors. Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context. The online version of this article (doi:10.1186/s12885-015-1278-x) contains supplementary material, which is available to authorized users

  6. Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses

    OpenAIRE

    Saifun Nahar; Manabu Nakamoto; Akira Hokama; Chiharu Kobashigawa; Masatoshi Kaida; Tetsu Kinjo; Tetsuo Hirata; Nagisa Kinjo; Masanao Saio; Naoki Yoshimi; Yuji Ohtsuki; Jiro Fujita

    2015-01-01

    We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus con...

  7. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, Milind; Meijer, Coby; de Bock, Geertruida H; Boersma-van Ek, Wytske; Terstappen, Leon W M M; Groen, Harry J M; Timens, Wim; Kruyt, Frank A E; Hiltermann, T Jeroen N

    2016-01-01

    BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epitheli

  8. FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis

    OpenAIRE

    Takenaka, Miki; Seki, Naoko; Toh, Uhi; Hattori, Satoshi; KAWAHARA, AKIHIKO; Yamaguchi, Tomohiko; KOURA, KEIKO; Takahashi, Ryuji; Otsuka, Hiroko; Takahashi, Hiroki; Iwakuma, Nobutaka; Nakagawa, Shino; Fujii, Teruhiko; Sasada, Tetsuro; Yamaguchi, Rin

    2013-01-01

    The forkhead box protein 3 (FOXP3) transcription factor is highly expressed in tumor cells as well as in regulatory T cells (Tregs). It plays a tumor-enhancing role in Tregs and suppresses carcinogenesis as a potent repressor of several oncogenes. The clinical prognostic value of FOXP3 expression has not yet been elucidated. In this study, immunohistochemistry was used to investigate the prognostic significance of FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in br...

  9. [A Case of Intra-Abdominal Desmoid Tumor with Abacterial Peritonitis].

    Science.gov (United States)

    Sumiyama, Fusao; Inada, Ryo; Nakamura, Fumiko; Ryota, Hironori; Miki, Hirokazu; Oishi, Masaharu; Matsumoto, Tomoko; Iwamoto, Shigeyoshi; Mukaide, Yumi; Ozaki, Takeshi; Michiura, Taku; Inoue, Kentaro; Kon, Masanori; Miyasaka, Chika; Uemura, Yoshiko; Hamada, Madoka

    2016-03-01

    A woman in her 50s visited our hospital in February 2015 with a complaint of dull abdominal pain in the right lower quadrant. She had a medical history of appendectomy for appendicitis in her 20s. Computed tomography(CT)revealed a tumor 90 mm in diameter near the ileocecum. Elective surgery was planned under the suspicion of gastrointestinal tumor, malignant lymphoma, or ileal cancer. She was emergently hospitalized 1 day earlier than scheduled because of high fever and severe abdominal pain. CT revealed that the tumor had increased to 120 mm in diameter without free air. Her white blood cell count was not elevated, and her symptoms improved readily with medical treatment. Thus, we performed the operation as scheduled. A tumor with a dark red recess on the surface had invaded the transverse colon intraoperatively, and a small amount of purulent ascites was present at the pouch of Douglas. We performed ileocecal resection with partial transverse colectomy. Histopathological examination led to the diagnosis of desmoid tumor in the mesentery of the terminal ileum. The surgical margins were negative for tumor cells. The tumor surface around the recess showed peritonitis, and the ascites showed no bacteria or tumor cells. The patient had been doing well without recurrence after discharge. Some cases of desmoid tumor with peritonitis have been reported, but most were caused by tumor penetration into the intestinal tract. We report herein a rare case of intra-abdominal desmoid tumor with abacterial peritonitis. PMID:27067862

  10. Review of juxtaglomerular cell tumor with focus on pathobiological aspect

    Directory of Open Access Journals (Sweden)

    Pan Chin-Chen

    2011-08-01

    Full Text Available Abstract Juxtaglomerular cell tumor (JGCT generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

  11. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis

    Science.gov (United States)

    Kawana, Kei; Adachi, Katsuyuki; Kawata, Akira; Ogishima, Juri; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Inoue, Tomoko; Nishida, Haruka; Furuya, Hitomi; Tomio, Kensuke; Arimoto, Takahide; Koga, Kaori; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Kiyono, Tohru; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression. PMID:27483433

  12. Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation

    DEFF Research Database (Denmark)

    Eichenlaub, Teresa; Cohen, Stephen M; Herranz, Héctor

    2016-01-01

    Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The...... mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells...... Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms...

  13. Control of T cell infiltration and tumor rejection by regulatory T cells, basophils and macrophages

    OpenAIRE

    Sektioglu, Ibrahim Murathan

    2015-01-01

    Most solid tumors are intrinsically resistant to immune rejection due to immunosuppressive mechanisms operative within the tumor microenvironment. Cancer patients frequently harbor elevated numbers of regulatory T cells (Tregs), which inhibit efficient anti-tumor T cell responses. We employed different mouse models for Treg depletion in order to study the mechanisms that control tumor rejection. Depletion of about 99% Tregs in Foxp3DTR knock-in mice resulted in complete rejection of transplan...

  14. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Roland El Ghazal

    2016-05-01

    Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

  15. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines

    International Nuclear Information System (INIS)

    To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR) in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20). In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41) and 36.6% (15/41), while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41) and 14.6% (6/41). In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7) and 14.3% (1/7). The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P < 0.05). Gene expression rate was not correlated with menopause or lymph node metastasis. Positive expression of MAGE-1 and MAGE-3 was positively correlated with tumor differentiation and the clinical stage of the ovarian cancer. In addition, the positive expression rate of BAGE was significantly higher in ovarian cancer patients with ascites (P < 0.05). The mRNA expression profiles of MAGE, GAGE and BAGE in ovarian carcinoma cell lines SKOV3, A2780 and COC1 varied, but there was at least one gene expressed in each cell line. Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer

  16. Research Advances on Th17 Cells in Tumor

    OpenAIRE

    Wang, Jiansheng; Yuan, Baozhu

    2011-01-01

    The Th17 cells, identified recently as a novel CD4+ T cell lineage, are characteristic of their production of IL-17 and distinct from Th1 and Th2 lineages. Their involvement in autoimmune and chronic inflammation diseases has been well observed. Recent evidence suggests that Th17 cells are also involved in tumor immunology. However, it remains unclear that how these cells regulate immune responses to tumor growth. In this review, we summarize the most recent findings about the biologics of th...

  17. MicroRNAs in tumor stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochen Hu; Junqiang Yang; Ruijie Yang; Ruina Yang; Xinshuai Wang; Shegan Gao

    2015-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs that are believed to have a significant role in tumori-genesis and cancer metastasis. Cancer stem cel s play a major role in tumor recurrence, metastasis, and drug resistance. Research has shown that miRNAs can promote or inhibit the stemness of cancer stem cel s and regulate the dif erentiation and self-renewal of cancer stem cel s. In this article, the phenotype and regulatory mechanisms of miRNAs in cancer stem cel s wil be described, together with an explanation of their potential role in tumor diagnosis and treatment.

  18. Distribution and differentiation of mesenchymal stem cells in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-feng; CHEN Jun; XU Zhi-shun; ZHANG Ke-qin

    2009-01-01

    Background Tumor has an ability to become enriched in mesenchymal stem cells (MSCs) and of guiding MSCs to migrate to tumor tissue. But there are lack of relevant reports on the distribution and differentiation of MSCs in tumor tissue and the effect on tumor growth after MSCs engrafted in tumor tissue. In this study, we observed the distribution of bone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment.Methods Twenty-four New Zealand rabbits were randomly classified into the control group and the test group. MSCs were isolated and cultured for each animal, vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. One week after the transplantation, the self F2 passage MSCs marked by 4',6-diamidino-2-phenylindole were transplanted into tumor tissue in the test group while only Dulbecco's modified Eagle's medium-low glucose was infused into the control group. Ultrasonography was performed for each animal 1,2, 3 and 4 week(s) after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameter of each animal was recorded and the mean value of each group was calculated. One animal from each group was sacrificed in the third week and the remaining animals in the fourth week to observe the tumor development. Another animal treated the same as the test group was sacrificed to observe the distribution of MSCs in tumor tissue one week after self MSCs transplantation. Immunofluorescence was used to trace MSCs in tumor tissue. The double labeling immunofluorescence for α-smooth muscle actin (α-SMA) and vimentin was performed to identify whether the MSCs can differentiate into myofibroblast.Results The ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. The mean maximum tumor diameter of the control group and test group was (0.70±0.14) cm and (0.78±0.14) cm, respectively, and there was no significant difference (t=1

  19. Adult granulosa cell tumor of the testis masquerading as hydrocele

    Directory of Open Access Journals (Sweden)

    Archana George Vallonthaiel

    2015-12-01

    Full Text Available Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view.

  20. Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2015-05-11

    Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  1. Isolation and characterization of circulating tumor cells in prostate cancer

    Directory of Open Access Journals (Sweden)

    Elan Shlomo Diamond

    2012-10-01

    Full Text Available Circulating tumor cells (CTCs are tumor cells found in the peripheral blood that originate from established sites of malignancy and likely have metastatic potential. Analysis of circulating tumor cells CTCs has shown great promise as a prognostic marker as well as a potential source of novel therapeutics. Isolation and characterization these cells for study, however, remain challenging due to their rarity in comparison with other cellular components of peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate isolation of these cells. Positive selection of CTCs is achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor specific antigens such as EpCAM or prostate specific membrane antigen (PSMA. Following isolation, characterization of CTCs may help guide clinical decision-making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced cancers, as well as efforts to characterize the CTCs. We will also review ways in which these analyses can assist in clinical decision-making,Conclusion: The study of CTCs provides insight into the molecular biology of their tumors of origin that will eventually guide the development tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells.

  2. The role of endogenous proteins in the protein-free maintenance of 3 distinct tumor-cell lines invitro.

    Science.gov (United States)

    Watanabe, H; Chigira, M

    1992-09-01

    We established new two protein-free culture subclones from murine well-characterized Ehrlich ascites carcinoma and P815 mastocytoma using intermittent protein-free culture performed previously for a protein-free subclone of fibrosarcoma (Gc-4 PF). The Ehrlich protein-free subclone (Ehrlich PF) grew much more slowly than the original cell line and showed a proliferative response to FCS. On the other hand, like Gc-4 PF, the P815 protein-free subclone (P815 PF) showed a similar growth rate to that of the original counterpart. Interestingly the original P815 mastocytoma cells also grew exponentially in protein-free medium. Although the protein-free culture exhibited cells that were more spheroid and spread less in each of these three cell lines, the major structure protein bands demonstrated on SDS-PAGE were virtually identical between the original and protein-free culture cells. In contrast to the structural peptides, the distribution of the secretory peptide differed among the three protein-free culture cell lines, which may reflect their state of differentiation. Growth-inhibiting activities were detected from the supernatant of all three protein-free culture cells, while no protein-free culture cells secreted predominantly growth-stimulating activity into their cultured media. These results suggest that autonomy in tumor cell proliferation may result from the acquisition of the ability to escape from negative control in multicellular organisms, as shown in monads, rather than an acquisition of further response to growth-stimulating control. PMID:21584570

  3. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of 188Re-DXR-liposome in C26 colon carcinoma ascites mice model

    International Nuclear Information System (INIS)

    The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated 188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (188Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality 188Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC(o→∞) of 188Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of 188Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated 188Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after 188Re-DXR-liposome (22.2 MBq of 188Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of 188Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P188Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel 188Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications

  4. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of (188)Re-DXR-liposome in C26 colon carcinoma ascites mice model.

    Science.gov (United States)

    Chen, Liang-Cheng; Chang, Chih-Hsien; Yu, Chia-Yu; Chang, Ya-Jen; Wu, Yu-Hsien; Lee, Wan-Chi; Yeh, Chung-Hsin; Lee, Te-Wei; Ting, Gann

    2008-11-01

    The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; Ppassive nanotargeted bimodality radiochemotherapeutics in oncology applications. PMID:19026950

  5. Cell proliferation during fractionated radiation in two experimental tumors

    International Nuclear Information System (INIS)

    Tumor cell proliferation kinetics after irradiation have been studied using the method of bromodeoxyuridine incorporation and flow cytometry. Labelling indices were obtained after single and multiple fractions of radiation in a mouse fibrosarcoma (FSa-II) and human squamous carcinoma (FADU) growing in nude mice. For 8 mm tumors mean L.I was 17.5 +- 2.6% and 21.5 + 3.2%, respectively. Both tumors showed a similar response to single dose of irradiation (10 and 20 Gy) with initial depression of labelling index and then a rapid increase after 3 days in the FSa-II tumors (mean L.I 24%) and 5 days in the FADU tumors (mean L.I 27%). During fractionated treatment, labelling index was dependent on dose per fraction (2.5-18 Gy) time interval between fractions and time of analysis. Tumors were biopsied during course of fractionated treatment to see if labelling index would act as a predictor of response. No significant difference could be determined between individual tumors that had received the same dose per fraction. However a labelling index the same or higher than control values were associated with lack of tumor control. Controlled tumors showed a significant depression of labelling index (rho<0.05)

  6. MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have been shown to enhance the generation of human tumor cells, which in turn have a greater ability to kill human tumor cells endogenously expressing the native MUC-1 epitope.

  7. 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.

  8. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors

    Science.gov (United States)

    Zhang, Peisheng; Chen, Lei; Baird, Jason R.; Demidenko, Eugene; Turk, Mary Jo; Hoopes, P. Jack; Conejo-Garcia, Jose R.; Fiering, Steven

    2014-01-01

    Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic filed (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 minutes activated dendritic cells (DCs) and subsequently CD8+ T cells in the draining lymph node (dLN) and conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung carcinoma) given 7 days post hyperthermia on both the primary tumor side and the contralateral side in a CD8+ T cell-dependent manner. Mice with heated primary tumors also resisted rechallenge given 30 days post hyperthermia. Mice with larger heated primary tumors had greater resistance to secondary tumors. No rechallenge resistance occurred when tumors were heated at 45°C. Our results demonstrate the promising potential of local hyperthermia treatment applied to identified tumors in inducing anti-tumor immune responses that reduce the risk of recurrence and metastasis. PMID:24566274

  9. Glioma Cells in the Tumor Periphery Have a Stem Cell Phenotype.

    Directory of Open Access Journals (Sweden)

    Sune Munthe

    Full Text Available Gliomas are highly infiltrative tumors incurable with surgery. Although surgery removes the bulk tumor, tumor cells in the periphery are left behind resulting in tumor relapses. The aim of the present study was to characterize the phenotype of tumor cells in the periphery focusing on tumor stemness, proliferation and chemo-resistance. This was investigated in situ in patient glioma tissue as well as in orthotopic glioblastoma xenografts. We identified 26 gliomas having the R132 mutation in Isocitrate DeHydrogenase 1 (mIDH1. A double immunofluorescence approach identifying mIDH1 positive tumor cells and a panel of markers was used. The panel comprised of six stem cell-related markers (CD133, Musashi-1, Bmi-1, Sox-2, Nestin and Glut-3, a proliferation marker (Ki-67 as well as a chemo-resistance marker (MGMT. Computer-based automated classifiers were designed to measure the mIDH1 positive nucleus area-fraction of the chosen markers. Moreover, orthotopic glioblastoma xenografts from five different patient-derived spheroid cultures were obtained and the tumor cells identified by human specific immunohistochemical markers. The results showed that tumor cells in the periphery of patient gliomas expressed stem cell markers, however for most markers at a significantly lower level than in the tumor core. The Ki-67 level was slightly reduced in the periphery, whereas the MGMT level was similar. In orthotopic glioblastoma xenografts all markers showed similar levels in the core and periphery. In conclusion tumor cells in the periphery of patient gliomas have a stem cell phenotype, although it is less pronounced than in the tumor core. Novel therapies aiming at preventing recurrence should therefore take tumor stemness into account. Migrating cells in orthotopic glioblastoma xenografts preserve expression and stem cell markers. The orthotopic model therefore has a promising translational potential.

  10. Hsp60 is actively secreted by human tumor cells.

    Directory of Open Access Journals (Sweden)

    Anna M Merendino

    Full Text Available BACKGROUND: Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. METHODOLOGY/PRINCIPAL FINDINGS: Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.

  11. The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

    OpenAIRE

    Zipori, Dov

    2010-01-01

    Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from...

  12. Sorafenib Inhibits Tumor Growth and Improves Survival in a Transgenic Mouse Model of Pancreatic Islet Cell Tumors

    OpenAIRE

    Volker Fendrich; Katja Maschuw; Johannes Rehm; Malte Buchholz; Julia P. Holler; Slater, Emily P; Bartsch, Detlef K.; Jens Waldmann

    2012-01-01

    Background. The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group...

  13. Comparison of three lines of broilers differing in ascites susceptibility or growth rate. 2. Egg weight loss, gas pressures, embryonic heat production, and physiological hormone levels.

    Science.gov (United States)

    De Smit, L; Tona, K; Bruggeman, V; Onagbesan, O; Hassanzadeh, M; Arckens, L; Decuypere, E

    2005-09-01

    Ascites is a metabolic disorder that accounts for over 25% of overall mortality in the broiler industry. This disorder is manifested between wk 5 and 6 posthatch, but there are previous indications that predisposition may be identified during embryonic development. In this current study, we determined embryonic physiological and metabolic parameters that may be associated with ascites predisposition. For this purpose, we used broiler eggs from 3 lines that differed in ascites sensitivity. These included an ascites-sensitive dam line (DAS), an ascites-resistant dam line (DAR), and an ascites-sensitive sire line (SASL). Eggs were incubated for 21 d under standard conditions. The following parameters were measured during incubation: egg weights at setting, egg weight losses at 18 d, embryo body weights and embryo heart weights throughout development, air cell partial gas pressures (pCO2 and pO2) levels at d 18 and at internal pipping (IP); plasma triiodothyronine, thyroxine, and corticosterone levels at d 18, IP, and hatch; heat production from d 17 until hatch, hematocrit values at hatch, and posthatch growth rate to 7 d along with hematocrit values. The data obtained revealed that selection for ascites sensitivity or rapid growth rate had no consistent influence on some of these parameters such that they could be wholly associated with ascites sensitivity for predictive purposes. Whereas differences in embryonic developmental patterns were apparent throughout embryonic development, these differences in physiological and metabolic parameters may be due partly to genetic differences unrelated to ascites sensitivity. PMID:16206567

  14. Waves of ratcheting cancer cells in growing tumor tissue layer

    Science.gov (United States)

    Yang, Taeseok; Kwon, Tae; Kim, Hyun; Lee, Kyoung; CenterCell Dynamics Team

    2015-03-01

    Over many years researchers have shown that the mechanical forces generated by, and acting on, tissues influence the way they grow, develop and migrate. As for cancer research goes, understanding the role of these forces may even be as influential as deciphering the relevant genetic and molecular basis. Often the key issues in the field of cancer mechanics are to understand the interplay of mechanics and chemistry. In this study, we discuss very intriguing population density waves observed in slowly proliferating of tumor cell layers. The temporal periods are around 4 hr and their wavelength is in the order of 1 mm. Tumor cell layer, which is initially plated in a small disk area, expands as a band of tumor cells is ``ratcheting'' in concert in radially outward direction. By adding Cytochalasin D and Latrunculin B, an inhibitor of actin polymerization, or Mytomycin, a chemotherapeutic agent, we could halt and modulate the wave activities reversibly. The observed waves are visually quite similar to those of chemotaxing dictyostelium discodium amoeba population, which are driven by nonlinear chemical reaction-diffusion waves of cAMP. So far, we have not been able to show any relevant chemo-attractants inducing the collective behavior of these tumor cells. Researchers have been investigating how forces from both within and outside developing cancer cells interact in intricate feedback loops. This work reports the example of periodic density waves of tumor cells with an explanation purely based on nonlinear mechanics.

  15. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

    Science.gov (United States)

    Ho, D M; Wong, T T; Guo, W Y; Chang, K P; Yen, S H

    1997-10-01

    Extramedullary myeloid cell tumors (EMCTs) are tumors consisting of immature cells of the myeloid series that occur outside the bone marrow. Most of them are associated with acute myelogenous leukemia or other myeloproliferative disorders, and a small number occur as primary lesions, i.e., are not associated with hematological disorders. Occurrence inside the cranium is rare, and there has been only one case of primary EMCT involving the cerebellum reported in the literature. The case we report here is a blastic EMCT occurring in the cerebellum of a 3-year-old boy who had no signs of leukemia or any hematological disorder throughout the entire course. The cerebellar tumor was at first misdiagnosed as an "oligodendroglioma" because of the uniformity and "fried egg" artifact of the tumor cells. The tumor disappeared during chemotherapy consisting of 12 treatments. However, it recurred and metastasized to the cerebrospinal fluid (CSF) shortly after the therapy was completed. A diagnosis of EMCT was suspected because of the presence of immature myeloid cells in the CSF, and was confirmed by anti-myeloperoxidase and anti-lysozyme immunoreactivity of the cerebellar tumor. The patient succumbed 1 year and 3 months after the first presentation of the disease. PMID:9341943

  16. Isolation and initial characterization of thermoresistant RIF tumor cell strains

    International Nuclear Information System (INIS)

    Heat-resistant cell strains were obtained from RIF-1 mouse tumor cells by repeated heatings of cells derived from survivors of previous heating cycles (60 min; 450C). Twenty thermally resistant (TR) strains were derived from single cells that had survived 11 heating and regrowth cycles. These were then analyzed for appropriate characteristics in vitro and in vivo. In vitro we looked for: marked heat resistance; high plating efficiency; growth rate similar to that of RIF-1 cells; and no obvious morphological abnormalities. In syngeneic hosts, we looked for: ability of the cells to form tumors whose growth rates were similar to that of RIF-1 tumors; high cellular heat resistance; good plating efficiency of tumor-derived cells; and low immunogenicity. Five strains having these desired characteristics were analyzed for survival kinetics. The heat-resistant phenotype was found to be stable in vitro, although partial reversion in vivo was seen occasionally. The break in the Arrhenius plot was found to occur at 450C in TR strains versus 430C in RIF-1. All TR strains and the RIF-1 line developed similar levels of thermotolerance (as defined by slope ratios) when given isosurvival heat exposures. X-ray responses of TR and RIF-1 cells were indistinguishable both with respect to survival and to heat-induced radiosensitization. While the number of live cells required to give tumor takes in 50% of the recipients for TR strains was appreciably higher than that for RIF-1 cells, radiation-killed cells from none of the strains were able to immunize efficiently against subsequent challenges by live cells

  17. Antiangiogenic Agent Might Upgrade tumor Cell Sensitivity to Ionizing Radiation

    International Nuclear Information System (INIS)

    The understanding of the fundamental role of angiogenesis and metastasis in cancer growth has led to tremendous interest in research regarding its regulatory mechanisms and clinical implications in the management of cancer. The present study was conducted to evaluate the influence of the angiogenic regulators modification on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. Accordingly, the antiangiogenic activity of apigenin and selenium was tested in vitro via MTT assay. The action of Apigenin and or Selenium was examined in vivo by using a model of solid tumor carcinoma (EAC). The growth rate of solid tumor in all experimental groups was measured by Caliper. The irradiated mice were exposed to 6.5 Gy of gamma rays. Apigenin 50 mg/kg body weight and selenium 5 μg per mice were daily administrated for 14 consecutive days after tumor volume reached 1mm3. The angiogenic activators TNF-α (key cytokine) in spleen, serum MMP 2 and MMP 9, liver and tumor NO, the lipid peroxidation (LPx) and angiogenic inhibitor TIMP-1 in spleen as well as, antioxidant markers (CAT, SOD, GPX) in tumor and liver tissue and DNA fragmentation in splenocytes were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm3. The using of MTT assay on EAC cells shows inhibition in EAC cell proliferation after the incubation with apigenin and /or selenium. The administration of apigenin and /or selenium to mice bearing tumor and to irradiated mice bearing tumor reduce significantly the TNF-α expression, MMP 2,9 , NO , LPx level and increased the antioxidant enzymes (GPx , SOD and CAT) activities. The DNA fragmentation and the antiangiogenic factors TIMP-1 were significantly increased when compared with their values in mice bearing tumor or in irradiated mice bearing tumor. From the results obtained

  18. Advances in Research on Circulating Tumor Cells in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingjian SONG

    2012-10-01

    Full Text Available Metastatic and recurrent tumors have been identified as the leading attribute to the lung cancer deaths. Cancer research has demonstrated the critical role circulating tumor cells (CTCs play in the metastatic spread of carcinomas and the recurrence of lung cancer. The rapid advancement of technology in targeted therapy resolves the embarrassing situation for those late-stage patients whose tumor tissues cannot be obtained. CTCs, as a substitute for the tumor tissues, represent a decisive tool to the cancer treatment strategy. Thus, CTCs exert a fundamental role in the early detection of micro-metastasis, assisting in diagnosis, prognosis and monitoring of the recurrent tumors, and subsequently choosing an individualized approach for the therapeutic treatment. This article will review the advances, which have been made in the research area of CTCs with the aid of its applications in cancer therapy.

  19. Advanced Research on Circulating Tumor Cells in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hui LI

    2012-11-01

    Full Text Available Lung cancer is the malignant disease with the highest rate in terms of incidence and mortality in China. Early diagnosis and timely monitoring tumor recurrence and metastasis are extremely important for improving 5-year survival rate of lung cancer patients. Circulating tumor cells (CTCs, as a "liquid biopsy specimens” for the primary tumor, provide the possibility to perform real-time, non-invasive histological identification for lung cancer patients. The detection of CTCs contributes to early diagnosis, surveillance of tumor recurrence and metastasis, and prediction of therapeutic efficacy and prognosis. Furthermore, CTCs-dependent detection emerges as a new approach for molecularly pathologic examination, study of molecular mechanisms involved in drug resistance, and resolution for tumor heterogeneity. This study reviewed the recent progress of CTCs in lung cancer research field.

  20. Dysfunction of Murine Dendritic Cells Induced by Incubation with Tumor Cells

    Institute of Scientific and Technical Information of China (English)

    Fengguang Gao; Xin Hui; Xianghuo He; Dafang Wan; Jianren Gu

    2008-01-01

    In vivo studies showed that dendritic cell (DC) dysfunction occurred in tumor microcnvironment. As tumors were composed of many kinds of cel