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Sample records for ascites tumor cells

  1. Effect of misonidazole on radiosensitivity of Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Takeuchi, Hiroshi

    1986-01-01

    The effect of Misonidazole on radiosensitivity of Ehrlich ascites tumor cells was studied in vivo. Ehrlich ascites tumor cells growing intraperitoneally (ICR/SIC mice) for either 1, 4, 6 or 10 days were irradiated in vivo (whole body irradiation) with or without Misonidazole. Immediately after irradiation tumor cells were transplanted intraperitoneally into new animals. Four days later, the propagated surviving cells were removed and counted for analyses. Enhancement ratio of Misonidazole at the surviving fraction of 0.1 were 1.0 (for 1-day-old), 1.3 (for 4-day-old), 1.9 (for 6-day-old), 1.9 (for 10-day-old) and 2.8 (for anoxic cells) respectively. The gradual increase of the enhancement ratio of the ascites tumore cells during intraperitoneal growth from 1 through 10 days might be attributed to an increase of hypoxic tumor cells. Cytotoxicity was not observed at 0.1 mg per gram body weight of Misonidazole but was at 1 mg per gram body weight of Misonidazole in 6-day-old and 10-day-old Ehrlich ascites tumor cells which were supposed to contain hypoxic cells. These results suggest that Misonidazole may prove an effective radiosensitizer for hypoxic tumor cells. (author)

  2. Immunogenicity of ascites tumor cells following in vitro hyperthermia

    International Nuclear Information System (INIS)

    Dickson, J.A.; Jasiewicz, M.L.; Simpson, A.C.

    1982-01-01

    The concept that host immunization may be achieved by heat-induced antigenic modifications of cancer cells and/or the release of immunogenic products by dead or dying tumor cells following in vitro heating was examined. Ehrlich ascites cells were used, inasmuch as it was claimed that in vitro hyperthermia increased the immunogenicity of these cells. Tumor cell populations of different viability were obtained by heating Ehrlich cells at 42.5 degrees, 45 degrees, or 60 degrees C. Viable and nonviable cells were separated by Ficoll-Hypaque density centrifugation; viable nonreplicating cells were obtained by treatment with mitomycin C. Cell populations of different viability after heating were left to die slowly over 3 days at 37 degrees C. Swiss TO mice were then given injections of the treated cells and/or medium. No survival benefit occurred in mice inoculated with any of these different components and then challenged with viable tumor cells. Injection of irradiated cells, however, did produce host immunity. Similarly, D23 rat hepatoma ascites cells produced host immunity after 15,000 rad but not after heating. The claim that in vitro hyperthermia increases the immunogenicity of tumor cells was not confirmed

  3. Study of the cellular uptake and distribution of 57cobalt bleomycin in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Metelmann, H.R.

    1980-01-01

    We investigated the dependence of the cellular uptake of 57 cobalt-bleomycin on the exposure time and on the dose. In addition we observed the influences due to the incubation temperature, to the growth phase of the tumor cells and due to the composition of the suspensory medium. In supplementary experiments we investigated the binding of the labelled cytostatic agent to erythrocytes, its adsorption to broken Ehrlich ascites tumor cells and the 57 cobalt-bleomycin outflow from pre-loaded intact Ehrlich ascites tumor cells. The 57 cobalt-bleomycin uptake of intact Ehrlich ascites tumor cells is determined by characteristic kinetics. Moreover, the erythrocytes and injured Ehrlich ascites tumor cells show a qualitatively similar graph of the 57 cobalt-bleomycin binding, which can clearly be distinguished from the kinetics found with intact Ehrlich ascites tumor cells. The uptake of this cytostatic agent depends on an unequivocal time-dose-temperature relationship. The transport mechanism of the 57 cobalt-bleomycin uptake was considered as endocytosis. An endocytosis-stimulating inducer could not be detected. However, we obtained indications that the cell-bound cytostatic agent is taken up in two compartments: on the cellular surface and in the interior of the cell. (orig./MG) [de

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

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

    NARCIS (Netherlands)

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

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

  6. 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...

  7. Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

    1980-01-01

    Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

  8. Effects of daily treatment with a radioprotector WR-2721 on Ehrlich's ascites tumors in mice

    International Nuclear Information System (INIS)

    Ikebuchi, Makoto; Shinohara, Shigeo; Kimura, Hiroshi; Morimoto, Kunio; Shima, Akihiro

    1981-01-01

    Mice were injected daily with a radioprotector WR-2721 (S-2-[3-aminopropyl-amino]ethylphosphorothioic acid) after inoculation with Ehrlich's ascites tumor cells. Increases in weight of mice, volume of ascitic fluid and number of ascitic cells per mouse were reduced by the daily administration of 5 mg/mouse of the drug, indicating a suppressive effect of WR-2721 on growth of ascitic cells. But daily treatment with 5 mg/mouse of WR-2721 caused earlier death of tumor-bearing mice. (author)

  9. Cell kinetics of Ehrlich ascites carcinoma transplanted in mice with different degrees of tumor resistance

    International Nuclear Information System (INIS)

    Brandt, K.L.B.

    1974-01-01

    Cell proliferation kinetics of Ehrlich ascites carcinoma grown in two strains of mice with different degrees of resistance to this tumor were examined. In the first portion of the study, growth of Ehrlich ascites carcinoma in nonresistant Swiss (Iowa) and slightly resistant CF1 mice was examined by measuring animal weight gain and host survival time after intraperitoneal injection of tumor cells. Since it appeared that CF1 mice were inherently more resistant than Swiss mice to the Ehrlich carcinoma, the second part of this investigation involved attempts to immunize CF1 mice against the tumor. Subcutaneous injections of Ehrlich cells previously exposed in vitro to 5000 R of 250 kVp x rays were utilized. One immunizing inoculation of lethally irradiated tumor cells afforded protection against an intraperitoneal challenge of 40 thousand Ehrlich cells. By varying the number and timing of immunizing inoculations it was possible to induce different degrees of tumor resistance in these mice. The most effective immunizing procedure utilized multiple inoculations of lethally irradiated tumor cells (LITC), followed by challenges with viable tumor cells (less than 1 million) which were rejected. These mice could then resist challenge inocula of 4 million viable tumor cells. In a few animals the immunizing procedures were ineffective; these animals, when challenged, developed even larger tumors than control mice. Tumor cell proliferation kinetics in these animals as well as in mice that were rejecting the tumor were examined in the third phase of the project. A shortening of the cell cycle was observed in almost all LITC-treated mice, whether tumor growth was eventually inhibited or stimulated. Decreased duration of the DNA-synthesis phase (S) of the tumor cell cycle was also a consistent finding. The role of the immune response in stimulating mitosis as well as in killing foreign cells was discussed. (U.S.)

  10. 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.

  11. Metabolism of 64Cu and transfer of 125I-MT in the bearing liver ascites tumor (H22) mice

    International Nuclear Information System (INIS)

    Huai Qing; Fang Xingwang; Wang Wenqing

    1998-01-01

    The metabolism of 64 Cu in some tissues of the bearing liver ascites tumor mice has been studied. The liver in normal and tumor bearing mice preferentially accumulates intravenous injection copper, however, the liver in the later mice accumulates much less copper than that of the former. It suggests that in the bearing ascites tumor mice, ascites tumor influences the metabolism of copper. It is found that the content of 64 Cu in the tumor cell is more than 85% in ascites tumor. Gel filtration profile of mice liver homogenate on Sephadex G-75 shows that injected 64 Cu is mainly bound with metallothionein. The tissues uptake of 125 I-labelled (Cd, Zn)-MT which is given in abdominal cavity are also reported. Of the tissues studied, the ascites tumor and kidney accumulate the highest concentration of given 125 I-MT, since over 20% of entire dose accumulated in them. After 125 I-MT is given, it soon goes into ascites tumor, and reaches the maximum in ascites as well as in tumor cell. Therefore, 125 I-MT can go through the membrane of tumor cell and reaches in the tumor cell

  12. Repair in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Wanna-Nakamura, S.S.

    1981-01-01

    Unscheduled DNA synthesis (UDS), an indicator of excision repair, was induced in freshly drawn Ehrlich ascites tumor cells (EAT), using ionizing radiation, far ultraviolet light (254 nm) or near uv light (365 nm) in combination with 8-methoxypsoralen. UDS was scored by grain counts in autoradiographs following the incorporation of tritium-labelled thymidine. The amount of UDS after each of these agents was expressed in terms of two parameters, viz. numer of cells showing repair and the mean number of grains per nucleus. The influence of radiation dose and of the duration of radioactive thymidine incubation were also examined. To test for a possible relationship between low mitotic index and repair capability, EAT cells were incubated in buffered salt media to lower the mitotic index. Cells kept in a buffered salt solution for 7 h show a marked drop in mitotic index compared to those incubated in minimal medium containing 15% fetal calf serum (MEM + FCS). This drop in mitotic index was reversible for up to 5 h, if cells were returned to MEM + FCS. Cells incubated in MEM + FCS also showed a decrease in mitotic activity compared to freshly drawn cells. This reduced mitotic index is approximately constant for up to 24 h. With the drop in mitotic index, EAT cells also show a drop in repair compared to freshly drawn cells. The repair capability of cells incubated in buffer can be restored by returning cells to MEM + FCS

  13. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

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    Nirmala Chandralega Kampan

    2017-11-01

    Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

  14. Use of raw Euphorbia tirucalli extract for inhibition of ascitic Ehrlich tumor

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    Orlando José dos Santos

    Full Text Available Objective: to evaluate the effect of the Euphorbia tirucalli hydroalcoholic extract (ETHE on the development of Ehrlich Tumor, in its ascitic form. Methods: we intraperitoneally inoculated 15 Swiss mice with 10.44 x 107 cells of Ehrlich Tumor and divided them in two groups one day after: ETHE Group (eight mice, treated with a dosage of 125 mg/kg/day of EHTE for five days; and Control Group (seven mice, treated only with 0.9% isotonic saline solution over the same period. The treatment was done by gavage. Ten days after inoculation, four mice from each group were sacrificed for quantification of tumor cell number, ascitic fluid volume and bone marrow cell number. The remaining animals were maintained to evaluate survival. Results: The ascitic fluid volume and the tumor cell number were decreased in the ETHE group when compared with the control group, but with no statistical significance. On the other hand, survival was higher in the ETHE group, as well as the number of bone marrow cells. Conclusion: Treatment with ETHE after inoculation of Ehrlich Tumor decreases its development and increases survival and the bone marrow cellularity, thus reducing the myelosuppression present in the Ehrlich Tumor bearing mice.

  15. Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

    International Nuclear Information System (INIS)

    Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

    1985-01-01

    The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

  16. 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...

  17. The anti-tumor effect of bee honey in Ehrlich ascite tumor model of mice is coincided with stimulation of the immune cells.

    Science.gov (United States)

    Attia, W Y; Gabry, M S; El-Shaikh, K A; Othman, G A

    2008-01-01

    Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells.

  18. Chronobiological organization of reproduction of Ehrlich's ascites tumor cells

    International Nuclear Information System (INIS)

    Romanov, Qu.A.; Stepanenko, V.A.

    1986-01-01

    The rhythms of cell proliferation and DNA synthesis were studied in a hypotetraploid strain of Ehrlich's ascites tumor (EAT) and compared with data obtained previously on the hyperdiploid strain of EAT. Eighty-five noninbred male albino mice were used. An injection of tritium-thymidine, with specific radioactivity of 4.1 Ci/mmole, was given to the mice one hour before sacrifice. The results obtained are presented; it is shown that the number of DNA-synthesizing cells in the hypotetraploid strain during the 5th and 6th days of growth of EAT was 503 and 479 0 /00, respectively. Fluctuations of the radioactive index during these days were not significant. Only a significant fall in the radioactive index toward noon on the seventh day of development of the hypotetraploid strain of EAT was observed

  19. Studies on the interaction between the Ehrlich ascites tumor cell and its fluid environment

    International Nuclear Information System (INIS)

    Magnani, B.

    1984-01-01

    In this dissertation, the glycolytic nature of the Ehrlich ascites tumor (EAT) cell is disclosed both in vivo and in vitro by experiments challenging it with glucose. It is demonstrated that EAT cells can cause the extracellular pH to drop to values sufficiently acidic so as to inhibit EAT glycolysis. However, the extracellular fluid or the Ascites Supernatant Fluid (ASF) reduced the extent to which the pH dropped during EAT cell glycolysis. A comparison of the activities of the sera from tumor-bearing mice and normal mice revealed that the serumfrom the tumor-bearing mice reduced the pH fall generated by the EAT cell in the same way as did ASF; normal mouse serum had no such effect. The metabolic pathways utilized during glucose catabolism were examined by radio-respirometry and the results demonstrated that the high percentage of the glucose conversion to lactate occurred because of partial blockade of the TCA cycle. The databolism of glutamine, glutamic acid, asparagine, aspartic acid, and alanine was enhanced by ASF as determined by measuring 14 CO 2 from 14 C-labelled amino acids, with glutamine catabolism enhanced about three-fold. Fractionation experiments revealed that ASF contained a factor(s) responsible for this enhancement that had a molecular weight greater than 300,000 daltons and was heat-labile

  20. Evaluation of tumor markers for the differential diagnosis of benign and malignant ascites.

    Science.gov (United States)

    Liu, Fang; Kong, Xinjuan; Dou, Qian; Ye, Jin; Xu, Dong; Shang, Haitao; Xu, Keshu; Song, Yuhu

    2014-01-01

    The diagnosis of malignant ascites is a challenging problem in clinical practice, non-invasive techniques should be developed to improve diagnostic accuracy. The diagnostic performances of tumor markers in malignant ascites remained unsettled. Our aim was to evaluate diagnostic performance of tumor markers in differential diagnosis of benign and malignant ascites. A total of 437 patients were enrolled, and the relevant parameters of the patients were analyzed for the differentiation of benign ascites from malignant ascites. At the predetermined cutoff values of tumor makers, tumor markers in ascitic fluid showed better diagnostic performance than those in serum. Combined use of tumor markers and the cytology increased the diagnostic yield of the latter by 37%. In cytologically negative malignant ascites, tumor markers provided assistance in differentiating malignant ascites from benign ascites, and the combination of ascitic tumor markers yielded 86% sensitivity, 97% specificity. Use of a panel of tumor markers exhibited excellent diagnostic performance in diagnosing malignant ascites, which indicated the detection of tumor markers may represent a beneficial adjunct to cytology, thus guiding the selection of patients who might benefit from further invasive procedures.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal...... 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...... reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1...

  2. 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

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    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.

  3. 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)

    Nikhil, Kumar; Sharan, Shruti; Chakraborty, Ajanta; Bodipati, Naganjaneyulu; Krishna Peddinti, Rama; Roy, Partha

    2014-01-01

    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 50 =25±0.38) when compared to reference compound PTER (IC 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

  4. A poly (U) polymerase in ribosome preparations from Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Guimaraes, R.C.; Bloch, D.P.

    1981-01-01

    A ribosome-bound poly (U) polymerase from Ehrlich ascites tumor cells is partially characterized. It adds UMPs to RNAs terminating in U-(3')-OH. The UMP-rich segments added reach average sizes of up to 18 nucleotides. CTP is strongly inhibitory to the enzyme. The main endogenous primers are low molecular weight RNAs which are found, after the addition of UMPs, mostly in the 6-8 S range. Some evidence suggests that a 5 S rRNA or polysome-associated 7 S RNA could be the main endogenous primers. (Author) [pt

  5. 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.

  6. 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.

  7. Distribution of copper-64 in control mice and in mice bearing ascitic Krebs tumor cells

    International Nuclear Information System (INIS)

    Apelgot, S.; Coppey, J.; Grisvard, J.; Guille, E.; Sissoeeff, I.

    1981-01-01

    Three to 20 hr after an i.p. injection of 64 Cu (half-life, 12.8 hr) into mice bearing Krebs ascites cells, a high amount of the radioisotope was recovered in the ascites cells themselves. In the control group, the radioisotope was mainly present in the liver. Similar amounts of 64 Cu were recovered in regenerating as well as in normal liver, whereas in the liver of mice bearing ascites cells, this amount was lower by 40 to 50% regardless of the ascitic volume. Thus, the copper metabolism seems to be disturbed at the hepatic level in mice bearing ascites cells. The distribution of 64 Cu was 'analyzed in DNA, RNA, and proteins from cellular lysates fractionated by CsCl gradient. There was a uniform pattern of distribution in the macromolecules from ascites cells, while 64 Cu' was preferentially associated with the protein fraction from liver. Further experiments indicated that, in vivo, 64 Cu was bound to the DNA of ascites cells

  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 unaffected by DIDS...

  9. A unique DNA found in post-mitochondrial fraction from Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Guimaraes, R.C.; Bloch, D.P.

    1982-01-01

    A DNA found in post-mitochondrial fractions from Ehrlich ascites cells, comprising 0.2% of the total cellular DNA, is partially characterized. It appears in cytoplasmic homogenates as a 14.6 S molecule, and is eluted from hydroxyapatite with 0.24 M sodium phosphate buffer. Its Cs 2 SO 4 buoyant density is lower than Erlich ascites tumor nuclear DNA and it has low dG+dC content, as determined by chromatography of hydrolysates of 32 P-labelled DNA. It is enriched in sequences which reassociate rapidly in the presence of excess nuclear DNA. It can be used as promoter for DNA synthesis by an endogenous DNA-dependent DNA polymerase found in association with the post-mitochondrial preparations. It is found to be associated with newly incorporated radioactivity following incubation in vitro with labelled UTP. Its localization in situ has not yet been attempled. It is thought to represent viral A-type particle associated, or plasma membrane associated DNA. (author) [pt

  10. The inhibition effect of 211At-Te colloid and Na211 at injections on murine Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Wang Juan; Wang Xizhong; Zhang Jiazao

    1992-01-01

    Na 211 At and 211 At-Te colloid injections are prepared. It has been demonstrated that the 211 At-Te colloid is stable in vivo and in vitro, and can be applied in the study of biology and medicine. In the report, the model of Murine Ehrlich Ascites Cells cultured in vivo and in vitro is elected for a series of experiments. It has been proved that Na 211 At and 211 At-Te colloid injections possess an inhibition effect on tumor cells. The inhibition effect was expressed in surviving of the mice and inhibiting growth of tumor as well as the changes of enzyme activity. Meanwhile, it was also noticed that Na 211 At and 211 At-Te colloid injections of various dose inhibited the absorb of pyrimidine nucleosides in Murine Ehrlich Ascites Cells. And the effect is not reversible. It is closely related to the dose administrated and 50% inhibition rate needs about 1.48 x 10 5 Bq/ml culture

  11. 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.

  12. In vitro binding of 67Ga to Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Kojima, S.; Kubodera, A.

    1984-01-01

    The binding of 67 Ga to Ehrlich ascites tumor cells (ETC) was studied in vitro. Acid mucopolysaccharide (AMPS) present at the cell surface of ETC was identified as heparan sulfate (HS). The extent of 67 Ga binding to ETC reached a plateau (ca. 10% of the added dose) at 1-2 h after the start of incubation. The binding was higher under neutral or alkaline conditions than under acidic conditions. Heparin and heparitinase treatment both significantly decreased the extent of 67 Ga binding to ETC. Mild treatment with protease, including trypsin or papain, also decreased the binding. On the contrary, the treatment with trypsin under severe conditions markedly increased the extent of 67 Ga binding to ETC. These results support the hypothesis that HS plays an important role as a 67 Ga receptor in the mechanism of gallium binding to ETC. (orig.)

  13. Immune mechanisms in Ehrlich ascites tumor growth in mice

    International Nuclear Information System (INIS)

    Marusic, M.

    1979-01-01

    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)

  14. 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)

    Sejlanov, A.S.

    1989-01-01

    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

  15. Isotope inequilibrium of glucose metabolites in intact cells and particlefree supernatants of Ehrlich ascites tumor

    International Nuclear Information System (INIS)

    Daehnfeldt, J.L.; Winge, P.

    1975-01-01

    With an enzyme degradative technique, isotope inequilibrium of glucose metabolites was demonstrated in intact cells and particle-free supernatants of Ehrlich ascites tumor using I- 14 C-glucose as tracer. Inequilibrium was found between glucose and glucose-6-phosphate, glucose and fructose-6-phosphate, glucose and 6-phosphogluconate, while glucose-6-phosphate and fructose-6-phosphate were found to be in near equilibrium within the incubation time investigated. Glucose and lactate were found to be in near equilibrium after 8 min in intact cells. Calculations based on the equilibrium levels found, showed that these inequilibria could not be explained by the effects of the pentose cycle. (U.S.)

  16. 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

    The Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 were all found to be expressed in Ehrlich ascites tumor cells, as evaluated by Western blotting and confocal microscopy. Under unstimulated conditions, NHE1 was found predominantly in the plasma membrane, NHE3 intracellularly, and NHE2 in both co....... It is concluded that shrinkage-induced NHE activation is dependent on PKC and p38 MAPK, but not on MLCK or ERK1/2. NHE activity under both iso- and hypertonic conditions is increased by inhibition of serine/threonine phosphatases, and this effect appears to be PKC-dependent....

  17. Effects of hyperthermia, x-ray irradiation and their combination on ascites tumor cells of mice

    International Nuclear Information System (INIS)

    Kaneko, Itsuo

    1982-01-01

    Fibrosarcoma ascites tumor cells (PB8) from NMRI mice were used to investigate cell loss by hyperthermia and/or x-ray irradiation. The tumor cells were labelled by an injection of 125 I-deoxyuridine to the abdominal cavity of the donors 2 days before the physical treatments. The labelled cells, transfered in test tubes, were heated at 44 0 C for 10-20 min and/or irradiated by x-ray at 250-1612 rad, and were transplanted in the recipient abdominal cavity as soon as possible after the treatments. The radioactivity of the tumor cells, as an indicator of cell loss, was measured with a gamma spectrometer. In the irradiated group, the ratio of cell loss increased in a dose-dependent manner, starting from the 4th day after the transplantation to the 9th day. In the heated group, the ratio of cell loss increased in proportion to the heating time, starting without delay after transplantation. In the combination group, the effect of the treatments was more marked than that by each single treatment. In the early stage of this group, cell loss was by heating and then, from the 4th day, the irradiation effect mostly dominated. It is concluded from the above results that cell loss by heating or irradiation is independent and that the effect of the combination is additive. (author)

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

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Santos, Raquel G. dos; Dias, Consuelo L. Fortes; Cassali, Geovanni D.

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  20. Research of ALA combined with HpD-PDT which induced s180 ascitic tumor cells, death or apoptosis on cytology

    Science.gov (United States)

    Zhu, Jing; Yan, Min; Zhang, Hui-Guo; Li, Enling; Luo, Hongyu

    2005-07-01

    To ascertain the adequate dosage of ALA combined with HpD-PDT which induced tumor cell death or apoptosis on cytology. And to study the different effect of ALA-PDT and HPD-PDT used only. Rat ascitic tumor cells(S180) were randomly divided into several groups and incubated with ALA(20μg/ml 、40μg/ml、80μg/ml 、160μg/ml)、HPD(2.5μg/ml、5μg/ml、10μg/ml)and their combination dosages. 630nm light (total output 2W) was delivered to tumor cells at a constant fluence rate: 200mw/cm2 and a constant irradiated time period: 20 minutes. We set 3 groups (no photosensitizers or no irradiation or neither) to be the control groups. We used inversion microscopy to observe the morphological change of tumor cells and flow cytometry technology to detect the death or apoptosis of tumor cells during the experiment. ..

  1. Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

    Science.gov (United States)

    Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

    2018-05-01

    The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

  2. 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

    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...

  3. 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.

  4. Inactivation of Ehrlich ascites tumor cells by heavy ions

    International Nuclear Information System (INIS)

    Bertsche, U.; Iliakis, G.; Kraft, G.

    1983-01-01

    Exponentially growing and plateau-phase cultures of Ehrlich ascites tumor cells were irradiated with heavy ions (Z greater than or equal to 20) and assayed for loss of reproductive capacity either immediately or at delayed times after irradiation. The results indicated no modification of the exponential dose response due to conditions which usually favor the repair of potentially lethal damage at low ionization density. Postirradiation treatment of the cells with a DNA synthesis inhibitor known to act on PLD repair resulted in effects similar to those observed without this drug and confirmed the hypothesis that at such high values of ionization density only lethal, unmodifiable damage can be expressed. The inactivation cross-section values calculated from the slope of the measured survival curves showed no significant correlations with commonly used parameters of radiation quality. Instead, a functional dependence on the primary ion energy was indicated, being smaller by a factor of two at low energies (less than or equal to 2 MeV/amu) compared with values at energies above 4 MeV/amu, where agreement with the morphological nuclear cross section of the culture was found. This suggests that at higher specific ion energies energetic secondary electrons contribute to the induction of lethal damage, and that interaction of damaged sites between the primary track and the track ends of delta electrons may occur. The data are therefore also discussed in terms of the penumbra model which emphasizes the role of delta electrons in cell killing when radiations with very high ionization density are applied

  5. Membrane damage effect of therapeutic ultrasound on Ehrlich ascitic tumor cells.

    Science.gov (United States)

    Hao, Qiao; Liu, Quanhong; Wang, Xiaobing; Wang, Pan; Li, Tao; Tong, Wan Yan

    2009-02-01

    The biologic effects and the underlying mechanisms of Ehrlich ascitic tumor (EAT) cells induced by ultrasound were investigated in this study. Cells were subjected to ultrasonic irradiation with a frequency of 2.17 MHz and an intensity of 3 W/cm(2) for variable periods of time. Trypan blue exclusion was used to detect the integrity of cellular membrane; the membrane permeability was investigated by the incorporation of fluorescein isothiocyanate dextran during ultrasound exposure; and the cell membrane ultrastructure changes were observed under a scanning electron microscope. The potential mechanism was estimated from the generation of hydroxyl radicals, the lipid peroxidation levels, and intracellular reactive oxygen radicals production. The cell membrane damage effects induced by ultrasound increased with a prolonged exposure time; the fluorescent rates of the cells irradiated with ultrasound for 30 and 60 seconds were 11.46% and 18.50%, respectively; the amount of hydroxyl radicals in 30 (26.10 U/mL) and 60 seconds (28.47 U/mL) were significantly enhanced, compared with the control group (24.44 U/mL); then, the level of lipid peroxidation was also changed from 0.27 to 0.54 (30 seconds) and 1.21 nmol/mL (60 seconds). Shear forces and free radicals produced by acoustic cavitation may play important roles in these actions.

  6. Ascites promotes cell migration through the repression of miR-125b in ovarian cancer.

    Science.gov (United States)

    Yang, Lan; Zhang, Xiaoli; Ma, Yiming; Zhao, Xinhua; Li, Bin; Wang, Hongying

    2017-08-01

    Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner. Mimic of miR-125b blocked ascites-induced cell migration. Furthermore, Gab2 (a target gene of miR-125b) was elevated by ascites in a TGF-β-dependent manner. And forced expression of Gab2 reversed the inhibition of migration induced by miR-125b mimic. Most importantly, the expression of miR-125b and Gab2 mRNA was negatively correlated in ovarian cancer specimens. Taken together, our finding suggested that TGF-β in ascites promoted cancer cell migration through repression of miR-125b in ovarian cancer. This might provide a novel therapeutic target for ovarian cancer in the future.

  7. Comparison of folylderivative biosynthesis in Ehrlich ascites carcinoma cells and in some organs of healthy and tumor-bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, E; Grzelakowska-Sztabert, B [Polska Akademia Nauk, Warsaw. Inst. Biologii Doswiadczelnej

    1984-01-01

    Biosynthesis of folyl derivatives derived from subcutaneously injected 2-(/sup 14/C)folate was studied in Ehrlich ascites carcinoma (EAC) cells and in mouse liver and kidneys. Retention of exogenous folate was followed by measurements of the total radioactivity of folyl derivatives present in the EAC cells and organs examined. Identification of unconjugated and conjugated folyl derivatives was done by means of column chromatography on Sephadex G-25, G-15 and cellulose sheets. The level of retained radioactivity in folyl derivatives, being 5% in the liver and 1% in the kidneys of the radioactivity administered to mice, was similar in healthy and tumor-bearing animals. Moreover, no quantitative and qualitative differences were found in folyl mono- and polyglutamates originating from the organs of healthy or tumor-bearing mice although the content of folyl polyglutamates rose faster in liver and kidneys of EAC cells-bearing mice as well as in the tumor cells, than in the organs of healthy mice.

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

    International Nuclear Information System (INIS)

    Witt, S.; Ziegler, B.; Kloeting, I.; Ziegler, M.; Nadrowitz, R.; Schmidt, W.

    1987-01-01

    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)

  9. A method for determining the biological effectiveness of ionizing radiation by evaluating the mitotic inhibition of Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Merkle, K.

    1977-03-01

    The mitotic response of mouse ascites tumor cells to in vivo 60 Co γ-irradiation (50, 100, 200, and 300 rad) was investigated on the fourth day after inoculation at 1 hour postirradiation. In the dose range applied the relationship between the mitotic index (MI) and the gamma dose (D, in rad) could be represented by MI = -35,07 lg D + 105,57. (author)

  10. Inactivation of Ehrlich ascites tumor cells by heavy ions

    International Nuclear Information System (INIS)

    Bertsche, U.; Iliakis, G.; Kraft, G.

    1983-01-01

    Exponentially growing and plateau-phase cultures of Ehrlich ascites tumor cells were irradiated with heavy ions (Z greater than or equal to 20) and assayed for loss of reproductive capacity either immediately or at delayed times after irradiation. The results indicated no modification of the exponential dose response due to conditions which usually favor the repair of potentially lethal damage at low ionization density. Postirradiation treatment of the cells with beta-arabinofuranosyladenine, a DNA synthesis inhibitor known to act on PLD repair, resulted in effects similar to those observed without this drug and confirmed the hypothesis that at such high values of ionization density only lethal, unmodifiable damage can be expressed. The inactivation cross-section values calculated from the slope of the measured survival curves showed no significant correlations with commonly used parameters of radiation quality such as LET or z 2 /beta 2. Instead, a functional dependence on the primary ion energy was indicated, being smaller by a factor of two at low energies (less than or equal to 2 MeV/amu) compared with values at energies above 4 MeV/amu, where agreement with the morphological nuclear cross section of the culture was found. This suggests that at higher specific ion energies energetic secondary electrons contribute to the induction of lethal damage, and that interaction of damaged sites between the primary track and the track ends of delta electrons may occur. The data are therefore also discussed in terms of the ''penumbra model'' which emphasizes the role of delta electrons in cell killing when radiations with very high ionization density are applied

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

    International Nuclear Information System (INIS)

    Edwards, E.H.

    1984-01-01

    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 ([ 3 H]H 2 DIDS) 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- 14 C]-D-glucosamine hydrochloride, D-[2- 3 H]-mannose and various [ 3 H]-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

  12. 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

    Intracellular free calcium concentration ([Ca2+]i) and intracellular pH (pHi) were monitored in Ehrlich ascites tumor cells using Fura-2 or 2',7',-bis-(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF), or both probes in combination. An increase in [Ca2+]i induced by thrombin or bradykinin, agonists...

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

    International Nuclear Information System (INIS)

    Arican, G. Oe.; Oezalpan, A.

    2001-01-01

    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

  14. Ehrlich ascites tumor-bearing mice treated with aqueous ethanol ...

    African Journals Online (AJOL)

    Conclusion: Euphorbia tirucalli extract inhibits Ehrlich ascites tumor in mice, but the therapeutic ... traditional treatment of cancer. ... can be used with therapeutic purposes, this .... investigation suggested an antitumor action of E. .... Prasad SB, Giri A. Antitumor effect of cisplatin against ... Identification of the molecular basis of.

  15. 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)

    Laudenbach, G.; Baganz, O.; Pfab, R.; Hess, F.; Schachtschabel, D.O.

    1987-01-01

    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.) [de

  16. Accumulation and suppressive function of regulatory T cells in malignant ascites: Reducing their suppressive function using arsenic trioxide in vitro.

    Science.gov (United States)

    Hu, Zilong; Hu, Shidong; Wu, Youjun; Li, Songyan; He, Changzheng; Xing, Xiaowei; Wang, Yufeng; Du, Xiaohui

    2018-04-01

    Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As 2 O 3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro . In this study, lymphocytes were separated from malignant ascites and T-cell subsets were detected via flow cytometry. Forkhead box P3 (FoxP3) expression was assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In addition, cytokines, including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ), were measured by enzyme-linked immunosorbent assay (ELISA). Abundant Tregs were observed in ascites lymphocytes, which and exhibited a significantly increased frequency compared with that in the peripheral blood of patients. Furthermore, As 2 O 3 treatment significantly reduced Treg numbers and Foxp3 mRNA levels in vitro (P<0.05). IFN-γ levels in the supernatant of ascites-derived TILs were increased by As 2 O 3 , whereas IL-10 and TGF-β levels were significantly reduced (P<0.05). As 2 O 3 may induce selective depletion and inhibit immunosuppressive function of Tregs, and may enhance the cytotoxic activity of ascites-derived TILs.

  17. Marcadores de proliferação celular na avaliação do crescimento do tumor sólido e ascítico de Ehrlich Cell proliferation markers for evaluating the growth of solid and ascitic forms of Ehrlich tumor

    Directory of Open Access Journals (Sweden)

    A.E. Silva

    2006-08-01

    Full Text Available Twenty BALB/c mice were inoculated with cell suspension of Ehrlich tumor. Ten mice were inoculated in the cushion plant (solid form and the other 10 in the peritoneum (ascitic form. Animals were euthanized on different times (7 and 14 days. Cytological and histological slides, immunohistochemical (PCNA analysis and NORs silver impregnation technique were performed. The results showed more proliferation on the 7th day in the ascitic form and on 14th day in the solid form, using both analyses (PCNA and AgNORs. The alterations observed in the Ehrlich tumor’s proliferation activity suggested that the growth curve is different between ascitic and solid forms. In the first one, the proliferation peak occurs on the seventh day and in the solid tumor the growth curve was more delayed, showing increased proliferative potential after seven days.

  18. The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Makiko; Kobayashi, Hisashi; Ichikawa, Taro; Cho, Keiichi; Gemma, Kazuhito; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan)

    1997-12-01

    CT characteristics of spontaneous rupture of HCC (n=13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary, (e.g., non-hemorrhagic) ascites (n=13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation. (author)

  19. The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites

    International Nuclear Information System (INIS)

    Ishihara, Makiko; Kobayashi, Hisashi; Ichikawa, Taro; Cho, Keiichi; Gemma, Kazuhito; Kumazaki, Tatsuo

    1997-01-01

    CT characteristics of spontaneous rupture of HCC (n=13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary, (e.g., non-hemorrhagic) ascites (n=13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation. (author)

  20. Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

    International Nuclear Information System (INIS)

    Liniecki, J.; Rembelska, M.; Koniarek, B.

    1983-01-01

    Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

  1. 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

  2. Weakening of the radioprotective action of gas hypoxia with growth of ascitic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Aytmagambetova, B Z; Shmakova, N L; Fadeyeva, T A

    1975-06-27

    It was shown previously that moderate hypoxia induced by breathing oxygen-poor air (5 percent O/sub 2/) reduces the lethal effect of the total irradiation of mice, while with local irradiation of tumors reduction of tumor growth rate is even more marked in hypoxia-protected animals than with irradiation of mice in normal air. This suggests the possible therapeutic application of hypoxia. It was found that acute gas hypoxia strongly retards radiation damage to bone marrow, both qualitatively (type of cells affected) and quantitatively. In addition, a definite weakening of the protective effect of hypoxia was observed, this being proportional to increase in tumor size. Planned future tests involving direct dynamic measurement of oxygen stress as a function of amount of ascites are expected to supply further information on reduction of radiosensitivity of normal tissues and on the selective intensification of tumor regression. Graphic data accompany the paper. (JPRS)

  3. Hypoxia targeting therapy with prodrug specifically stabilized and activated in hypoxic tumor cells

    International Nuclear Information System (INIS)

    Kondoh, S.K.; Ueda, T.; Harada, H.; Hiraoka, M.; Akagi, K.

    2003-01-01

    Hypoxia fraction in tumors is associated with increased metastasis and poor survival in patients suffering from malignant tumors such as the head and neck, cervical or breast cancers. Hypoxia can be a direct cause of therapeutic resistance because some drugs and radiation require oxygen to be maximally cytotoxic. Recently we have reported a novel hypoxia targeting prodrug, TOP3, which is a fusion protein, composed of HIV TAT protein transduction domain, a part of HIF1 α ODD domain, and Procaspase-3. TOP3 can be transferred into every cell both in vitro and in vivo but becomes stable only in hypoxic cells, in which TOP3 is activated and induces apoptosis. The application of this fusion protein to a tumor-bearing mouse resulted in significant suppression of the tumor growth and even in reduction of the tumor mass without any obvious side effects. The administrations of TOP3 in combination with a low dose of X-ray showed an additive antitumor effect on pancreatic tumor cells. Furthermore, we show that the rodent model of ascites generated by malignant cells provides an excellent platform of testing hypoxia targeting drugs, since it comprises homogeneous fluid with tumor cells surviving and proliferating under hypoxic condition. TOP3 induced apoptosis of AH130, rat ascites hepatoma cells, in vitro only under hypoxic but not normoxic condition. Intraperitoneal administration of TOP3 prolonged life span of the rats with AH130 derived malignant ascites. Sixty percent of the treated rats were cured of ascites without recurrence for more than six months, in contrast all untreated rats died within 20 days after tumor cell inoculation. These results strongly suggest that TOP3 would provide a new strategy for hypoxia targeting therapy and that the combination of TOP3 with radiotherapy or chemotherapy may provide a new strategy for annihilating malignant tumors

  4. 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

    Cell-attached patch-clamp recordings from Ehrlich ascites tumor cells reveal nonselective cation channels which are activated by mechanical deformation of the membrane. These channels are seen when suction is applied to the patch pipette or after osmotic cell swelling. The channel activation does...... system. In isolated insideout patches a Ca2+-dependent, inwardly rectifying K+ channel is demonstrated. The single-channel conductance recorded with symmetrical 150 mm K+ solutions is for inward current estimated at 40 pS and for outward current at 15 pS. Activation of the K+ channel takes place after...... 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...

  5. Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation.

    Science.gov (United States)

    Zhou, Y; Wen, F; Zhang, P; Tang, R; Li, Q

    2013-03-01

    Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6-8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 μg VSVMP/250 μg liposome complexes, 50 μg empty plasmid/250 μg liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation.

  6. Aqueous extract from pecan nut [Carya illinoinensis (Wangenh) C. Koch] shell show activity against breast cancer cell line MCF-7 and Ehrlich ascites tumor in Balb-C mice.

    Science.gov (United States)

    Hilbig, Josiane; Policarpi, Priscila de Britto; Grinevicius, Valdelúcia Maria Alves de Souza; Mota, Nádia Sandrine Ramos Santos; Toaldo, Isabela Maia; Luiz, Marilde Terezinha Bordignon; Pedrosa, Rozangela Curi; Block, Jane Mara

    2018-01-30

    In Brazil many health disorders are treated with the consumption of different varieties of tea. Shell extracts of pecan nut (Carya illinoinensis), which have significant amounts of phenolic compounds in their composition, are popularly taken as tea to prevent diverse pathologies. Phenolic compounds from pecan nut shell extract have been associated with diverse biological effects but the effect on tumor cells has not been reported yet. The aim of the current work was to evaluate the relationship between DNA fragmentation, cell cycle arrest and apoptosis induced by pecan nut shell extract and its antitumor activity. Cytotoxicity, proliferation, cell death and cell cycle were evaluated in MCF-7 cells by MTT, colony assay, differential coloring and flow cytometry assays, respectively. DNA damage effects were evaluated through intercalation into CT-DNA and plasmid DNA cleavage. Tumor growth inhibition, survival time increase, apoptosis and cell cycle arrest were assessed in Ehrlich ascites tumor in Balb/C mice. The cytotoxic effect of pecan nut shell extracts, the induction of cell death by apoptosis and also the cell cycle arrest in MCF-7 cells have been demonstrated. The survival time in mice with Ehrlich ascites tumor increased by 67%. DNA damage was observed in the CT-DNA, plasmid DNA and comet assays. The mechanism involved in the antitumor effect of pecan nut shell extracts may be related to the activation of key proteins involved in apoptosis cell death (Bcl-XL, Bax and p53) and on the cell cycle regulation (cyclin A, cyclin B and CDK2). These results were attributed to the phenolic profile of the extract, which presented compounds such as gallic, 4-hydroxybenzoic, chlorogenic, vanillic, caffeic and ellagic acid, and catechin, epicatechin, epigallocatechin and epicatechin gallate. The results indicated that pecan nut shell extracts are effective against tumor cells growth and may be considered as an alternative to the treatment of cancer. Copyright © 2017

  7. Genetic constraints in the induction of the immune response to Ehrlich ascites tumor in mice

    International Nuclear Information System (INIS)

    Marusic, M.; Perkins, E.H.

    1981-01-01

    A single injection of irradiated Ehrlich ascites tumor (EAT) cells induces immunity in normal mice but fails to do so in T-cell-deficient-thymectomized, lethally irradiated, bone marrow-reconstituted (TIR) mice. TIR mice injected with normal syngeneic T cells develop an immune response to EAT when injected with irradiated EAT cells and reject a subsequent tumor cell challenge. In the present studies allogeneic T cells were unable to protect against EAT in TIR recipients even if harvested from donors tolerant to the recipient's transplantation antigens and injected into the TIR mice tolerant to the transplantation antigens of the injected T cells. Tolerance was produced by establishing long-term radiation chimeras of the P → F 1 type. Semiallogeneic T cells also failed to afford protection against EAT in TIR recipients. Whereas tolerance to other parental-strain transplantation antigens did not reverse the inability of parental T cells (cells from P → F 1 chimeric donors) to protect against EAT in F 1 TIR mice, it did enable F 1 T cells to afford protection in P → F 1 TIR mice

  8. Diagnostic value of serum and ascitic fluid AFP, CEA and CA125 contents determination for differentiation of benign from malignant ascites

    International Nuclear Information System (INIS)

    Zhu Huanxing; Yang Yongqing

    2003-01-01

    Objective: To investigate the diagnostic value of determination of serum and ascitic fluid AFP, CEA and CA125 contents for differentiating benign from malignant ascites. Methods: Serum and ascitic fluid contents of the three tumor markers were measured with RIA in 86 patients with ascites due to various causes. Results: The serum and ascitic fluid AFP, CEA and CA125 levels in patients with malignant ascites were very significantly higher than those in patients with benign ascites (p<0.01). For differentiation of benign (mainly T.B and liver cirrhosis) from malignant ascites, CA125≥500 IU/ml and AFP≥300 ng/ml could be taken as the critical value with high specificity and accuracy. Conclusion: Determinations of the three tumor markers levels in serum and ascitic fluid were of high value for differential diagnosis of the etiology of ascites

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Tulika Mishra

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Nielsen, Dorte; Maare, Christian; Eriksen, Jens; Litman, Thomas; Skovsgaard, Torben

    2001-01-01

    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), 3 H-vincristine (VCR), and 3 H-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 3 H-VCR and 3 H-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

  12. Ca2+ Transport by Mitochondria from L1210 Mouse Ascites Tumor Cells

    Science.gov (United States)

    Reynafarje, Baltazar; Lehninger, Albert L.

    1973-01-01

    Mitochondria isolated from the ascites form of L1210 mouse leukemia cells readily accumulate Ca2+ from the suspending medium and eject H+ during oxidation of succinate in the presence of phosphate and Mg2+, with normal stoichiometry between Ca2+ uptake and electron transport. Ca2+ loads up to 1600 ng-atoms per mg of protein are attained. As is the case in mitochondria from normal tissues, Ca2+ uptake takes precedence over oxidative phosphorylation. However, Ca2+ transport by the L-1210 mitochondria is unusual in other respects, which may possibly have general significance in tumor cells. The apparent affinity of the L1210 mitochondria for Ca2+ in stimulation of oxygen uptake is about 3-fold greater than in normal liver mitochondria; moreover, the maximal rate of Ca2+ transport is also considerably higher. Furthermore, when Ca2+ pulses are added to L1210 mitochondria in the absence of phosphate or other permeant anions, much larger amounts of Ca2+ are bound and H+ ejected per atom of oxygen consumed than in the presence of phosphate; up to 7 Ca2+ ions are bound per pair of electrons passing each energy-conserving site of the electron-transport chain. Such “superstoichiometry” of Ca2+ uptake can be accounted for by two distinct types of respiration-dependent interaction of Ca2+ with the L1210 mitochondria. One is the stimulation of oxygen consumption, which is achieved by relatively low concentrations of Ca2+ (Km ≅ 8 μM) and is accompanied by binding of Ca2+ up to 40 ng-atoms per mg of protein. The second process, also dependent on electron transport, is the binding of further Ca2+ from the medium in exchange with previously stored membrane-bound protons, in which the affinity for Ca2+ is much lower (Km ≅ 120 μM). PMID:4515933

  13. N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

    Science.gov (United States)

    Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

    2016-07-01

    N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

  14. Effect of 5-fluorouracil on the cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo

    International Nuclear Information System (INIS)

    Lewin, F.; Skog, S.; Tribukait, B.; Ringborg, U.; Karolinska Sjukhuset, Stockholm

    1987-01-01

    The effect of 12, 24 and 36 mg/kg body weight doses of fluoro-uracil (5-FU) on the Bp 8 ascites sarcoma growing in vivo was studied. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the cell cycle flow was calculated and correlated to the pharmacokinetics, which was determined by using 3 He-5-FU. The dose of 12 mg/kg 5-FU affected cell growth between 24 and 72 hours, while the effect of higher doses was immediate. An early block in outflow of cells from G 1 was followed by an increased outflow, indicating an early inhibition followed by an enhancement of the initiation of the DNA synthesis. This increased outflow from G 1 together with the decrease in outflow from the early S-phase, i.e. decreased DNA synthesis, resulted in an accumulation of cells in the early part of the S-phase. The prolonged effects on the cell growth and the cell cycle flow despite the very fast decline in the drug concentration both in the ascites fluid and within the cells, together with a constant level of the drug in the macromolecular fraction, suggest an interaction between 5-FU and RNA/DNA at later times rather than an inhibition of the thymidylate synthetase activity. (orig.)

  15. Inhibition of adenocarcinoma TA3 ascites tumor growth by rifamycin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, A M; Tenforde, T S; Calvin, M; Bissell, M J; Tischler, A N; Bennett, E L

    1978-01-01

    A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF/sub 1//J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)/sup 1/, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-8/sub 2/ (R-8/sub 2/). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and and R-8/sub 2/. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

  16. 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.

  17. 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)

    Shu, Guangwen; Yang, Tianming; Wang, Chaoyuan; Su, Hanwen; Xiang, Meixian

    2013-01-01

    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

  18. 103Ru for tumor scanning, 2

    International Nuclear Information System (INIS)

    Mizukawa, Kiichiro

    1979-01-01

    The mechanism of 103 Ru-uptake in tumors was investigated through the incubation of rat ascites hepatoma cells (AH-130) in vitro with various concentrations of Ru-chloride containing 103 Ru-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 103 Ru is related to specific binding to glycopeptides on the tumor cell surface. (author)

  19. Palliative treatment of malignant ascites: profile of catumaxomab

    Directory of Open Access Journals (Sweden)

    Lila Ammouri

    2010-05-01

    Full Text Available Lila Ammouri, Eric E PrommerMayo Clinic Hospice and Palliative Medicine Program, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Malignant ascites is the abnormal accumulation of fluid in the peritoneal cavity associated with several intrapelvic and intra-abdominal malignancies. The development of ascites leads to significant symptoms and poor quality of life for the cancer patient. Available therapies for palliation include treatment of the underlying disease, but when there are no treatment options, the use of diuretics, implantation of drainage catheters, and surgical shunting techniques are considered. None of these symptom palliation options affect the course of disease. The development of trifunctional antibodies, which attach to specific overexpressed surface markers on tumor cells, and trigger an immune response leading to cytoreductive effects, represents a new approach to the management of malignant ascites. The purpose of this review is to highlight current therapies for malignant ascites and review data as to the effectiveness of a new trifunctional antibody, catumaxomab.Keywords: catumaxomab, ascites, trifunctional

  20. Polysaccharides Extracted from Rhizoma Pleionis Have Antitumor Properties In Vitro and in an H22 Mouse Hepatoma Ascites Model In Vivo

    Directory of Open Access Journals (Sweden)

    Yukun Fang

    2018-05-01

    Full Text Available Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383.57 kDa, were mannose and glucose. We also found that PRP reduced the occurrence of abdominal ascites and increased survival in our mouse model. An immune response in the ascites tumor model was observed by performing a lymphocytes proliferation experiment and an E-rosette test. The ratios of CD8+ cytotoxic T cells and NK cells in the spleen were examined by flow cytometry, and the mRNA expression of Foxp3+in CD4+CD25+ (T regulatory Tregs was measured by RT-PCR (reverse transcription-polymerase chain reaction. The levels of the cytokines TNF-α (tumor necrosis factor, VEGF (vascular endothelial growth factor, IL-2 (interleukin, and IFN-γ (interferon in the serum and ascites supernatants were measured by ELISA. The expression of Foxp3 and Stat3 in peritoneal cells in the mouse model was measured by immunocytochemistry. The results indicated that PRP increased H22 tumor cell apoptosis in vivo by activating and enhancing the immune response. Furthermore, the effects of PRP on the proliferation of H22 cells were assessed by the CCK8 assay, Hoechest 33258, and TUNEL staining in vitro. We found that PRP suppressed the proliferation of H22 tumor cells but had no effect on BRL (Big rat liver -3A rat hepatoma normal cells in vitro. Next, we investigated the underlying immunological mechanism by which PRP inhibits malignant ascites. PRP induced tumor cell apoptosis by inhibiting the Jak1–Stat3

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

    International Nuclear Information System (INIS)

    Mesalam, N.M.A.

    2013-01-01

    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 10 6 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

  2. Granulosa cell tumor of ovary: US findings

    International Nuclear Information System (INIS)

    Jin, Yong Hyun; Jeon, Hae Jeong; Lee, Chang Dea; Cho, Young Kwon; Kang, Chang Ho; Park, Yong Hyun; Kim, Myung Gyu; Lee, Yeon Hee; Kim, Young Hwa; Lee, Hye Kyung

    1999-01-01

    To describe ultrasonographic findings of ovarian granulosa cell tumor (GCT) and to determine their possible value in the differential diagnosis of ovarian tumors. Sonographic appearances of ten cases of pathologically proven GC Ts were retrospectively reviewed regarding their location, size, outer margin, the echo pattern of the tumor, endometrial thickness, presence of ascites, and metastasis to adjacent tissue or distant sites. 3.0-3.5 MHz trans-abdominal US or 5.0-6.5 MHz transvaginal US were used. The sonographic features could be classified as follows: unilocular cystic mass without nodule or septation (type 1), multilocular cystic mass (type 2), and solid mass (type 3). Pathologically nine cases were adult type granulosa cell tumors (GCT) and one was a juvenile type. All cases were unilateral. GCT arising from left ovary were seven, right, three. The largest diameter of the tumors ranged from 6.8 to 24 cm (mean: 11.9 cm). All had well-defined margins. Ascites was seen in four cases. Among ten cases of GCT, six were mainly solid (type 3). One case manifested as a unilocular cystic mass without mural nodule or septation. Three were multilocular cystic masses and no mural nodule was found in all three cases. Metastases to peritoneum and lymph nodes was seen in one case. The ultrasonographic findings of GCT are various but combined with clinical and laboratory findings they could be helpful in the differential diagnosis of ovarian tumors.

  3. Granulosa cell tumor of ovary: US findings

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Yong Hyun; Jeon, Hae Jeong; Lee, Chang Dea; Cho, Young Kwon [Kun Kuk University School of Medicine, Seoul (Korea, Republic of); Kang, Chang Ho; Park, Yong Hyun [Korea University School of Medicine, Seoul (Korea, Republic of); Kim, Myung Gyu [Korea University School of Medicine, Seoul (Korea, Republic of); Lee, Yeon Hee [Kang Nam Cha General Hospital, Seoul (Korea, Republic of); Kim, Young Hwa; Lee, Hye Kyung [Dan Kuk University School of Medicine (Korea, Republic of)

    1999-06-15

    To describe ultrasonographic findings of ovarian granulosa cell tumor (GCT) and to determine their possible value in the differential diagnosis of ovarian tumors. Sonographic appearances of ten cases of pathologically proven GC Ts were retrospectively reviewed regarding their location, size, outer margin, the echo pattern of the tumor, endometrial thickness, presence of ascites, and metastasis to adjacent tissue or distant sites. 3.0-3.5 MHz trans-abdominal US or 5.0-6.5 MHz transvaginal US were used. The sonographic features could be classified as follows: unilocular cystic mass without nodule or septation (type 1), multilocular cystic mass (type 2), and solid mass (type 3). Pathologically nine cases were adult type granulosa cell tumors (GCT) and one was a juvenile type. All cases were unilateral. GCT arising from left ovary were seven, right, three. The largest diameter of the tumors ranged from 6.8 to 24 cm (mean: 11.9 cm). All had well-defined margins. Ascites was seen in four cases. Among ten cases of GCT, six were mainly solid (type 3). One case manifested as a unilocular cystic mass without mural nodule or septation. Three were multilocular cystic masses and no mural nodule was found in all three cases. Metastases to peritoneum and lymph nodes was seen in one case. The ultrasonographic findings of GCT are various but combined with clinical and laboratory findings they could be helpful in the differential diagnosis of ovarian tumors.

  4. RNA and protein synthesis of irradiated Ehrlich ascites tumour cells. Pt. 2

    International Nuclear Information System (INIS)

    Skog, S.; Tribukait, B.; Nygard, O.; Wenner-Gren-Center foer Vetenskaplig Forskning, Stockholm

    1985-01-01

    Poly(A)-containing RNA (m-RNA) was studied in in vivo growing Ehrlich ascites tumour cells following a roentgen irradiation dose of 5 Gy. m-RNA increased significantly during the first 12 hours after irradiation. Thus, the observed decrease in protein synthesis rate during this time seems not to be due to radiation induced changes at the transcriptional level. The protein synthesis rate of in vivo irradiated cells incubated in vitro in culture medium was unchanged. On the other hand, the protein synthesis rate of non-irradiated cells incubated in vitro in ascites fluid from irradiated animals was decreased. We concluded that factor(s) inhibiting protein synthesis or the lack of factor(s) promoting protein synthesis in the ascites fluid is(are) of significance for the reduced protein synthesis of tumour cells found in irradiated in vivo growing cells. (orig.)

  5. 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.

  6. CHANGES IN THE ELECTRICAL SURFACE CHARGE AND TRANSPLANTATION PROPERTIES OF TA3 ASCITES TUMOR CELLS DURING SHORT-TERM MAINTENANCE IN AN ISOTONIC SALT SOLUTION

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T. S.; Richards, W. R.; Kelly, L. S.

    1980-12-01

    TA3 ascites tumor cells maintained in vitro as a dilute suspension in 0.9% NaCl solution (physiological saline) were found to undergo time-dependent degenerative processes leading to alterations in both membrane characteristics and tumor transplantation properties. A 30% decrease in the negative cellular surface charge density occurred within 2 hr. when TA3 cells were incubated in a 0.9% NaCl solution at 23 °C. A similar reduction in negative surface charge density occurred within 0.5 hr. when the medium was maintained at 37 °C. This time-dependent reduction in surface charge was prevented when cellular metabolism was blocked either by maintaining the medium at 4 °C. or by adding 1 mM cyanide ion to a 23 °C medium. TA3 cells incubated as a dilute suspension in 0.9% NaCl solution at 23 °C also exhibited a large 9 time-dependent reduction in proliferative capacity in isogeneic LAF1/J hosts, as indicated by an increase in the tumor dose for 50% mortality (TD50). Lowering the temperature of the medium to 4 °C was observed to slow the onset of the degenerative processes that lead to a decreased transplantability of TA3 cells. The modification in growth properties of TA3 cells maintained in vitro was found to be attributable in part to an alteration in tumor histocompatibility. This effect was demonstrated by comparing the tumor growth kinetics and TD50 values in normal hosts versus hosts that had been immunosuppressed by whole-body irradiation. Following the in vitro maintenance of TA3 cells, nigrosin dye exclusion tests were performed as a means of assessing cell viability. Evidence obtained in this series of experiments indicated that vital staining is an inadequate criterion for judging either the extent of cell membrane damage or the loss of cellular proliferative capacity.

  7. Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

    Science.gov (United States)

    Seppänen, P; Alhonen-Hongisto, L; Jänne, J

    1981-05-05

    1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

  8. Multicystic mesothelioma--a rare case of ascites: case report.

    Science.gov (United States)

    Manuc, M; Lamatic, C; Pop, C; Dobrea, C; Becheanu, G; Grasu, M; Iosif, D; Diculescu, M

    2007-01-01

    We present the case of a 37-year-old male, admitted to our clinic with abdominal tenderness, right supraclavicular tumour, and ascites. The presence of ascites was incidentally reported 6 years before, but no other evaluation was done at that moment or during this period. Abdominal ultrasound and CT scan revealed moderate ascites, perivascular adenopathies, and multiple abdominal cystic lesions, while thoracic CT scan revealed the same lesions in mediastinum. Laboratory data were within normal limits, including the tumoral markers, and the tests for hydatid cysts. A biopsy from the right supraclavicular nodule was performed, and based on usual and immunohistochemical stains (calretinin, mesotheline, CK 5/6, CK 7, CK18 diffusely positive in mesothelial cells, and CEA -M, bcl-2 and vimentin negative), suggested the diagnosis of mesothelioma. Based on these results, the diagnosis of "multicystic mesothelioma" was made. The patient was referred for surgery.

  9. Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line.

    Science.gov (United States)

    Dolgova, Evgeniya V; Potter, Ekaterina A; Proskurina, Anastasiya S; Minkevich, Alexandra M; Chernych, Elena R; Ostanin, Alexandr A; Efremov, Yaroslav R; Bayborodin, Sergey I; Nikolin, Valeriy P; Popova, Nelly A; Kolchanov, Nikolay A; Bogachev, Sergey S

    2016-05-25

    Previously, we demonstrated that poorly differentiated cells of various origins, including tumor-initiating stem cells present in the ascites form of mouse cancer cell line Krebs-2, are capable of naturally internalizing both linear double-stranded DNA and circular plasmid DNA. The method of co-incubating Krebs-2 cells with extracellular plasmid DNA (pUC19) or TAMRA-5'-dUTP-labeled polymerase chain reaction (PCR) product was used. It was found that internalized plasmid DNA isolated from Krebs-2 can be transformed into competent Escherichia coli cells. Thus, the internalization processes taking place in the Krebs-2 cell subpopulation have been analyzed and compared, as assayed by E. coli colony formation assay (plasmid DNA) and cytofluorescence (TAMRA-DNA). We showed that extracellular DNA both in the form of plasmid DNA and a PCR product is internalized by the same subpopulation of Krebs-2 cells. We found that the saturation threshold for Krebs-2 ascites cells is 0.5 μg DNA/10(6) cells. Supercoiled plasmid DNA, human high-molecular weight DNA, and 500 bp PCR fragments are internalized into the Krebs-2 tumor-initiating stem cells via distinct, non-competing internalization pathways. Under our experimental conditions, each cell may harbor 340-2600 copies of intact plasmid material, or up to 3.097 ± 0.044×10(6) plasmid copies (intact or not), as detected by quantitative PCR. The internalization dynamics of extracellular DNA, copy number of the plasmids taken up by the cells, and competition between different types of double-stranded DNA upon internalization into tumor-initiating stem cells of mouse ascites Krebs-2 have been comprehensively analyzed. Investigation of the extracellular DNA internalization into tumor-initiating stem cells is an important part of understanding their properties and possible destruction mechanisms. For example, a TAMRA-labeled DNA probe may serve as an instrument to develop a target for the therapy of cancer, aiming at elimination of

  10. The relationship between DNA synthesis and incorporation of (14C) lysine into different histone fractions in Ehrlich ascites tumour cells

    International Nuclear Information System (INIS)

    Malec, J.; Kornacka, L.; Wojnarowska, M.; Moscicka, M.

    1974-01-01

    The effect of inhibition of DNA synthesis by hydroxyurea on ( 14 C) lysine incorporation into the main four histone fractions in Ehrlich ascites tumor cells, was examined in vitro. The radioactivity of lysine-rich histones, especially of histone f1, was preferentially decreased. The smallest decrease was observed for histone f3. The incorporation into other cellular proteins was but slightly affected. (author)

  11. Influence of serum extraction from the culture medium and of sublethal X-ray irradiation upon microvilli and invaginations of the membrane of Ehrlich ascites tumor cells in monolayer culture

    International Nuclear Information System (INIS)

    Laudenbach, G.; Pfab, R.; Hess, F.; Schachtschabel, D.O.

    1984-01-01

    In order to find out modifications of microvilli and invaginations, the cellular surfaces of Ehrlich ascites tumor cells in monolayer culture (basal medium of Eagle + 10% fetal calf serum) were investigated with the aid of electron-microscopic cross-sections. The tumor cells had been cultured without serum 24 hours prior to investigation or irradiated with 2 Gy. Morphometric evaluation after cell culture in a serum-free medium showed a reduced number of microvilli and a diminution of sections of microvilli. As already described before, a reduction of cell proliferation, of the microtubule-microfilament system, and of the endocytosis activity occurs under these serum-free conditions. The number of invaginations (related to a constant membrane part) was reduced by nearly 50% after serum extraction. Similarly to serum extraction, sublethal X-ray irradiation reduced the sections of microvilli, whereas the number of microvilli increased slightly. Contrary to the effect of serum extraction, the irradiated cells showed twice as many invaginations as the non-irradiated control cells. These differences in the surface structures are interpreted as a result of modified growth stimulations (+- serum) and radiogenic reparation processes. (orig.) [de

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

    Science.gov (United States)

    Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick; Ørtoft, Gitte; Vestergaard, Poul; Magnusson, Nils E.; Conover, Cheryl A.; Tramm, Trine; Hager, Henrik; Høgdall, Claus; Høgdall, Estrid; Oxvig, Claus; Frystyk, Jan

    2015-01-01

    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 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 IGF-I receptor (IGF-IR) in vitro (+31%, P IGF-I, and lower levels of IGF-II (P IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P IGFs and these proteins are also present in ascites. We suggest that both soluble PAPP-A in ascites and tissue-associated PAPP-A serve to increase IGF bioactivity and, thereby, to stimulate IGF-IR-mediated tumor growth. PMID:26336825

  13. Altered thymidylate synthetase in 5-fluorodeoxyuridine-resistant Ehrlich ascites carcinoma cells.

    Science.gov (United States)

    Jastreboff, M M; Kedzierska, B; Rode, W

    1983-07-15

    Thymidylate synthetase from 5-fluorodeoxyuridine-resistant Ehrlich ascites carcinoma cells was purified to a state close to electrophoretical homogeneity (sp. act. = 1.3 mumoles/min/mg protein) and studied in parallel with the homogeneous preparation of the enzyme from the parental Ehrlich ascites carcinoma cells. The enzyme from the resistant cells compared to that from the parental cells showed: (i) a higher turnover number (at least 91 against 31 min-1), (ii) a higher inhibition constant (19 against 1.9 nM) for FdUMP (a tight-binding inhibitor of both enzymes), (iii) a lower activation energy at temps above 36 degrees (1.37 against 2.59 kcal/mole), and (iv) a lower inhibition constant (26 against 108 microM) for dTMP, inhibiting both enzymes competitively vs dUMP.

  14. Effects of β-arabinofuranosyladenine on the growth and repair of potentially lethal damage in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Iliakis, G.

    1980-01-01

    β-D-Arabinofuranosyladenine (β-araA) inhibit the growth of Ehrlich ascites tumor cells by selective inhibition of DNA polymerases. RNA and protein synthesis are not significantly affected. Addition of β-araA to the cells after irradiation resulted in a concentration-dependent decrease in survival, presumably due to the inhibition of the repair of potentially lethal damage. Since β-araA selectively inhibits DNA polymerases it is suggested that repair of potentially lethal damage involves steps at the DNA level which require some polymerization. These repair steps take place in the DNA with a velocity comparable to that of the repair of potentially lethal damage. The inhibition of the repair of potentially lethal damage by β-araA was modified by the addition of deoxyadenosine; this supports the finding that β-araA acts competitively against dATP at the molecular level. The inhibition of the repair of potentially lethal damage by β-araA, which is partly reversible, resulted in a concentration-dependent modification of the survival curve. At low concentrations of β-araA a dose-modifying decrease in survival was observed. At higher concentrations (more than 12 μM) the decrease in survival resulted in a decrease of the shoulder width of the survival curve. Eventually an exponential curve was obtained. We suggest therefore that the shoulder of the survival curve results from some repair or potentially lethal damage. Preliminary information has been obtained on the time course of this repair

  15. Cross-immunity between syngeneic tumors in mice immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Kudo, Hajime; Waga, Takashi; Sato, Tatsusuke; Ogasawara, Masamichi; Ito, Izumi

    1980-01-01

    C3H/He mice immunized repeatedly with irradiated (13,000 rads 60 Co) MM46 or MM48, both transplantable ascites mammary carcinomas of the same strain, were subcutaneously challenged with the identical or the different tumor. In mice immunized with irradiated MM46, the growth of challenges of not only MM46 but also MM48 was inhibited. On the other hand, in mice immunized with irradiated MM48, the growth of challenges of MM48 was inhibited, but the inhibition of the growth of MM46 was not observed. Cross-immunity, therefore, was shown by immunization with MM46 but not with MM48. These findings were considered to indicate that MM46 expressed cross-immunity against MM48 because of its high resistance to the irradiation, and that MM48 did not show cross-immunity to MM46 because of its low resistance to the irradiation. (author)

  16. Cell cycle analyses with a pulse cytophotometer: the effect of chemical and physical noxae on the kinetics of the proliferation of tumor cells

    International Nuclear Information System (INIS)

    Goehde, W.

    The following studies were conducted on Ehrlich ascites tumor cells using the pulse cytophotometer: rate of DNA synthesis during the S phase; the effect of cytostatic drugs, endoxan, bleomycin, and other antibiotics on cell kinetics; and effects of x radiation and 1 to 6 MeV neutrons on cell kinetics

  17. Membrane fatty acid composition and radiation response of Bp8 sarcoma ascites tumour cells

    International Nuclear Information System (INIS)

    Harms-Ringdahl, M.

    1987-01-01

    Radiation responses of Bp8 sarcoma ascites tumour cells with differences in membrane fatty acid composition was studied. The cells were grown i.p. in NMRI mice and their membrane composition was changed in response to different dietary regimes provided to the hosts. Cell survival, varied insignificantly between the four dietary groups, while repair capacity differed significantly. Increased repair capacity was observed for ascites cells grown in animals on diets enriched in sunflower seed oil and coconut oil, compared with cells from mice fed the hydrogenated lard diet or from cells from the control animals. The membrane fatty acid composition of the cells from the two dietary groups with increased levels of repair capacity differed extensively, and in general there was no correlation between radiation response and the membrane fatty acid composition of the four groups. For coconut oil and control groups with marked differences in membrane fatty acid composition, the effects of irradiation on ascites tumour growth rate and cell cycle distribution were followed in vivo. For none of the parameters was an effect on membrane fatty acid composition on radiation response observed. (author)

  18. 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.

  19. 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.

  20. Evaluation of ascitic soluble human leukocyte antigen-G for distinguishing malignant ascites from benign ascites.

    Science.gov (United States)

    Sun, Juan; Chang, Yan-Xiang; Niu, Chun-Yan

    2017-11-01

    The overexpression of soluble human leukocyte antigen-G is associated with malignant tumours. The purpose of our study was to detect soluble human leukocyte antigen-G concentrations in ascites and to evaluate the value of ascitic soluble human leukocyte antigen-G for the diagnosis of malignant ascites. Enzyme-linked immunosorbent assay was used to detect soluble human leukocyte antigen-G levels in 64 patients with malignant ascites and 30 patients with benign ascites. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of ascitic soluble human leukocyte antigen-G for the detection of malignant ascites. Ascitic soluble human leukocyte antigen-G levels were significantly higher in the malignant ascites group than in the benign ascites group (20.718 ± 3.215 versus 12.467 ± 3.678 µg/L, t = 7.425, p human leukocyte antigen-G was 0.957 (95% confidence interval, 0.872-0.992). At a cut-off value of 19.60 µg/L, the sensitivity and specificity of ascitic soluble human leukocyte antigen-G were 87.5% (95% confidence interval, 71.0%-96.5%) and 100% (95% confidence interval, 88.4%-100%), respectively. With respect to area under the receiver operating characteristic curve, sensitivity and specificity, ascitic carcinoembryonic antigen (0.810, 68.75% and 83.33%, respectively) and carbohydrate antigen 19-9 (0.710, 65.63% and 70%, respectively) significantly differed (all p human leukocyte antigen-G was 75%, which was higher than the corresponding rates for ascitic carcinoembryonic antigen (31.25%) and carbohydrate antigen 19-9 (6.25%; both p human leukocyte antigen-G exhibited good performance for diagnosing malignant ascites, and particularly those that were cytology-negative and biopsy-positive.

  1. Clinical value of combined detection of tumor markers in effusion fluid for diagnosis of malignant pleural effusion and ascites

    International Nuclear Information System (INIS)

    Li Jiangang; Ji Zhigu; Cui Xuejun; Zhu Zili

    2010-01-01

    Objective: To study the clinical usefulness of combined detection of tumor markers in effusion fluid in patients with malignant pleural effusion or ascites. Methods: Combined detection of six tumor markers (CA125, CA50, CA15-3, CYFRA21-1, βHCG, HCG) in effusion fluid was performed in 92 patients with malignant pleural effusion and 78 patients with malignant ascites as well as 100 control benign specimens. These tumor markers were examined with CLIA, except CA50, which was examined with RIA. Exfoliative cytology was also examined in the malignant specimens. Results: The positive rate of these markers was highest with CA125, followed by CA50, CA15-3, CYFRA21-1, βHCG and HCG in order. βHCG and HCG, though with quite low positive rate, were still useful markers due to the almost zero false-positive rate, i.e. very high specificity. For combined determination of two markers, CA15 + CYFRA21-1 or CA125 + CA50 would result in the highest positive rate. For highly suspected but undetermined cases, the following criteria for malignancy would be helpful: (1) two or more positive among CA125, CA50, CA15-3, CYFRA21-1 (2) One of the four CAs positive + either βHCG or HCG (3) Both βHCG and HCG positive. Tumor markers positiveness would be supplementary to doubtful cytological studies. Conclusion: Combined detection of tumor markers in effusion fluid would be very helpful for diagnosis of malignancy. (authors)

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

    International Nuclear Information System (INIS)

    Tomioka, Yukiko; Morimatsu, Masami; Nishijima, Ken-ichi; Usui, Tatsufumi; Yamamoto, Sayo; Suyama, Haruka; Ozaki, Kinuyo; Ito, Toshihiro

    2014-01-01

    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

  3. 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.

  4. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  5. Synchronization of tumor cells with 5-fluorouracil plus uracil and with vinblastine and irradiation of synchronized cultures

    International Nuclear Information System (INIS)

    Severin, E.; Hagenhoff, B.

    1988-01-01

    In this article, some arguments are put forward which support the conception of a combined radio-chemotherapy acting by a reversible inhibition of tumor cells with cytostatic drugs in a not cytocidal dose and the following selective killing by irradiation of the cells blocked in a radiosensitive phase. The two cytostatic drugs 5-fluorouracil (FU) and vinblastine (VLB), as inhibitors of DNA synthesis and mitosis, respectively, are tested in vitro both separately and combined in two tumor cell lines of the mouse, i.e. the Ehrlich ascites tumor and the sarcoma S 180. A cell-proliferative and, as far as possible, not cytocidal dose is used because of the inevitable side effects exerted by these drugs on normal tissues. A reversible synchronization of the ascites tumor is achieved even in the young mouse by FU in a dose of 15 ng to 500 ng (applied seven times every two hours), if the synchronization is controlled by applying the antimetabolite together with uracil in an equimolar concentration and then stimulating the growth of the cells inhibited during DNA synthesis by the administration of thymidine. The statistical analysis of dose-effect curves after X-ray irradiation shows an increased radiosensitivity of the synchronized cell population, provided that the optimum moment had been chosen for the irradiation. (orig.) [de

  6. Expression and significance of cyclooxygenase-2 mRNA in benign and malignant ascites

    Science.gov (United States)

    Lu, Jing; Li, Xiao-Feng; Kong, Li-Xia; Ma, Lin; Liao, Su-Huan; Jiang, Chang-You

    2013-01-01

    AIM: To investigate the mRNA expression of cyclooxygensae-2 (COX-2) in benign and malignant ascites, and to explore the difference in COX-2 mRNA expression among different diseases. METHODS: A total of 36 samples were collected from the Fifth Affiliated Hospital of Sun Yat-Sen University and divided into two experimental groups: benign ascites (n = 21) and malignant ascites (n = 15). Benign ascites included cirrhotic ascites (n = 10) and tuberculous ascites (n = 5). Malignant ascites included oophoroma (n = 7), cancer of colon (n = 5), cancer of the liver (n = 6), gastric cancer (n = 2), and bladder carcinoma (n = 1). The mRNA expression of COX-2 in ascites was examined with reverse transcriptase polymerase chain reaction (RT-PCR) technology, and the positive rate of COX-2 mRNA was compared between different diseases. RESULTS: The positive rate of COX-2 mRNA in malignant ascites was 42.9% (9/21), which was significantly higher than in benign ascites, 6.7% (1/15), difference being significant between these two groups (χ2 = 4.051, P = 0.044). The proportion of the positive rate in the malignant ascites was as follows: ovarian cancers 57.1% (4/7), colon cancer 40.0% (2/5), liver cancer 33.3% (2/6), gastric cancer 50.0% (1/2), and bladder cancer 0.00% (0/1). However, there was no significant difference in COX-2 mRNA expression among various tumors with malignant ascites (χ2 = 1.614, P = 0.806). Among the benign ascites, COX-2 mRNA levels were different between the tuberculous ascites (0/5) and cirrhotic ascites (1/10), but there was no significant difference (P = 1.000). CONCLUSION: COX-2 mRNA, detected by RT-PCR, is useful in the differential diagnosis of benign and malignant ascites, which also has potential value in the clinical diagnosis of tumors. PMID:24187465

  7. Ehrlich ascites carcinoma | Ozaslan | African Journal of Biotechnology

    African Journals Online (AJOL)

    Experimental tumors have great importance in modeling, and Ehrlich ascites carcinoma (EAC) is one of the commonest tumors. EAC is referred to as an undifferentiated carcinoma and is originally hyperdiploid, has high transplantable capability, no-regression, rapid proliferation, shorter life span, 100% malignancy and also ...

  8. Technical Performance and Clinical Effectiveness of Drop Type With Adjustable Concentrator-Cell Free and Concentrated Ascites Reinfusion Therapy.

    Science.gov (United States)

    Yamada, Yosuke; Harada, Makoto; Yamaguchi, Akinori; Kobayashi, Yasuko; Chino, Takashi; Minowa, Takashi; Kosuge, Takashi; Tsukada, Wataru; Hashimoto, Koji; Kamijo, Yuji

    2017-12-01

    Cell-free and concentrated ascites reinfusion therapy (CART) is a very useful treatment method for refractory ascites but is difficult for many hospitals to employ due to its need for specialized equipment. We have therefore developed drop-type with adjustable concentrator CART (DC-CART) that uses a drop-type filtration mechanism and requires only a simple pump and pressure monitor for its concentration process. Easy adjustment of ascites concentration is possible through a recirculation loop, and filter membrane washing is aided by DC-CART's external pressure-type filtration to enable the processing of any quality or quantity of ascites. Moreover, the absence of a roller pump before filtration avoids inflammatory substance release from compressed cells. A total of 268 sessions of DC-CART using ascites from 98 patients were performed with good clinical results at our hospitals between January 2012 and June 2016. This report presents the detailed methods of DC-CART and summarizes its clinical effectiveness using patient ascites and blood data obtained from 59 sessions between March 2015 and February 2016. This novel technique successfully processed refractory ascites in numerous diseases with no serious adverse events. DC-CART could concentrate large amounts of ascites (from median weight: 4900 g [max: 20 200 g] to median weight: 695 g; median concentration ratio: 7.4), and a high amount of protein (median weight: 73 g [max: 294 g]) could be reinfused. Serum albumin levels were significantly increased (P = 0.010) and kidney function and systemic hemodynamics were well maintained in treated subjects. Additional concentration of ascites and adjustment of ascites volume were easily performed by recirculation (from median weight: 615 g to median weight: 360 g; median concentration ratio: 1.5). Time was needed during DC-CART for filter membrane cleaning, especially for viscous ascites. Overall, DC-CART represents a safe and useful treatment method for various forms

  9. Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.

    Science.gov (United States)

    Justo, G Z; Durán, N; Queiroz, M L S

    2003-08-01

    The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

  10. Lysophosphatidylcholine-induced taurine release in HeLa cells involves protein kinase activity

    DEFF Research Database (Denmark)

    Lambert, Ian H.; Falktoft, Birgitte

    2001-01-01

    Calmodulin; CaMKII; Ehrlich ascites tumor cells; Ischemia; Lysophospholipids; NIH/3T3; Chelerythrine; Reactive oxygen species......Calmodulin; CaMKII; Ehrlich ascites tumor cells; Ischemia; Lysophospholipids; NIH/3T3; Chelerythrine; Reactive oxygen species...

  11. 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

    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...... effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G(1). Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl(-) may regulate proliferation by fine...

  12. Anti-tumour action of 64Cu-bleomycin on Ehrlich ascites tumour cells in vivo

    International Nuclear Information System (INIS)

    Maki, Hirotoshi; Kawai, Kenichi; Akaboshi, Mitsuhiko

    1979-01-01

    The anti-tumor action of the complex of Bleomycin (BLM) with high specific-radioactivity 64 Cu on Ehrlich ascites tumour (EAT) was studied in vivo. The 64 Cu-BLM was administered into intraperitoneal cavity of mice from 1 to 4 days after inoculation of EAT cells. The effect of 64 Cu-BLM to suppress the tumour growth as demonstrated by prolonging life span was observed. The amounts of 64 Cu-BLM (800 μCi-8 mg/Kg) were administered at 4, 8 and 16 times separately. Then, the shorter the time interval and the less the amounts of drugs at a time, the higher the suppressing effect for the tumour growth was. It was confirmed that anti-tumour action of 64 Cu-BLM was in all the cases higher than that of BLM alone. (author)

  13. ACTIVITY OF NATURAL KILLER CELLS IN BIOLOGICAL FLUIDS FROM PATIENTS WITH COLORECTAL AND OVARIAN CANCERS

    Directory of Open Access Journals (Sweden)

    N. V. Yunusova

    2017-01-01

    Full Text Available Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009, 5 patients with benign ovarian tumors (BOTs, and 15 patients with colorectal cancer (T2–4N0–2M0 . The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB (CD56 + CD107a + GB + PF- was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF- was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p<0.05. The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant

  14. Observations on the mechanism and location of ascites reabsorption in man

    International Nuclear Information System (INIS)

    Rector, W.G. Jr.; Ibarra, F.

    1987-01-01

    Animal data indicate that ascites is reabsorbed by a lymphatic mechanism and that these vessels are subdiaphragmatic in location. We evaluated the relative role of lymphatics in ascites reabsorption in man by comparing the ascites clearance and plasma appearance rates of intraperitoneally injected radiolabeled albumin to those of intraperitoneally injected labeled autologous red blood cells, which require, owing to their large size, lymphatic removal, in patients with cirrhosis and ascites. To evaluate the location of reabsorption, we repeated these measurements after replacing ascites in the subdiaphragmatic region with 500-1000 ml of intraperitoneally injected air, reasoning that this maneuver should slow or eliminate ascites reabsorption occurring at this site. We found that the transfer rates of albumin and red cells out of ascites were similar and that creation of pneumoperitoneum did not influence these rates. These data confirm that ascites protein reabsorption occurs via a lymphatic mechanism in man. They suggest, however, that these vessels may not be subdiaphragmatic in location

  15. 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).

  16. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

    Directory of Open Access Journals (Sweden)

    Abu-lail Rasha

    2010-07-01

    Full Text Available Abstract Introduction Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences. Case presentation A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events. Conclusion On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.

  17. Increase of antitumor activity of cisplatin using agonist of gonadotropin-realising hormone and inhibitor of aromatase on the model of ascites ovarian tumor.

    Science.gov (United States)

    Tkalia, I G; Vorobyova, L I; Grabovoy, A N; Svintsitsky, V S; Tarasova, T O; Lukyanova, N Y; Todor, I N; Chekhun, V F

    2014-09-01

    To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in monotherapy and in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant ascites transplantable ovarian tumor (TOT), to assess therapeutic pathomorphosis and level of VEGF expression in tumor cells using diffe-rent combinations of cytostatics and hormonal drugs. 72 female Wistar rats, which underwent intraperitoneal transplantation of ascitic TOT, by 5·10(6) cells per animal, have been involved in the study. Rats were divided into 8 groups, 9 rats in each group. Histological study with assessment of therapeutic pathomorphosis in TOT and immunohistochemical study has been carried out. Survival of animals in the studied groups has been evaluated. Among animals treated in regimen of monotherapy, the most pronounced antiangiogenic activity in TOT has been observed on application of hormonal drugs (triptorelin - 39.4 ± 1.9 and exemestane - 33.9 ± 1.4%; р = 0.003), the highest grade of treatment pathomorphosis in TOT has been observed at treatment with cisplatin (11.7%; р = 0.001). Combination of triptorelin and exemestane has amplified antiangiogenic activity in TOT (12.2 ± 0.9%; р = 0.001), but has not significantly changed rates of pathomorphosis (22.1 ± 0.4%; р=0.005) and survival of animals (32.2%; р = 0.007) as compared with the same rates in rats treated with hormonal drugs in monotherapy. Significant correlation between VEGF expression and pathomorphosis has been established (relative part of viable tumor tissue (RPVTT)) in TOT (r = 0.712; р = 0.001), as well as between RPVTT and life-span of animals (r = -0.320; р = 0.007). However, lack of correlation between VEGF expression in cells of TOT and survival of rats has been determined (r = -0.194; р = 0.11). Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly high rates of therapeutic

  18. Desmoplastic small round cell tumor: a case report and review of the literature

    International Nuclear Information System (INIS)

    Pinto, Luiz Gustavo Teixeira; Isberner, Rony Klaus; Scolaro, Bruno Lorenzo; Sezerino, Daniel Oseias; Almeida, Daniel da Silva

    2006-01-01

    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)

  19. Differential response of human melanoma and Ehrlich ascites cells in vitro to the ribosome-inactivating protein luffin.

    Science.gov (United States)

    Poma, A; Miranda, M; Spanò, L

    1998-10-01

    The cytotoxicity and inhibitory effect on proliferation of the type 1 ribosome-inactivating protein luffin purified from the seeds of Luffa aegyptiaca were investigated both in human metastatic melanoma cells and in murine Ehrlich ascites tumour cells. Results indicate that luffin from the seeds of Luffa aegyptiaca is cytotoxic to the cell lines tested, with approximately 10 times greater potency in Ehrlich cells. Luffin was found to induce an increase in cytosolic oligonucleosome-bound DNA in both melanoma and Ehrlich ascites tumour cells, the level of DNA fragmentation in the former cell line being higher than in the latter. Experiments with melanoma cells indicate that an increase in cytosolic nucleosomes could be supportive of apoptosis as the type of cell death induced by luffin.

  20. 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

  1. 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.

  2. Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains.

    Directory of Open Access Journals (Sweden)

    Huiqiang Wang

    Full Text Available Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV. In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

  3. Cross-immunity among mammary carcinomas in C3H/HE mice immunized with gamma-irradiated tumor cells

    International Nuclear Information System (INIS)

    Waga, Takashi

    1980-01-01

    By immunization with gamma-irradiated (13,000 rad) tumor cells, cross-immunity between ascites mammary carcinomas and among solid mammary carcinomas in C3H/He mice was studied. The results were as follows: (1) Two ascites mammary carcinomas designated MM 46 (high vitality) and MM 48 (intermediate vitality) were used in this experiment. The immunization with the tumor of high vitality (MM 46) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MM 48). The immunization with the tumor of intermediate vitality (MM 48) induced weak cross-immunity against the challenge of the tumor of high vitality (MM 46). (2) Three solid mammary carcinomas designated MT 10 (intermediate vitality), MT 7 (high vitality) and MT X (the highest vitality) were used in this experiment. The immunization with the tumor of high vitality (MT 7) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MT 10), and induced moderate cross-immunity against the challenge of the tumor of the highest vitality (MT X). The immunization with the tumor of intermediate vitality (MT 10) induced moderate cross-immunity against the challenge of the tumor of high vitality (MT 7), but could not induce any cross-immunity against the challenge of the tumor of the highest vitality (MT X). (author)

  4. [Identification of occult disseminated tumor cells by recombinant herpes simplex virus expressing GFP (HSV(GFP))].

    Science.gov (United States)

    Han, Xiang-ping; Shi, Gui-lan; Wang, Cheng-feng; Li, Jie; Zhang, Jian-wei; Zhang, Yu; Zhang, Shu-ren; Liu, Bin-lei

    2012-12-01

    To develop a novel rapid protocol for the detection of occult disseminated tumor cells by a recombinant herpes simplex virus expressing GFP (HSV(GFP)). Tumor cells of seven cell lines were exposed to HSV(GFP) and then examined for GFP expression by fluorescence microscopy. Various numbers of tumor cells (10, 100, 1000, 10 000) were mixed into 2 ml human whole blood, separated with lymphocytes separation medium, exposed to HSV(GFP), incubated at 37°C for 6 - 24 h and then counted for the number of green cells under the fluorescence microscope. Some clinical samples including peripheral blood, pleural effusion, ascites, spinal fluid from tumor-bearing patients were screened using this protocol in parallel with routine cytological examination. HSV(GFP) was able to infect all 7 tumor cell lines indicating that the HSV(GFP) can be used to detect different types of tumor cells. The detection sensitivity was 10 cancer cells in 2 ml whole blood. In the clinical samples, there were 4/15 positive by routine cytological examination but 11/15 positive by HSV(GFP), indicating a higher sensitivity of this new protocol. Recombinant herpes simplex virus-mediated green fluorescence is a simple and sensitive technique for the identification of occult disseminated cancer cells including circulating tumor cells (CTCs).

  5. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  7. Radiologic findings of ovarian granulosa cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Chul [Chungnam National Univ. College of Medicine, Taejon (Korea, Republic of)

    1997-10-01

    To determine, through an analysis of radiologic findings, whether the findings of granulosa cell tumors (GCTs) of the ovary are specific. The radiologic findings (ultrasonography, computed tomography, and magnetic resonance imaging) of 16 pathologically proven ovarian GCTs in 15 patients were retrospectively analysed for the site of origin, staging, largest diameter, margin, solid and/or cystic components, degree of enhancement, and associated endometrial hyperplasia, ascites, and local and/or distant metastasis. Unilateral ovarian GCTs were found in 14 patients, and bilateral tumors in one. Of a total of 16 tumors, 13 were of the adult type, and three were juvenile; their largest diameter ranged from 1 to 26(mean, 15.6)cm. Eleven tumors were well-defined, two were cystic, and one small tumor was solid. Of 13 mixed tumors, three had hemorrhagic portions, and five had multilocular cystic portions. Metastases to the uterus, tubes, rectum, lymph nodes, or liver were found in six patients, and associated endometrial hyperplasia in two. Radiologically, ovarian GCTs showed well-defined or encapsulated soft tissue masses with some hemorrhagic, multilocular or focal cystic components, as well as associated endometrial thickening and local or distant metastasis. These and clinical findings may be useful in the diagnosis of ovarian GCTs.

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

    Science.gov (United States)

    Spencer, T L; Lehninger, A L

    1976-01-01

    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

  9. X-radiation effect on water transport in ascite cells of Ehrlich carcinoma

    International Nuclear Information System (INIS)

    Barnov, V.A.; Ajvazishvili, M.A.; Kartvelishvili, I.I.; Tushishvili, D.I.

    1988-01-01

    Effect of local X radiation with doses 0.05 and 0.15 C/kg on water transport in ascitic cells of Erlich carcinoma is studied in rats. To study water transport through cell membranes, tritium mark was used. It is concluded that radiation effect on water transport in cells of Erlich carcinoma may be related to change in ionic permittivity of the membrane, because small changes in transmembrane ion transport affect immediately the osmotic motion of water. 5 refs

  10. 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

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

    International Nuclear Information System (INIS)

    Wang, Yijun; Lu, Hongjuan; Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun; Taylor, Ethan Will; Zhang, Jinsong

    2012-01-01

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

  12. Infectious peritonitis after endoscopic ultrasound-guided biliary drainage in a patient with ascites

    Directory of Open Access Journals (Sweden)

    Nozomi Okuno

    2018-04-01

    Full Text Available Summary of Event: Bacterial, mycotic peritonitis and Candida fungemia developed in a patient with moderate ascites who had undergone endoscopic ultrasound-guided biliary drainage (EUS-BD. Antibiotics and antifungal agent were administered and ascites drainage was performed. Although the infection improved, the patient’s general condition gradually deteriorated due to aggravation of the primary cancer and he died.Teaching Point: This is the first report to describe infectious peritonitis after EUS-BD. Ascites carries the potential risk of severe complications. As such, in patients with ascites, endoscopic retrograde cholangiopancreatography (ERCP is typically preferred over EUS-BD or percutaneous drainage to prevent bile leakage. However, ERCP may not be possible in some patients with tumor invasion of the duodenum or with surgically altered anatomy. Thus, in patients with ascites who require EUS-BD, we recommend inserting the drainage tube percutaneously and draining the ascites before and after the intervention in order to prevent severe infection.

  13. 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)

  14. Management of cirrhotic ascites

    DEFF Research Database (Denmark)

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

    2015-01-01

    The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the na......The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark...... in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic...

  15. Bilateral Ovarian Fibrothecoma Associated with Ascites, Bilateral Pleural Effusion, and Marked Elevated Serum CA-125

    Directory of Open Access Journals (Sweden)

    Védi André Serges Loué

    2013-01-01

    Full Text Available Background. The risk of ovarian cancer is increased in the association of ovarian tumor, ascites, and hydrothorax with the significant elevated tumor marker CA-125. However, this association can be observed in a rare clinical and benign pathological entity, that is Demons-Meigs’ syndrome. Objective. To describe a rare case of Demons-Meigs' syndrome observed in our department. Methods. A black African woman of 35 years old, seventh gravida and fourth parous, underwent a total abdominal hysterectomy with bilateral salpingoophorectomy for large bilateral ovarian masses associated with significant ascites, bilateral pleural effusion, and particular highly elevated tumor marker CA-125 (1835 UI/mL in a pronounced general alteration condition. Results. The postoperative course was uneventful characterized by a complete remission of hydrothorax and ascites with normal level of CA-125 three months after tumor excision. Histology of both masses revealed a bilateral ovarian fibrothecoma, a benign tumor of the ovary, thus confirming the diagnosis of Demons-Meigs’ syndrome. Conclusion. The Demons-Meigs syndrome, although it strongly mimics the clinical picture of malignant metastatic ovarian cancer, remains a disease with benign prognosis after surgical tumor resection. This is a rare condition that must be known and recognized by practitioners to avoid unnecessary practices.

  16. Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients

    International Nuclear Information System (INIS)

    Gericke, Beate; Raila, Jens; Sehouli, Jalid; Haebel, Sophie; Könsgen, Dominique; Mustea, Alexander; Schweigert, Florian J

    2005-01-01

    Transthyretin (TTR), a traditional biomarker for nutritional and inflammatory status exists in different molecular variants of yet unknown importance. A truncated form of TTR has recently been described to be part of a set of biomarkers for the diagnosis of ovarian cancer. The main aim of the study was therefore to characterize differences in microheterogeneity between ascitic fluid and plasma of women affected with ovarian cancer and to evaluate the tumor site as the possible source of TTR. Subjects were 48 women with primary invasive epithelial ovarian cancer or recurrent ovarian carcinoma. The control group consisted of 20 postmenopausal women. TTR and retinol-binding protein (RBP) levels were measured by enzyme-linked immunoassay (ELISA) and C-reactive protein (CRP) levels by a high-sensitivity latex particle turbidimetric assay. The molecular heterogeneity of TTR was analysed using immunoprecipitation and matrix-associated laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Presence of TTR in tumor tissue was determined with indirect peroxidase immunostaining. TTR and RBP (μg/ml) levels in serum were 148.5 ± 96.7 and 22.5 ± 14.8 in affected women compared to 363.3 ± 105.5 and 55.8 ± 9.3 in healthy postmenopausal women (p < 0.01). In ascitic fluid, levels were 1.02 ± 0.24 and 4.63 ± 1.57 μg/ml, respectively. The mean levels of TTR and RBP in serum showed a tendency to decrease with the severity of the disease and were lower in affected women whose CRP levels were > 40 mg/ml (p = 0.08 for TTR; p < 0.05 for RBP). No differences in TTR microheterogeneity were observed between TTR isolated from serum of affected and healthy women or from ascitic fluid. TTR occurred rather consistently in four variants. Mass signals were at 13758 ± 7, 13876 ± 13 (greatest intensity), 13924 ± 21 and 14062 ± 24 Da, representing native, S-cysteinylated, S-cysteinglycinylated and glutathionylated TTR, respectively. Serum of healthy and affected women

  17. 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

    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.......03). Ascites was more potent than serum in activating the IGF-I receptor (IGF-IR) in vitro (+31%, P IGF-I, and lower levels of IGF-II (P ... of IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P IGFs and these proteins...

  18. 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 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.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.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.

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

    International Nuclear Information System (INIS)

    Topcul, M.; Topcul, F.; Oezalpan, A.

    2001-01-01

    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

  20. 17-AAG mediated targeting of Hsp90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry.

    Science.gov (United States)

    Chaklader, M; Das, P; Pereira, J A; Law, A; Chattopadhyay, S; Chatterjee, R; Mondal, A; Law, S

    2012-07-01

    Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery - heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.

  1. [Ascites drainage at home].

    Science.gov (United States)

    Lutjeboer, Jacob; van Erkel, Arian R; van der Hoeven, J J M Koos; van der Meer, Rutger W

    2015-01-01

    Ascites can lead to many symptoms, and often occurs in patients with an end-stage malignancy such as ovarian, pancreatic, colonic, or gastric cancer. Intermittent ascites drainage is applied in these patients as a palliative measure. As frequent drainage is necessary, a subcutaneously tunnelled permanent ascites catheter is a good alternative for intermittent drainage. The patient can open - and then re-close - the catheter when abdominal pressure increases. We inserted 35 subcutaneously permanent ascites catheters in the course of the past 3.5 years in the Leiden University Medical Centre. The success rate was 100% and the complication risk was 2.9%. A subcutaneously tunnelled ascites catheter is an effective and safe palliative treatment for patients with end-stage malignant disease and suffering from ascites.

  2. Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

    Directory of Open Access Journals (Sweden)

    W.M. Quinteiro-Filho

    2009-10-01

    Full Text Available Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days isogenic BALB/c mice in each experiment. Cyhalothrin i increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05, concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05, and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05; ii increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05, and iii decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05 and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05 in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

  3. Study on anti-ehrlich ascites tumor effect of Pinellia Ternata ...

    African Journals Online (AJOL)

    The study concluded that Pinellia ternata polysaccharide extract had some in vivo anti-tumour effects, which were probably associated with the enhancement of the body's ability to scavenge excess free radicals by improving the body's enzyme activity. Key words: Pinellia ternata polysaccharide, ascites tumour, SOD, MDA, ...

  4. Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques

    DEFF Research Database (Denmark)

    Issinger, O G; Beier, H

    1978-01-01

    Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according...... to a modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. "three-dimensional" gel...... using the pH 4.5/pH 8.6 SDS system. The molecular weights Krebs II ascites and HeLa ribosomal proteins are compared with those obtained by other authors for different mammalian species....

  5. Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-11-01

    We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Radiation-induced dissociation of stable DNA-protein complexes in Erlich ascites carcinoma cells

    International Nuclear Information System (INIS)

    Juhasz, P.P.; Sirota, N.P.; Gaziev, A.I.

    1982-01-01

    DNA of Ehrlich ascites carcinoma cells prepared under conditions that were highly denaturing for proteins but not for DNA, contained a group of nonhistone residual proteins. The amount of these proteins increased during DNA replication. The DNA-protein complex observed was sensitive to proteolytic enzymes and/or SH-reagents. γ-irradiation cells with moderate doses leads to a decrease in the amount of DNA-protein complexes. High-dose gamma-irradiation produces enhanced linking of chromosomal proteins with DNA. (author)

  7. Diagnostic value of adenosine deaminase in ascites for tuberculosis ascites: a meta-analysis.

    Science.gov (United States)

    Tao, Lin; Ning, Hong-Jian; Nie, Hai-Ming; Guo, Xiao-Yun; Qin, Shan-Yu; Jiang, Hai-Xing

    2014-05-01

    The diagnosis of tuberculosis (TB) ascites using standard diagnostic tools is difficult. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of adenosine deaminase (ADA) levels in ascites for diagnosing TB ascites. A systematic review was performed of English language publications prior to April 2013. Sensitivity, specificity, and other measures of the accuracy of ADA for the diagnosis of TB ascites using ascites fluid were summarized using a random-effects model or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance. Seventeen studies involving 1797 subjects were eligible for the analysis. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under cure of overall analysis were: 0.93, 0.94, 13.55, 0.11, 169.83, and 0.976, respectively; the results of sensitivity analysis of studies that used Giusti method were 0.94, 0.94, 12.99, 0.08, 183.18, and 0.977, respectively. Our results suggest that ADA in the ascites can be a sensitive and specific target and a critical criterion for the diagnosis of TB ascites. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

    Science.gov (United States)

    Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

    2015-05-14

    To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200

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

    International Nuclear Information System (INIS)

    Belousova, A.K.; Solntseva, T.I.; Khabarov, S.V.

    1986-01-01

    The sites of specific binding of [L- 3 H]dihydroalprenolol ([ 3 H]DHA), possessing the properties of β-adrenergic receptors, coupled with adenylate cyclase, were detected by methods of competitive displacement and binding of β-adrenoblockers: [ 3 H]-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 10 3 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 [ 3 H]DHA. The number of receptors of the first type is (5.0-7.5) x 10 3 , and of the second (20-30) x 10 3 per cell. Sarcolysine in 1-10 μM concentrations is capable of displacing [ 3 H]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

  10. Lethal Effect of Thermal Neutrons on Hypoxic Elirlich Ascites Tumour Cells in vitro

    OpenAIRE

    MITSUHIKO, AKABOSHI; KENICHI, KAWAI; HIROTOSHI, MAKI; Research Reactor Institute, Kyoto University; Research Reactor Institute, Kyoto University; Research Reactor Institute, Kyoto University

    1985-01-01

    Ehrlich ascites tumour cells were irradiated in vitro with thermal neutrons under aerobic and hypoxic conditions, and the survival of their reproductive capacity was assayed in vivo. Only a slight hypoxic protection was observed for thermal neutron irradiation with an oxygen enhancement ratio (OER) of 1.2, as compared with OER of 3.3 for ^Co-γ-rays. Absorbed dose of thermal neutrons was calculated by assuming that the energies of recoiled nuclei were completely absorbed within a cell nucleus....

  11. Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

    Science.gov (United States)

    Scheulen, M E; Hoensch, H; Kappus, H; Seeber, S; Schmidt, C G

    1987-01-01

    From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured....... Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused...

  13. Ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, Søren

    clinical sign. It has a severe prognosis, which is mainly dependent on the aetiology and progression of the underlying disease. However, among patients with ascites, the prognosis may be very different, mainly owing to the presence of portal venous hypertension, malignancy in the abdominal cavity, and end......-stage congestive heart failure. The addition of complications like the hepatorenal syndrome and bacterial peritonitis, whether spontaneous or secondary, adds heavily to the bad prognosis. Since hepatic ascites are by far the most complex with respect to pathophysiology, complications, and treatment, emphasis...

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

    International Nuclear Information System (INIS)

    Blattmann, H.; Cabeza, L.; Fritz-Niggli, H.

    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

  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 Cl(-) conductances could be observed. The H2O2-induced cell shrinkage was unaffected by the presence of clofilium and clotrimazole, that block volume-sensitive and Ca(2+)-activated K(+) channels, respectively, and unaffected by a raise in extracellular K(+) concentration to a value which eliminates...... 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...

  16. Intensification of the inhibitory effect of X-rays on the growth of Ehrlich ascites tumor cells in monolayer culture by quinacrine (atebrine) or chloroquine (resochine)

    International Nuclear Information System (INIS)

    Biller, H.; Pfab, R.; Hess, F.; Schachtschabel, D.O.; Leising, H.B.

    1980-01-01

    Monolayers of Ehrlich ascites tumor cells in their logarithmic phase of growth were exposed to a single X-ray dose of 1 to 16 Gy. Following exposure, the monolayers were cultured for several days or weeks with or without an addition of 4 x to 6 x 10 -6 M of quinacrine (atebrine) or 3.3 x 10 -5 to 1 x 10 -4 M of chloroquine. Proliferation activity was controlled by the daily microscopical count of representative areas out of the total population. A significant delay resulted from exposure to 4 Gy (particularly during the 1st day), while sole irradiation with 1 or 2 Gy did not much influence the proliferation of the cells. An 8-Gy dose and to a larger extent 16 Gy led to a fall of the cell number down to 20% (8 Gy) or around 10% (16 Gy) of the initial value between the 7th and the 10th day. The cells subsequently multiplied with nearly the growth rate of controls. The inhibitory effect on cells proliferation produced by an exposure to X-rays was distinctly intensified by means of incubation with continuously replaced quinacrine or chloroquine containing culture media. Treatment with 1 x 10 -4 mol chloroquine thus brought about a more pronounced inhibition after pre-irradiation with a single dose of 2 or 8 Gy. If 4 x 10 -6 or 6 x 10 -6 M of quinacrine were added to cultures pretreated with 4 Gy, a more intense inhibition of growth resulted therefrom than from sole treatment with either quinacrine or X-rays. Incubation of cultures pretreated with 8 Gy in the presence of 6 x 10 -6 M quinacrine led to the death of all the cells within 8 days. Quinacrine and chloroquine effects on cells previously exposed to X-rays are discussed in view of the well-known effects these agents exert by inhibiting enzymatic repair processes of DNA damage. (orig.) [de

  17. Uptake of 153Sm-DTPA-bis-biotin and 99mTc-DTPA-bis-biotin in rat as-30D-hepatoma cells

    International Nuclear Information System (INIS)

    Correa-Gonzalez, Luis; Arteaga de Murphy, Consuelo; Ferro-Flores, Guillermina; Pedraza-Lopez, Martha; Murphy-Stack, Eduardo; Mino-Leon, Dolores; Perez-Villasenor, Graciela; Diaz-Torres, Yaneth; Munoz-Olvera, Rodrigo

    2003-01-01

    Labeled biotin has been used mainly for pretargeted therapy, an approach for increasing the amount of radioactivity delivered to a cancer cell. The aim of this investigation was to prepare 153 Sm-DTPA-bis-biotin and 99m Tc-DTPA-bis-biotin in order to study their in vitro and in vivo uptake in rat AS-30D hepatoma cells found in ascites and in implanted tumor. DTPA-bis-biotin (pH 8) was 153 Sm labeled with 153 SmCl 3 and 99m Tc-DTPA-bis-biotin was prepared via SnCl 2 reduction. Radiochemical purity was >98% in both cases. AS-30D hepatoma cells were obtained from ascites of a rat with hepatoma and were propagated in the peritoneum cavity of normal rats. In vitro ascites cell 153 Sm-DTPA-bis-biotin uptake was compared with 153 SmCl 3 cell uptake. The ratio cell 153 Sm-DTPA-bis-biotin/ 153 SmCl 3 was 39.6 and when avidin was added it increased to 50. The ratio 99m Tc-DTPA-bis-biotin/TcO 4 Na was 8.7. Concentration of 153 Sm-DTPA-bis-biotin in tumor 2, 3 and 24 h after administration, was 5, 15 and 3 times higher than in normal muscle (T/nT). Biodistribution in a 0.083-24 h time period showed that 153 Sm-DTPA-bis-biotin was taken up only by ascites tumor cells and hepatoma cells. Two and 3 h ratio ascites/liver (As/Lv) was 6.4 and 6.0. For 99m Tc-DTPA-bis-biotin 2 and 3 h T/nT was 15.7 and 4.7 and 2 h As/Lv was 1.4. In conclusion, both radiopharmaceuticals show high uptake in rat AS-30D hepatoma cells in ascites and in implanted tumor. Since lung, thyroid, kidney, liver or pancreas carcinomas are ascites producing cancers 153 Sm-DTPA-bis-biotin would be an adequate therapeutic radiopharmaceutical for these patients whose life quality would be enhanced with control of ascites, and a reduction of the primary tumor and its metastases

  18. [Protective effect of polysaccharides extracts from corn silk against cyclophosphamide induced host damages in mice bearing H22 tumors].

    Science.gov (United States)

    Wu, Xian-chuang; Du, Gang-jun; Song, Xiao-yong; Zhang, Yong-zhou; Liu, Yu-xin

    2014-10-01

    To study the protective effect of polysaccharides from corn silk (PCS) against cyclophosphamide (CTX) induced host damages in mice bearing H22 tumors. The ascitic and solid tumor bearing mice model were established to investigate the anti-tumor effects of different dose of PCS (100, 200 and 300 mg/kg). The effects of PCS alone and with combination of CTX on tumor weight, survival time, thymus and spleen index, white blood cell, nucleated cell of marrow, serum ALT and AST level were tested. The high-dose PCS (300 mg/kg) had significant inhibitory effects on tumor. After combination with CTX, the tumor inhibitory ratio was enhanced to 68.71%, the survival time of tumor-burdened ascites tumor mice was significantly prolonged to 72.07% compared with CTX group. The Q value of combination group was 0.997. Thymus and spleen index, white blood cell, nucleated cell of marrow decreased by CTX were ameliorated significantly. The level of ALT and AST increased by CTX were reduced by combination with PCS. PCS has a potent inhibitory effect on the growth of implanted H22 tumors in mice and has a synergetic effect and an attenuated toxic effect in combination with CTX.

  19. Selective incorporation of various C-22 polyunsaturated fatty acids in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Masuzawa, Y.; Okano, S.; Waku, K.; Sprecher, H.; Lands, W.E.

    1986-01-01

    Three 14 C-labeled 22-carbon polyunsaturated fatty acids, 7,10,13,16-[ 14 C]docosatetraenoic acid (22:4(n-6)), 7,10,13,16,19-[ 14 C]docosapentaenoic acid (22:5(n-3)), and 4,7,10,13,16,19-[ 14 C]docosahexaenoic acid (22:6(n-3)), were compared with [ 3 H]arachidonic acid (20:4(n-6] and [14C]linoleic acid (18:2(n-6)) to characterize their incorporation into the lipids of Ehrlich ascites cells. The relatively rapid incorporation of the labeled 22-carbon acids into phosphatidic acid indicated that substantial amounts of these acids may be incorporated through the de novo pathway of phospholipid synthesis. In marked contrast to 20:4(n-6), the 22-carbon acids were incorporated much less into choline glycerophospholipids (CGP) and inositol glycerophospholipids (IGP). No selective preference was apparent for the (n-3) or (n-6) type of fatty acids. The amounts of the acids incorporated into diacylglycerophosphoethanolamine were in the order of: 22:6(n-3) greater than 20:4(n-6) much greater than 22:5(n-3) greater than or equal to 22:4(n-6) greater than 18:2(n-6), whereas for alkylacylglycerophosphoethanolamine they were in the order of: 22:4(n-6) greater than 22:6(n-3) greater than 22:5(n-3) much greater than 20:4(n-6) greater than 18:2(n-6). Of the mechanisms possibly responsible for the selective entry of 22-carbon acids into ethanolamine glycerophospholipids, the most reasonable explanation was that the cytidine-mediated ethanolamine phosphotransferase may have a unique double selectivity: for hexaenoic species of diacylglycerol and for 22-carbon polyunsaturated fatty acid-containing species of alkylacylglycerol. The relative distribution of fatty acids between newly incorporated and already maintained lipid classes suggested that IGP may function in Ehrlich cells as an intermediate pool for the retention of polyunsaturated fatty acids in glycerolipids

  20. Effect of uracil on the intracellular distribution of 1-(2-tetrahydrofuryl)-5-fluorouracil in the mouse tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, J.; Kosaki, G. (Osaka Univ. (Japan). Faculty of Medicine)

    1980-12-01

    Fifteen ..mu..g/g 1-(2-tetrahydrofuryl)-5-fluoro (-6-/sup 3/H) uracil (/sup 3/H-FT) were injected i.p. into mice bearing Fujimoto ascites tumor. Tumor cells were removed at various intervals and the autoradiographs were prepared. The specimens were treated first with chloroform before being coated with emulsion, so as to remove /sup 3/H-FT in the specimens and to preserve 5-fluoro (-6-/sup 3/H) uracil (/sup 3/H-FU) which was released from /sup 3/H-FT. Autoradiographs revealed a higher concentration of silver grains which localized over the nucleus, especially over the nucleoli, of tumor cells than over the cytoplasm. When 33.6 ..mu..g uracil/g was coadministered with 15.0 ..mu..g /sup 3/H-FT/g into tumor-bearing mice, intracellular distribution of /sup 3/H-FU released from /sup 3/H-FT was unchanged and an incorporation of /sup 3/H-FU into the tumor cells was higher than when /sup 3/H-FT alone.

  1. Effects of Atenolol on Growth Performance, Mortality Due to Ascites, Antioxidant Status and Some Blood Parameters in Broilers under Induced Ascites

    Directory of Open Access Journals (Sweden)

    mokhtar fathi

    2016-11-01

    Full Text Available Introduction Broiler chickens are intensively selected for productive traits. The management of these highly productive animals must be optimal to allow their full genetic potential to be expressed. If this is not done, inefficient production and several metabolic diseases such as ascites become apparent. Investigations in mammals indicated that the b- adrenoreceptor characteristics are differentially regulated by chronic hypoxia and play an important role in the cardiovascular system. The density of b-adrenergic receptors was higher in cardiac cells of ascites sensitive birds compared with ascites-resistant ones. Moreover, the characteristics of b-adreno receptors are different in cardiac cells of birds with right ventricular hypertrophy and heart failure compared with healthy birds. Treatment with the selective b1-adrenoceptor blocker, atenolol, abolished right ventricular hypertrophy in response to hypoxia compared with normoxic condition in rats. Materials and Methods This study investigated the comparative effects of different levels of atenolol Growth performance, Mortality due to ascites, antioxidant status and blood parameters in broilers under induced ascites. Six hundred one-day-old male broilers (Ross 308 in a completely randomized experimental design with four treatments (Positive control, negative control, and two levels of 30 and 60 ppm atenolol with five replicates of thirty birds were applied. Birds in positive control were reared in natural temperature without atenolol, the other bird groups were reared in cold temperature with 0, 30 and 60 ppm atenolol. The average daily feed intake (ADFI, average daily weight gain (ADWG and feed conversion ratio (FCR for each group of birds were calculated and mortality was daily weighed, recorded and used to correct the FCR. Observations were made daily to record the incidence of ascites and mortality. Diagnosis of ascites generally depends on observation of the following symptoms: (1 right

  2. 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.

  3. Proton stoichiometry of electron transport in rodent tumor mitoplasts.

    Science.gov (United States)

    Ferreira, J; Reynafarje, B; Costa, L E; Lehninger, A L

    1988-02-01

    The mechanistic vectorial H+/O translocation ratios characteristic of energy-conserving sites 2 + 3 and site 3 of the respiratory chain of two tumor cell lines were determined using succinate and ferrocytochrome c, respectively, as electron donors. The measurements were carried out on mitoplasts in order to allow ferrocytochrome c free access to its binding site on the inner mitochondrial membrane. The tumor cell lines used were Ehrlich ascites tumor and the AS30-D ascites tumor. K+ was used as charge-compensating cation in the presence of valinomycin. The O2 uptake rate measurements were made with a fast-responding membrane-less electrode whose response time was closely matched with that of a pH electrode. The rates of O2 uptake and H+ ejection during the apparent zero-order rate phase of respiration, analyzed by computer, were extrapolated to zero time. The observed H+/O ratios for succinate oxidation in both tumors exceeded 7 and approached 8 and the H+/O ratios for the cytochrome oxidase reaction closely approached 4.0, in agreement with data or normal mitochondria. However, the rates of H+ back decay in the tumor mitochondria are relatively high and may influence the net efficiency of oxidative phosphorylation under intracellular conditions.

  4. On a accumulation of 131-I-RNase by ascites tumour cells of mice

    International Nuclear Information System (INIS)

    Sarrach, D.; Waldner, H.

    1976-01-01

    The accumulation of 131-I-labelled RNase by Ehrlich ascites tumour cells of mice was investigated in dependence on time, concentration, and pH. Kinetically a fast and a slow stage of reaction is distinguished. In both, the dependence on concentration is of the Langmuir type. Only the stage-I binding is reversibly diminished with increasing pH. Absorption due to electrostatic forces is suggested for this stae. (author)

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    In whole-cell recordings on Ehrlich-Lettre-ascites tumour (ELA) cells, the shrinkage-induced activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(choline):P(NMDG) of 1.00:0.97:0.88:0.03:0.01 was observed. In order of potency, this conductance was blocked by Gd(3+)=benzam......-sensitive and -insensitive channels. In addition, because of its pharmacological profile, it may possibly be related to epithelial Na+ channels (ENaCs)....

  6. Effect of misonidazole (Ro-07-0582) on the incidence of micronuclei in irradiated Ehrlich tumour ascites cells

    Energy Technology Data Exchange (ETDEWEB)

    Olinici, C D; Mustea, I [Institute of Oncology, Cluj (Romania)

    1978-12-01

    Misonidazole (1-(2-nitro-1-imidazole)-3-methoxy-2-propanol) was injected intraperitoneally into mice on the fifth day of development of Ehrlich ascites tumours. The animals were then /sup 60/Co ..gamma..-irradiated (100 to 400 R) and killed at 24 to 72 hours post-irradiation. Ascites tumour cells from the mice were stained by the Feulgen reaction and the incidence of micronuclei determined. Pretreatment with misonidazole induced an increase in the incidence of micronuclei in the irradiated tumour cells. This increase was most conspicuous at higher radiation doses and at 48 hours post-irradiation. The results suggest the possibility of using the micronucleus assay for the screening of substances with radio-sensitizing potential. The method would be especially suitable for the study of tumours irradiated in vivo with high doses of radiation, since cytogenetic methods present difficulties under these conditions.

  7. Inhibition by derivatives of diguanidines of cell proliferation in Ehrlich ascites cells grown in cultures.

    Science.gov (United States)

    Alhonen-Hongisto, L; Pösö, H; Jänne, J

    1980-01-01

    The anti-proliferative effects of 1,1'-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1'-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1'-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4--8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1'-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular

  8. Effect of pH on tumor cell uptake of radiogallium in vitro and in vivo

    International Nuclear Information System (INIS)

    Vallabhajosula, S.R.; Hartwig, J.F.; Wolf, W.

    1982-01-01

    When injected at tracer levels into the blood, radiogallium as 67 Ga-citrate binds to, and is transported to, the site of the tumor by transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully unterstood, but may involve the differential physicology of neoplasmas compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injected with 67 Ga-citrate was dialyzed at pH 6.5-7.5, disociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-12-01

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

  10. Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

    Science.gov (United States)

    Liu, Changmei; Yang, Fangmei

    2015-09-01

    Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

  11. Radiosensitization of hypoxic tumor cells by simultaneous administration of hyperthermia and nitroimidazoles

    International Nuclear Information System (INIS)

    Hofer, K.G.; Hofer, M.G.; Ieracitano, J.; McLaughlin, W.H.

    1977-01-01

    The radiation response of oxygenated and hypoxic L1210 leukemia cells subjected to in vivo treatments with hyperthermia and/or chemical radiosensitizers was evaluated with the [ 125 I]iododeoxyuridine prelabeling assay. X irradiation of L1210 cells at body temperatures of 41 0 C or higher resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic L1210 cells were particularly sensitive to heat induced enhancement of radiation damage, i.e., the sensitizing effects were more pronounced and occurred at lower temperatures. Chemical radiosensitizers (metronidazole, Ro 7-0582) selectively sensitized hypoxic L1210 populations; fully oxygenated cells were not affected. Considerable radiosensitization was achieved at nontoxic dose levels of the two sensitizers. Experiments designed to determine the degree of radiosensititization as a function of drug dose showed that Ro 7-0582 was consistently more effective than metronidazole in sensitizing hypoxic tumor populations. At the highest drug dose used (3 mg/g body wt) the DMF was 2.2 for metronidazole and 2.8 for Ro 7-0582. Combined administration of hyperthermia and Ro 7-0582 (or metronidazole) produced synergistic potentiation of radiation damage in hypoxic L1210 populations (DMF of 4.2). Under optimal conditions, hypoxic L1210 cells subjected simultaneously to both modes of radiosensitization became more radiosensitive than untreated, fully oxygenated L1210 cells. Experiments on two other tumor lines (BP-8 murine sarcoma and Ehrlich ascites cells) indicate that such synergistic radiosensitization effects are not unique to L1210 cells

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

    Science.gov (United States)

    Landry, Y; Lehninger, A L

    1976-01-01

    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

  13. Effect of hypolipidemic drugs on basal and stimulated adenylate cyclase activity in tumor cells

    International Nuclear Information System (INIS)

    Bershtein, L.M.; Kovaleva, I.G.; Rozenberg, O.A.

    1986-01-01

    This paper studies adenylate cyclase acticvity in Ehrlich's ascites carcinoma (EAC) cells during administration of drugs with a hypolipidemic action. Seven to eight days before they were killed, male mice ingested the antidiabetic biguanide phenformin, and the phospholipid-containing preparation Essentiale in drinking water. The cAMP formed was isolated by chromatography on Silufol plates after incubation of the enzyme preparation with tritium-ATP, or was determined by the competitive binding method with protein. It is shown that despite the possible differences in the concrete mechanism of action of the hypolipidemic agents chosen for study on the cyclase system, the use of such agents, offers definite prospects for oriented modification of the hormone sensitivity of tumor cells

  14. Therapy of malignant ascites in vivo by 211At-labelled microspheres

    International Nuclear Information System (INIS)

    Bredow, J.; Wunderlich, G.; Pohl, T.; Franke, W.G.; Kotzerke, J.; Kretzschmar, M.; Doerr, W.

    2004-01-01

    Aim: determination of the biological effect of the alpha emitter 211 At on cellular level as well as the assessment of dosimetric data in a tumour model in vivo. Methods: transplantation of malignant ascitic cells in mice intraperitoneally and estimation of tumour characteristics (doubling time of the cells, mean survival of the animals following an i.p. application of a defined tumour cell number). 211 At labelled human serum albumine microspheres B-20 (MSP) of variing activity were injected into tumour bearing mice intraperitoneally. The effectiveness of the therapy was evaluated by means of determination of the duration of cell cycle arrest as well as the microscopic analysis of the rate of abnormal mitotic cells due to radiation induced damage. Furthermore, dose dependence of survival was evaluated. Results: three days following the intraperitoneally application of 8 x 10 6 tumour cells, 50-600 kBq 211 At-MSP were applied into the abdominal cavity. Considering the volume of ascites at this time and the administered activity, dose calculations were performed. An activity of 50 kBq caused a dose of 0.84 Gy. The increase of radiation induced effect on ascitic tumour cells was correlated with the dose. Between the duration of the cell cycle arrest and the administered activity, a directly proportional correlation was found. The mean survival of non-treated animals was 16.9 ± 3.7 days. The prolongation of the survival was proportional to the activity administered. Using a dosage of 10 Gy, five animals out of 16 survived. Conclusion: therapy of malignant ascitic cells using 211 At-MSP was effective in vivo. For tumour therapy, the 211 At represents a highly effective alternative to usually applied beta emitters. (orig.) [de

  15. A case of inflammatory ascites

    Directory of Open Access Journals (Sweden)

    Marco Biolato

    2008-03-01

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

  16. Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zhao, K-X; Dai, G-Z; Zhu, J-F

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

  17. Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

    International Nuclear Information System (INIS)

    Hara, H.; Seon, B.K.

    1987-01-01

    In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment

  18. Response of the tumor and organs of the tumor-bearing animal to the action of an ionizing radiation

    International Nuclear Information System (INIS)

    Burlakova, E.B.; Gaintseva, V.D.; Pal'mina, N.P.; Sezina, N.P.

    1977-01-01

    Changes in the antioxigenic activity (AOA) of the liver of the tumor-bearing animals and the tumor have been studied after a single whole-body exposure of animals to a dose of 600 R. AOA of the liver of animals having hepatoma 22-a and Ehrlich ascites tumor (EAT) was found to decrease immediately after irradiation while that of the tumor itself can both increase (hepatoma 22-a) and decrease (EAT). Proceeding from the assumption that AOA is connected with tissue radiosensitivity it is suggested that the observed variations in the response of tumor cells and normal tissue to the action of ionizing radiation should be taken into account when developing the schemes of radiation effect on the tumor

  19. Congenital chylous ascites

    International Nuclear Information System (INIS)

    Romanska-Kita, J.; Borszewska-Kornacka, M. K.; Rudzinska, I.; Wawrzoniak, T.; Dobrzanska, A.; Czech-Kowalska, J.

    2011-01-01

    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. (authors)

  20. Occurrence of the malate-aspartate shuttle in various tumor types.

    Science.gov (United States)

    Greenhouse, W V; Lehninger, A L

    1976-04-01

    The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.

  1. Cross-immunity among allogeneic tumors of rats immunized with solid tumors

    International Nuclear Information System (INIS)

    Ogasawara, Masamichi

    1979-01-01

    Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

  2. [Ascites drainage at home

    NARCIS (Netherlands)

    Lutjeboer, J.; Erkel, A.R. van; Hoeven, J.J.M. van der; Meer, R.W. van der

    2015-01-01

    Ascites can lead to many symptoms, and often occurs in patients with an end-stage malignancy such as ovarian, pancreatic, colonic, or gastric cancer. Intermittent ascites drainage is applied in these patients as a palliative measure. As frequent drainage is necessary, a subcutaneously tunnelled

  3. 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)

    Abubaker, Khalid; Luwor, Rodney B; Zhu, Hongjian; McNally, Orla; Quinn, Michael A; Burns, Christopher J; Thompson, Erik W; Findlay, Jock K; Ahmed, Nuzhat

    2014-01-01

    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

  4. Effect of Bidens pilosa extract on renal functions and some tumor markers of Ehrlich Ascites Carcinoma bearing mice exposed to γ-radiation

    International Nuclear Information System (INIS)

    El-Kabany, H.; Ibrahim, S.I.

    2013-01-01

    The Ethanolic extract of Bidens pilosa (EtBP) was tested in Swiss albino mice transplanted with Ehrlich ascites carcinoma (EAC) and exposed to γ-radiation. EAC mice received intraperitoneal (i.p) 250 mg/kg body weight EtBP for nine days , 24hr after tumor inoculation. Mice exposed to 4 Gy γ-radiation 30 min after the first dose of EtBP. Seventy female mice were classified into 6 groups (15 mice in each group) as follows, control, mice treated with EtBP for 9 consecutive days, mice bearing EAC cells, EAC bearing mice treated with EtBP, 24 hour after tumor inoculation, EAC bearing mice and irradiated, and EAC bearing mice treated with EtBP and exposed to γ-radiation. Five animals from each group were sacrificed 18 hr after administration of the last EtBP dose. Blood and ascetic fluid were collected and kidneys were removed for biochemical and histopathological studies. The remaining animals were observed daily for recording survival percentage and body weight. Results showed that treatment of EAC bearing mice with EtBP and/or exposure to γ- radiation increased the survival percentage of the animals and decreased their body weight compared to EAC group. Inoculation of mice with EAC cells resulted in biochemical and histopathological changes leading to kidney damage. Animals of EAC bearing mice with EtBP and /or exposure to γ- radiation significantly restored the elevated levels of serum urea and creatinine, tumor necrosis factor-alpha (TNF-α), metalo matrix protein (mmp-2 and mmp9), also the elevated level of lipid peroxidation (MDA) in kidneys tissue, compared to EAC group. On the other hand, a significantly decline was observed in glutathione (GSH) and super oxide dismutase (SOD) contents in kidney tissue of EAC group. Treatment of EAC bearing mice with EtBP and/or exposure to γ-radiation resulted in increase GSH and SOD in kidney tissue and increased caspase-3 in ascetic fluid, comparing to EAC group. It could be concluded that EtBP through its antioxidant

  5. Effect of irradiation on microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers

    International Nuclear Information System (INIS)

    Mal'tseva, E.L.; Goloshchapov, A.N.; Pal'mina, N.P.; Burlakova, E.B.

    1982-01-01

    Changes of microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers with developing Ehrlich ascites tumor (EAT) at various terms after lethal irradiation (650 R) were studied by spin probe method. Two iminoxyl radicals localized mainly in lipid bilayer and near probein layers of membrane lipids were used. The character and the degree of microviscosity changes in different zones of nuclear membranes point to different responses towards effect of radiation of cells of tumor-carrier organ and tumor both in viscosity properties, and in change of lipid-protein relations. The significant contribution of near protein lipid layers into general change of nuclear membrane microviscosity is marked. Microviscosity of nuclear membrane causes different responses of cellular nuclear membranes of liver of tumor-carriers and healthy animals as well as considerable (3 times) dilution of nuclear membrane of EAT cells after irradiation. It is shown that temperature dependence of times of rotatory correlation of both probes is more expressed in EAT cells of irradiated tumor-carriers, than in liver

  6. Chylous ascites associated with intestinal obstruction from volvulus due to Petersen's hernia: report of a case.

    Science.gov (United States)

    Akama, Yuichi; Shimizu, Tetsuya; Fujita, Itsuo; Kanazawa, Yoshikazu; Kakinuma, Daisuke; Kanno, Hitoshi; Yamagishi, Aya; Arai, Hiroki; Uchida, Eiji

    2016-12-01

    Chylous ascites is an uncommon finding which is usually associated with recent abdominal/oncologic or retroperitoneal surgery. It is not usually seen in cases of acute obstruction. A patient who had previously undergone a laparoscopy-assisted distal gastrectomy with Roux-en-Y reconstruction for early gastric cancer presented with acute abdominal pain and epigastric fullness. Computed tomography suggested small bowel obstruction due to volvulus. We were able to reduce the volvulus and close a Petersen's hernia without resecting the bowel; a large amount of chylous ascites was an incidental finding. We present a case of chylous ascites occurring in a setting of small bowel obstruction due to Petersen's hernia, 3 years after successful distal gastrectomy for early gastric cancer, with no evidence of tumor recurrence.

  7. MR imaging of malignant ovarian tumors

    International Nuclear Information System (INIS)

    Kim, Jun Ho; Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Choi, Ho Sun

    1994-01-01

    To evaluate MRI findings of malignant ovarian tumors. MRI findings were retrospectively reviewed in 25 patients with surgically confirmed 30 malignant ovarian tumors(common epithelial tumor; 23, sex cord stromal tumor; 2, endo dermal sinus tumor; 1, metastatic tumor; 4). The findings evaluated were the lesion size, solid and/or cystic component, wall thickness, septal thickness, necrosis, invasion of adjacent organ, ascites, and adenopathy. MRI findings of the malignant ovarian tumors were as follow: Size of lesion was 5-35cm(mean 14cm); solid component was present in 80%(24/30); wall thickness was more than 3mm in 90%(27/30); septal thickness was more than 3mm in 70%(21/30); tumor necrosis was present in 40%(12/30%); invasion of adjacent organ was present in 76%(19/25); ascites was present in 56%(14/25); lymphadenopathy was present in 24% (6/25). MRI findings of absence of solid component(6/6), even wall and septal thickness(7/7, 19/19) were found only in epithelial tumors. Uneven septal thickness more than 3mm(7/11) was a predominant MRI findings of non-epithelial tumors. Well-defined cystic lesion within solid component was seen in Krukenberg tumors. Evaluation of the lesion size, internal architecture, invasion of adjacent organ, ascites, and lymphadenopathy in MRI would enable diagnosis of malignant ovarian tumors and could lead to possible differential diagnosis of epithelial tumors from non-epithelial tumors

  8. Genetic Recombination Between Stromal and Cancer Cells Results in Highly Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kousuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-12-01

    The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma TME model with red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell transplantation. The subcutaneous tumors were harvested and transplanted to the abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the ascites and bone marrow. These results indicate genetic exchange between the stromal and cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

  10. Pathophysiology and management of pediatric ascites.

    Science.gov (United States)

    Sabri, Mahmoud; Saps, Miguel; Peters, John M

    2003-06-01

    Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

  11. Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Xanthium strumarium in transplantable tumors in mice.

    Science.gov (United States)

    Aranjani, Jesil Mathew; Manuel, Atulya; Mallikarjuna Rao, Chamallamudi; Udupa, Nayanabhirama; Rao, Josyula Venkata; Joy, Ann Mary; Gandhi, Prajay; Radhakrishnan, Ethiraj Kannat

    2013-01-01

    In the present study, active fractions of the methanolic extract of Xanthium strumarium (XS) showing potent cytotoxicity were determined using microculture tetrazolium (MTT) and sulforhodamine B (SRB) assays in selected cancer cell lines. The active fractions viz., chloroform soluble fraction of root (CEXSR), hexane soluble fraction of leaf (HEXSL), hexane soluble fraction of fruits (HEXSF) and chloroform soluble fraction of fruits (CEXSF) of XS were tested in transplantable animal tumor models for their antitumor potential. Dalton's ascitic lymphoma (DLA) cells were used to induce solid and liquid (ascites) tumor in mice. The tumor bearing animals were treated with active fractions at two dose levels (100 and 200 mg/kg). The antitumor activities of the active fractions in tumor bearing animals were monitored with parameters such as body weight and increase in life-span as well as biochemical and hematological modalities (in the case of liquid tumor). Tumor incidence and tumor volume were the parameters monitored in the case of the solid tumor model. The results were analyzed by one-way ANOVA followed by Tukey's post hoc test. The extracts were found to increase the life-span of tumor bearing animals and restore the altered hematological and biochemical parameters significantly.

  12. Anti-tumor and Chemoprotective Effect of Bauhinia tomentosa by Regulating Growth Factors and Inflammatory Mediators.

    Science.gov (United States)

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2015-01-01

    Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and α-esterase activity. Extract treatment also attenuated any increases in serum levels of TNFα, iNOS, IL-1β, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.

  13. 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

    An Ehrlich ascites tumour cell line (EHR2) was selected in vivo for resistance to mitoxantrone (MITOX). The resistant cell line (EHR2/MITOX) was 6123-, 33-, and 30-fold-resistant to mitoxantrone, daunorubicin, and etoposide, respectively, but retained sensitivity to vincristine. The resistant cel...... to be associated with: 1) a quantitative reduction in topoisomerase IIalpha and beta protein; 2) reduced drug accumulation, probably as a result of increased expression of a novel transport protein with ATPase activity; and 3) increased expression of MRP mRNA....

  14. PGE from Octopus aegina Induces Apoptosis in Ehrlich's Ascites Carcinoma of Mice.

    Science.gov (United States)

    Karthigayan, S; Balasubashini, M Sri; Balasubramanian, T; Somasundaram, S T

    2007-01-01

    ABSTRACT The present study was carried out to assess the antitumor effect of venomous peptide from the cephalopod Octopus aegina on Ehrlich's ascites carcinoma (EAC). Male albino Swiss mice were used in the present study. Four groups of animals were treated with three doses of the sublethal dose of venom, 15, 75, and 150 mug/kg body weight (intraperitoneal injection), along with the standard drug 5-fluorouracil (20 mg/kg b.w.). After 10 days of treatment, six animals from each group were sacrificed for the biochemical analysis and the rest were left to calculate the mean survival time. In EAC-bearing mice, mean lifespan, tumor volume, hemoglobin, red blood cells, and lymphocytes were significantly decreased when compared to the normal animals. While body weight, neutrophils, and viable tumor cell count were increased in the EAC-bearing mice, these changes were brought back to near normal levels in different treatment groups. The macromolecule concentration of peritoneal cells, such as DNA, RNA, and protein, were altered in the EAC-bearing mice and observed to be near normal in the treatment groups. The caspase-3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC-bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, octopus venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Therefore, the venom from O. aegina has a potential antitumor effect on the EAC-bearing mice.

  15. Model for the radionuclide measurement of ascitic fluid volumes

    International Nuclear Information System (INIS)

    Kaplan, W.D.; Davis, M.A.; Uren, R.F.; Wisotsky, T.; LaTegola, M.

    1978-01-01

    Technetium-99m phytate colloids formed in vitro and in vivo were examined as radioindicators for estimation of the volume of third-space fluid in an ovarian ascites model using C3HeB/FeJ mice. In double-label experiments, the accuracy of the colloids for dilution analysis was found to be equal or superior to that of I-125 HSA. Sampling times 3 to 5 min after intraperitoneal administration were found to produce the best volume estimates. Four needle-stopcock assemblies inserted sequentially into the quadrants of the peritoneal cavity were used for administration and sampling of the radioindicators. The stopcocks could be closed to prevent leakage of ascitic fluid during the procedure. In contrast to radiolabeled albumin, Tc-99m phytate colloids have clinical use for simultaneous imaging of radiotracer migration to assess potential occlusion of diaphragmatic lymphatics by neoplastic cells, and for dilution analysis to estimate volume of ascitic fluid

  16. Diagnosis and treatment procedure for intractable liver ascites

    Directory of Open Access Journals (Sweden)

    FAN Zhidong

    2015-03-01

    Full Text Available Ascites is a common complication of liver cirrhosis. Liver ascites may occur repeatedly, which increases the therapeutic difficulty. This paper reviews the definition of intractable liver ascites, general treatment measures, and current treatment of common complications such as spontaneous bacterial peritonitis and hepatorenal syndrome, as well as the advances in conventional, unconventional, and surgical treatment of intractable liver ascites. It is pointed out that abdominocentesis for excessive drainage and active preparation for liver transplantation are the preferred approach to the treatment of intractable liver ascites.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

  18. Postoperative ascitic leaks: the ongoing challenge.

    Science.gov (United States)

    Rosemurgy, A S; Statman, R C; Murphy, C G; Albrink, M H; McAllister, E W

    1992-06-01

    The leak of ascitic fluid from surgical incisions is thought to be associated with a very high mortality rate. There have been few reports, however, focusing on the clinical characteristics, management, or mortality rates of this condition. During a 10-year period, 18 patients with postoperative ascitic fluid leaks were treated. All patients had ascites before surgery and all had liver disease; in 13 of the 18 patients alcoholic liver disease was the cause of ascites. Ten of the 18 patients died (56%). Midline incisions were more often associated with recalcitrant leaks and fatal complications than were transverse incisions. Early consideration of fascial dehiscence and prompt repair is emphasized. The most effective predictor of survival was cessation of the leak.

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

    Science.gov (United States)

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

    2016-04-30

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

  20. Intraperitoneal pressure: ascitic fluid and splanchnic vascular pressures, and their role in prevention and formation of ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Stage, J G; Schlichting, P

    1980-01-01

    Seventeen patients with ascites due to cirrhosis underwent hepatic venous catheterization and pressure measurement in the ascitic fluid. Intraperitoneal fluid hydrostatic pressure (IFP) ranged 3.5-22, mean 11.2 mm Hg, and correlated closely to the pressure in the inferior vena cava (r = 0.97, P ... that ascitic fluid stems the pressures in the splanchnic venous vascular bed up to a higher level, but that the transmural hydrostatic pressure difference decreases simultaneously. The results are discussed in relation to the local 'oedema-preventing' mechanisms: (a) increased interstitial hydrostatic fluid.......001), which was on average 1.8 mmHg above that of ascitic fluid (P pressure (WHVP) (range 19-43, mean 32 mmHg) correlated directly to IFP (0.89, P

  1. Transformation of Epithelial Ovarian Cancer Stemlike Cells into Mesenchymal Lineage via EMT Results in Cellular Heterogeneity and Supports Tumor Engraftment

    Science.gov (United States)

    Jiang, Hua; Lin, Xiaolong; Liu, Yingtao; Gong, Wenjia; Ma, Xiaoling; Yu, Yinhua; Xie, Yi; Sun, Xiaoxi; Feng, Youji; Janzen, Viktor; Chen, Tong

    2012-01-01

    Ovarian cancers are heterogeneous and contain stemlike cells that are able to self-renew and are responsible for sustained tumor growth. Metastasis in the peritoneal cavity occurs more frequently in ovarian cancer than in other malignancies, but the underlying mechanism remains largely unknown. We have identified that ovarian cancer stemlike cells (CSCs), which were defined as side population (SP) cells, were present in patients’ ascitic fluid and mesenchymally transformed cell lines, ES-2 and HO-8910PM. SP cells, which were sorted from both cell lines and implanted into immunocompromised mice, were localized to the xenografted tumor boundary. In addition, SP cells exhibited an epithelial phenotype and showed a distinct gene expression profile with reduced expression of cell adhesion molecules (CAMs), indicating that SP cells exert an important role in ovarian cancer progression on the basis of their delicate interaction with the surrounding microenvironment and anatomical localization in tumors. In contrast, non-SP cells exhibited a more mesenchymal phenotype and showed more increased invasive potential than SP cells. This heterogeneity was observed as an endogenous transformation via the epithelial–mesenchymal transition (EMT) process. Inhibition of the EMT process by Snail1 silencing reduced the SP cell frequency, and affected their invasive capacity and engraftment. These findings illustrate the interplay between epithelial ovarian CSCs and the EMT, and exert a link to explain tumor heterogeneity and its necessity for ovarian cancer maintenance, metastasis and progression. PMID:22801793

  2. 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.

  3. Bazex Syndrome with Hypoalbuminemia and Severe Ascites

    OpenAIRE

    Matsui, Hidetoshi; Iwae, Shigemichi; Hirayama, Yuji; Yonezawa, Koichiro; Shigeji, Jun

    2016-01-01

    Bazex syndrome is a rare paraneoplastic dermatosis. The underlying malignancy frequently is squamous cell carcinoma of the upper aerodigestive tract or cervical lymph nodes from an unknown primary site. We report a 63-year-old man with squamous cell carcinoma of cervical lymph nodes from an unknown primary site. He developed a mass on the right side of his neck, cutaneous lesions diagnosed as Bazex syndrome, hypoalbuminemia, and severe ascites. Right neck dissection was performed. After neck ...

  4. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Federico Battisti

    2017-09-01

    Full Text Available Dendritic cells (DCs are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  5. RNA and protein synthesis of irradiated Ehrlich ascites tumour cells. Pt. 1

    International Nuclear Information System (INIS)

    Skog, S.; Tribukait, B.; Sundius, G.

    1985-01-01

    The effects of roentgen irradiation on the incorporation of 3 H-uridine and 14 C-leucine into RNA and protein and the RNA and protein contents of in vivo growing Ehrlich ascites tumour cells were studied. The results were related to changes in the composition of cells in cell cycle and compared with the synthesis of RNA and protein in cell material from various parts of the cell cycle obtained by means of elutriator centrifuging. The incorporation expressed by the ratio between acid insoluble/acid soluble activity was unchanged for RNA during the observation period up to 24 hours after a dose of 5.0 Gy. The ratio for protein was markedly decreased between 4 and 24 hours. This decrease was partly due to a decrease of the pool size of leucine as studied by changing the amounts of 14 C leucine used. From these studies, the existence of at least two pools, an expandable and a non-expandable fixed pool can be concluded. There were no differences in the decrease of protein-synthesis between cells from the various parts of the cell cycle. The RNA and protein contents of the irradiated cells from various parts of the cell cycle corresponded to those of non-irradiated cells except for G 1 /early S-phase cells at 15 and 24 hours after irradiation. Possible reasons for this discrepancy are discussed. (orig.)

  6. Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

    Science.gov (United States)

    Payne, Kyle K; Keim, Rebecca C; Graham, Laura; Idowu, Michael O; Wan, Wen; Wang, Xiang-Yang; Toor, Amir A; Bear, Harry D; Manjili, Masoud H

    2016-09-01

    Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy. © The Author(s).

  7. Evaluation of antitumor activity and in vivo antioxidant status of Anthocephalus cadamba on Ehrlich ascites carcinoma treated mice.

    Science.gov (United States)

    Dolai, Narayan; Karmakar, Indrajit; Suresh Kumar, R B; Kar, Biswakanth; Bala, Asis; Haldar, Pallab Kanti

    2012-08-01

    Anthocephalus cadamba (Roxb.) Miq. (Family: Rubiaceae) is commonly known as "Kadamba" in Sanskrit and Hindi in India. Various parts of this plant have been used as a folk medicine for the treatment of tumor, wound healing, inflammation and as a hypoglycemic agent. The purpose of this investigation was to evaluate the antitumor activity and antioxidant status of defatted methanol extract of A. cadamba (MEAC) on Ehrlich ascites carcinoma (EAC) treated mice. In vitro cytotoxicity assay has been evaluated by using the trypan blue method. The determination of in vivo antitumor activity was performed by using different EAC cells (2 × 10(6) cells, i.p.) inoculated mice groups (n=12). The groups were treated for 9 consecutive days with MEAC at the doses of 200 and 400 mg/kg b.w. respectively. After 24h of last dose and 18 h of fasting, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of MEAC was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. MEAC showed direct cytotoxicity on EAC cell line in a dose dependant manner. MEAC exhibited significant (P<0.01) decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. The hematological profile, biochemical estimations and tissue antioxidant assay were reverted to normal level in MEAC treated mice. Experimental results revealed that MEAC possesses potent antitumor and antioxidant properties. Further research is going on to find out the active principle(s) of MEAC for better understanding of mechanism of its antitumor and antioxidant activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. [Ascites. Tuberculous peritonitis].

    Science.gov (United States)

    Osterwalder, P; Widmer, M; Widmer, U; Schulthess, G

    1998-03-04

    Because of deteriorating general health, weight loss of 5 kg and leftsided epigastric pain a 44 year old innkeeper was evaluated unsuccessfully for 1 month. Thereafter a protein- and lymphocyte-rich ascites developed. CT-scans revealed a thickened visceral peritoneum and multiple, marginally increased retroperitoneal lymph nodes. The history of the patient originating from former Jugoslavia was suspicious for inadequately treated tuberculous pericarditis. Hence this diagnosis tuberculous peritonitis became probable but for practical reasons could not be proven neither by biopsy nor by culture. Under probatory antituberculous treatment the patient's general condition improved rapidly, the ascites disappeared and initially elevated parameters for infection normalized.

  9. Isolation of nucleoli from Ehrlich ascites tumor cells and dynamics of nascent RNA within isolated nucleoli.

    Science.gov (United States)

    Thiry, Marc; Ploton, Dominique

    2008-01-01

    Here we describe a new, rapid method for isolating nucleoli from Ehrlich tumor cells that preserves their morphological integrity and high transcriptional activity. Until now, methods for isolation of nucleoli were generally assumed to empty one of their three main compartments, the fibrillar center, of its contents. This new method consists of sonicating cells in an isotonic medium containing MgSO(4), spermidine, and spermine, followed by separation of nucleoli through a Percoll density gradient. Using the nonisotopic approach of labelling with BrUTP, we have further investigated the dynamics of nascent ribosomal RNAs (rRNAs) within morphologically intact isolated nucleoli at the electron microscope level. We show that ribosomal transcripts are elongated in the cortex of the fibrillar center and then enter the surrounding dense fibrillar component.

  10. STUDY ON ETIOLOGY OF ASCITES

    Directory of Open Access Journals (Sweden)

    Konatham

    2015-07-01

    Full Text Available In this study 100 cases of ascites, evaluated for the etiological causes. And observed as cirrhosis with portal hypertension 82%, heart failure 8%, chronic kidney disease 3%, nephritic syndrome 2%, peritoneal calcinomatosis 2%, chronic pancreatitis 1% por tal vein thrombosis 1%, Budd - chiari syndrome 1%. AIM OF THE STUDY: To study the various etiologies and their incidence of Ascites.

  11. Chylous ascites post open cholecystectomy after severe pancreatitis.

    LENUS (Irish Health Repository)

    Cheung, Cherry X

    2012-05-01

    Chylous ascites a rare complication post cholecystectomy. There are to our knowledge only 3 reported cases in the literature. We describe a case of chylous ascites post open cholecystectomy in a patient with recent severe pancreatitis. We propose a potential relationship between acute biliary pancreatitis and the development of chylous ascites.

  12. Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

    DEFF Research Database (Denmark)

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

    1986-01-01

    A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different...... sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow...

  13. SERTOLI-LEYDIG CELL TUMOR; A RARE CASE IN A POSTMENOPAUSAL PATIENT – CASE REPORT

    Directory of Open Access Journals (Sweden)

    Petra Krajnc

    2018-02-01

    Full Text Available Background. Sertoli-Leydig cell tumors belong to the group of sex cord stromal tumors of the ovary. They account for less than 0.5 % of all ovarian tumors and occur primarily in young women between 20 and 30 years of age. This type of tumors can secrete androgens, causing virilisation, and are extremely rarely presented in postmenopausis. Methods. A 73-year old multiparous woman was presented to our institution with complaints of abdominal distention and abdominal pain in her lower abdomen. On physical examination, she had a large, fixed palpable abdominal mass, approximately 20 cm in diameter, arising from the pelvis. The laboratoric tests revealed an elevated level of CA125 of 221.3 U/ml of serum. The ultrasound showed a complex cystic and solid pelvic tumor. There was no sign of ascites. Her hormonal status was within normal range and she also showed no signs of virilisation. On laparotomy a complex left ovarian mass, measuring 30 × 27 × 15 cm was found and sent to frozen section. The result of frozen section was a malignant tumor of unknown origin, therefore a radical surgical procedure was performed. The histopathological examination established the diagnosis of a malignant Sertoli-Leydig cell tumor of the left ovary, of intermediate differentiation. Other removed tissue was free of malignant cells. The early postoperative course was uneventful and the patient was released from hospital 10 days after surgery. However, she returned to our institution 16 days after surgery due to a proximal thrombosis of v. saphena magna. The patient was treated with low-molecularweight heparin and later warfarin for 6 weeks post operation. 16 months after the operation she was symptomatically treated for severe microcytic anemia. She showed no signs of a relapse. 27 months after primary surgery she was operated for the second time due to acute bowel obstruction. She had large masses of necrotic tumor removed from abdomen and transversostomia was performed

  14. Successful treatment of massive ascites due to lupus peritonitis with hydroxychloroquine in old- onset lupus erythematosus.

    Science.gov (United States)

    Hammami, Sonia; Bdioui, Fethia; Ouaz, Afef; Loghmari, Hichem; Mahjoub, Sylvia; Saffar, Hamouda

    2014-01-01

    Systemic lupus erythematous (SLE) is an auto-immune disease with multiple organ involvements that occurs mainly in young women. Literature data suggest that serositis is more frequent in late-onset SLE. However, peritoneal serositis with massive ascites is an extremely rare manifestation. We report a case of old-onset lupus peritonitis treated successfully by Hydroxychloroquine. A 77-year-old Tunisian woman was hospitalized because of massive painful ascites. Her family history did not include any autoimmune disease. She was explored 4 years prior to admission for exudative pleuritis of the right lung without any established diagnosis. Physical examination showed only massive ascites. Laboratory investigations showed leucopenia: 3100/mm3, lymphopenia: 840/mm3 and trace protein (0.03 g/24 h). Ascitic fluid contained 170 cells mm(3) (67% lymphocytes), 46 g/L protein, but no malignant cells. The main etiologies of exudative ascites were excluded. She had markedly elevated anti-nuclear antibody (ANA) titer of 1/1600 and a significantly elevated titer of antibody to double-stranded DNA (83 IU/mL) with hypo-complementemia (C3 levl was at 67 mg/dL). Antibody against the Smith antigen was also positive. Relying on these findings, the patient was diagnosed with SLE and treated with Hydroxychloroquine 200 mg daily in combination with diuretics. One month later, there was no detectable ascitic fluid and no pleural effusions. Five months later she remained free from symptoms while continuing to take chloroquine. This case was characterized by old age of onset of SLE, the extremely rare initial presentation with lupus peritonitis and massive painful ascites with dramatic response to only hydroxychloroquine treatment.

  15. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  16. Posttransplant Lymphoproliferative Disorder in a Patient with Worsening Ascites after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Harsh D. Patel

    2017-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a spectrum of diseases that involves abnormal lymphoid and/or plasmacytic proliferation in patients with solid organ or hematopoietic cell transplantation. It is a condition with a low incidence of 3.5–4.3% in liver transplant (LT recipients. This case involves a 63-year-old male with history of LT for chronic HCV induced cirrhosis who presented with abdominal distension related to worsening ascites. Cytological ascitic fluid analysis revealed EBV (+ malignant cells without a malignant focal point on imaging. Diagnosis of monomorphic PTLD with primary effusion lymphoma-like morphology and immunophenotype was established. This case highlights the complexity in diagnosis, different diagnostic modalities, and rare clinical presentations of PTLD.

  17. Ascite meconial - relato de caso

    Directory of Open Access Journals (Sweden)

    Celeste Gomez Sardinha Oshiro

    2016-10-01

    Full Text Available INTRODUÇÃO: A ascite meconial resultante da perfuração intestinal fetal tem baixa incidência (1:30.000 nascimentos e elevada mortalidade (50%. Os achados ecográficos fetais incluem ascite e calcificações intra-abdominais. OBJETIVO: Relatar um caso de ascite meconial neonatal no Conjunto Hospitalar de Sorocaba. METODOLOGIA: Descrição do referido caso e revisão de literatura. RELATO DE CASO: Recém-nascido de J.A.P., masculino, de parto cesáreo por iteratividade em 12/05/2016, cuja mãe com 44 anos, sem intercorrências no pré-natal, negou consanguinidade, vícios e infecções; ultrassonografia obstétrica evidenciou ascite moderada, circunferência abdominal >p95, hepatomegalia e hidrocele. Ao nascimento, idade gestacional 3 8 2 /7 semanas, peso=3630g, comprimento=49 cm, Apgar 8/9. Apresentava abdome globoso, fígado a 4 cm do rebordo costal direito e hidrocele volumosa. Realizada paracentese com saída de 310 ml de líquido esverdeado (meconial. No 5o dia de vida, durante laparotomia, observou-se aderência de alças intestinais, perfuração de íleo terminal a 8 cm da vávula íleo-cecal, sendo realizada ileostomia. O anátomo-patológico de apêndice cecal evidenciou processo inflamatório crônico, neovascularização e fibrose. Paciente recebeu nutrição parenteral por 14 dias; houve progressão da dieta do 6o ao 36o dia de vida, recebendo alta em aleitamento materno e boa recuperação clínica. CONCLUSÃO: A ascite meconial por perfuração intestinal deve ser considerada no diagnóstico diferencial de ascite fetal. O diagnóstico ecográfico pré-natal é fundamental para o prognóstico pós-natal.

  18. Eosinophilic ascites due to severe eosinophilic ileitis.

    Science.gov (United States)

    Setia, Namrata; Ghobrial, Peter; Liron, Pantanowitz

    2010-09-17

    There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

  19. Successful radiation treatment of chylous ascites following pancreaticoduodenectomy

    International Nuclear Information System (INIS)

    Corradini, Stefanie; Niemoeller, Olivier M.; Liebig, Sylke; Zwicker, Felix; Lamade, Wolfram

    2015-01-01

    Chylous ascites is a rare complication following pancreaticoduodenectomy. We report on a case of chylous ascites following pancreaticoduodenectomy in a 76-year-old patient diagnosed with pancreatic cancer. There are various known conservative management strategies, including dietary measures or total parenteral nutrition. Unfortunately, conservative treatment - with total parenteral nutrition and fasting over a period of 4 weeks - was not successful in the present case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on clinical experiences with successfully treated lymphocutaneous fistulas, low-dose radiotherapy was initiated. External beam radiotherapy comprising a total dose of 8.0 Gy to the paraaortic lymph node region was administered in daily single fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in complete resolution after 2 weeks. There was no clinical evidence of chylous ascites on follow-up. As a result of this experience, we believe that external beam radiotherapy should be considered as an alternative therapy in refractory cases of chylous ascites. (orig.) [de

  20. Cirrhosis related chylous ascites successfully treated with TIPS.

    Science.gov (United States)

    de Vries, G J; Ryan, B M; de Bièvre, M; Driessen, A; Stockbrugger, R W; Koek, G H

    2005-04-01

    We describe a patient with chylous ascites, who was extensively investigated for the cause. No malignant or lymphatic disease could be found, but a liver biopsy revealed liver cirrhosis. The chylous ascites was unsuccessfully treated with a sodium restriction diet, diuretics and a medium chain triglyceride diet. After the placement of a transjugular intrahepatic portosystemic shunt the ascites disappeared.

  1. Distribution of pleural effusion associated with ascites on abdominal CT

    Energy Technology Data Exchange (ETDEWEB)

    Bae, In Young; Park, Chan Sup; Yeon, Jae Woo; Jeon, Yong Sun; Choi, Sung Kyu; Chung, Won Kyun [Inha Univ. Hospital, Songnam (Korea, Republic of)

    1997-04-01

    To determine through an analysis of the location of pleural effusion associated with ascites, as seen on abdominal CT scan, differences in the distribution of pleural effusion according to the etiology and distribution of ascites. We retrospectively evaluated 77 consecutive patients in whom abdominal CT scan revealed pleural effusion associated with ascites. Patients with history of surgery or trauma and those with clinically and radiologically diagnosed lung or pleural diseases were excluded. We compared the location of pleural effusion with the etiology and distribution of ascites. Forty-two patients were suffering from hepatobiliary diseases, mainly right dominant pleural effusion (26/42, 62%). Fourteen had intraperitoneal carcinomatosis with no significant difference between the frequency of right dominant (5/14, 36%) and of left dominant (6/14, 43%) pleural effusion. Eleven patients had pancreatic diseases, with mainly left dominant pleural effusion (6/11, 55%). Patients with right dominant ascites usually had right dominant pleural effusion (22/24, 92%) and those with left dominant ascites had left dominant pleural effusion (9/10, 90%). Ascites-associated pleural effusion correlated with the anatomical location of the etiology of ascites; its laterality was, in addition, usually the same as that of ascites.

  2. Distribution of pleural effusion associated with ascites on abdominal CT

    International Nuclear Information System (INIS)

    Bae, In Young; Park, Chan Sup; Yeon, Jae Woo; Jeon, Yong Sun; Choi, Sung Kyu; Chung, Won Kyun

    1997-01-01

    To determine through an analysis of the location of pleural effusion associated with ascites, as seen on abdominal CT scan, differences in the distribution of pleural effusion according to the etiology and distribution of ascites. We retrospectively evaluated 77 consecutive patients in whom abdominal CT scan revealed pleural effusion associated with ascites. Patients with history of surgery or trauma and those with clinically and radiologically diagnosed lung or pleural diseases were excluded. We compared the location of pleural effusion with the etiology and distribution of ascites. Forty-two patients were suffering from hepatobiliary diseases, mainly right dominant pleural effusion (26/42, 62%). Fourteen had intraperitoneal carcinomatosis with no significant difference between the frequency of right dominant (5/14, 36%) and of left dominant (6/14, 43%) pleural effusion. Eleven patients had pancreatic diseases, with mainly left dominant pleural effusion (6/11, 55%). Patients with right dominant ascites usually had right dominant pleural effusion (22/24, 92%) and those with left dominant ascites had left dominant pleural effusion (9/10, 90%). Ascites-associated pleural effusion correlated with the anatomical location of the etiology of ascites; its laterality was, in addition, usually the same as that of ascites

  3. Ascites Neutrophil Gelatinase-Associated Lipocalin Identifies Spontaneous Bacterial Peritonitis and Predicts Mortality in Hospitalized Patients with Cirrhosis.

    Science.gov (United States)

    Cullaro, Giuseppe; Kim, Grace; Pereira, Marcus R; Brown, Robert S; Verna, Elizabeth C

    2017-12-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of both tissue injury and infection. Urine NGAL levels strongly predict acute kidney injury and mortality in patients with cirrhosis, but ascites NGAL is not well characterized. We hypothesized that ascites NGAL level is a marker of spontaneous bacterial peritonitis (SBP) and mortality risk in patients with cirrhosis. Hospitalized patients with cirrhosis and ascites undergoing diagnostic paracentesis were prospectively enrolled and followed until death or discharge. Patients with secondary peritonitis, prior transplantation, or active colitis were excluded. NGAL was measured in the ascites and serum. Ascites NGAL level was evaluated as a marker of SBP (defined as ascites absolute neutrophil count > 250 cells/mm 3 ) and predictor of in-patient mortality. A total of 146 patients were enrolled, and of these, 29 patients (20%) had SBP. Baseline characteristics were similar between subjects with and without SBP. Median (IQR) ascites NGAL was significantly higher in patients with SBP compared to those without SBP (221.3 [145.9-392.9] vs. 139.2 [73.9-237.2], p peritonitis in hospitalized patient with cirrhosis and an independent predictor of short-term in-hospital mortality, even controlling for SBP and MELD.

  4. 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.

  5. Ascites: Pathogenesis and therapeutic principles

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H; Bendtsen, Flemming

    2009-01-01

    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...... antagonists and vasoconstrictors. Since formation of ascites is associated with a poor prognosis, and treatment of fluid retention does not substantially improve survival, such patients should always be considered for liver transplantation....

  6. Eosinophilic ascites due to severe eosinophilic ileitis

    Directory of Open Access Journals (Sweden)

    Setia Namrata

    2010-01-01

    Full Text Available Background: There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. Case Presentation: A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Conclusion: Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

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

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Grønbæk, Henning; Hansen, Jesper Bach

    2012-01-01

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

  8. Coccidioidomycosis Masquerading as Eosinophilic Ascites.

    Science.gov (United States)

    Alavi, Kourosh; Atla, Pradeep R; Haq, Tahmina; Sheikh, Muhammad Y

    2015-01-01

    Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as "Valley Fever," is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm(3), and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

  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. 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

  11. The clinical diagnostic value of determination of contents of HCG and β-HCG in ascitic and pleural effusion fluid for differentiating malignant from benign diseases

    International Nuclear Information System (INIS)

    Li Jiangang; Ji Zhigu; Zhu Zili; Xu Ping; Liu Yun; Lu Xiaopeng; Zhang Fuming

    2007-01-01

    Objective: To investigate the chinical value of effusion fluid HCG and β-HCG content determination in the differentiation of malignant from benign disorders. Methods: Fluid contents of HCG and β-HCG were determined with RIA in (1) 50 cases with benign pleural effusion. (2) 50 eases with benign ascites. (3) 79 cases with malignant pleural effusion. (4) 78 eases with malignant ascites and (5) 13 cases with malignant pericardial effusion. Results: (1) No false positive cases were present among the 100 benign eases, suggesting a high specificity with HCG and β-HCG determination. (2) Positive rate of HCG in malignancy: malignant pleural effusion, 55.64% (44/79), malignant ascites, 43.58% (34/76), malignant pericardial effusion 92.30% (12/13). (3) Positive rate of β-HCG in malignancy: malignant pleura[ effusion, 62.02% (49/79), malignant ascites, 66.66% (52/78), malignant pericardial effusion, 92.30% (12/13). (4) Coincidence of 91 eases of positive exfoliative cytology and tumor markers: HCG, 65.93% (60/91), β-HCG 73.62% (67/91), combined HCG and β-HCG, 47.25% (43/91). (5) In 79 eases with negative cytology, HCG was positive in 50 eases (63.29%) and β-HCG was positive in 60 cases (75.94%). A remarkable event was: both HCG and β-HCG were positive in 6 cases of malignant pericardial effusion with negative cytology. (6) In malignant pleural effusions, positive rate of HCG was much higher in the 14 eases with squamous cell carcinoma (78.57%, 11/14) than that in the 33 eases with adenocarcinoma (48.48%), 16/33) (P <0.05), therefore, HCG was the marker of choice in eases with effusion from squamous cell carcinoma. Conclusion: In the abscence of pregnancy, malignancy is highly probable with positive HCG or β-HCG in ascitic or pleural effusion fluid and the diagnosis is almost certain with combined positiveness. (authors)

  12. The effect of vinblastine on DNA metabolism in tumour cells

    International Nuclear Information System (INIS)

    Cabela, E.; Klein, W.

    1976-01-01

    Studies on the influence of Vinblastine on normal and tumor cells show that semiconservative DNA-synthesis correlates with the enzymatic activity of thymidinkinase. DNA-repair-investigations performed with Yoshida-Ascites cells indicate an inhibition effect on the ligase system after Vinblastine-treatment and gamma irradiation. (author)

  13. [Postsurgical chylous ascites: case report and literature review].

    Science.gov (United States)

    Olivar Roldán, J; Fernández Martínez, A; Martínez Sancho, E; Díaz Gómez, J; Martín Borge, V; Gómez Candela, C

    2009-01-01

    Chylous ascites derives from chyle leakage into the peritoneal cavity, either due to rupture or obstruction of abdominal lymphatic vessels. The main clinical sign is abdominal distention, while diagnosis requires the presence of triglycerides in ascitic fluid. Neoplasms are the most common cause of chylous ascites, although less common causes, such as abdominal surgery, should also be considered. The mainstay of therapy is hyperproteic diet with fat restriction and middle-chain triglycerides. Parenteral nutrition is reserved for cases in which dietary treatment fails to restore an optimal nutritional status or is contraindicated, whereas surgery is considered for patients that are deemed refractory to conservative therapy. We present a case of chylous ascites secondary to retroperitoneal lymphadenectomy.

  14. Clinical Meaning of Ascites in Patients with Endomyocardial Fibrosis

    Directory of Open Access Journals (Sweden)

    Barretto Antonio Carlos Pereira

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%. Eighty-one (50.6% had biventricular, 28 (17.5% had right ventricular, and 51 (31.8% had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8% patients, and right ventricular involvement was present in 59 (88%. In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively. Patients with ascites had a higher incidence of edema (95% vs. 43%, hepatomegaly (5.8cm vs. 4.1cm, mean right atrium pressure (19.3 vs. 12mmHg, and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg. Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively and had atrial fibrillation more frequently (44.7% vs. 30.1%. CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.

  15. CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

    1999-06-01

    On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

  16. Ultrasonic Diagnosis of Fetal Ascites and Toxoplasmosis

    DEFF Research Database (Denmark)

    Blaakær, Jan

    1986-01-01

    The ultrasonic diagnosis of fetal ascites caused by Toxoplasma Gondii is presented. When a diagnosis of fetal ascites without obvious etiological malformation is established, toxoplasmosis should be suspected. A serological test should be performed, in view of the possibility of antenatal treatme...

  17. Coccidioidomycosis Masquerading as Eosinophilic Ascites

    Directory of Open Access Journals (Sweden)

    Kourosh Alavi

    2015-01-01

    Full Text Available Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as “Valley Fever,” is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA. A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG, PMN count >250/mm3, and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

  18. Congenital transmesenteric hernia presenting as neonatal ascites

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    Andreia Felizes

    2018-01-01

    Full Text Available Transmesenteric hernia is an internal hernia without sac, which forms through a congenital mesentery defect. Mostly diagnosed intraoperatively, it as a variable prognosis, which can lead to high morbidity and mortality.The authors describe a case of transmesenteric hernia that presented as isolated fetal ascites. A 34 week preterm baby was delivered by forceps, with respiratory compromise due to abdominal distension. Orotracheal intubation and evacuation paracentesis were performed. After excluding major causes of neonatal ascites and persistent bowel loop distension, the newborn underwent an exploratory laparotomy, where a transmesenteric hernia and pellets of meconium were identified. Hernia reduction, enterectomy and enterostomies were performed, with good outcome. Cystic fibrosis was diagnosed during post-operatory period.This is the first reported case of transmesenteric hernia presenting as fetal ascites, without associated morbidity or mortality due to an early intervention. Keywords: Transmesenteric hernia, Fetal ascites, Cystic fibrosis

  19. RhoC is essential for TGF-β1-induced invasive capacity of rat ascites hepatoma cells

    International Nuclear Information System (INIS)

    Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M.

    2006-01-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-β1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-β1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-β1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-β1 in MM1 cells plays a critical role in TGF-β1-induced cell migration

  20. Tumor cell proliferation kinetics and tumor growth rate

    Energy Technology Data Exchange (ETDEWEB)

    Tubiana, M

    1989-01-01

    The present knowledge on the growth rate and the proliferation kinetics of human tumor is based on the measurement of the tumor doubling times (DT) in several hundred patients and on the determination of the proportion of proliferating cells with radioactive thymidine or by flow cytometry in large numbers of patients. The results show that the DT of human tumor varies widely, from less than one week to over one year with a median value of approximately 2 months. The DTs are significantly correlated with the histological type. They depend upon (1) the duration of the cell cycle whose mean duration is 2 days with small variations from tumor to tumor, (2) the proportion of proliferating cells and consequently the cell birth rate which varies widely among tumors and which is significantly correlated to the DT, (3) the cell loss factors which also vary widely and which are the greatest when proliferation is most intensive. These studies have several clinical implications: (a) they have further increased our understanding of the natural history of human tumor, (b) they have therapeutic implications since tumor responsiveness and curability by radiation and drugs are strongly influenced by the cell kinetic parameters of the tumor, (c) the proportion of proliferating cells is of great prognostic value in several types of human cancers. The investigation of the molecular defects, which are correlated with the perturbation of control of cell proliferation, should lead to significant fundamental and therapeutic advances. (orig.).

  1. Tumor cell surface proteins

    International Nuclear Information System (INIS)

    Kennel, S.J.; Braslawsky, G.R.; Flynn, K.; Foote, L.J.; Friedman, E.; Hotchkiss, J.A.; Huang, A.H.L.; Lankford, P.K.

    1982-01-01

    Cell surface proteins mediate interaction between cells and their environment. Unique tumor cell surface proteins are being identified and quantified in several tumor systems to address the following questions: (i) how do tumor-specific proteins arise during cell transformation; (ii) can these proteins be used as markers of tumor cell distribution in vivo; (iii) can cytotoxic drugs be targeted specifically to tumor cells using antibody; and (iv) can solid state radioimmunoassay of these proteins provide a means to quantify transformation frequencies. A tumor surface protein of 180,000 M/sub r/ (TSP-180) has been identified on cells of several lung carcinomas of BALB/c mice. TSP-180 was not detected on normal lung tissue, embryonic tissue, or other epithelial or sarcoma tumors, but it was found on lung carcinomas of other strains of mice. Considerable amino acid sequence homology exists among TSP-180's from several cell sources, indicating that TSP-180 synthesis is directed by normal cellular genes although it is not expressed in normal cells. The regulation of synthesis of TSP-180 and its relationship to normal cell surface proteins are being studied. Monoclonal antibodies (MoAb) to TSP-180 have been developed. The antibodies have been used in immunoaffinity chromatography to isolate TSP-180 from tumor cell sources. This purified tumor antigen was used to immunize rats. Antibody produced by these animals reacted at different sites (epitopes) on the TSP-180 molecule than did the original MoAb. These sera and MoAb from these animals are being used to identify normal cell components related to the TSP-180 molecule

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

    Energy Technology Data Exchange (ETDEWEB)

    Slyshenkov, Vyacheslav S.; Rakowska, Mariola; Wojtczak, Lech [Polska Akademia Nauk, Warsaw (Poland). Inst. Biologii Doswiadczalnej

    1996-12-31

    Preincubation of Ehrlich ascites tumour cells with millimolar concentrations of pantothenic acid, pantothenol or panthethine, but not with homopantothenic acid, at 22 C or 32 C, but not at 0 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 [{sup 14}C]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 and Wojtczak, L. (1995) Free Radical Biol. Med. 19, 767-772]. (author). 9 refs, 2 figs, 1 tab.

  3. Peritonite meconial como diagnóstico diferencial de ascite fetal: relato de caso Meconium peritonitis in the differential diagnosis of fetal ascites: a case report

    Directory of Open Access Journals (Sweden)

    Melania Maria Ramos de Amorim

    1999-07-01

    include fetal ascites and intra-abdominal calcifications. Evidence suggests that prenatal diagnosis can improve postnatal prognosis. Case Report: R.C.M.S., 22 years, II pregnancy O para, presented ultrasound (12/02/98 with diagnosis of fetal ascites. Investigation for hydrops fetalis was performed and immune and nonimmune causes were excluded. Severe fetal ascites persisted on subsequent ultrasound examinations, without calcifications. Vaginal delivery occurred at 36 weeks (01/02/99, with polyhydramnios. Female neonate weighing 2,670 g, with signs of respiratory distress, abdominal distension and petechiae. Abdominal distension worsened progressively, with palpation of a petrous tumor in the right upper quadrant and elimination of white mucus at rectal examination. Radiological findings (01/04/99 were disseminated abdominal calcifications, intestinal dilatation and absence of gas at rectal ampulla. Exploratory laparotomy was indicated with diagnosis of meconium peritonitis. A giant meconium cyst and ileal atresia were observed and lysis of adhesions and ileostomy were performed. Initial postoperative evolution was satisfactory but was subsequently complicated by sepsis and neonatal death occurred (01/09/99. Conclusion: meconium peritonitis should be remembered at differential diagnosis of fetal ascites. In the present case, surgical indication could be anticipated if prenatal diagnosis were established, with improvement of neonatal evolution.

  4. Development and characteristics of a subline of Ehrlich ascites carcinoma cells persistently resistant to 5-fluoro-2'-deoxyuridine.

    Science.gov (United States)

    Jastreboff, M M; Zielińska, Z M

    1983-01-01

    A subline of Ehrlich ascites carcinoma (EAC) cells resistant to 5-fluoro-2'-deoxy-uridine (FdUrd) was developed by continuous exposure to progressively increasing concentrations of the drug (35-75 mg/kg per day) during 15 passages through mice. Since then, the EAC cells have been retransplanted more than 80 times through drug-untreated mice and continue to be resistant. After adaptation to growth in suspension culture the drug-adapted cells were 1000 times more resistant to FdUrd in comparison with parental ones, and remained near-tetraploid with doubling time longer than in parental line. The activity of thymidine kinase was deeply depressed (100-fold) whereas that of thymidylate synthetase several-fold increased in the resistant EAC cells, both grown in vivo and in vitro.

  5. Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using cytokeratin gating

    International Nuclear Information System (INIS)

    Haustermans, K.; Hofland, I.; Ramaekers, M.; Ivanyi, D.; Balm, A.J.M.; Geboes, K.; Lerut, T.; Schueren, E. van der; Begg, A.C.

    1996-01-01

    Purpose: To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies. Material and methods: A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor. Results: The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. >From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors. Conclusions: We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements

  6. Radioimmunoassay of aldosterone in ascitic fluid

    Energy Technology Data Exchange (ETDEWEB)

    Maleeva, A; Kekhajova, M [Nauchno-Izsledovatelski Inst. po Radiologiya i Radiatsionna Khigiena, Sofia (Bulgaria)

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level.

  7. Radioimmunoassay of aldosterone in ascitic fluid

    International Nuclear Information System (INIS)

    Maleeva, A.; Kekhajova, M.

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level

  8. Improved migration of tumor ascites lymphocytes to ovarian cancer microenvironment by CXCR2 transduction

    DEFF Research Database (Denmark)

    Idorn, Manja; Olsen, Maria; Halldórsdóttir, Hólmfrídur Rósa

    2018-01-01

    Chemokines are essential mediators of cellular trafficking, interactions and tumor development. Though adoptive cell therapy (ACT) has been a tremendous success in the treatment of metastatic melanoma (MM), a major obstacle for successful ACT, is limited homing of effector T cells to immune...

  9. Pancreatobiliary Reflux Resulting in Pancreatic Ascites and Choleperitoneum after Gallbladder Perforation

    Directory of Open Access Journals (Sweden)

    Rachele Rapetti

    2008-11-01

    Full Text Available A 65-year-old man with chronic hepatitis C and no history of alcohol abuse was admitted to our liver unit for the recent development of massive ascites and presumed hepatorenal syndrome. In the preceding two weeks, he had received medical treatment for acute pancreatitis and cholecystitis. Abdominal paracentesis demonstrated a cloudy, orange peritoneal fluid, with total protein concentration 3.6 g/dl, serum-ascites albumin gradient 1.0 g/dl, and ratios of ascites-serum bilirubin and amylase approximately 8:1. Diagnostic imaging demonstrated no pancreatic pseudocysts. Ten days later, at laparotomy, acalculous perforation of the gallbladder was identified. After cholecystectomy, amylase concentration in the ascitic fluid dropped within a few days to 40% of serum values; ascites disappeared within a few weeks. We conclude that in the presence of a perforated gallbladder, pancreatobiliary reflux was responsible for this unusual combination of choleperitoneum and pancreatic ascites, which we propose to call pancreatobiliary ascites.

  10. 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)

    Goncharenko, E.N.; Gorskaya, T.G.; Gusareva, Eh.V.; Konstantinova, M.M.; Panyushkina, N.V.; AN SSSR, Moscow. Inst. Biologii Razvitiya)

    1976-01-01

    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

  11. Transient elastography with the XL probe rapidly identifies patients with nonhepatic ascites

    Directory of Open Access Journals (Sweden)

    Mueller S

    2012-05-01

    Full Text Available Anna Kohlhaas1, Esteban Durango1, Gunda Millonig1, Cecile Bastard2, Laurent Sandrin2, Mohammad Golriz3, Arianeb Mehrabi3, Markus W Büchler3, Helmut Karl Seitz1, Sebastian Mueller11Department of Medicine and Center for Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, Heidelberg, Germany; 2Department of Research and Development, Echosens, Paris, France; 3Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyBackground: In contrast with other elastographic techniques, ascites is considered an exclusion criterion for assessment of fibrosis stage by transient elastography. However, a normal liver stiffness could rule out hepatic causes of ascites at an early stage. The aim of the present study was to determine whether liver stiffness can be generally determined by transient elastography through an ascites layer, to determine whether the ascites-mediated increase in intra-abdominal pressure affects liver stiffness, and to provide initial data from a pilot cohort of patients with various causes of ascites.Methods and results: Using the XL probe in an artificial ascites model, we demonstrated (copolymer phantoms surrounded by water that a transient elastography-generated shear wave allows accurate determination of phantom stiffness up to a water lamella of 20 mm. We next showed in an animal ascites model that increased intra-abdominal pressure does not affect liver stiffness. Liver stiffness was then determined in 24 consecutive patients with ascites due to hepatic (n = 18 or nonhepatic (n = 6 causes. The cause of ascites was eventually clarified using routine clinical, imaging, laboratory, and other tools. Valid (75% or acceptable (25% liver stiffness data could be obtained in 23 patients (95.8% with ascites up to an ascites lamella of 39 mm. The six patients (25% with nonhepatic causes of ascites (eg, pancreatitis, peritoneal carcinomatosis had a

  12. Transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites

    International Nuclear Information System (INIS)

    Zhu Wenke; Shan Hong; Zhu Kangshun; Jiang Zaibo; Li Zhengran; Huang Mingsheng; Guan Shouhai; Shen Xinying

    2004-01-01

    Objective: To assess the clinical efficacy of TIPS in the treatment of patients with refractory ascites and investigate the clinical factors associated with TIPS. Methods: 21 consecutive patients with refractory ascites, 16 men and 5 women with mean age of 45 years (range 22-69 years) were followed up for an average of 337 days (range 50-1323 days). Ascites/abdomen circumference, serum parameters, stents function, time of followed up and survival rate were analyzed. Results: The ascites was significantly reduced as compared with basal values (P<0.05). 81% and 91% patients had no or mild ascites during 3 to 6 months and 9 to 12 after TIPS respectively. According to responses to treatment within 3 months, using Logistic regression predicated the control of ascites with relation to Child class C for severe prognosis (P<0.05). There were significant change in serum sodium, serum creatinine as compared with baseline at follow-up (P<0.05). Their mortality were 14% during follow-up for 3 months, 20% in 6 and the survival rate was 72% at 1 year. According to COX regression analysis showed that age, Child class C, serum albumin, hepatic encephalopathy, serum total bilirubin were related to severe prognosis; but only hepatic encephalopathy and Child class C had an effect on survival rate. Conclusion: TIPS is an effective method for refractory ascite caused by hepatitis cirrhosis, and also effective for patients with functional renal failure but retaining of liver compensation

  13. Transfer of intestine-derived diamines into tumour cells during treatment of Ehrlich-ascites--carcinoma-bearing mice with polyamine anti-metabolites.

    Science.gov (United States)

    Kallio, A; Nikula, P; Jänne, J

    1984-01-01

    Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells. Difluoromethylornithine alone did not have any effect on the accumulation of intestine-derived diamines in the tumour cells. The frequently reported restoration of difluoromethylornithine-induced polyamine depletion on administration of methylglyoxal bis(guanylhydrazone) is in all likelihood attributable to a profound inhibition of intestinal diamine oxidase (EC 1.4.3.6), resulting in an enhanced entry of intestinal (bacterial) diamines into general circulation and finally into tumour cells. PMID:6424664

  14. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Joana Maia

    2018-02-01

    Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

  15. The behavior of the vascular system in the experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Yamaura, Hirotsugu; Matsuzawa, Taiju; Sato, Haruo; Ito, Yasuhiko.

    1975-01-01

    The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm 3 of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of 60 Co γ-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R. (auth.)

  16. Application of lectins to tumor imaging radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kojima, Shuji; Jay, M.

    1986-01-01

    We investigated the in vitro binding of 125 I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of 125 I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of 125 I-lectins showed 125 I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of 125 I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid disappearance of the radioactivity from blood and its excretion into kidney soon after injection of 125 I-PSA were observed. When compared with the biodistribution of 67 Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for 125 I-PSA. At 6 h postinjection, the T/B-ratio of 125 I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical. (orig.)

  17. Percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the diaphragm and gastrointestinal tracts with the use of artificial ascites: safety and technical efficacy in 143 patients

    International Nuclear Information System (INIS)

    Song, Inyoung; Rhim, Hyunchul; Lim, Hyo K.; Kim, Young-sun; Choi, Dongil

    2009-01-01

    The purpose of this study was to assess the feasibility, safety and efficacy of radiofrequency ablation (RFA) with the use of artificial ascites for hepatocellular carcinoma (HCC) adjacent to the diaphragm and gastrointestinal tract. One hundred forty-three patients with 181 HCCs who underwent US-guided percutaneous RFA with the use of artificial ascites were retrospectively reviewed. Among the 181 HCCs, 148 HCCs were defined as problematic nodules for two major reasons: poor sonic window or possible thermal injury. We artificially induced ascites before performing RFA by dripping 5% dextrose in a water solution. We assessed the technical success of introducing artificial ascites, technical feasibility of the use of artificial ascites and complications. The technical success rate, as well as the primary and secondary technique success rate, was assessed by regular follow-up CT examinations. RFA with artificial ascites was successfully achieved in 130 of 143 patients. The primary technique effectiveness was 85.3%. During follow-up (mean, 20.4 months), remote intrahepatic recurrence occurred in 49 patients and local tumor progression occurred in 15 patients. Three (2.1%) of the 143 patients experienced major complications (hemoperitoneum, lobar infarction and biloma) related to the RFA procedure. The use of artificial ascites is a simple and useful technique to minimize collateral thermal injury and to improve the sonic window. (orig.)

  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...... 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, demonstrating a role...... 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...

  19. 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.

  20. Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

    Directory of Open Access Journals (Sweden)

    Yan-gao Man, Alexander Stojadinovic, Jeffrey Mason, Itzhak Avital, Anton Bilchik, Bjoern Bruecher, Mladjan Protic, Aviram Nissan, Mina Izadjoo, Xichen Zhang, Anahid Jewett

    2013-01-01

    Full Text Available It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.

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

    International Nuclear Information System (INIS)

    Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

    2014-01-01

    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 TCD 50 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

  2. Congenital chylous ascites in infants: another presentation of intestinal malrotation.

    Science.gov (United States)

    Long, Li; Zhen, Chen; Yandong, Wei; Ning, Dong; Qi, Li; Qing, Gao

    2018-03-01

    The cause of the chylous ascites in infants isn't completely clear. The purpose of this study is to discuss our experience of recognition of intestinal malrotation as a cause of congenital chylous ascites in infants. Medical information of 10 infants with chylous ascites, who were admitted to the hospital between 2001 and 2014, was retrospective analyzed. Preoperatively, all patients underwent a period of conservative treatment. We found that nine of ten patients with intestinal malrotation, six of them underwent laparoscopic Ladd's procedure and three patients underwent open Ladd's procedure. The remaining one patient suffered from mesenteric lymph nodes rupture and laparoscopic resection was performed. The cylous ascites subsided in all patients after the surgery and no significant recurrence was encountered during follow-up time. Our study demonstrates that congenital chylous ascites could be caused by intestinal malrotation, causing the obstruction of the lymphatic flow in the mesenteric lymphatic channels. Ladd's procedure maybe a safe and effective treatment for infantile intractable chylous ascites. Treatment study. Level IV. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    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.

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

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    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. Tumor stem cells: A new approach for tumor therapy (Review)

    Science.gov (United States)

    MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

    2012-01-01

    Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

  6. Core temperature rhythms in normal and tumor-bearing mice.

    Science.gov (United States)

    Griffith, D J; Busot, J C; Lee, W E; Djeu, D J

    1993-01-01

    The core temperature temporal behavior of DBA/2 mice (11 normal and 13 with an ascites tumor) was studied using surgically implanted radio telemetry transmitters. Normal mice continuously displayed a stable 24 hour temperature rhythm. Tumor-bearers displayed a progressive deterioration of the temperature rhythm following inoculation with tumor cells. While such disruptions have been noted by others, details on the dynamics of the changes have been mostly qualitative, often due to time-averaging or steady-state analysis of the data. The present study attempts to quantify the dynamics of the disruption of temperature rhythm (when present) by continuously monitoring temperatures over periods up to a month. Analysis indicated that temperature regulation in tumor-bearers was adversely affected during the active period only. Furthermore, it appears that the malignancy may be influencing temperature regulation via pathways not directly attributable to the energy needs of the growing tumor.

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

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    C.M. Souza

    2014-10-01

    Full Text Available 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. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

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

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    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.

  9. Genetic parameters of body weight and ascites in broilers: effect of different incidence rates of ascites syndrome.

    Science.gov (United States)

    Ahmadpanah, J; Ghavi Hossein-Zadeh, N; Shadparvar, A A; Pakdel, A

    2017-02-01

    1. The objectives of the current study were to investigate the effect of incidence rate (5%, 10%, 20%, 30% and 50%) of ascites syndrome on the expression of genetic characteristics for body weight at 5 weeks of age (BW5) and AS and to compare different methods of genetic parameter estimation for these traits. 2. Based on stochastic simulation, a population with discrete generations was created in which random mating was used for 10 generations. Two methods of restricted maximum likelihood and Bayesian approach via Gibbs sampling were used for the estimation of genetic parameters. A bivariate model including maternal effects was used. The root mean square error for direct heritabilities was also calculated. 3. The results showed that when incidence rates of ascites increased from 5% to 30%, the heritability of AS increased from 0.013 and 0.005 to 0.110 and 0.162 for linear and threshold models, respectively. 4. Maternal effects were significant for both BW5 and AS. Genetic correlations were decreased by increasing incidence rates of ascites in the population from 0.678 and 0.587 at 5% level of ascites to 0.393 and -0.260 at 50% occurrence for linear and threshold models, respectively. 5. The RMSE of direct heritability from true values for BW5 was greater based on a linear-threshold model compared with the linear model of analysis (0.0092 vs. 0.0015). The RMSE of direct heritability from true values for AS was greater based on a linear-linear model (1.21 vs. 1.14). 6. In order to rank birds for ascites incidence, it is recommended to use a threshold model because it resulted in higher heritability estimates compared with the linear model and that BW5 could be one of the main components of selection goals.

  10. Diltiazem enhances tumor blood flow: MRI study in a murine tumor

    International Nuclear Information System (INIS)

    Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

    1999-01-01

    Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

  11. Bile ascites in adults. Diagnosis using hepatobiliary scintigraphy and paracentesis

    International Nuclear Information System (INIS)

    Nagle, C.E.; Fink-Bennett, D.; Freitas, J.E.

    1985-01-01

    Hepatobiliary scintigraphy has been recognized as a useful diagnostic tool in detecting the presence and site of bile leaks. The authors report a case of bile ascites secondary to a postsurgical biliary leak, the scintigraphic findings in bile ascites, and the potential use of paracentesis, in combination with hepatobiliary scintigraphy, in confirming the presence of bile ascites and a bile leak

  12. Metabolic turnover of pyridine nucleotides in ascites cells of sarcoma Sa 180 and in the liver tissue of rats before and after ionizing radiation

    International Nuclear Information System (INIS)

    Kunz, K.; Musil, J.

    1979-01-01

    The metabolic turnover of NADP + labeled with 14 C in the ribose moiety of their molecules was determined in the ascites cells of sarcoma Sa 180 and in the rat liver tissue. The half-lives of NAD + and NADP + in the Sa 180 sarcoma cells were 60 mins (NAD + ) and 90 mins (NADP + ), the corresponding values in the liver cells were 80 mins (NAD + ) and 120 mins (NADP + ). Experiments were conducted on animals aimed at ascertaining the time-dependent effect of ionizing radiation on the values of pooled NAD + and NADP + after 0.129 C/kg (500 R) and 0.387 C/kg (1500 R) whole-body irradiation, and the metabolic turnover of these nucleotides 5 h after whole-body irradiation with 0.387 C/kg (1500 R). Exposure to 0.129 C/kg (500 R) whole-body irradiation induced no apparent changes compared with the controls. Within 5 h of irradiation the whole-body dose of 0.387 C/kg (1500 R) produced changes in rat liver cells characterized by a reduction in the nucleotide biological half-lives (NAD + from 80 to 60 mins and NADP + from 120 to 70 mins). No such changes in the pyridine nucleotide turnover were detected in the Sa 180 ascites sarcoma cells. (author)

  13. Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice.

    Science.gov (United States)

    Esener, Obb; Balkan, B M; Armutak, E I; Uvez, A; Yildiz, G; Hafizoglu, M; Yilmazer, N; Gurel-Gurevin, E

    2018-04-12

    Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5 ml water; group 2, administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk + EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We introduced 2.5 x 10 6 EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10 days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to

  14. [Octreotide treatment for postoperative chylous ascites in an adult].

    Science.gov (United States)

    Senosiain Lalastra, Carla; Martínez González, Javier; Mesonero Gismero, Francisco; Moreira Vicente, Víctor

    2012-10-01

    Chylous ascites is infequent after abdominal surgery. We describe the case of a 43-year-old man with portal cavernomatosis who underwent surgery to insert a splenorenal shunt, which was not placed due to the absence of signs of portal hypertension. On postoperative day 20, the patient developed abdominal distension and mild dyspnea and was diagnosed with chylous ascites, which was related to the surgery. The patient was initially treated with diet and diuretics, with no clinical response, and consequently octreotide therapy was started. Four days later, the ascites was almost resolved and an ultrasound scan at 4 months showed its complete disappearance. This article demonstrates the effectiveness of octreotide in the treatment of postsurgical chylous ascites. Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  15. The role of preoperative serum cancer antigen 125 in malignant ovarian germ cell tumors

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    Ju-Hyun Kim

    2018-04-01

    Full Text Available Objective: To determine the role of preoperative serum cancer antigen 125 (CA 125 in malignant ovarian germ cell tumors (MOGCTs. Materials and methods: Using information from medical databases of Asan Medical Center (Seoul, Korea, we investigated 161 patients with histologically diagnosed MOGCTs and whose preoperative serum CA 125 had been checked. We determined the optimal cutoff value of CA 125 as > 249.5 U/mL in MOGCTs using a receiver operating characteristic curve. Results: The median patient age was 24 years (range, 6–52 years. The most common histologic type was immature teratoma. Most patients had stage I disease. Thirty-two patients (19.9% had elevated preoperative serum CA 125 levels over 249.5 U/mL. On univariate analysis, tumor size, advanced stage, the presence of ascites, ovarian surface involvement, and tumor rupture were significantly associated with elevated preoperative CA 125 levels (>249.5 U/mL. In the median follow-up time of 87 months (range, 9–271 months, 14 patients had a recurrence, and 5 died of the disease. Patients with an elevated serum preoperative CA 125 level (>249.5 U/mL had poorer disease-free survival, but this was not statistically significant. However, elevated preoperative CA 125 (>249.5 U/mL was significantly associated with poorer overall survival. Conclusions: Elevated preoperative serum CA 125 may have prognostic value in patients with MOGCTs. Keywords: CA-125 antigen, Ovarian germ cell cancer, Prognosis

  16. The behavior of the vascular system in the experimental tumor radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamaura, H; Matsuzawa, T; Sato, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer; Ito, Yasuhiko

    1975-07-01

    The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm/sup 3/ of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of /sup 60/Co ..gamma..-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R.

  17. Beta-blockers in cirrhosis and refractory ascites

    DEFF Research Database (Denmark)

    Kimer, Nina; Feineis, Martin; Møller, Søren

    2015-01-01

    OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker......-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

  18. Clinical impression and ascites appearance do not rule out bacterial peritonitis.

    Science.gov (United States)

    Chinnock, Brian; Hendey, Gregory W; Minnigan, Hal; Butler, Jack; Afarian, Hagop

    2013-05-01

    Previous research has demonstrated that physician clinical suspicion, determined without assessing fluid appearance, is not adequate to rule out spontaneous bacterial peritonitis (SBP) without fluid testing. To determine the sensitivity of physician clinical suspicion, including a bedside assessment of fluid appearance, in the detection of SBP in Emergency Department (ED) patients undergoing paracentesis. We conducted a prospective, observational study of ED patients with ascites undergoing paracentesis at three academic facilities. The enrolling physician recorded the clinical suspicion of SBP ("none," "low," "moderate," or "high"), and ascites appearance ("clear," "hazy," "cloudy," or "bloody"). SBP was defined as an absolute neutrophil count ≥ 250 cells/mm(3), or culture pathogen growth. We defined "clear" ascites fluid as negative for SBP, and "hazy," "cloudy," or "bloody" as positive. A physician clinical suspicion of "none" or "low" was considered negative for SBP, and an assessment of "moderate" or "high" was considered positive. The primary outcome measure was sensitivity of physician clinical impression and ascites appearance for SBP. There were 348 cases enrolled, with SBP diagnosed in 43 (12%). Physician clinical suspicion had a sensitivity of 42% (95% confidence interval [CI] 29-55%) for the detection of SBP. Fluid appearance had a sensitivity of 72% (95% CI 58-83%). Physician clinical impression, which included an assessment of fluid appearance, had poor sensitivity for the detection of SBP and cannot be used to exclude the diagnosis. Routine laboratory fluid analysis is indicated after ED paracentesis, even in patients considered to have a low degree of suspicion for SBP. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Variability of hydrostatic hepatic vein and ascitic fluid pressure, and of plasma and ascitic fluid colloid osmotic pressure in patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    1980-01-01

    The variability of hydrostatic hepatic vein and ascitic fluid pressures and of plasma and ascitic fluid colloid osmotic (oncotic) pressures was assessed during hepatic venous catheterization by repeated measurements on different days and at different locations in patients with cirrhosis...... of the liver. Furthermore, calculation of oncotic pressure from protein determinations was compared to the directly measured value of plasma and ascitic fluid samples. Repeated measurements of hydrostatic pressure in the same hepatic vein within 15 min showed a standard deviation (SD) below 1 mm......Hg. The variation in hydrostatic hepatic vein pressures, pressure differences and ascitic fluid pressures (when measured at different locations within the liver and peritoneal space during a single examination) was 1.5, 1.0 and 1.0 mmHg (SD), respectively. When measured on different days, the variation...

  20. Risks of PEG tube placement in patients with cirrhosis-associated ascites

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    Al-Abboodi Y

    2017-09-01

    Full Text Available Yasir Al-Abboodi,1 Ali Ridha,2 Matthew Fasullo,3 Tarek H Naguib4 1Internal Medicine Department, Saint Davis Round Rock Medical Centre, Round Rock, TX, USA, 2Internal Medicine Department, University of Arkansas for Medical Science, Little Rock, AR, USA, 3Internal Medicine Department, Umass Memorial Medical Center, Worcester, MA, USA, 4Internal Medicine Department, Texas Tech University Health and Sciences Center, Amarillo, TX, USA Abstract: This study examined the safety of placing percutaneous endoscopic gastrostomy (PEG tube in people with liver cirrhosis. The target population was further subdivided into people with ascites (case group and people without ascites (control. We compare the morbidity and the mortality difference of PEG placement in cirrhotic patients with ascites vs cirrhotic patients without ascites. We then examined multiple factors including sex, race, chronic illness including hypertension, congestive heart failure, and others and their influence on the inpatient mortality of all cirrhotic patients who had PEG placement. A total of 38,175 inpatient PEG tube placements were identified. Only 583 patients out of 38,175 had a history of cirrhosis. One hundred seven had ascites and the rest did not. Mean age of the patients was 61.14 years. Patient demography included (65.2% male and the rest were female, 359 were white (64.4%, 90 black (14.8%, 84 Hispanic (13.7%, 23 Asians (3.3%, 7 Native Americans (0.4%, and 20 others (3.5%. Complications from PEG procedure in cirrhosis with ascites vs non-ascites included bleeding of 4 (0.8% vs 2 (1.9% (P=0.35, surgical site infection 2 (0.4% vs 1 (0.9% (P=0.51, and urinary tract infection 105 (22.1% vs 34 (23.8% (P=0.34, respectively. There was no colonic injury in either group. The total inpatient mortality was 75 out of the 583. Fifty-six (11.8% were in the ascites group and 19 (17.8% in the non-ascites group (P=0.097. Factors including ascites, postsurgical bleeding, and surgical site

  1. Lymphography in chylothorax and chylous ascites

    International Nuclear Information System (INIS)

    Rabkin, I.Kh.; Lein, A.P.

    1982-01-01

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

  2. 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

  3. Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice

    Directory of Open Access Journals (Sweden)

    Fakhry S. Salem

    2011-01-01

    Full Text Available Clinicopathological studies on the effects of combining immunostimulant drugs (levamisole with anti-cancer drugs (chlorambucil revealed the enhancement of the latter against Ehrlich ascites carcinoma-bearing mice and resulted in a reduction in the size of tumour. An evaluation of liver and kidney functions showed a significant increase of alanine transaminase (ALT, aspartate transaminase (AST and creatinine in all groups. Histopathological studies of one group that received an intraperitoneal injection of Ehrlich ascites carcinoma cells (2.5 × 106 showed that hepatic parenchyma revealed degenerative changes. The portal area was oedematous and showed rounded cell aggregations. Cell death within hypertrophied Kupper cells was observed in some hepatic cells. The neoplastic emboli could be seen either inside blood vessels or hepatic sinusoids, while another group which had been treated orally with a combination of Leukeran™ (0.2 mg/kg body weight and levamisole (5 mg/kg body weight revealed that hepatic parenchyma revealed massive necrosis with proliferative bile duct epithelium. No neoplastic cells were observed without the hepatic parenchyma, while the renal cortex presented a large number of lymphocytes and plasma cells forming bands or aggregates, mainly around the blood vessels. It was concluded that the addition of levamisole to chlorambucil improved the anti-cancer effect of chlorambucil against Ehrlich ascites carcinoma. However, it had adverse effects on the liver and kidneys as shown by liver and kidney function tests and confirmed by histopathology.

  4. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  5. 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.

  6. Effect of doxorubicin/pluronic SP1049C on tumorigenicity, aggressiveness, DNA methylation and stem cell markers in murine leukemia.

    Directory of Open Access Journals (Sweden)

    Daria Y Alakhova

    Full Text Available Pluronic block copolymers are potent sensitizers of multidrug resistant cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox has completed Phase II clinical trial and demonstrated safety and efficacy in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. This study elucidates the ability of SP1049C to deplete cancer stem cells (CSC and decrease tumorigenicity of cancer cells in vivo.P388 murine leukemia ascitic tumor was grown in BDF1 mice. The animals were treated with: (a saline, (b Pluronics alone, (c Dox or (d SP1049C. The ascitic cancer cells were isolated at different passages and examined for 1 in vitro colony formation potential, 2 in vivo tumorigenicity and aggressiveness, 3 development of drug resistance and Wnt signaling activation 4 global DNA methylation profiles, and 5 expression of CSC markers.SP1049C treatment reduced tumor aggressiveness, in vivo tumor formation frequency and in vitro clonogenic potential of the ascitic cells compared to drug, saline and polymer controls. SP1049C also prevented overexpression of BCRP and activation of Wnt-β-catenin signaling observed with Dox alone. Moreover, SP1049C significantly altered the DNA methylation profiles of the cells. Finally, SP1049C decreased CD133(+ P388 cells populations, which displayed CSC-like properties and were more tumorigenic compared to CD133(- cells.SP1049C therapy effectively suppresses the tumorigenicity and aggressiveness of P388 cells in a mouse model. This may be due to enhanced activity of SP1049C against CSC and/or altered epigenetic regulation restricting appearance of malignant cancer cell phenotype.

  7. Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

    Science.gov (United States)

    Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

    2010-03-18

    Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

  8. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  9. Effect of anhydrosophoradiol-3-acetate of Calotropis gigantea (Linn.) flower as antitumoric agent against Ehrlich's ascites carcinoma in mice.

    Science.gov (United States)

    Habib, Muhammad R; Karim, Muhammad R

    2013-01-01

    Over 60% of currently used anti-cancer agents are derived in one-way or another from natural sources, including plants, marine organisms and microorganisms. Calotropis gigantea (Linn.) (Family: Asclepiadaceae) is a perennial shrub and it is used as a traditional folk medicine for the treatment of various health complications. But there is no report on isolation of anticancerous chemicals from the flower of Calotropis gigantea. The objective of the present study is to explore the antitumor effect of anhydrosophoradiol-3-acetate (A3A), isolated from the flower of Calotropis gigantea (Linn.) against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. Antitumoric effect of A3A was assessed by evaluating viable tumor cell count, survival time, body weight gain due to tumor burden, hematological and biochemical (glucose, cholesterol, triglyceride, blood urea, SALP, SGPT and SGOT) parameters of EAC bearing host at doses of 10 and 20 mg/kg body weight. Treatment with A3A decreased the viable tumor cells and body weight gain thereby increasing the life span of EAC bearing mice. A3A also brought back the altered hematological (Hb, total RBC and total WBC) and biochemical parameters more or less to normal level. Results of this study conclude that in vivo the A3A was effective in inhibiting the growth of EAC with improving in cancer induced complications.

  10. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  11. Association between ascites and primary hyperfibrinolysis : A cohort study in 210 dogs

    NARCIS (Netherlands)

    Zoia, Andrea; Drigo, Michele; Simioni, Paolo; Caldin, Marco; Piek, Christine J

    2017-01-01

    Coagulation profiles were determined in 70 dogs with ascites, 70 healthy control dogs and 70 sick control dogs without ascites. Dogs with ascites were divided into four sub-groups based on the pathophysiology of fluid formation. Coagulation profile, serum C-reactive protein and frequency of

  12. Involvement of the thoracic duct in liver cirrhosis patients with ascites. Using MR lymphography

    International Nuclear Information System (INIS)

    Kuboyama, Shin-ichi; Ishii, Kunihide; Koga, Hiroyuki

    2003-01-01

    To elucidate whether the morphological changes of the thoracic duct are observed in patients with liver cirrhosis and ascites, the thoracic duct was examined at magnetic resonance (MR) lymphography without contrast agent. In 7 healthy volunteers, the thoracic duct was clearly visualized as an intermittent or continuous straight line along the thoracic aorta (its mean diameter was 3.9 mm). In 20 liver cirrhosis without ascites, its mean diameter was 3.6 mm. In 6 liver cirrhosis with refractory ascites, the thoracic duct was visualized as straight or slightly tortuous and slender line (its mean diameter was 2.5 mm). On the other hand, 7 cases with ascites which respond well to the administration of diuretics showed tortuous and dilated thoracic duct (its mean diameter was 4.3 mm). In cases with refractory ascites, mean diameter of the thoracic duct was significantly reduced, compared with the cases without ascites and with ascites that respond well to the administration of diuretics. Thus, it was found that the morphological differences of the thoracic duct depend on the response to the diuretics in liver cirrhosis patients with ascites. To elucidate whether the morphological changes of the thoracic duct are observed in patients with liver cirrhosis and ascites, the thoracic duct was examined at magnetic resonance lymphography without contrast agent. In cases with refractory ascites, mean diameter of the thoracic duct was significantly reduced, compared with the cases without ascites and with ascites that respond well to the administration of diuretics. (author)

  13. The effects of increasing levels of dietary garlic bulb on growth performance, systolic blood pressure, hematology, and ascites syndrome in broiler chickens.

    Science.gov (United States)

    Varmaghany, Saifali; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Lotfollahian, Houshang; Hassanzadeh, Mohammad

    2015-08-01

    The effects of dietary garlic bulb were studied separately on hematological parameters, ascites incidence, and growth performance of an ascites susceptible broiler hybrid under both standard temperature conditions ( STC: ) and cold temperature conditions ( CTC: ). A total of 336 one-day-old male broiler chickens were allocated to 4 experimental groups with 4 replicates of 21 birds each under STC. In addition, the same grouping with another 336 birds was used for CTC. Under CTC, the birds were exposed to cold temperatures for induction of ascites. Experimental groups were defined by the inclusion of 0 (control), 5, 10 or 15 g/kg garlic bulbs in the diets under both STC and CTC. Growth performance, systolic blood pressure (as a measure of systemic arterial blood pressure), physiological and biochemical parameters, as well as ascites indices (right ventricle [ RV: ], total ventricle [ TV: ] weights, and RV/TV: ) were evaluated. Systolic blood pressure was determined using an indirect method with a sphygmomanometer, a pediatric cuff, and a Doppler device. The final body weight decreased quadratically (P = 0.003), with increasing garlic bulb levels in the diets under STC. The feed conversion ratio showed no significant differences among all groups under both STC and CTC. No significant differences were observed in total mortality and ascites-related mortality in all groups under STC, although total mortality (L: P = 0.01; Q: P = 0.001) and ascites-related mortality (L: P = 0.007; Q: P = 0.001) were significantly different among the diets under CTC. Under STC, the systolic blood pressure, packed cell volume, hemoglobin, RV, TV, and RV/TV did not vary significantly among the diets. However, red blood cell count and erythrocyte osmotic fragility decreased linearly (P garlic bulb levels in the diets under STC. Under CTC, the systolic blood pressure, packed cell volume, red blood cell count, and erythrocyte osmotic fragility decreased (P garlic levels. It is

  14. Heat-induced alterations in the cell nucleus

    International Nuclear Information System (INIS)

    Kampinga, H.H.

    1989-01-01

    Hyperthermia may kill eukaryotic cells and may also enhance the radiosensitivity of those cells that survive the heat treatment. Clinically, the possible use of hyperthermia as an adjuvant in the radiotherapeutic treatment of cancer needs the understanding of mechanisms that underlay heat-induced cell death and radiosensitization. By in vitro heating of established human (HeLaS3) and rodent (Ehrlich Ascites Tumor and LM fibroblast) cell lines, both killing and radiosensitization were investigated. (author). 1067 refs.; 76 figs.; 19 tabs

  15. Clinical Features of Refractory Ascites in Outpatients

    Directory of Open Access Journals (Sweden)

    Wanda Regina Caly

    Full Text Available OBJECTIVES: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R and 11 non-refractory ascites (NR]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034. The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively. Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262. CONCLUSION: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

  16. Ascitic Fluid Culture In Cirrhotic Patients With Spontaneous Bacterial Peritonitis

    International Nuclear Information System (INIS)

    Sajjad, M.; Khan, Z.A.; Khan, M.S.

    2016-01-01

    Objective: To determine the frequency and compare the culture yield of bacterial isolation by conventional and blood culture BACTEC bottle techniques in cirrhotic patients with spontaneous bacterial peritonitis (SBP). Study Design: Cross-sectional comparative study. Place and Duration of Study: Pathology Department, Bannu Medical College, Bannu, KPK, from January 2012 to December 2013. Methodology: Paracentesis of 20 ml of ascitic fluid tapped from cirrhotic patients with SBP was carried out by a single technologist. The analysis included differential leukocyte count (DLC), while 5 ml each of the fluid was inoculated into conventional culture media and BACTEC blood culture bottle. All the data were analysed on (SPSS) version 16 to determine frequencies with percentages and mean values with standard deviation. Chi-square test was used for comparing the yield of conventional and blood culture bottle methods. P-value was considered significant if < 0.05. Results: In 105 cases of ascitic fluid analyses, 27 (25.72 percent) had positive ascitic fluid culture whereas 78 (74.28 percent) had negative ascitic fluid culture. Ascitic fluid culture was positive in 6 cases by conventional culture media and in 27 cases by BACTEC culture bottle media (p < 0.001). Bacterial isolation was obtained by both culture methods in 6 cases (p < 0.001). Conclusion: Direct bedside inoculation of ascitic fluid by BACTEC culture bottle method has better yield as compared to conventional culture method. (author)

  17. Radionuclide Peritoneal Scintigraphy in Patients with Ascites and Pleural Effusion

    International Nuclear Information System (INIS)

    Lee, Jae Tae; Lee, Kyu Bo; Whang, Kee Suk; Kim, Gwang Won; Chung, Byung Chun; Cho, Dong Kyu; Chung, Joon Mo

    1990-01-01

    Simultaneous presence of ascites and pleural effusion has been documented in patients with cirrhosis of the liver, renal disease, Meigs' syndrome and in patients undergoing peritoneal dialysis. Mechanisms proposed in the formation of pleural effusion in most of the above diseases are lymphatic drainage and diaphragmatic defect. But sometimes, hepatic hydrothoraxes in the absence of clinical ascites and pleural effusion secondary to pulmonary or cardiac disease are noted. It is not always possible to differentiate between pleural effusion caused by transdiaphragmatic migration of ascites and by other causes based solely on biochemical analysis. Authors performed radionuclide scintigraphy after intraperitoneal administration of 99m Tc-labeled colloid in 23 patients with both ascites and pleural effusion in order to discriminate causative mechanisms responsible for pleural effusion. Scintigraphy demonstrated the transdiaphtagmatic flow of fluid from the peritoneum to pleural cavities in 13 patients correctly. In contrast, in 5 patients with pleural effusion secondary to pulmonary, pleural and cardiac diseases, radiotracers fail to traverse the diaphragm and localize in the pleural space. Ascites draining to mediastinal lymph nodes and blocked passage of lymphatic drainage were also clarified, additionally. Conclusively, radionuclide peritoneal scintigraphy is an accurate, rapid and easy diagnostic tool in patients with both ascites and pleural effusion. It enables the causes of pleural effusion to be elucidated, as well as providing valuable information required when determining the appropriate therapy.

  18. Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

    Science.gov (United States)

    Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

    2017-08-01

    To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. 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.

  20. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  1. Comparative proteomic analysis of human malignant ascitic fluids for the development of gastric cancer biomarkers.

    Science.gov (United States)

    Jin, Jonghwa; Son, Minsoo; Kim, Hyeyoon; Kim, Hyeyeon; Kong, Seong-Ho; Kim, Hark Kyun; Kim, Youngsoo; Han, Dohyun

    2018-04-11

    Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites

  2. Diagnostic Accuracy of Ascites Fluid Gross Appearance in Detection of Spontaneous Bacterial Peritonitis.

    Science.gov (United States)

    Aminiahidashti, Hamed; Hosseininejad, Seyed Mohammad; Montazer, Hosein; Bozorgi, Farzad; Goli Khatir, Iraj; Jahanian, Fateme; Raee, Behnaz

    2014-01-01

    Spontaneous bacterial peritonitis (SBP) as a monomicrobial infection of ascites fluid is one of the most important causes of morbidity and mortality in cirrhotic patients. This study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of SBP in cirrhotic cases referred to the emergency department. Cirrhotic patients referred to the ED for the paracentesis of ascites fluid were enrolled. For all studied patients, the results of laboratory analysis and gross appearance of ascites fluid registered and reviewed by two emergency medicine specialists. The sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ration of the ascites fluid gross appearance in detection of SBP were measured with 95% confidence interval. The present project was performed in 80 cirrhotic patients with ascites (52.5 female). The mean of the subjects' age was 56.25±12.21 years (35-81). Laboratory findings revealed SBP in 23 (29%) cases. Fifty nine (73%) cases had transparent ascites fluid appearance of whom 17 (29%) ones suffered from SBP. From 21 (26%) cases with opaque ascites appearance, 15 (71%) had SBP. The sensitivity and specificity of the ascites fluid appearance in detection of SBP were 46.88% (Cl: 30.87-63.55) and 87.50% (95% Cl: 75.3-94.14), respectively. It seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of SBP and considering its low sensitivity, it could not be used as a good screening tool for this propose.

  3. Diagnostic Accuracy of Ascites Fluid Gross Appearance in Detection of Spontaneous Bacterial Peritonitis

    Directory of Open Access Journals (Sweden)

    Hamed Aminiahidashti

    2014-08-01

    Full Text Available Introduction: Spontaneous bacterial peritonitis (SBP as a monomicrobial infection of ascites fluid is one of the most important causes of morbidity and mortality in cirrhotic patients. This study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of SBP in cirrhotic cases referred to the emergency department. Methods: Cirrhotic patients referred to the ED for the paracentesis of ascites fluid were enrolled. For all studied patients, the results of laboratory analysis and gross appearance of ascites fluid registered and reviewed by two emergency medicine specialists. The sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ration of the ascites fluid gross appearance in detection of SBP were measured with 95% confidence interval. Results: The present project was performed in 80 cirrhotic patients with ascites (52.5 female. The mean of the subjects’ age was 56.25±12.21 years (35-81. Laboratory findings revealed SBP in 23 (29% cases. Fifty nine (73% cases had transparent ascites fluid appearance of whom 17 (29% ones suffered from SBP. From 21 (26% cases with opaque ascites appearance, 15 (71% had SBP. The sensitivity and specificity of the ascites fluid appearance in detection of SBP were 46.88% (Cl: 30.87-63.55 and 87.50% (95% Cl: 75.3-94.14, respectively. Conclusion: It seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of SBP and considering its low sensitivity, it could not be used as a good screening tool for this propose.

  4. 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.

  5. T-regulatory cells depletion is the main cause for enhanced antitumor immunity during radio-sensitization of tumors by 2-deoxy-D-glucose

    International Nuclear Information System (INIS)

    Farooque, Abdullah; Verma, Amit; Singh, Niharika; Chauhan, Sachin Kumar Singh; Jethani, Jyoti; Adhikari, J.S.; Dwarakanath, B.S.; Afrin, Farhat

    2014-01-01

    Regulatory T cells (Tregs) are known to have profound effects in blocking anti-tumor immunity. Therefore, Tregs are seen as a major hurdle that must be overcome in order to improve the efficacy of cancer therapy. The glycolytic inhibitor, 2-deoxy-d-glucose (2-DG) enhances radiation and chemotherapeutics induced death of many cancer cells in vitro and local tumor control in vivo, which was found to be associated with the enhanced anti-tumor immunity. Therefore, we investigated the role of Tregs in determining the tumor response to the combined treatment of 2-DG plus ionizing radiation. Ehrlich ascites tumor bearing mice were administered with a single dose of 2-DG (2 gm/Kg/b.wt) intravenously just before focal irradiation (10 Gy). Immuno-phenotyping of Tregs in secondary lymphoid organs was carried out using flow cytometry, while related cytokines were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells and CD4 + CD25 + using real time PCR and Western blot techniques. Results clearly showed depletion (TRAIL mediated apoptosis) of T regs (CD4 + CD25 + FoxP3 + CD39 + FR4 + GITR + CD127 - ), in blood, spleen, lymph node and tumor following the combined treatment. This led to the immune activation in the periphery, secondary lymphoid organs and massive infiltration of CD4 + , CD8 + and NK cells in the tumor, which correlated well with the complete response (cure; tumor free survival). Association of Treg depletion with the tumor response was further confirmed using low doses of cyclophosphamide (which depletes Tegs) and rapamycin (activator of Tregs),wherein the depletor of Tregs enhanced the efficacy of combined treatment, while Tregs enhancer compromised the efficacy. These studies unequivocally established the role of Tregs in determining the therapeutic response and can be used as a target for enhancing the efficacy of this combined treatment, besides establishing the potential of

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

    International Nuclear Information System (INIS)

    Tazoe, Makoto; Miyagami, Mitsusuke; Tsubokawa, Takashi

    1991-01-01

    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)

  7. Effects of a combined Bleomycin/radiotherapy on the increase of cell numbers in Ehrlich ascitic carcinoma

    International Nuclear Information System (INIS)

    Mueller, W.A.

    1980-01-01

    The effects of separate and combined application of the cytostatic Bleomycin and X-radiation on the multiplication of the Ehrlich ascitic tumour cells in vivo and on the survival time of tumourous mice was examined by applying automatic, electronic cell counting. If this cytostatic is administered alone up to 100 mg/kg the growth curve of the EAT-cells shows, after a 24 hours' delay, hardly any difference to that of untreated tumour cells. The separate administration of such Bleomycin doses and the separate X-radiation of the EAT cells with doses of up to 1000 rad had no significant influence on the survival time of tumourous mice. The combined application of Bleomycin and X-radiation elongates the 50%-survival time of the tumourous mice. If the X-radiation takes place 12 hours after the Bleomycin treatment the animals survive longer than is the case with simultaneous treatment. Although no dose effect curves could be set up the results obtained let assume a synergistic effect of Bleomycin and irradiation which is especially significant if the radiation is carried out 12 hours after a Bleomycin treatment. The reasons of this are assumed to lie in the increased radiation sensitivity of the tumour cells caused by the bleomycin-induced partial synchronisation of the EAT cells. (orig.) [de

  8. 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.

  9. Successful radiation treatment of chylous ascites following pancreaticoduodenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Corradini, Stefanie; Niemoeller, Olivier M. [University of Munich, Department of Radiation Oncology, Munich (Germany); Liebig, Sylke [Gemeinschaftspraxis Prof. Zwicker and Partner, Konstanz (Germany); Zwicker, Felix [Gemeinschaftspraxis Prof. Zwicker and Partner, Konstanz (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Molecular and Radiation Oncology, Heidelberg (Germany); Lamade, Wolfram [Helios Privatklinik, Allgemein- and Viszeralchirurgie, Ueberlingen (Germany)

    2015-05-01

    Chylous ascites is a rare complication following pancreaticoduodenectomy. We report on a case of chylous ascites following pancreaticoduodenectomy in a 76-year-old patient diagnosed with pancreatic cancer. There are various known conservative management strategies, including dietary measures or total parenteral nutrition. Unfortunately, conservative treatment - with total parenteral nutrition and fasting over a period of 4 weeks - was not successful in the present case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on clinical experiences with successfully treated lymphocutaneous fistulas, low-dose radiotherapy was initiated. External beam radiotherapy comprising a total dose of 8.0 Gy to the paraaortic lymph node region was administered in daily single fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in complete resolution after 2 weeks. There was no clinical evidence of chylous ascites on follow-up. As a result of this experience, we believe that external beam radiotherapy should be considered as an alternative therapy in refractory cases of chylous ascites. (orig.) [German] Das Chyloperitoneum ist eine seltene Komplikation nach Pankreatikoduodenektomie. Wir berichten ueber einen 76-jaehrigen Patienten mit Chyloperitoneum nach Resektion eines Pankreaskarzinoms. Die konservativen Therapiestrategien, wie beispielsweise diaetetische Massnahmen oder totale parenterale Ernaehrung, waren im vorliegenden Fall ueber einen Zeitraum von 4 Wochen nicht erfolgreich. Es bestand eine persistierende Sekretion von Chylaszites von bis zu 2500 ml/Tag. Basierend auf den klinischen Erfahrungen bei erfolgreich behandelten lymphokutanen Fisteln, wurde eine perkutane Radiotherapie eingeleitet. Die Bestrahlung des paraaortalen Lymphabflusses ueber ventrodorsale Gegenfelder wurde bis zu einer Gesamtdosis von 8,0 Gy in 1,0 Gy Einzeldosis (5 Fraktionen

  10. In vivo and in vitro radiosensitivities ofnewly established mouse ascites tumors

    International Nuclear Information System (INIS)

    Okamoto, M.; Tsuboi, A.; Tsuchiya, T.

    1981-01-01

    The response of two newly established mouse mammary tumors to x irradiation in vitro and in vivo was studied by colony-forming assay in soft agar. Cells irradiated in vivo were more resistant than those irradiated in vitro. The D 0 values for in vitro irradiation were 112 rad at both exponential and stationary phases, while those for in vivo irradiation were 303 rad at exponential phase and 556 rad at stationary phase. This increase in D 0 value, which is greater than the OER, suggests that radiosensitivity in vivo cannot be explained only by hypoxia

  11. Dynamics of albumin in plasma and ascitic fluid in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Siemssen, O; Krintel, J J

    2001-01-01

    BACKGROUND/AIMS: To determine dynamics of albumin in plasma and ascitic fluid of patients with cirrhosis. METHODS: Forty-seven patients were classified in four groups: I--patients without fluid retention; II--patients with ascites not resistant to subsequent diuretic treatment; III......--recompensated patients during diuretic treatment; and IV--patients with diuretic-resistant ascites. Transvascular and transperitoneal albumin transports were quantified by 131I-/125I-labelled human albumin. RESULTS: TER(P) (i.e. the fraction of intravascular albumin (IVM) passing from plasma into the interstitial space...... per hour) was increased in all groups. In group IV patients the transport rate of albumin from plasma into the ascitic fluid (TER(PA)) was significantly higher than the transport rate from the ascitic fluid back into the plasma: TER(AP) (0.45 vs. 0.26% IVM/h, P

  12. Role of Omega 3 Fatty Acids Against Ehrlich Ascites Carcinoma-Induced Hepatic and Brain Dysfunctions in Gamma Irradiated Mice

    International Nuclear Information System (INIS)

    El-Gharib, M.M.M.

    2014-01-01

    Cancer is a deadly disease that has touched the lives of many people in the world today. Omega 3 essential fatty acids (ω-3 FAs); found in high concentrations in fish oil, claim a plethora of health benefits. The present study aimed to evaluate the role of ω-3 FAs supplementation either alone or combined with fractionated γ-radiation exposure against Ehrlich solid tumor-induced inflammation, oxidative stress, biochemical alterations and histopathological changes in the liver, brain and tumor tissues of Albino mice. ω-3 FAs were orally administered via gavages to mice for a period of 30 consecutive days at a dose of 300 mg/kg body weight. On the 7th day of experiment, mice were subcutaneously transplanted in the neck region with 0.2 ml of Ehrlich ascites carcinoma cells for solid tumor induction and on the 17th and 25th days, mice were exposed to a fractionated whole body γ-radiation (0.5 Gy/week for two weeks). The results of the present work showed that Ehrlich carcinoma (EC) and/or γ-irradiation led to systemic inflammation (elevated TNF-α, TLC and CRP levels), hepatic oxidative stress (elevated TBARs level, decreased GSH, GSH-Px, CAT and SOD levels) and biochemical alterations in liver (elevated AST, ALT, ALP and LDH activities) and brain (dopamine, EP,NE and serotonin levels) tissues. On the other hand, ω-3 FAs supplementation to the experimentally irradiated EC-bearing mice, significantly reduced tumor size, depressed the concentrations of inflammatory markers, reduced oxidative stress and also ameliorated the biochemical alterations in liver and brain tissues. Histopathological examinations showed that treatment with ω-3 FAs recorded great destruction of tumor tissue, great disappearance of metastatic EC cells from the liver tissue and normal appearance in cerebrum and cerebellum of brain tissue layers in EC-bearing mice. Combined treatment of EC-bearing mice with ω-3 FAs and γ-irradiation showed necrotic cells and remnant tumor cells in tumor

  13. Differential Diagnosis of Gynecologic Organ-Related Diseases in Women Presenting with Ascites

    Directory of Open Access Journals (Sweden)

    Ming-Huei Cheng

    2008-12-01

    Full Text Available Ascites is a pathologic accumulation of fluid within the peritoneal cavity, and usually develops as a result of liver disease, congestive heart failure or nephrotic syndrome. Ascites is also a common manifestation of some gynecologic diseases. It is important that health care workers consider gynecologic problems among the potential differential diagnoses in patients presenting with ascites. Various kinds of ovarian diseases, such as epithelial ovarian cancer, benign ovarian fibroma, stromal hyperplasia, ovarian hyperstimulation syndrome, primary peritoneal serous carcinoma, endometriosis and peritoneal tuberculosis, should be kept in mind when women are found to have ascites.

  14. 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

  15. Ascitic microbiota composition is correlated with clinical severity in cirrhosis with portal hypertension.

    Directory of Open Access Journals (Sweden)

    Geraint B Rogers

    Full Text Available Identification of pathogenic bacteria in ascites correlates with poor clinical outcomes. Ascites samples are commonly reported culture-negative, even where frank infection is indicated. Culture-independent methods have previously reported bacterial DNA in ascites, however, whether this represents viable bacterial populations has not been determined. We report the first application of 16S rRNA gene pyrosequencing and quantitative PCR in conjunction with propidium monoazide sample treatment to characterise the viable bacterial composition of ascites. Twenty five cirrhotic patients undergoing paracentesis provided ascites. Samples were treated with propidium monoazide to exclude non-viable bacterial DNA. Total bacterial load was quantified by 16S rRNA Q-PCR with species identity and relative abundance determined by 16S rRNA gene pyrosequencing. Correlation of molecular microbiology data with clinical measures and diagnostic microbiology was performed. Viable bacterial signal was obtained in 84% of ascites samples, both by Q-PCR and pyrosequencing. Approximately 190,000 ribosomal pyrosequences were obtained, representing 236 species, including both gut and non gut-associated species. Substantial variation in the species detected was observed between patients. Statistically significant relationships were identified between the bacterial community similarity and clinical measures, including ascitic polymorphonuclear leukocyte count and Child-Pugh class. Viable bacteria are present in the ascites of a majority of patients with cirrhosis including those with no clinical signs of infection. Microbiota composition significantly correlates with clinical measures. Entry of bacteria into ascites is unlikely to be limited to translocation from the gut, raising fundamental questions about the processes that underlie the development of spontaneous bacterial peritonitis.

  16. Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.

    Science.gov (United States)

    Albini, Adriana; Bruno, Antonino; Gallo, Cristina; Pajardi, Giorgio; Noonan, Douglas M; Dallaglio, Katiuscia

    2015-01-01

    Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a "proliferating" cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.

  17. Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

    Science.gov (United States)

    Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

    2018-01-15

    Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. In vivo inhibition of tumor progression by 5 hydroxy-1,4-naphthoquinone (juglone) and 2-(4-hydroxyanilino)-1,4-naphthoquinone (Q7) in combination with ascorbate

    Energy Technology Data Exchange (ETDEWEB)

    Ourique, Fabiana [Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC (Brazil); Kviecinski, Maicon R. [Postgraduate Programe of Health Science, Universidade do Sul de Santa Catarina (UNISUL), Palhoça, SC (Brazil); Zirbel, Guilherme; Castro, Luiza S.E.P.W.; Gomes Castro, Allisson Jhonatan; Mena Barreto Silva, Fátima Regina [Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC (Brazil); Valderrama, Jaime A.; Rios, David; Benites, Julio [Department of Chemical and Pharmaceutical Sciences, Universidad Arturo Prat, Iquique (Chile); Calderon, Pedro Buc [Toxicology and Cancer Biology Research Group (GTOX), Louvain Drug Research Institute, Université Catholique de Louvain, Brussels (Belgium); Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com [Department of Biochemistry, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC (Brazil)

    2016-09-02

    The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with {sup 14}C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism. - Highlights: • Ascorbate potentiates the inhibition caused by juglone and Q7on tumor progress in vivo. • Juglone and Q7 with ascorbate caused widespread oxidative stress in tumor tissue. • Treatments inhibited HIF-1 and GLUT1 expression causing

  19. Prognostic Significance of Blood, Serum, and Ascites Parameters in Patients with Malignant Peritoneal Mesothelioma or Peritoneal Carcinomatosis.

    Science.gov (United States)

    Su, Shan-Shan; Zheng, Guo-Qi; Yin, Wen-Jie; Liang, Yu-Fei; Liu, Ying-Ying; Song, Hui; Sun, Ning-Ning; Yang, Yu-Xin

    2018-01-01

    To determine effects of the biochemical and cytological properties of blood, serum, and ascites on survival of patients with malignant peritoneal effusion (MPeE), including malignant peritoneal mesothelioma (MPeM) and peritoneal carcinomatosis (PC), we conducted a retrospective study of patients with MPeE and healthy controls. Potential prognostic factors were identified as follows: age, sex, blood neutrophil-to-lymphocyte ratio (NLR), serum parameters, ascites parameters, serum-ascites albumin gradient, and the ascites-serum LDH ratio. Compared to those of the control group, serum albumin levels were significantly lower, and the NLR and serum LDH levels were significantly higher in the MPeE group. Overall survival (OS) was longer in patients with MPeM compared to that in patients with PC. Compared with patients in the MPeM, patients with PC had higher NLRs, ascites glucose levels, serum-ascites albumin gradients, and serum LDH levels. In contrast, their ascites albumin levels and ascites-serum LDH ratios were lower. Univariate analyses indicated that the NLR, serum LDH levels, ascites LDH levels, ascites coenocyte levels, and the ascites coenocyte-to-monocyte ratios affected the OS. Multivariate analyses identified only serum and ascites LDH levels as independent prognostic factors.

  20. Is Palliative Laparoscopic Hyperthermic Intraperitoneal Chemotherapy Effective in Patients with Malignant Hemorrhagic Ascites?

    Science.gov (United States)

    de Mestier, Louis; Volet, Julien; Scaglia, Elodie; Msika, Simon; Kianmanesh, Reza; Bouché, Olivier

    2012-01-01

    Malignant hemorrhagic ascites may complicate the terminal evolution of digestive cancers with peritoneal carcinomatosis. It has a bad influence on prognosis and may severely impair patients’ quality of life. Palliative laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to treat debilitating malignant ascites. Two cases of peritoneal carcinomatosis causing hemorrhagic ascites and severe anemia that needed iterative blood transfusions are reported. These patients were treated by laparoscopic HIPEC (mitomycin C and cisplatin with an inflow temperature of 43°C), resulting in cessation of peritoneal bleeding. No postoperative complication or relapse of ascites occurred during the following months. No more blood transfusion was needed. Laparoscopic HIPEC might be an effective and safe therapeutic option to consider in patients with malignant hemorrhagic ascites. PMID:22679405

  1. Anti-tumor activity of tetrodotoxin extracted from the Masked Puffer ...

    African Journals Online (AJOL)

    Anti-tumor activity of tetrodotoxins extracted from the skin of the Masked Puffer fish (Arothron diadematus) from the Red Sea was evaluated using the Ehrlich ascite carcinoma tumor model in mice. Activity was assessed using a variety of cellular and liver biochemical parameters. Experimental mice were divided into 4 equal ...

  2. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

    Science.gov (United States)

    Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

    2016-04-01

    Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

  3. Effects of Mg2+ and adenine nucleotides on thymidylate synthetase from different mouse tumors.

    Science.gov (United States)

    Rode, W; Jastreboff, M M

    1984-01-01

    Magnesium ions variably influenced activity of highly purified thymidylate synthetase preparations from different mouse tumors, activating the enzyme from Ehrlich ascites carcinoma (EAC) cells and inhibiting the enzyme from L1210 and L5178Y cells and from 5-fluorodeoxyuridine (FdUrd)-resistant EAC cells. In the presence of Mg2+ in a concentration resulting in either maximum activation or inhibition (25-30 mM) the enzymes from both the sensitive and FdUrd-resistant EAC lines and L5178Y cells were activated by ATP. Under the same conditions of Mg2+ concentration ADP and AMP inhibited the enzyme from the parental but not from the FdUrd-resistant EAC cells.

  4. [Supportive care for malignant ascites in palliative phase: Place of paracentesis and diuretics].

    Science.gov (United States)

    Gamblin, Vincent; Da Silva, Arlette; Villet, Stéphanie; El Hajbi, Farid

    2015-11-01

    Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. 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

    that 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...... hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...

  6. Non-cell autonomous or secretory tumor suppression.

    Science.gov (United States)

    Chua, Christelle En Lin; Chan, Shu Ning; Tang, Bor Luen

    2014-10-01

    Many malignancies result from deletions or loss-of-function mutations in one or more tumor suppressor genes, the products of which curb unrestrained growth or induce cell death in those with dysregulated proliferative capacities. Most tumor suppressors act in a cell autonomous manner, and only very few proteins are shown to exert a non-cell autonomous tumor suppressor function on other cells. Examples of these include members of the secreted frizzled-related protein (SFRP) family and the secreted protein acidic and rich in cysteine (SPARC)-related proteins. Very recent findings have, however, considerably expanded our appreciation of non-cell autonomous tumor suppressor functions. Broadly, this may occur in two ways. Intracellular tumor suppressor proteins within cells could in principle inhibit aberrant growth of neighboring cells by conditioning an antitumor microenvironment through secreted factors. This is demonstrated by an apparent non-cell autonomous tumor suppressing property of p53. On the other hand, a tumor suppressor produced by a cell may be secreted extracellularly, and taken up by another cell with its activity intact. Intriguingly, this has been recently shown to occur for the phosphatase and tensin homolog (PTEN) by both conventional and unconventional modes of secretion. These recent findings would aid the development of therapeutic strategies that seek to reinstate tumor suppression activity in therapeutically recalcitrant tumor cells, which have lost it in the first place. © 2014 Wiley Periodicals, Inc.

  7. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

    2008-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  8. Chylous Ascites Secondary to Giant Liver Hemangioma

    Directory of Open Access Journals (Sweden)

    Darius L. Lazarus

    2012-07-01

    Full Text Available Chylous ascites is rare in clinical practice. It is characterized by milky-appearing peritoneal fluid with a triglycerides concentration of >1.25 mmol/l (110 mg/dl. Its pathophysiology is related to a disruption in the normal lymphatic flow. It is more common after trauma (including post surgery, neoplasia or atypical infections such as tuberculosis or filariasis. Other rare medical causes have been reported. The treatment is supportive and focused on correction of the underlying pathology. We report here the first case of chylous ascites caused by giant liver hemangioma and discuss the management of this condition.

  9. NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

    Science.gov (United States)

    Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

    2016-01-01

    Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

  10. Experimental rat lung tumor model with intrabronchial tumor cell implantation.

    Science.gov (United States)

    Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

    2008-01-01

    The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

  11. Pulmonary Hypoplasia Caused by Fetal Ascites in Congenital Cytomegalovirus Infection Despite Fetal Therapy

    Directory of Open Access Journals (Sweden)

    Kazumichi Fujioka

    2017-11-01

    Full Text Available We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.

  12. Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression.

    Science.gov (United States)

    Han, Yanmei; Liu, Qiuyan; Hou, Jin; Gu, Yan; Zhang, Yi; Chen, Zhubo; Fan, Jia; Zhou, Weiping; Qiu, Shuangjian; Zhang, Yonghong; Dong, Tao; Li, Ning; Jiang, Zhengping; Zhu, Ha; Zhang, Qian; Ma, Yuanwu; Zhang, Lianfeng; Wang, Qingqing; Yu, Yizhi; Li, Nan; Cao, Xuetao

    2018-04-19

    Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119 + CD45 - CD71 + phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor artemin into the blood. Transforming growth factor β (TGF-β) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells' tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Inhibitory efficacy of the quantified prunellae spica extract on H22 tumor bearing mice

    Science.gov (United States)

    Wang, Zhi-ping; Chen, Tong-sheng

    2013-02-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistence of the advanced hepatocarcinoma to chemotherapy. In this report, we assessed the antitumor activity of a prunellae spica aqueous extract (PSE) in vitro and in vivo. PSE was quantified by HPLC and UV. MTT assay showed that PSE did not effectively inhibit the growth of H22 cells. The in vivo anti-tumor activity was assessed by using the mice bearing H22 tumor. In vivo studies showed the higher antitumor efficacy of PSE without significant side effect assessed by the reduced tumor weight, and the extended survival time of the mice bearing H22 solid and ascites tumor. Collectively, PSE is a promising Chinese medicinal herb for treating hepatocarcinoma.

  14. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

    2013-01-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells

  15. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dudás, József, E-mail: jozsef.dudas@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullár, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Romani, Angela, E-mail: angela.romani@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pritz, Christian, E-mail: christian.pritz@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Hans Schartinger, Volker, E-mail: volker.schartinger@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Mathias Sprinzl, Georg, E-mail: georg.sprinzl@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: herbert.riechelmann@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2013-04-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

  16. Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

    Directory of Open Access Journals (Sweden)

    Antonio Miguel

    2014-02-01

    Full Text Available The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok and a low producer (p2F. Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01. When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05. Significant survival (40% was only observed in the groups vaccinated with free transfected B16 cells.

  17. Studies on cross-immunity among syngeneic tumors by immunization with gamma-irradiated tumor cells

    International Nuclear Information System (INIS)

    Ito, Izumi

    1977-01-01

    In order to clarify whether cross-immunity among 3-methyl-cholanthrene (MCA)-induced sarcomas in C3H/He mice can be established or not, transplantations of syngeneic tumors were carried out in mice immunized with gamma-irradiated (13,000 rad 60 Co) tumor cells and in those immunized with living tumor cells thereafter. The following results were obtained. By using immunizing procedure with only gamma-irradiated tumor cells, a pair of tumors originating from one and the same mouse showed cross-resistance to each other. However, no such evidence was seen among tumors originating from different mice. Cross-immunity among syngeneic tumors originating from different mice could be clearly observed, when immunizing procedure using living tumor cells was added after the treatment with gamma-irradiated tumor cells. It was considered that common antigenicity among MCA-induced sarcoma cells was decreased by gamma-irradiation and that individual differences of tumor antigenecity were shown distinctly under such conditions. (auth.)

  18. Role of Axumin PET Scan in Germ Cell Tumor

    Science.gov (United States)

    2018-05-01

    Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

  19. Idiopathic myelofibrosis accompanied by peritoneal extramedullary hematopoiesis presenting as refractory ascites in a dog.

    Science.gov (United States)

    Rautenbach, Yolandi; Goddard, Amelia; Clift, Sarah J

    2017-03-01

    A 2.5-year-old spayed female American Pit Bull Terrier dog presented with a primary complaint of chronic refractory ascites. The dog's CBC displayed a moderate to severe macrocytic, hypochromic, nonregenerative anemia, and a moderate leukopenia as result of a moderate neutropenia and monocytopenia. Microscopic examination of the blood smear showed marked anisocytosis, mild polychromasia, mild acanthocytosis and ovalocytosis, moderate schistocytosis and poikilocytosis, and 4 metarubricytes/100 WBC. Abdominal ultrasonography revealed a homogenous, mild to moderately hyperechoic appearing liver as well as marked amounts of speckled anechoic to slightly hypoechoic peritoneal fluid. Cytology of the ascitic fluid demonstrated a sterile transudate, with evidence of a chronic inflammatory reaction as well as erythroid and myeloid precursor cells, and a few megakaryocytes with occasional micromegakaryocytes. Histologic sections of bone marrow, spleen, and liver were examined, using routine H&E stains, as well as a variety of immunohistochemistry and other special stains. Histopathology of the bone marrow and spleen revealed varying degrees of fibrosis, erythroid, and myeloid hyperplasia, as well as multiple small hyperplastic clusters of megakaryocytes. The megakaryocytes displayed many features of atypia such as increased cytoplasmic basophilia and occasional abnormal chromatin clumping with mitoses. Histopathologic examination of the liver disclosed evidence of mild extramedullary hematopoiesis. This case represents the first report of canine idiopathic myelofibrosis associated with peritoneal extramedullary hematopoiesis, resulting in refractory ascites. Although idiopathic myelofibrosis is a relatively rare condition in dogs, this case demonstrates that ascites caused by peritoneal implants of hematopoietic tissue may be the initial manifestation of myelofibrosis. © 2016 American Society for Veterinary Clinical Pathology.

  20. Efeito do miriadenolídeo isolado de Alomia myriadenia (Asteraceae sobre o tumor de Erlich ascítico no camundongo Effect of myriadenolide isolated from Alomia myriadenia (Asteraceae on Ehrlich tumor in its ascitic form

    Directory of Open Access Journals (Sweden)

    D. Verçosa Júnior

    2006-10-01

    II: 31µg/kg myriadenolide; and group III: 139µg/kg myriadenolide. On the eighth day of the experiment blood profile and protein serum electrophoresis were performed. All ascitic liquid was collected to evaluate the volume and pH; to observe the aspect; to count viable and no viable cells, dark and clear cells, leukocytes and nucleolar organizer regions (NORs. Macro and microscopic exams were performed and bone marrow was aspirated from right and left femurs of each animal to evaluate myeloid:erythroid ratio. It was not observed difference in volume, pH, counts viable and no viable cells in the groups, although group III showed smaller number of viable tumoral cells (17.6 x 10(4 when compared to the group II (27.7 x 10(4 and group I (21.1 x 10(4. The investigation of NORs to evaluate the proliferative capacity of tumoral cells after myriadenolide treatment showed that cells were smaller, uncountable and with diffuse distribution in group I. They were in lower quantity in group III. These results suggest that myriadenolide in dose 139µg/kg (group III delay the tumoral growing and, probably, cell proliferation. The animals of group III showed lower value of total protein (4.7g/dl (P<0.05 when compared to animals from group II (5.3g/dl and group I (5.1g/dl. The values of albumin were similar in all groups (2.6g/dl and total globulin was higher (P<0.05 in group II (2.71g/dl when compared to mean values of group III (2.11g/dl and similar to group I (2.43g/dl. The decrease of total protein in group III occurred by globulin reduction. There was no difference in alpha and beta globulin in the three studied groups, although the immunoglobulins were higher (P<0.05 in group II (1.72g/dl when compared to group III (1.13g/dl. These results suggest the viable number of tumoral cells in group II could cause the increase response of IgM reflecting on the final value of immunoglobulins. In relation to erythrogram and leukogram there was no statistical difference. The myeloid

  1. Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary

    DEFF Research Database (Denmark)

    Bige, Ozgur; Demir, Ahmet; Koyuncuoglu, Meral

    2008-01-01

    INTRODUCTION: Collision tumor means the coexistence of two adjacent, but histologically distinct tumors without histologic admixture in the same tissue or organ. Collision tumors involving ovaries are extremely rare. CASE: We present a case of 45-year-old parous woman with a left dermoid cyst......, with unusual imaging findings, massive ascites and peritoneal carcinomatosis. The patient underwent cytoreductive surgery. The histopathology revealed a collision tumor consisting of an invasive serous cystadenocarcinoma and a dermoid cyst....

  2. Ascites in chickens : oxygen consumption and requirement related to its occurrence

    NARCIS (Netherlands)

    Scheele, C.W.

    1996-01-01


    The present thesis describes the etiology of heart failure syndrome (HFS) and ascites in broiler chickens.

    In The Netherlands, ascites, as a cause of mortality in broiler chickens, is increasing steadily. Rates of mortality in broiler flocks in practice, related to HFS and

  3. In vitro antitumour activity, safety testing and subcellular distribution of two poly[oxyethylene(aminophosphonate-co-H-phosphonate]s in Ehrlich ascites carcinoma and BALB/c 3T3 cell culture systems

    Directory of Open Access Journals (Sweden)

    Ani Georgieva

    2016-01-01

    Full Text Available Two polyphosphoesters containing anthracene-derived aminophosphonate and hydrophilic H-phosphonate repeating units, poly[oxyethylene(aminophosphonate-co-H-phosphonate]s (1 and 2, were tested for the in vitro antitumour activity on cell cultures derived from ascitic form of Ehrlich mammary adenocarcinoma by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT-dye reduction assay. The in vitro safety testing of the copolymers was performed by BALB/c 3T3 neutral red uptake assay. A study on their uptake and subcellular distribution in non-tumourigenic and tumour cells was performed by means of fluorescence microscopy. Both copolymers showed significant antitumour activity towards Ehrlich ascites carcinoma (EAC cells. However, the in vitro safety testing revealed significant toxicity of polymer 2 to BALB/c 3T3 mouse embryo cells. In contrast, polymer 1 showed complete absence of cytotoxicity to BALB/c 3T3 cells. The fluorescent studies showed that the substances were diffusely distributed in the cytoplasm in both cell culture systems. As opposed to BALB/c 3T3 cells, in EAC cells, intense fluorescent signal was observed in the nuclei and in the perinuclear region. The tested polyphosphoesters are expected to act under physiological conditions as prodrugs of aminophosphonates.

  4. Dendrobium chrysanthum ethanolic extract induces apoptosis via p53 up-regulation in HeLa cells and inhibits tumor progression in mice.

    Science.gov (United States)

    Prasad, Ritika; Rana, Nishant Kumar; Koch, Biplob

    2017-06-01

    Background Dendrobium is one of the diverse genus of orchid plants. It possesses a number of pharmacological activities and has long been used in traditional system of medicine. The goal of this study was to investigate the apoptosis inducing property of the ethanolic extract from the leaves of Dendrobium chrysanthum, a species of Dendrobium whose anticancer role has not been ascertained yet. Methods To evaluate the anticancer activity of the ethanolic extract of D. chrysanthum in vitro in HeLa (human cervical cancer) cells, cytotoxic activity, generation of reactive oxygen species (ROS), induction of apoptosis and effect on cell cycle were determined. The in vivo study was carried out in Dalton's lymphoma (DL) bearing mice to assess the tumor growth delay. Results Our study demonstrated that the ethanolic extract showed dose-dependent cytotoxicity against HeLa cells. The extract exhibited dose-dependent increase in ROS production as well as apoptotic cell death which was further confirmed through presence of DNA fragmentation. Cell cycle analysis by flow cytometry suggests that the ethanolic extract perturbed cell cycle progression and leads to the delay of the cells in S phase. Further, the real-time PCR studies also showed up-regulation of apoptotic genes p53 and Bax. The in vivo antitumor activity exhibited significant increase in the life span of DL bearing mice as compared to control with significant decrease in abdominal size along with reduced tumor ascites. Conclusions These observations demonstrate the anticancer potential of the D. chrysanthum ethanolic extract mediated through p53-dependent apoptosis.

  5. Management of ascites in patients with liver cirrhosis: Recent evidence and controversies

    Directory of Open Access Journals (Sweden)

    Shao-Jung Hsu

    2013-03-01

    Full Text Available Ascites formation in patients with cirrhosis, portal hypertension, or both usually results from hyperdynamic circulatory dysfunction, where the retention of sodium and water is associated with the activation of the sympathetic and renin–angiotensin–aldosterone systems. The presence of ascites indicates the development of liver decompensation. Furthermore, complications seen in conjunction with ascites such as spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic hydrothorax may result in increased morbidity and mortality. Although nonpharmacological, pharmacological, and surgical approaches have been introduced and clinically practiced, their therapeutic effects are still suboptimal or limited by their potential side effects, such as large-volume paracentesis-induced postparacentesis circulatory dysfunction. Herein, we discuss strategies to prevent and properly manage ascites-related complications, including a review of the literature and controlled studies that assess these strategies.

  6. Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

    Directory of Open Access Journals (Sweden)

    Aziz Mahmoudzadeh

    2016-07-01

    Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

  7. Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

    Science.gov (United States)

    Mahmoudzadeh, Aziz; Mohammadpour, Hemn

    2016-07-01

    Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

  8. Myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Youn; Lee, Hae Kyung; Yi, Boem Ha; Lee, Min Hee; Kim, Hee Kyung; Park, Seong Kyu [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2017-03-15

    Multiple myeloma is a common hematological malignancy. Aggressive myeloma invades the organs outside the bone marrow, lymph, or reticuloendothelial systems. Among the extramedullary involvements of multiple myeloma, myelomatous ascites are extremely rare and are associated with a poor prognosis. We describe a case of myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma in 39-year-old patient. The patient was treated with high-dose chemotherapy, but extensive extramedullary involvement progressed, and the patient expired approximately five months after the initial detection of ascites.

  9. Intervention for pleural effusions and ascites following liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Adetiloye, V.A. [Radiology Department, Birmingham Children`s Hospital NHS Trust, Ladywood Middleway, Birmingham B16 8ET (United Kingdom)]|[Radiology Department, College of Health Sciences, Obafemi Awolowo University, Ile-Ife (Nigeria); John, P.R. [Radiology Department, Birmingham Children`s Hospital NHS Trust, Ladywood Middleway, Birmingham B16 8ET (United Kingdom)

    1998-07-01

    Background. Small volumes of fluid in the pleural and peritoneal cavities are common after paediatric liver transplantation. Occasionally, larger fluid collections develop and need intervention by aspiration or insertion of a drain. Objective. To assess the incidence of moderate and large pleural and peritoneal fluid collections following paediatric liver transplantation, the need for intervention and the outcome following radiological and non-radiological treatment, with the ultimate objective of recommending a treatment protocol for such post-operative fluid collections. Materials and methods. A total of 184 consecutive liver grafts in 164 children were reviewed. Results. Of 184 grafts, 31 (16.8 %) developed excessive fluid collections requiring intervention (19 pleural effusions, 8 ascites and 4 effusions and ascites). The effusions were first diagnosed between days 1 and 44 after transplant and the ascites between days 1 and 14. The initial diagnosis was made radiologically in 21 (91 %) of 23 pleural effusions and in 10 (83 %) of 12 ascites. No identifiable cause or association was seen in 18 (58 %) of 31 cases. The mean duration of the pleural effusions and ascites, from onset of treatment to resolution, ranged from 33 {+-} 42 days (SD) to 35 {+-} 48 days and from 36 {+-} 47 days to 39 {+-} 46 days respectively. Comparison of the modes of interventional treatment (i. e. unguided, radiological and surgical) showed no statistically significant difference in the outcome of the management. Conclusions. Post-transplantation pleural effusions and ascites requiring intervention are often without definite cause. They are more common with reduced grafts, but this cannot completely explain the occurrence or the protracted duration of accumulation in spite of combined interventional management. The outcome of treatment is not significantly influenced by the mode of intervention except in cases where surgical intervention is indicated. Patients could be managed

  10. Intervention for pleural effusions and ascites following liver transplantation

    International Nuclear Information System (INIS)

    Adetiloye, V.A.; John, P.R.

    1998-01-01

    Background. Small volumes of fluid in the pleural and peritoneal cavities are common after paediatric liver transplantation. Occasionally, larger fluid collections develop and need intervention by aspiration or insertion of a drain. Objective. To assess the incidence of moderate and large pleural and peritoneal fluid collections following paediatric liver transplantation, the need for intervention and the outcome following radiological and non-radiological treatment, with the ultimate objective of recommending a treatment protocol for such post-operative fluid collections. Materials and methods. A total of 184 consecutive liver grafts in 164 children were reviewed. Results. Of 184 grafts, 31 (16.8 %) developed excessive fluid collections requiring intervention (19 pleural effusions, 8 ascites and 4 effusions and ascites). The effusions were first diagnosed between days 1 and 44 after transplant and the ascites between days 1 and 14. The initial diagnosis was made radiologically in 21 (91 %) of 23 pleural effusions and in 10 (83 %) of 12 ascites. No identifiable cause or association was seen in 18 (58 %) of 31 cases. The mean duration of the pleural effusions and ascites, from onset of treatment to resolution, ranged from 33 ± 42 days (SD) to 35 ± 48 days and from 36 ± 47 days to 39 ± 46 days respectively. Comparison of the modes of interventional treatment (i. e. unguided, radiological and surgical) showed no statistically significant difference in the outcome of the management. Conclusions. Post-transplantation pleural effusions and ascites requiring intervention are often without definite cause. They are more common with reduced grafts, but this cannot completely explain the occurrence or the protracted duration of accumulation in spite of combined interventional management. The outcome of treatment is not significantly influenced by the mode of intervention except in cases where surgical intervention is indicated. Patients could be managed effectively

  11. 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.

  12. Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

    International Nuclear Information System (INIS)

    Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

    1988-01-01

    Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

  13. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  14. A flavonoid component from Docynia delavayi (Franch.) Schneid represses transplanted H22 hepatoma growth and exhibits low toxic effect on tumor-bearing mice.

    Science.gov (United States)

    Zhao, Xiangpei; Shu, Guangwen; Chen, Lvyi; Mi, Xue; Mei, Zhinan; Deng, Xukun

    2012-09-01

    The fruit of Docynia delavayi (Franch.) Schneid is a kind of popular food in southwestern areas of China. Additionally, its rhizome has been long used as a folk medicine in the treatment of liver cancer by local people. Chrysin is a kind of flavonoid which induces cancer cell death in vitro. However, its anti-tumor activity in vivo and toxicological effects on the tumor-bearing animals still remain poorly understood. In this study, we obtained four flavonoids from this herb. Among them, chrysin showed the strongest cytotoxic effect on an array of cultured tumor cells. Further investigations revealed that it significantly repressed transplanted H22 ascitic hepatic tumor cell growth in vivo. Moreover, this compound displayed little toxic effects. Additionally, we demonstrated that in transplanted tumor tissues, chrysin not only activated caspase-3 and induced apoptosis, but also inhibited the production of vascular endothelial growth factor (VEGF) and suppressed angiogenesis. These data showed that chrysin exhibited prominent anti-tumor activities and low toxic effects in vivo. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  16. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

    Directory of Open Access Journals (Sweden)

    Aya Matsui

    Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

  17. Evaluation of Hollow Fiber And Miniperm Bioreactors as An Alternative to Murine Ascites for Small Scale Monoclonal Antibody Production

    International Nuclear Information System (INIS)

    Abedalla, O. M.

    2007-01-01

    The objective of this study was to compare monoclonal antibody production in hollow fiber, miniPERM bioreactor systems and murine ascites to determine the feasibility of the bioreactor system as a potential alternative to the use of mice. One hybridoma cell line was grown in hollow fiber, miniPERM bioreactor systems and in groups of 5 mice. Mice were primed with 0.5 ml pristane intraperitoneally 14 days prior to inoculation of 1X10 7 hybridoma cells. Each mouse was tapped a maximum of three times for collection of ascites. Bioreactors were harvested three times weekly for 30 days and were monitored by cell counts, cell viability and media consumption. Time and materials logs were maintained. The total quantity of monoclonal antibody produced in 5 mice versus the total production for the two different bioreactors (hollow fiber and miniPERM) in 30 days was as follows: cell line 2AC10E6C7 produce 158 mg vs.97.5 mg; vs 21.54 mg respectively. Mean monoclonal antibody concentration ranged from 4.07 to 8.37 mg/ml in murine ascites, from 0.71 to 3.8 mg/ml in hollow fiber bioreactor system, and from 0.035 to 1.06 in miniPERM. Although time and material costs were generally greater for the bioreactors, these results suggest that hollow fiber and miniPERM bioreactor systems merit further investigations as potentially viable in vitro alternatives to the use of mice for small scale (< 1 g) monoclonal antibody production.

  18. An experimental study on the anti-Ehrlich ascites carcinoma effect of ...

    African Journals Online (AJOL)

    The objective of this paper was to study the anti-Ehrlich ascites carcinoma effect of purified toad venom extract and its mechanism. Mouse model of Ehrlich ascites carcinoma was established with cisplatin as the control to observe the inhibitory effect of purified toad venom extract on malignant peritoneal effusion in mice.

  19. Metaphyseal giant cell tumor

    International Nuclear Information System (INIS)

    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.

    1986-01-01

    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) [pt

  20. Antigen localization controls T cell-mediated tumor immunity.

    Science.gov (United States)

    Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

    2011-08-01

    Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

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

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Moulder, J.E.

    1989-01-01

    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

  2. Role of ascitic fluid C3 in spontaneous bacterial peritonitis | Kamal ...

    African Journals Online (AJOL)

    Background: The C3 component of complement tends to be reduced in cirrhosis and patients with reduced ascitic fluid C3 concentration and reduced opsonic activities have been shown to be predisposed to SBP. Aim of the work: To compare the level of ascitic fluid C3 concentration in cirrhotic patients with and without ...

  3. 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.

  4. Giant ovarian cyst masquerading as a massive ascites: a case report.

    Science.gov (United States)

    Yeika, Eugene Vernyuy; Efie, Derrick Tembi; Tolefac, Paul Nkemtendong; Fomengia, Joseph Nkeangu

    2017-12-19

    Giant ovarian cysts are tumours of the ovary presenting with diameters greater than 10 cm. Giant ovarian cysts have become rare in recent days as they are diagnosed and managed early due to the availability of good imaging modalities. The aim of this case report is to show how a huge cystic ovarian mass can mislead the diagnosis of ascites in a postmenopausal woman. Factors associated with late presentation of giant ovarian cysts in sub-Saharan Africa have also been discussed. We present the case of a 65-year-old grand multiparous woman who was referred to our centre with a grossly distended abdomen misdiagnosed as a massive ascites. Abdominopelvic ultrasound scan revealed a right giant multiloculated ovarian cyst. She benefited from a cystectomy with an uneventful postoperative stay. Histopathology revealed mucinous cystadenoma. Large cystic ovarian tumours can present masquerading as massive ascites and misleading diagnosis as in this case report. We report this case to increase the suspicion index of a large ovarian cyst in all women presenting with massive ascites.

  5. NKT cells as an ideal anti-tumor immunotherapeutic.

    Science.gov (United States)

    Fujii, Shin-Ichiro; Shimizu, Kanako; Okamoto, Yoshitaka; Kunii, Naoki; Nakayama, Toshinori; Motohashi, Shinichiro; Taniguchi, Masaru

    2013-12-02

    Human natural killer T (NKT) cells are characterized by their expression of an invariant T cell antigen receptor α chain variable region encoded by a Vα24Jα18 rearrangement. These NKT cells recognize α-galactosylceramide (α-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-γ, 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 α-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-γ production had significantly prolonged median survival times of 29.3 months 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 weeks after the combination therapy of α-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 α-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 1 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-γ in vitro and in vivo upon

  6. 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.

  7. The Role of Tumor Associated Macrophage in Recurrent Growth of Tumor Stem Cell

    Science.gov (United States)

    2011-09-01

    recent cancer stem cell (CSC) theory, recurrent tumor must arise from a dormant tumor stem cell whose re-growth is triggered by shifting of...microenvironment. This project aims at clarifying the roles of TAM in recurrent growth of dormant stem cell in breast cancer. We hypothesize that the balance of...dormancy and recurrence is determined by the ability of the tumor stem cells to recruit TAM which in turn promotes self-renewal of the stem cell . We

  8. Radiologic findings of malignant tumors arising from ovarian endometriosis

    International Nuclear Information System (INIS)

    Lee, Eun Ju; Joo, Hee Jae; Kim, Bo Hyun

    1999-01-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  9. Radiologic findings of malignant tumors arising from ovarian endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Joo, Hee Jae [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Kim, Bo Hyun [SungkyunKwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-11-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  10. Sertoli-Leydig cell tumor

    Science.gov (United States)

    Sertoli-Leydig cell tumor (SLCT) is a rare cancer of the ovaries. The cancer cells produce and release a male sex hormone ... lead to cancer. SLCT starts in the female ovaries. The cancer cells release a male sex hormone. As a ...

  11. Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

    International Nuclear Information System (INIS)

    Streeter, P.R.; Fortner, G.W.

    1986-01-01

    Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

  12. Urinary Ascites in Newborn – A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Suryakant Y. Ingale

    2014-01-01

    Full Text Available Urinary Ascites in the newborn is a very rare condition. It is commonly secondary to posterior urethral valves (PUV which are membranous folds extending from proximal urethra leading to obstruction to urine flow. Here we report a two days old male neonate delivered full term in a hospital who presented with gross, uniform tense distension of abdomen with massive scrotal oedema, secondary to massive urinary ascites as a result of rupture of renal calyces. In addition there was a peri-renal urinoma.

  13. Hyperosmotic stress strongly potentiates serum response factor (SRF)-dependent transcriptional activity in ehrlich lettré ascites cells through a mechanism involving p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej; Wiwel, Maria; Klingberg, Henrik

    2011-01-01

    Long-term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1-ERK1/2 pathway is transien......Long-term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1-ERK1/2 pathway......) and cAMP response element-binding protein (CREB) are differentially regulated in ELA cells. SRF Ser103 phosphorylation and SRF-dependent transcriptional activity were strongly augmented 5–30¿min and 24¿h, respectively, after hyperosmotic stress (50% increase in extracellular ionic strength), in a p38...... dephosphorylated within 5¿min of shrinkage. MSK1 phosphorylation recovered within 30¿min in a p38-MAPK-dependent manner. CREB was transiently dephosphorylated after shrinkage in a manner exacerbated by p38 MAPK inhibition or MSK1 knockdown, but unaffected by inhibition of RSK. In conclusion, in ELA cells...

  14. Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

    Science.gov (United States)

    Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

    2015-05-01

    Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

  15. Radiologically placed tunneled peritoneal catheter in palliation of malignant ascites

    International Nuclear Information System (INIS)

    Akinci, Devrim; Erol, Bekir; Ciftci, Tuerkmen T.; Akhan, Okan

    2011-01-01

    The purpose of this study was to evaluate retrospectively the safety and effectiveness of radiologically placed tunneled peritoneal catheter in palliation of malignant ascites. Between July 2005 and June 2009, 41 tunneled peritoneal catheters were placed under ultrasonographic and fluoroscopic guidance in 40 patients (mean age, 55 years; 22 women) who had symptomatic malignant ascites. No procedure related mortality was observed. Major complication occurred in one patient (2.5%) in the form of serious bacterial peritonitis that necessitated catheter removal. Minor complications such as minor bacterial peritonitis, catheter dislodgement, tunnel infection, and catheter blockage occurred in 11 patients (27.5%). The mean duration of survival after catheter placement was 11.8 weeks. All patients expired of their primary malignancies in the follow-up. Radiologically placed tunneled peritoneal catheter is safe and effective in palliation of symptomatic malignant ascites.

  16. Radiologically placed tunneled peritoneal catheter in palliation of malignant ascites

    Energy Technology Data Exchange (ETDEWEB)

    Akinci, Devrim; Erol, Bekir; Ciftci, Tuerkmen T. [Hacettepe University, Faculty of Medicine, Department of Radiology, 06100 Ankara (Turkey); Akhan, Okan, E-mail: akhano@tr.net [Hacettepe University, Faculty of Medicine, Department of Radiology, 06100 Ankara (Turkey)

    2011-11-15

    The purpose of this study was to evaluate retrospectively the safety and effectiveness of radiologically placed tunneled peritoneal catheter in palliation of malignant ascites. Between July 2005 and June 2009, 41 tunneled peritoneal catheters were placed under ultrasonographic and fluoroscopic guidance in 40 patients (mean age, 55 years; 22 women) who had symptomatic malignant ascites. No procedure related mortality was observed. Major complication occurred in one patient (2.5%) in the form of serious bacterial peritonitis that necessitated catheter removal. Minor complications such as minor bacterial peritonitis, catheter dislodgement, tunnel infection, and catheter blockage occurred in 11 patients (27.5%). The mean duration of survival after catheter placement was 11.8 weeks. All patients expired of their primary malignancies in the follow-up. Radiologically placed tunneled peritoneal catheter is safe and effective in palliation of symptomatic malignant ascites.

  17. Evaluation of hollow fiber and mini perm bioreactors as an alternative to murine ascites for small scale monoclonal antibody production

    International Nuclear Information System (INIS)

    Abdalla, O. M.

    2006-12-01

    The objective of this study was to compare monoclonal antibody production in hollow fiber, mini perm bioreactor systems and murine ascites to determine the feasibility of the bioreactor system as a potential alternative to the use of mice. One hybridoma cell line was grown in hollow fiber, mini perm bioreactor systems and in groups of 5 mice. Mice were primed with 0.5 ml pristane intraperitoneally 14 days prior to inoculation of 1x10 7 hybridoma cells. Each mouse was tapped a maximum of three times for collection of ascites. Bioreactors were harvested three times weekly for 30 days and were monitored by cell counts, cell viability and media consumption. Time and materials logs were maintained. The total quantity of monoclonal antibody produced in 5 mice versus the total production for the two different bioreactors (hollow fiber and mini perm) in 30 days was as follows: cell line 2AC10E6C7 produce 158 mg vs.97.5 mg, vs 21.54 mg respectively. Mean monoclonal antibody concentration ranged from 4.07 to 8.37 mg/ml in murine ascites, from 0.71 to 3.8 mg/ml in hollow fiber bioreactor system, and from 0.035 to 1.06 in mini perm. Although time and material costs were generally greater for the bioreactors, these results suggest that hollow fiber and mini perm bioreactor systems merit further investigations as potentially viable in vitro alternatives to the use of mice for small scale (<1mg) monoclonal antibody production.(Author)

  18. 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.

  19. Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

    Science.gov (United States)

    Chandra, Subhash; Parker, Dylan J.; Barth, Rolf F.; Pannullo, Susan C.

    2016-01-01

    Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets. PMID:26703785

  20. Tumors of germinal cells

    International Nuclear Information System (INIS)

    Plazas, Ricardo; Avila, Andres

    2002-01-01

    The tumors of germinal cells (TGC) are derived neoplasia of the primordial germinal cells that in the life embryonic migrant from the primitive central nervous system until being located in the gonads. Their cause is even unknown and they represent 95% of the testicular tumors. In them, the intention of the treatment is always healing and the diagnostic has improved thanks to the results of the handling multidisciplinary. The paper includes topics like their incidence and prevalence, epidemiology and pathology, clinic and diagnoses among other topics

  1. 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.

  2. Role of an external cell membrane and its thiols in realization of the radioprotective effect of anoxia

    International Nuclear Information System (INIS)

    Konstantinova, M.M.; Dontsova, G.V.; Panaeva, S.V.

    1988-01-01

    In experiments with Ehrlich ascites tumor cells using a specific thiol blocker 6.6-dithiodinicitinic acid that does not penetrate the cell and therefore only binds SH-groups of peripheral areas of an external cell membrane it was demonstrated that (1) the external cell membrane is the site where the radioprotective effect of anoxia (the oxygen effect) is realized (2) thiols of the esternal cell membrane contribute markedly to the oxygen effect and (3) they are needed at both stages of its realization

  3. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

    DEFF Research Database (Denmark)

    Krag, Aleksander; Møller, Søren; Henriksen, Jens H

    2007-01-01

    Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study...

  4. Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

    Science.gov (United States)

    Kolson Kokohaare, Eva; Riva, Francesco M G; Bernstein, Jonathan M; Miah, Aisha B; Thway, Khin

    2018-04-01

    We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

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

    International Nuclear Information System (INIS)

    Miyagami, Mitsusuke; Tazoe, Makoto; Tsubokawa, Takashi

    1989-01-01

    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 T 1 -weighted image revealed a slightly low or iso signal intensity, while the T 2 -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)

  6. Primary Volvulus of the Small Intestine Exhibiting Chylous Ascites: A Case Report.

    Science.gov (United States)

    Hayama, Tamuro; Shioya, Takeshi; Hankyo, Meishi; Shimizu, Takao; Shibuya, Hajime; Komine, Osamu; Watanabe, Yoshimasa; Nanbu, Kotaro; Yamada, Taro

    2017-01-01

    Primary volvulus of the small intestine associated with chylous ascites is very rare, with only four reported cases. In this paper, we report a new case of primary volvulus associated with chylous ascites. The patient was a 70-year-old man. After experiencing bloating and abdominal pain for several hours, he called an ambulance and underwent an emergency examination at our hospital. Abdominal distension, pressure pain, and rebound tenderness were observed throughout his entire abdomen. The patient had a history of hypertension for which he was receiving oral treatment. Abdominal contrast-enhanced computed tomography (CT) revealed an edematous change in the intestinal membrane and volvulus of the small intestine. As findings suggestive of ischemia were observed in part of the intestines, emergency surgery was performed on the day of admission. Open surgery revealed approximately 500 mL of chylous ascites in the abdominal cavity. The small intestine had twisted 180° in a counter-clockwise direction at the root of the superior mesenteric artery, and the mesentery appeared milky white with edematous changes extending 75 to 240 cm from the ligament of Treitz. There was no evidence of intestinal necrosis; therefore intestinal resection was not performed. The volvulus of the small intestine was corrected. Moreover, because there was no other underlying disease observed, surgery was completed. The ascites collected during surgery revealed high levels of triglycerides at 332 mg/dL, and chylous ascites was diagnosed. An abdominal CT performed on the third day after surgery showed an improvement in intestinal edema, and primary volvulus of the small intestine associated with chylous ascites was diagnosed. Postoperative progress was good, and the patient was discharged on hospital day 10.

  7. The Ehrlich Tumor Induces Pain-Like Behavior in Mice: A Novel Model of Cancer Pain for Pathophysiological Studies and Pharmacological Screening

    Directory of Open Access Journals (Sweden)

    Cassia Calixto-Campos

    2013-01-01

    Full Text Available The Ehrlich tumor is a mammary adenocarcinoma of mice that can be developed in solid and ascitic forms depending on its administration in tissues or cavities, respectively. The present study investigates whether the subcutaneous plantar administration of the Ehrlich tumor cells induces pain-like behavior and initial pharmacological susceptibility characteristics. The Ehrlich tumor cells (1 × 104–107 cells induced dose-dependent mechanical hyperalgesia (electronic version of the von Frey filaments, paw edema/tumor growth (caliper, and flinches compared with the saline group between days 2 and 12. There was no difference between doses of cells regarding thermal hyperalgesia in the hot-plate test. Indomethacin (a cyclooxygenase inhibitor and amitriptyline hydrochloride (a tricyclic antidepressant treatments did not affect flinches or thermal and mechanical hyperalgesia. On the other hand, morphine (an opioid inhibited the flinch behavior and the thermal and mechanical hyperalgesia. These effects of morphine on pain-like behavior were prevented by naloxone (an opioid receptor antagonist treatment. None of the treatments affected paw edema/tumor growth. The results showed that, in addition to tumor growth, administration of the Ehrlich tumor cells may represent a novel model for the study of cancer pain, specially the pain that is susceptible to treatment with opioids, but not to cyclooxygenase inhibitor or to tricyclic antidepressant.

  8. Anidulafungin Pharmacokinetics in Ascites Fluid and Pleural Effusion of Critically Ill Patients.

    Science.gov (United States)

    Welte, R; Eller, P; Lorenz, I; Joannidis, M; Bellmann, R

    2018-04-01

    Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulafungin levels in ascites fluid (0.12 to 0.99 μg/ml) and in pleural effusion (0.32 to 2.02 μg/ml) were below the simultaneous levels in plasma (1.04 to 7.70 and 2.48 to 13.36 μg/ml, respectively) and below the MIC values for several pathogenic Candida strains. Copyright © 2018 American Society for Microbiology.

  9. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth.

    Science.gov (United States)

    Bennewith, Kevin L; Huang, Xin; Ham, Christine M; Graves, Edward E; Erler, Janine T; Kambham, Neeraja; Feazell, Jonathan; Yang, George P; Koong, Albert; Giaccia, Amato J

    2009-02-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer.

  10. Anti-tumor therapy with macroencapsulated endostatin producer cells

    Directory of Open Access Journals (Sweden)

    Balduino Keli N

    2010-03-01

    Full Text Available Abstract Background Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Results Mice were inoculated subcutaneously with melanoma (B16F10 cells or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. Conclusions This study indicates that

  11. Anti-tumor therapy with macroencapsulated endostatin producer cells.

    Science.gov (United States)

    Rodrigues, Danielle B; Chammas, Roger; Malavasi, Natália V; da Costa, Patrícia L N; Chura-Chambi, Rosa M; Balduino, Keli N; Morganti, Ligia

    2010-03-02

    Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. This study indicates that immunoisolation devices containing endostatin

  12. Application of Balloon-Occluded Retrograde Transvenous Obliteration to Gastric Varices Complicating Refractory Ascites

    International Nuclear Information System (INIS)

    Fukuda, Tetsuya; Hirota, Shozo; Matsumoto, Shinichi; Sugimoto, Koji; Fujii, Masahiko; Tsurusaki, Masakatsu; Izaki, Kenta; Sugimura, Kazuro

    2004-01-01

    We report two cases of gastric varices complicated by massive ascites that disappeared after balloon-occluded retrograde transvenous obliteration (B-RTO). The first patient had progressive gastric varices that continued to enlarge even after three episodes of esophagogastric variceal bleeding, and the second patient was admitted to our hospital because of the bleeding from gastric varices. After B-RTO procedures in both patients, significant improvement of the ascites, hepatic function reserve, and hypoalbuminemia was observed. Although further experience is needed, our experience points to the likelihood of the amelioration of ascites after B-RTO

  13. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

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

    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 of cancer therapies are discussed

  14. Activation of specific cellular immunity toward murine leukemia in mice rejecting syngeneic somatic hybrid cells

    International Nuclear Information System (INIS)

    Liang, W.; Cohen, E.P.

    1977-01-01

    ASL-1 x LM(TK) - somatic hybrid cells form both H-2/sup a/ and H-2/sup k/ antigen complexes. After forming a localized tumor in syngeneic (A/J x C 3 H/HeJ)F 1 mice, they are rejected. Such mice are resistant to otherwise invariably lethal injections of ASL-1 cells, surviving for prolonged and, in some instances, indefinite periods. To examine the basis of immunity, the capacity of spleen cells from mice rejecting hybrid cells to stimulate the release of 51 Cr from labeled ASL-1 cells was investigated. Cells from the spleens of mice rejecting ASL-1 x LM(TK) - cells stimulated the release of 51 Cr from labeled ASL-1 cells, but not from Ehrlich ascites or P815 cells. Cells from mice injected with mitomycin-C-treated ASL-1 cells led to the release of 51 Cr from labeled ASL-1 cells as well, but the extent of 51 Cr release was approximately one-third as occurred in the presence of cells from hybrid cell-injected mice. Cells from noninjected mice or from mice injected with LM(TK) - cells failed to lead to the specific release of 51 Cr from ASL-1 cells. The presence of unlabeled ASL-1 cells, but not Ehrlich ascites cells, competitively inhibited the spleen cell-stimulated release of 51 Cr from labeled ASL-1 cells. Sera from A/J mice injected with mitomycin-C-treated ASL-1 cells contained antibodies specific for the tumor-associated antigen of ASL-1 cells

  15. Characterization of cell suspensions from solid tumors

    International Nuclear Information System (INIS)

    Pallavicini, M.

    1985-01-01

    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

  16. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

    International Nuclear Information System (INIS)

    Kalra, Neetu; Zhang, Jingli; Thomas, Anish; Xi, Liqiang; Cheung, Mitchell; Talarchek, Jacqueline; Burkett, Sandra; Tsokos, Maria G; Chen, Yuanbin; Raffeld, Mark; Miettinen, Markku; Pastan, Ira; Testa, Joseph R; Hassan, Raffit

    2015-01-01

    The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient derived xenografts were generated by injecting the cells in nude or SCID mice, and malignant potential of the cells was analyzed by soft agar colony assay. Molecular profiles of the primary patient tumors, early passage cell cultures, and patient derived xenografts were assessed using mutational analysis, fluorescence in situ hybridization (FISH) analysis and IHC. Primary cultures from all five tumors exhibited morphologic and IHC features consistent to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected in four tumors. BAP1 mutation was associated with the lack of expression of BAP1 protein. Three cell cultures, all of which were derived from BAP1 mutant primary tumors, exhibited anchorage independent growth and also formed tumors in mice, suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A deletions identical to those found in the corresponding primary patient tumors. The mesothelioma patient derived tumor xenografts with mutational alterations that mimic those observed in patient tumors which we established can be used for preclinical development of novel drug regimens and for studying the functional aspects of BAP1 biology in mesothelioma. The online version of this article (doi:10.1186/s12885-015-1362-2) contains supplementary material, which is available to authorized users

  17. Strategies to alleviate the incidence of ascites in broilers: a review

    Directory of Open Access Journals (Sweden)

    U Aftab

    2005-12-01

    Full Text Available Ascites is a complex problem caused by many interacting factors such as genetics, environment and management. Many nutritional, medicinal and management strategies have been proposed to alleviate the problem. Higher levels of dietary vitamin C and E along with selenium yeast might be beneficial, presumably because of their role in improving cellular integrity. Oils rich in n-3 fatty acids have been shown to reduce pulmonary hypertension and, consequently, ascites incidence. The potential use of flax oil has already been demonstrated, whereas the effects of other oils rich in n-3 fatty acids (fish, linseed and canola oils remain to be investigated. The assessment of the effects of dietary electrolyte balance on ascites incidence seems to be a promising field of research in broiler nutrition. In general, reducing the dietary level of salt (NaCl and adding bicarbonates to the diet and drinking water have been proposed as potential "cost-effective" methods to reduce ascites incidence. The use of nutrients/drug agents that increase the vascular capacity of the lungs or decrease the pulmonary vascular resistance may help to alleviate the problem, but economic and local feed regulations might restrict such use. Diuretics have also shown positive effects, presumably because there is a reduction of sodium and fluid retention in the body; litter humidity however must be closely monitored if diuretics are continuously administered. As the high metabolic rate (fast growth is a major factor contributing to the susceptibility of broilers to ascites, early-age feed or nutrient restriction (qualitative or quantitative or light restriction in order to slow down the growth rate seem practically viable methods, since final body weight is not compromised. Optimization of the house temperature and ventilation in cold weather seem helpful practices to decrease ascites incidence. Under practical conditions, it might be interesting to test the additive effects of

  18. Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Günther, T-hat nia Mara Fischer; Kviecinski, Maicon Roberto; Baron, Carla Cristine; Felipe, Karina Bettega; Farias, Mirelle Sifroni; Ourique da Silva, Fabiana; Bücker, Nádia Cristina Falcão [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Pich, Claus Tröger [Campus de Araranguá, Universidade Federal de Santa Catarina, Araranguá (Brazil); Ferreira, Eduardo Antonio [Universidade de Brasília, Faculdade de Ceilândia, DF (Brazil); Filho, Danilo Wilhelm [Departamento de Ecologia e Zoologia, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Verrax, Julien; Calderon, Pedro Buc [Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels (Belgium); Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil)

    2013-01-18

    Graphical abstract: -- Abstract: Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na{sub 3}VO{sub 4}) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na{sub 3}VO{sub 4} was cytotoxic against T24 cells (EC{sub 50} = 5.8 μM at 24 h), but in the presence of ascorbate (100 μM) the EC{sub 50} fell to 3.3 μM. Na{sub 3}VO{sub 4} plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na{sub 3}VO{sub 4} did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na{sub 3}VO{sub 4} and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na{sub 3}VO{sub 4} alone, or combined with ascorbate, increased catalase activity, but only Na{sub 3}VO{sub 4} plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na{sub 3}VO{sub 4} plus ascorbate (2–3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na{sub 3}VO{sub 4}. The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na{sub 3}VO{sub 4} in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

  19. Periurethral granular cell tumor: a case report

    International Nuclear Information System (INIS)

    Kim, Jeong Kon; Choi, Hyo Gyeong; Cho, Kyoung Sik

    1998-01-01

    Granular cell tumors are uncommon soft tissue tumors which arise as solitary or multiple masses. Lesions commonly arise in the head, neck, and chest wall, but can occur in any part of the body. To our knowledge, periurethral granular cell tumor has not been previously reported. We report one such case

  20. [Circulating tumor cells: cornerstone of personalized medicine].

    Science.gov (United States)

    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  1. Tumor Immunology meets…Immunology: Modified cancer cells as professional APC for priming naïve tumor-specific CD4+ T cells.

    Science.gov (United States)

    Bou Nasser Eddine, Farah; Ramia, Elise; Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S

    2017-01-01

    Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer. Here we describe emerging new strategies to increase the TH cell recognition of tumor antigens. In particular, we review recent data indicating that tumor cells themselves can act as surrogate antigen presenting cells for triggering TH response and how these findings can help in constructing immunotherapeutic protocols for anti-cancer vaccine development.

  2. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy.

    Science.gov (United States)

    Hatfield, Paul; Merrick, Alison E; West, Emma; O'Donnell, Dearbhaile; Selby, Peter; Vile, Richard; Melcher, Alan A

    2008-09-01

    The immune response to cancer is critically determined by the way in which tumor cells die. As necrotic, stress-associated death can be associated with activation of antitumor immunity, whole tumor cell antigen loading strategies for dendritic cell (DC)-based vaccination have commonly used freeze-thaw "necrotic" lysates as an immunogenic source of tumor-associated antigens. In this study, the effect of such lysates on the ability of DCs to mature in response to well-established maturation stimuli was examined, and methods to enhance lysate-induced DC activation explored. Freeze-thaw lysates were prepared from murine tumor cell lines and their effects on bone marrow-derived DC maturation and function examined. Unmodified freeze-thaw tumor cell lysates inhibited the toll-like receptor-induced maturation and function of bone marrow-derived DCs, preventing up-regulation of CD40, CD86, and major histocompatibility complex class II, and reducing secretion of inflammatory cytokines [interleukin (IL)-12 p70, tumor necrosis factor-alpha, and IL-6]. Although IL-10 secretion was increased by lysate-pulsed DCs, this was not responsible for the observed suppression of IL-12. Although activation of the nuclear factor-kappaB pathway remained intact, the kinase activity of phosphorylated p38 mitogen-activated protein kinase was inhibited in lysate-pulsed DCs. Lysate-induced DC suppression was partially reversed in vitro by induction of tumor cell stress before lysis, and only DCs loaded with stressed lysates afforded protection against tumor challenge in vivo. These data suggest that ex vivo freeze-thaw of tumor cells does not effectively mimic in vivo immunogenic necrosis, and advocates careful characterization and optimization of tumor cell-derived vaccine sources for cancer immunotherapy.

  3. Chylous ascites and lymphangiectasia in focal segmental glomerulosclerosis--a rare coexistence: a case report.

    Science.gov (United States)

    Lahiri, Durjoy; Agarwal, Rakesh; Roy, Manoj Kumar; Biswas, Amrita

    2015-02-09

    Nephrotic syndrome is considered a rare cause of chylous ascites. Intestinal lymphangiectasia in a background of chylous ascites and without any lymphatic obstruction has been reported in association with yellow nail syndrome, which is a rare clinical occurrence in itself. The existence of chylous ascites, duodenal and splenic lymphangiectasia (without any lymphatic obstruction) and nephrotic syndrome in the form of focal segmental glomerulosclerosis in the same patient makes this case the first of its kind to be reported in the literature. Here we report the case of a 54-year-old Asian man who presented with recurrent episodes of anasarca for approximately 25 years. He was subsequently found to have chylous ascites, lymphangiectasia and persistent proteinuria. A renal biopsy revealed focal segmental glomerulosclerosis, not otherwise specified. A lymphangiogram, which was performed with the purpose of addressing the intestinal lymphangiectasia, failed to demonstrate any abnormality of lymphatic channels. He was put on oral steroids with consequent remission of his oedema and proteinuria. This case highlights the fact that duodenal and splenic lymphangiectasia can exist in a scenario of chylous ascites without any obvious obstruction of lymphatic channels and in the absence of yellow nail syndrome. This case also signifies that chylous ascites may be a rare presenting feature of nephrotic syndrome and hence this aspect should be considered while in diagnostic dilemma regarding such a clinical presentation.

  4. Eosinophilic ascites: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Raed M Alsulaiman

    2015-01-01

    Full Text Available Eosinophilic gastroenteritis is a rare gastrointestinal (GI disorder characterized by nonspecific GI symptoms, peripheral eosinophilia, and eosinophilic infiltration of the intestinal wall. The disorder is classified into mucosal, muscular, and sub-serosal types, depending on the clinical picture and the depth of eosinophilic infiltration within the GI wall. Sub-serosal disease, which is complicated by ascites, usually results in the most severe clinical form of eosinophilic gastroenteritis and requires early corticosteroid therapy. In such cases, a favorable outcome can be achieved after a short course of corticosteroids. We present the case of a 28-year-old female with diffuse abdominal pain and distention for 2 weeks. Her physical examination was significant for moderate ascites. Initial work-up demonstrated severe peripheral blood eosinophilia, normal liver function tests, and elevated serum immunoglobulin E (IgE. Upper endoscopy, colonoscopy showed a thickening of the stomach and colon, and biopsies showed marked eosinophilic infiltration of the mucosa. Ascitic fluid analysis showed significant eosinophilia. Subsequent treatment with oral prednisone resulted in the normalization of laboratory and radiologic abnormalities 45 days after the start of the treatment. Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because the disease is treatable, and timely diagnosis and initiation of treatment could be of major importance.

  5. 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.

  6. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  7. Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Rohit B. [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States); Wang, Qingde [Department of Surgery, University of Pittsburgh, PA 15261 (United States); Khillan, Jaspal S., E-mail: khillan@pitt.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States)

    2013-07-12

    Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

  8. Glioma Cells in the Tumor Periphery Have a Stem Cell Phenotype

    DEFF Research Database (Denmark)

    Munthe, Sune; Petterson, Stine Asferg; Dahlrot, Rikke Hedegaard

    2016-01-01

    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...... 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...

  9. Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1beta-dependent stabilization of Snail in tumor cells.

    Directory of Open Access Journals (Sweden)

    Pawan Kaler

    2010-07-01

    Full Text Available We recently reported that colon tumor cells stimulate macrophages to release IL-1beta, which in turn inactivates GSK3beta and enhances Wnt signaling in colon cancer cells, generating a self-amplifying loop that promotes the growth of tumor cells.Here we describe that macrophages protect HCT116 and Hke-3 colon cancer cells from TRAIL-induced apoptosis. Inactivation of IL-1beta by neutralizing IL-1beta antibody, or silencing of IL-1beta in macrophages inhibited their ability to counter TRAIL-induced apoptosis. Accordingly, IL-1beta was sufficient to inhibit TRAIL-induced apoptosis. TRAIL-induced collapse of the mitochondrial membrane potential (Delta psi and activation of caspases were prevented by macrophages or by recombinant IL-1beta. Pharmacological inhibition of IL-1beta release from macrophages by vitamin D(3, a potent chemopreventive agent for colorectal cancer, restored the ability of TRAIL to induce apoptosis of tumor cells cultured with macrophages. Macrophages and IL-1beta failed to inhibit TRAIL-induced apoptosis in HCT116 cells expressing dnIkappaB, dnAKT or dnTCF4, confirming that they oppose TRAIL-induced cell death through induction of Wnt signaling in tumor cells. We showed that macrophages and IL-1beta stabilized Snail in tumor cells in an NF-kappaB/Wnt dependent manner and that Snail deficient tumor cells were not protected from TRAIL-induced apoptosis by macrophages or by IL-1beta, demonstrating a crucial role of Snail in the resistance of tumor cells to TRAIL.We have identified a positive feedback loop between tumor cells and macrophages that propagates the growth and promotes the survival of colon cancer cells: tumor cells stimulate macrophages to secrete IL-1beta, which in turn, promotes Wnt signaling and stabilizes Snail in tumor cells, conferring resistance to TRAIL. Vitamin D(3 halts this amplifying loop by interfering with the release of IL-1beta from macrophages. Accordingly, vitamin D(3 sensitizes tumor cells to TRAIL

  10. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    OpenAIRE

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages pro...

  11. Monoclonal TCR-redirected tumor cell killing.

    Science.gov (United States)

    Liddy, Nathaniel; Bossi, Giovanna; Adams, Katherine J; Lissina, Anna; Mahon, Tara M; Hassan, Namir J; Gavarret, Jessie; Bianchi, Frayne C; Pumphrey, Nicholas J; Ladell, Kristin; Gostick, Emma; Sewell, Andrew K; Lissin, Nikolai M; Harwood, Naomi E; Molloy, Peter E; Li, Yi; Cameron, Brian J; Sami, Malkit; Baston, Emma E; Todorov, Penio T; Paston, Samantha J; Dennis, Rebecca E; Harper, Jane V; Dunn, Steve M; Ashfield, Rebecca; Johnson, Andy; McGrath, Yvonne; Plesa, Gabriela; June, Carl H; Kalos, Michael; Price, David A; Vuidepot, Annelise; Williams, Daniel D; Sutton, Deborah H; Jakobsen, Bent K

    2012-06-01

    T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of patients with cancer. In the majority of these individuals, however, there is a failure of the specific T cell receptor (TCR)–mediated immune recognition and activation process. Here we describe the engineering and characterization of new reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Four such ImmTACs, each comprising a distinct tumor-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities. Furthermore, these reagents potently suppressed tumor growth in vivo. Thus, ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy.

  12. Mesothelioma tumor cells modulate dendritic cell lipid content, phenotype and function.

    Directory of Open Access Journals (Sweden)

    Joanne K Gardner

    Full Text Available Dendritic cells (DCs play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay, upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+ CD8α- DCs, CD4- CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.

  13. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    Science.gov (United States)

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  14. An Effective Approach for Immunotherapy Using Irradiated Tumor Cells

    International Nuclear Information System (INIS)

    Mostafa, D.M.B.

    2011-01-01

    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.

  15. Childhood Central Nervous System Germ Cell Tumors Treatment

    Science.gov (United States)

    ... make hormones. Yolk sac tumors make the hormone alpha-fetoprotein (AFP). Mixed germ cell tumors are made of ... used to diagnose some CNS germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Blood ...

  16. Transfer of allogeneic CD4+ T cells rescues CD8+ T cells in anti-PD-L1–resistant tumors leading to tumor eradication

    Science.gov (United States)

    Arina, Ainhoa; Karrison, Theodore; Galka, Eva; Schreiber, Karin; Weichselbaum, Ralph R.; Schreiber, Hans

    2017-01-01

    Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. PMID:28077434

  17. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert 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 important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  18. Mast cells: potential positive and negative roles in tumor biology.

    Science.gov (United States)

    Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

    2013-11-01

    Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

  19. In vivo studies of radiation potentiaton by iodoacetamide and observations on tumor transplantation immunity

    Energy Technology Data Exchange (ETDEWEB)

    Richards, W. Robert [Univ. of California, Berkeley, CA (United States); Kelly, Lola S. [Univ. of California, Berkeley, CA (United States)

    1970-10-01

    Iodoacetamide has been shown by others to be a radiation sensitizer for bacteria and for certain mammalian cells tested in vitro. This work describes an examination of the effectiveness of iodoacetamide used in vivo. Survival of ascites tumor cells maintained in the peritoneal cavity of mice was used as an indicator of sensitization. Survival was assessed using TD50 and total tumor cell population determination methods. A comparison of results obtained by these methods is made. The effects of oxygen tension and radiation dose rate upon results was examined. Iodoacetamide was found to be effective as a radiation sensitizer under all conditions although to a lesser degree than that reported by others for in vitro experiments with bacteria. Radioactive tracer studies indicate that iodoacetamide has rapid and total access to most if not all tissues of the body. This fact coupled with the observation of a sensitization in an in vivo system where the anoxia so prevalent in well developed tumors was present, suggests the possibility of clinical usefulness of iodoacetamide in cancer radiation therapy. Certain observations are reported on the effect of various cell and host treatment procedures upon cell population growth kinetics seen subsequent to inoculation of hosts with the cells. A hypothesis is presented which can account for the observations made by the author and also for those made by some others who report that large inocula, i.e., greater than 10 cells, are required to give rise to a lethal tumor in isologous hosts of the strain of tumor origin. The hypothesis may also account for what is known in the literature as the 'Hybrid Effect.'

  20. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

    Directory of Open Access Journals (Sweden)

    Ferrone Soldano

    2007-06-01

    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  1. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  2. Beta-trace protein in ascites and pleural effusions: limits of CSF leakage detection.

    Science.gov (United States)

    Dietzel, Joanna; Krebs, Alexander; Böttcher, Dominique; Sieb, Manuela; Glocker, Michael O; Lüdemann, Jan; Roser, Markus; Dressel, Alexander

    2012-06-10

    Rhino- and/or otoliquorrhea can be diagnosed by detecting beta-trace protein (β-TP) in nasal or ear secretions, as β-TP is found in high concentrations in cerebrospinal fluid (CSF) but not in serum. CSF fistulae following trauma or surgery can also occur at other anatomical sites, resulting in CSF leakage into the thoracic and abdominal cavities. By analogy, determination of ß-TP has also been used to diagnose CSF admixture in pleural effusions and ascites. However, no systematic study has yet evaluated the concentrations of β-TP in such fluids in the absence of CSF. To determine the validity of β-TP determination as a marker for the presence of CSF, we investigated β-TP concentrations in pleural effusions and ascites without CSF admixture. Patients from whom samples of ascites or pleural effusion and a paired plasma sample were available were investigated. One hundred sixty-four patients were prospectively recruited. ß-TP concentrations were determined by nephelometry. Mass spectrometric proteome analysis confirmed the presence of ß-TP in the samples. Median β-TP concentrations detected in ascites and pleural effusions (range, 0.014-26.5 mg/L, median 2.29 mg/L) exceeded the corresponding plasma concentrations 2.6-fold. According to cutoffs published to diagnose rhino- and otoliquorrhea, between 6.1% and 95.7% of the specimens would have been erroneously rated CSF-positive. Protein analysis confirmed the presence of β-TP in pleural effusion and ascites. Ascites and pleural effusion contain high concentrations of β-TP that exceed the levels in corresponding plasma. Therefore, β-TP is not a specific marker for the presence of CSF in these fluids.

  3. Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing rats supplemented with fish oil rich in EPA and DHA

    Energy Technology Data Exchange (ETDEWEB)

    Borghetti, G.; Yamazaki, R.K.; Coelho, I.; Pequito, D.C.T.; Schiessel, D.L.; Kryczyk, M.; Mamus, R.; Naliwaiko, K.; Fernandes, L.C. [Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2013-08-23

    We investigated the effect of fish oil (FO) supplementation on tumor growth, cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma (PPARγ), and RelA gene and protein expression in Walker 256 tumor-bearing rats. Male Wistar rats (70 days old) were fed with regular chow (group W) or chow supplemented with 1 g/kg body weight FO daily (group WFO) until they reached 100 days of age. Both groups were then inoculated with a suspension of Walker 256 ascitic tumor cells (3×10{sup 7} cells/mL). After 14 days the rats were killed, total RNA was isolated from the tumor tissue, and relative mRNA expression was measured using the 2{sup -ΔΔCT} method. FO significantly decreased tumor growth (W=13.18±1.58 vs WFO=5.40±0.88 g, P<0.05). FO supplementation also resulted in a significant decrease in COX-2 (W=100.1±1.62 vs WFO=59.39±5.53, P<0.001) and PPARγ (W=100.4±1.04 vs WFO=88.22±1.46, P<0.05) protein expression. Relative mRNA expression was W=1.06±0.022 vs WFO=0.31±0.04 (P<0.001) for COX-2, W=1.08±0.02 vs WFO=0.52±0.08 (P<0.001) for PPARγ, and W=1.04±0.02 vs WFO=0.82±0.04 (P<0.05) for RelA. FO reduced tumor growth by attenuating inflammatory gene expression associated with carcinogenesis.

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

    International Nuclear Information System (INIS)

    Addison, Christina L; Belperio, John A; Burdick, Marie D; Strieter, Robert M

    2004-01-01

    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

  5. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  6. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

  7. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells.

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

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

    KAUST Repository

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-01-01

    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.

  9. 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.

  10. 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...

  11. Migratory neighbors and distant invaders: tumor-associated niche cells

    Science.gov (United States)

    Wels, Jared; Kaplan, Rosandra N.; Rafii, Shahin; Lyden, David

    2008-01-01

    The cancer environment is comprised of tumor cells as well as a wide network of stromal and vascular cells participating in the cellular and molecular events necessary for invasion and metastasis. Tumor secretory factors can activate the migration of host cells, both near to and far from the primary tumor site, as well as promote the exodus of cells to distant tissues. Thus, the migration of stromal cells and tumor cells among specialized microenvironments takes place throughout tumor and metastatic progression, providing evidence for the systemic nature of a malignancy. Investigations of the tumor–stromal and stromal–stromal cross-talk involved in cellular migration in cancer may lead to the design of novel therapeutic strategies. PMID:18316475

  12. CD200-expressing human basal cell carcinoma cells initiate tumor growth.

    Science.gov (United States)

    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

    2013-01-22

    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  13. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

    Science.gov (United States)

    Netea-Maier, Romana T; Smit, Johannes W A; Netea, Mihai G

    2018-01-28

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Ultrasound-guided biopsy of greater omentum: An effective method to trace the origin of unclear ascites

    Energy Technology Data Exchange (ETDEWEB)

    Que Yanhong [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: quebaobao@yahoo.com.cn; Wang Xuemei [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: wxmlmt@yahoo.com.cn; Liu Yanjun [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: lyj7512@sina.com; Li Ping [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: liping7213@sina.com; Ou Guocheng [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: yang9951@126.com; Zhao Wenjing [Department of Ultrasound, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001 (China)], E-mail: awk999@163.com

    2009-05-15

    Objectives: Thickened greater omentum is encountered with high frequency in patients with ascites. The purpose of our study was to assess the utility of greater omentum biopsy under the guidance of ultrasound (US) in tracing the origin of unclear ascites and differentiating benign and malignant ascites. Materials and methods: We retrospectively reviewed our institutional database for all records of greater omentum biopsy cases. One hundred and ninety-four patients with unclear ascites and thickened greater omentum were included in the study. The sonograms of greater omentum were evaluated before undergoing the ultrasound-guided biopsy and a biopsy was considered successful if a specific benign or malignant diagnosis was rendered by the pathologist. Results: Successful biopsy was rendered for 182 biopsy procedures (93.8%, 182/194) including tuberculosis (n = 114), chronic inflammation (n = 3), metastases (n = 58), malignant mesothelioma (n = 6) and pseudomyxoma peritonei (n = 1). Twelve biopsies were non-diagnostic. According to the results of biopsy and follow-up, the sensitivity and specificity of biopsy in distinguishing malignant ascites from benign ascities were respectively 95.6% (65/68) and 92.9% (117/126). The greater omentum of 84 cases of tuberculous peritonitis showed 'cerebral fissure' sign and was well seen as an omental cake infiltrated with irregular nodules when involved by carcinomatosis. No 'cerebral fissure' sign was observed in peritoneal carcinomatosis. The sensitivity and specificity of this sign in indicating the existence of tuberculous peritonitis were 73.5% (89/121) and 100% (73/73). Moreover, if the specific 'cerebral fissure' sign was combined with the biopsy results, the specificity of biopsy in distinguishing malignant ascites from benign ascits increased to 96.8% (122/126). Conclusion: Ultrasound-guided biopsy of greater omentum is an important and effective method to diagnose the unclear ascites for

  15. Measurement of tumor volumes of hepatocellular carcinoma (HCC) by computed tomography (CT). Correlation with several tumor markers

    Energy Technology Data Exchange (ETDEWEB)

    Yoneshima, Manabu; Sawabu, Norio; Toya, Daishu

    1984-09-01

    Tumor volumes of HCC were measured by CT using planimeter and the clinical value of this measurement was evaluated by comparing several tumor markers. Tumor volumes measured by CT roughly agreed with those measured by angiography. In some cases, volumes from ultrasonography were smaller than those from CT and angiography. Tumor volumes measured by CT correlated significantly with the levels of ..cap alpha..-fetoprotein (AFP) but didn't relate to the presence of hepatoma specific ..gamma..-GTP isoenzyme (novel ..gamma..-GTP) nor to the values and positivities of LAI assay. In small HCCs (<=30 cm/sup 3/), the presence of novel ..gamma..-GTP and the levels of AFP were significantly lower than for larger tumors of HCC, but LAI assay wasn't lower. The non-tumorous volumes and the ratio of the non-tumorous volume to the whole liver volume didn't relate to the tests of liver function except for the presence of ascites.

  16. Cytotoxicity of extracts of spices to cultured cells.

    Science.gov (United States)

    Unnikrishnan, M C; Kuttan, R

    1988-01-01

    The cytotoxicity of the extracts from eight different spices used in the Indian diet was determined using Dalton's lymphoma ascites tumor cells and human lymphocytes in vitro and Chinese Hamster Ovary cells and Vero cells in tissue culture. Alcoholic extracts of the spices were found to be more cytotoxic to these cells than their aqueous extracts. Alcoholic extracts of several spices inhibited cell growth at concentrations of 0.2-1 mg/ml in vitro and 0.12-0.3 mg/ml in tissue culture. Ginger, pippali (native to India; also called dried catkins), pepper, and garlic showed the highest activity followed by asafetida, mustard, and horse-gram (native to India). These extracts also inhibited the thymidine uptake into DNA.

  17. Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.

    Science.gov (United States)

    Habib, M Rowshahul; Karim, M Rezaul

    2011-10-01

    To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (PSALP) and serum glutamate oxaloacetate transaminase (SGOT). Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  18. Radiosensitivity of four human tumor xenografts. Influence of hypoxia and cell-cell contact

    International Nuclear Information System (INIS)

    Guichard, M.; Dertinger, H.; Malaise, E.P.

    1983-01-01

    Contact effect (CE) and hypoxia have been studied in human tumor cell lines transplanted in athymic nude mice. Four cell lines - one melanoma (Bell) and three colorectal adenocarcinomas (HT29, HRT18, and HCT8) - were studied. Cell survival was determined with an in vivo in vitro colony-forming assay. Survival curves were obtained under three different conditions: (1) tumor cells irradiated in air-breathing mice, (2) tumor cells irradiated in animals asphyxiated for 10 min, and (3) tumor cells plated and irradiated either immediately or 5 hr later. For all cell lines, radiosensitivity appeared to be lower when cells were irradiated in vivo than when they were irradiated in vitro. Only in the case of the HCT8 tumor did the relative in vivo radioresistance seem to be linked to hypoxia; in the other cell lines, hypoxia alone could not account for the lower in vivo radiosensitivity. Our results suggest that a CE plays an important role in the response of human xenografts to irradiation

  19. Peritoneal implants without ascites. Preoperative CT diagnosis in colon carcinoma patients

    International Nuclear Information System (INIS)

    Saida, Yukihisa; Itai, Yuji; Tsunoda, Hiroko; Matsueda, Kiyoshi.

    1994-01-01

    We evaluated the preoperative CT findings in 10 patients with colon carcinoma in whom peritoneal metastases had been surgically confirmed. Seven patients lacked ascites. No CT findings suggestive of peritoneal metastasis were observed in two patients without ascites even by retrospective evaluation. A large mass was observed in the cul-de-sac in another. In the remaining four patients, small peritoneal metastases ranging from 8 to 11 mm in diameter were observed at the omentum in two, along the falciform ligament in one, and at both the omentum and the iliac fossa in one; three of these patients had received no prospective diagnosis of peritoneal metastasis prior to the surgery. In patients with advanced colon carcinoma with suspected serosal invasion, the entire peritoneal cavity should be carefully examined and interpreted using CT in order to detect small peritoneal implants even when ascites is absent. (author)

  20. Chylous ascites and chylothorax due to constrictive pericarditis in a patient infected with HIV: a case report

    Directory of Open Access Journals (Sweden)

    Summachiwakij Sarawut

    2012-06-01

    Full Text Available Abstract Introduction Chylothorax and chylous ascites are uncommon and usually associated with trauma or neoplasms. To the best of our knowledge, constrictive pericarditis leading to chylothorax and chylous ascites in a person infected with HIV has never previously been described. Case presentation A 39-year-old Thai man was referred to our institute with progressive dyspnea, edema and abdominal distension. His medical history included HIV infection and pulmonary tuberculosis that was complicated by tuberculous pericarditis and cardiac tamponade. Upon further investigation, we found constrictive pericarditis, chylothorax and chylous ascites. A pericardiectomy was performed which resulted in gradual resolution of the ascites and chylous effusion. Conclusions Although constrictive pericarditis is an exceptionally rare cause of chylothorax and chylous ascites, it should nonetheless be considered in the differential diagnosis as a potentially reversible cause.

  1. Percutaneous microwave ablation with artificial ascites for symptomatic uterine adenomyosis: initial experience.

    Science.gov (United States)

    Hai, Ning; Zhang, Jing; Xu, Ruifang; Han, Zhi-Yu; Liu, Fang Yi

    2017-09-01

    To evaluate the feasibility, safety and technical efficacy of ultrasound-guided percutaneous microwave ablation with artificial ascites for adenomyosis. Between May 2015 and May 2016, a total of 25 patients with symptomatic adenomyosis who underwent ultrasound-guided percutaneous microwave ablation with artificial ascites were included in this retrospective study. A matching cohort of 50 patients underwent ultrasound-guided percutaneous microwave ablation without artificial ascites as controls. The technical efficacy, complications and short-term treatment effectiveness were assessed and compared with the controls. Artificial ascites was successfully achieved in all of the 25 patients with the administration of a median of 550 mL (range, 250-1200 mL) of solution. There was substantial improvement in achieving a better antenna path in 100% (20/20) of the cases with a poor antenna path. The complete separation was achieved in 23 of 25 patients. The mean ablation time was 26.5 ± 7.3 min and the median non-perfusion volume ratio was 76% which was similar to the control group (p > .05). No serious complications were observed. Patient pain scores for dysmenorrhoea showed a statistically significant decline from the baseline of 6.71 ± 0.96 to 2.92 ± 0.79 and the symptom severity score declined statistically significantly from 21.8 ± 5.5 to 16.4 ± 4.8 at 3 months follow-up. Percutaneous microwave ablation with artificial ascites is feasible, safe and can be effective in improving access for treatment of adenomyosis.

  2. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  3. 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.

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

    Science.gov (United States)

    Mahadimane, Periyapatna Vishwaprakash; Vasudev, Venkateshaiah

    2014-01-01

    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.

  5. Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

    Directory of Open Access Journals (Sweden)

    Adriana Albini

    2018-04-01

    Full Text Available The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression. In our review, we discuss the regulation of angiogenesis by innate immune cells in the tumor microenvironment, specific features, and roles of major players: macrophages, neutrophils, myeloid-derived suppressor and dendritic cells, mast cells, γδT cells, innate lymphoid cells, and natural killer cells. Anti-VEGF or anti-inflammatory drugs could balance an immunosuppressive microenvironment to an immune permissive one. Anti-VEGF as well as anti-inflammatory drugs could therefore represent partners for combinations with immune checkpoint inhibitors, enhancing the effects of immune therapy.

  6. Dynamic Changes of Endothelium Derived Factors and Cyclic Nucleotides in Ascites Broilers and Control of L-arginine

    Institute of Scientific and Technical Information of China (English)

    HAN Bo; WANG Xiao-long

    2003-01-01

    A flock of AA breed chickens were reared in peterstme brood-vait chamber using high energypelleted feed, at 14 days of age, 400 birds were separated into 3 groups randomly as follows: 100 birds wereexposed to normal ambient temperature (20℃) as control group, 150 birds were exposed to low ambient tem-perature (11℃) in order to induce ascites as treatment Ⅰ group, another 100 birds were also exposed to lowambient temperature (11℃) and fed the diets containing 1% L-arginine for ascitic prophylactic treatment astreatment Ⅱ group. The blood samples were collected on 3, 4, 5, 6, 7 wk, respectively, to measure the con-tents of plasma endothelin (ET-1), angiotensin Ⅱ (Ang Ⅱ ) and cyclic adenosine monophosphate (cAMP) andcyclic guanosine monophosphate (cGMP). The results indicated that the contents of cAMP, cGMP, Ang Ⅱand the ratio of cAMP/cGMP in treatment Ⅰ and ascitic broilers were higher than that of correspondent con-trol group(P<0.01, P<0.05), ET-1 of preascitic broilers were higher than that of control group(P<0.05),while there were insignificant differences with later ascitic broilers, the contents of cAMP and cGMP in treat-ment Ⅱ were higher than treatment Ⅰ and control group(P<0.01, P<0.05), whereas, the ratio of cAMP/cGMP and the contents of Ang Ⅱ were gradually decreased than that of control group(P<0.05), the contentsof ET-1 were not changed. By further analysis, the increased plasma Ang Ⅱ at low ambient temperature condi-tion in broilers made endothelium cell secretion of increased ET-1, cAMP, cGMP and decreased NO. So lowtemperature accelarated ascites syndrome in broilers. Supplemented L-arginine can decrease ET-1, cAMP andcAMP/cGMP. It is concluded that cAMP mediated pulmonary hypertension syndrome in broilers.

  7. 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....

  8. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  9. The Impact of Tunneled Catheters for Ascites and Peritoneal Carcinomatosis on Patient Rehospitalizations

    International Nuclear Information System (INIS)

    Qu, Chuanxing; Xing, Minzhi; Ghodadra, Anish; McCluskey, Kevin M.; Santos, Ernesto; Kim, Hyun S.

    2016-01-01

    PurposeThe aim of the study is to assess patient outcomes, complications, impact on rehospitalizations, and healthcare costs in patients with malignant ascites treated with tunneled catheters.Materials and MethodsA total of 84 patients with malignant ascites (mean age, 60 years) were treated with tunneled catheters. Patients with peritoneal carcinomatosis and malignant ascites treated with tunneled drain catheter placement over a 3-year period were studied. Overall survival from the time of ascites and catheter placement were stratified by primary cancer and analyzed using the Kaplan–Meier method. Complications were graded by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). The differences between pre- and post-catheter admissions, hospitalizations, and Emergency Department (ED) visits, as well as related inpatient expenses were compared using paired t tests.ResultsThere were no significant differences in gender, age, or race between different primary cancer subgroups. One patient (1 %) developed bleeding (CTCAE-2). Four patients (5 %) developed local cellulitis (CTCAE-2). Three patients (4 %) had prolonged hospital stay (between 7 and 10 days) to manage ascites-related complications such as abdominal distention, discomfort, or pain. Comparison between pre- and post-catheter hospitalizations showed significantly lower admissions (−1.4/month, p < 0.001), hospital stays (−4.2/month, p = 0.003), and ED visits (−0.9/month, p = 0.002). The pre- and post-catheter treatment health care cost was estimated using MS-DRG IPPS payment system and it demonstrated significant cost savings from decreased inpatient admissions in post-treatment period (−$9535/month, p < 0.001).ConclusionsTunneled catheter treatment of malignant ascites is safe, feasible, well tolerated, and cost effective. Tunneled catheter treatment may play an important role in improving patients’ quality of life and outcomes while controlling health care expenditures.

  10. The Impact of Tunneled Catheters for Ascites and Peritoneal Carcinomatosis on Patient Rehospitalizations

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Chuanxing [University of Pittsburgh School of Medicine, Division of Interventional Radiology, Department of Radiology (United States); Xing, Minzhi [Yale University School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale Cancer Center (United States); Ghodadra, Anish; McCluskey, Kevin M.; Santos, Ernesto; Kim, Hyun S., E-mail: kevin.kim@yale.edu [University of Pittsburgh School of Medicine, Division of Interventional Radiology, Department of Radiology (United States)

    2016-05-15

    PurposeThe aim of the study is to assess patient outcomes, complications, impact on rehospitalizations, and healthcare costs in patients with malignant ascites treated with tunneled catheters.Materials and MethodsA total of 84 patients with malignant ascites (mean age, 60 years) were treated with tunneled catheters. Patients with peritoneal carcinomatosis and malignant ascites treated with tunneled drain catheter placement over a 3-year period were studied. Overall survival from the time of ascites and catheter placement were stratified by primary cancer and analyzed using the Kaplan–Meier method. Complications were graded by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). The differences between pre- and post-catheter admissions, hospitalizations, and Emergency Department (ED) visits, as well as related inpatient expenses were compared using paired t tests.ResultsThere were no significant differences in gender, age, or race between different primary cancer subgroups. One patient (1 %) developed bleeding (CTCAE-2). Four patients (5 %) developed local cellulitis (CTCAE-2). Three patients (4 %) had prolonged hospital stay (between 7 and 10 days) to manage ascites-related complications such as abdominal distention, discomfort, or pain. Comparison between pre- and post-catheter hospitalizations showed significantly lower admissions (−1.4/month, p < 0.001), hospital stays (−4.2/month, p = 0.003), and ED visits (−0.9/month, p = 0.002). The pre- and post-catheter treatment health care cost was estimated using MS-DRG IPPS payment system and it demonstrated significant cost savings from decreased inpatient admissions in post-treatment period (−$9535/month, p < 0.001).ConclusionsTunneled catheter treatment of malignant ascites is safe, feasible, well tolerated, and cost effective. Tunneled catheter treatment may play an important role in improving patients’ quality of life and outcomes while controlling health care expenditures.

  11. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Science.gov (United States)

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

  12. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Marc Baay

    2011-01-01

    Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

  13. Evidence that progression of cells into S-phase is not a prerequisite for recovery between split doses of U.V.-light in synchronized and plateau phase cultures of Ehrlich ascites tumour cells

    International Nuclear Information System (INIS)

    Iliakis, G.; Nuesse, M.

    1982-01-01

    The ability of Ehrlich ascites tumour cells (EAT-cells) to perform split-dose recovery after U.V. exposure was studied with unfed plateau phase as well as with synchronized cells selected from exponentially growing cultures. The cells were kept in balanced salt solution which inhibited the progression of the cells through the cell cycle. The results indicated that split-dose recovery occurred in EAT-cells in all phases of the cell cycle and that progression of the cells into S-phase was not a prerequisite for this type of repair. The second-dose survival curves of G 1 -and S-phase cells showed, 24 hours after the first U.V. exposure, a shoulder width comparable to that of singly irradiated cells. Second-dose survival curves for G 2 -cells showed, after the same time interval, a shoulder width smaller than that for singly exposed cells, presumably due to some cell division. The recovery time constant (t 50 between 4 and 8 hours) increased with increasing U.V. exposure. (author)

  14.  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.

  15. Primary malignant mixed müllerian tumor of the peritoneum a case report with review of the literature

    DEFF Research Database (Denmark)

    Kurshumliu, Fisnik; Rung-Hansen, Helle; Skovlund, Vibeke Ravn

    2011-01-01

    Malignant mixed Müllerian tumor is a rare malignancy of the genital tract and extremely uncommon in extragenital sites. This report describes a case of malignant mixed Müllerian tumor arising in the lower peritoneum of a 72-year-old female patient. The patient presented with ascites, lower...

  16. Intra-abdominal desmoplastic small round cell tumors: CT findings and clinicopathological correlations in 13 cases

    Energy Technology Data Exchange (ETDEWEB)

    Chouli, Malik [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Viala, Juliette [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Dromain, Clarisse [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Fizazi, Karim [Department of Medicine, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Duvillard, Pierre [Department of Histopathology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Vanel, Daniel [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France)]. E-mail: vanel@igr.fr

    2005-06-01

    Purpose: We report computed tomography (CT) findings in 13 patients with a primary abdominal desmoplastic small round cell tumor. Materials and methods: 13 cases (12 men, 1 woman, mean age = 24.8 years) were found in our hospital database between 1991 and 2003. Clinical, CT and histopathological features were studied retrospectively. Results: Peritoneal involvement was the most common feature. In 10 cases, several lobulated peritoneal soft tissue masses (with a mean of four masses per patient) were seen. Two patients had diffused irregular peritoneal carcinomatosis without any distinct peritoneal masses. One patient had a solitary mass in the pelvic space. The main sites of peritoneal involvement were the pelvic space (n 7), omentum (n = 5), retroperitoneal space (n = 4), small bowel mesentery (n = 3), paracolic gutter (n = 2 on the right and n = 1 on the left), transverse colon mesentery (n = 1), peri-splenic space (n = 1), peri-hepatic space (n 1). The soft tissue masses were often bulky (mean 6 cm, range 1-28 cm), lobulated and heterogeneous with hypodense areas (in 73% of cases). In six cases, moderate ascites was seen. In one case of pelvic involvement, unilateral hydronephrosis was seen. Adenopathies were present in seven cases at the time of the diagnosis (at intraperitoneal, retroperitoneal and pelvic sites in six patients and in the groin in one patient). Five patients had liver metastases (four lesions per case excepted one patient with 30 metastases). Associated thoracic metastases were seen in three patients. The diagnosis was confirmed with four CT-guided percutaneous biopsies. Conclusion: Although CT features are nonspecific, the diagnosis of desmoplastic small round cell tumor may be suspected in young men with multiple bulky heterogeneous peritoneal soft tissue masses. Imaging is useful for staging and also to guide biopsies.

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

    Science.gov (United States)

    Hoffmann, Else Kay

    2011-01-01

    This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

  18. 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.

  19. The use of bispecific antibodies in tumor cell and tumor vasculature directed immunotherapy

    NARCIS (Netherlands)

    Molema, G; Kroesen, BJ; Helfrich, W; Meijer, DKF; de Leij, LFMH

    2000-01-01

    To overcome dose limiting toxicities and to increase efficacy of immunotherapy of cancer, a number of strategies are under development for selectively redirecting effector cells/molecules towards tumor cells. Many of these strategies exploit the specificity of tumor associated antigen recognition by

  20. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells.

    Science.gov (United States)

    Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

    2017-03-07

    Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.

  1. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    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)

  2. Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.

    Science.gov (United States)

    Dakwar, George R; Braeckmans, Kevin; Demeester, Joseph; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien

    2015-11-04

    Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.

  3. Effects of low dose radiation combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation of bone marrow in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2004-01-01

    Objective: To study the effect of low dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle, and proliferation of bone marrow in mice tumor-bearing mice. Methods: Kunming strain male mice were implanted with S180 sarcoma cells in the left hind leg subcutaneously as an experimental animal model. Five and 8 days after implantation, the mice were given 75 mGy whole-body γ-ray radiation and CTX(300 mg/kg) by intraperitoneal injection 36 hour after LDR. All mice were sacrificed to measure the tumor volume, tumor cell apoptosis, and cell cycle; the proliferation of bone marrow was analyzed by flow cytometry. Results: Tumor growth was significantly slowed down in the treated groups. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G 1 phase in CTX and CTX+LDR groups, more significantly in the latter group than in the former group. Concentration of bone marrow cells and proliferation index in CTX + LDR group were higher than those in CTX group, although concentration of bone marrow cells in CTX and CTX+LDR groups were much lower than that in normal mice. Conclusion: Low dose radiation combined with cyclophosphamide causes more significant G 1 -phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. At the same time LDR significantly protects hematopoietic function of bone marrow, which is of practical significance as an adjuvant chemotherapy

  4. The Human Cell Surfaceome of Breast Tumors

    Science.gov (United States)

    da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

    2013-01-01

    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. PMID:24195083

  5. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

    Directory of Open Access Journals (Sweden)

    Alessandra M. Welker

    2016-02-01

    Full Text Available Glioblastoma (GBM is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a

  6. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.

    Science.gov (United States)

    Carlson, David J; Keall, Paul J; Loo, Billy W; Chen, Zhe J; Brown, J Martin

    2011-03-15

    Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. CD4 cells can be more efficient at tumor rejection than CD8 cells.

    Science.gov (United States)

    Perez-Diez, Ainhoa; Joncker, Nathalie T; Choi, Kyungho; Chan, William F N; Anderson, Colin C; Lantz, Olivier; Matzinger, Polly

    2007-06-15

    Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell in tumor immunotherapy.

  8. Tumor and Endothelial Cell Hybrids Participate in Glioblastoma Vasculature

    Directory of Open Access Journals (Sweden)

    Soufiane El Hallani

    2014-01-01

    Full Text Available Background. Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM. Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM. Materials and Methods. We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact. Results. In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF. By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation. Conclusion. A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.

  9. Chylous ascites and chylothorax: a case study

    African Journals Online (AJOL)

    2010-09-07

    Sep 7, 2010 ... find out the possible etiology. It showed bilateral ... abdominal process such as nephrotic syndrome, hy- pothyroidism, cirrhosis of the liver, abdominal opera- tions, and pancreatitis (1). In our patient, CT of thorax and abdomen were not contributory. The treatment of the chylothorax and chylous ascites.

  10. Immunotherapy with neuraminidase-treated tumor cells after radiotherapy

    International Nuclear Information System (INIS)

    Song, C.W.; Levitt, S.H.

    1975-01-01

    The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma, M-79, transplanted to the thigh of C3H/HeJ mice. When the tumors reached 4 to 8 mm in diameter, various treatments were started. X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (23.3 percent). The inoculation of 1 x 10 6 of VCN-cells to the tumor-bearing animals, every other day for a total of three doses, caused a complete regression of 6 out of 57 tumors (10.5 percent). Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (37.9 percent). The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone

  11. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

    Science.gov (United States)

    Testa, Ugo; Pelosi, Elvira; Castelli, Germana

    2018-04-13

    Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

  12. Lethal effect of glucose load on malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Kozubek, S.

    1987-01-01

    Ehrlich ascites tumor (EAT) cells were treated with glucose load under anoxic conditions (for 15 or 60 min) and/or with γ radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells using glucose load in anoxia and γ radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. (author). 5 figs., 2 tabs., 12 refs

  13. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

  14. 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.

  15. The expression of VE-cadherin in breast cancer cells modulates cell dynamics as a function of tumor differentiation and promotes tumor-endothelial cell interactions.

    Science.gov (United States)

    Rezaei, Maryam; Cao, Jiahui; Friedrich, Katrin; Kemper, Björn; Brendel, Oliver; Grosser, Marianne; Adrian, Manuela; Baretton, Gustavo; Breier, Georg; Schnittler, Hans-Joachim

    2018-01-01

    The cadherin switch has profound consequences on cancer invasion and metastasis. The endothelial-specific vascular endothelial cadherin (VE-cadherin) has been demonstrated in diverse cancer types including breast cancer and is supposed to modulate tumor progression and metastasis, but underlying mechanisms need to be better understood. First, we evaluated VE-cadherin expression by tissue microarray in 392 cases of breast cancer tumors and found a diverse expression and distribution of VE-cadherin. Experimental expression of fluorescence-tagged VE-cadherin (VE-EGFP) in undifferentiated, fibroblastoid and E-cadherin-negative MDA-231 (MDA-VE-EGFP) as well as in differentiated E-cadherin-positive MCF-7 human breast cancer cell lines (MCF-VE-EGFP), respectively, displayed differentiation-dependent functional differences. VE-EGFP expression reversed the fibroblastoid MDA-231 cells to an epithelial-like phenotype accompanied by increased β-catenin expression, actin and vimentin remodeling, increased cell spreading and barrier function and a reduced migration ability due to formation of VE-cadherin-mediated cell junctions. The effects were largely absent in both MDA-VE-EGFP and in control MCF-EGFP cell lines. However, MCF-7 cells displayed a VE-cadherin-independent planar cell polarity and directed cell migration that both developed in MDA-231 only after VE-EGFP expression. Furthermore, VE-cadherin expression had no effect on tumor cell proliferation in monocultures while co-culturing with endothelial cells enhanced tumor cell proliferation due to integration of the tumor cells into monolayer where they form VE-cadherin-mediated cell contacts with the endothelium. We propose an interactive VE-cadherin-based crosstalk that might activate proliferation-promoting signals. Together, our study shows a VE-cadherin-mediated cell dynamics and an endothelial-dependent proliferation in a differentiation-dependent manner.

  16. Ganglioside GD2 in reception and transduction of cell death signal in tumor cells

    International Nuclear Information System (INIS)

    Doronin, Igor I; Vishnyakova, Polina A; Kholodenko, Irina V; Ponomarev, Eugene D; Ryazantsev, Dmitry Y; Molotkovskaya, Irina M; Kholodenko, Roman V

    2014-01-01

    Ganglioside GD2 is expressed on plasma membranes of various types of malignant cells. One of the most promising approaches for cancer immunotherapy is the treatment with monoclonal antibodies recognizing tumor-associated markers such as ganglioside GD2. It is considered that major mechanisms of anticancer activity of anti-GD2 antibodies are complement-dependent cytotoxicity and/or antibody-mediated cellular cytotoxicity. At the same time, several studies suggested that anti-GD2 antibodies are capable of direct induction of cell death of number of tumor cell lines, but it has not been investigated in details. In this study we investigated the functional role of ganglioside GD2 in the induction of cell death of multiple tumor cell lines by using GD2-specific monoclonal antibodies. Expression of GD2 on different tumor cell lines was analyzed by flow cytometry using anti-GD2 antibodies. By using HPTLC followed by densitometric analysis we measured the amount of ganglioside GD2 in total ganglioside fractions isolated from tumor cell lines. An MTT assay was performed to assess viability of GD2-positive and -negative tumor cell lines treated with anti-GD2 mAbs. Cross-reactivity of anti-GD2 mAbs with other gangliosides or other surface molecules was investigated by ELISA and flow cytometry. Inhibition of GD2 expression was achieved by using of inhibitor for ganglioside synthesis PDMP and/or siRNA for GM2/GD2 and GD3 synthases. Anti-GD2 mAbs effectively induced non-classical cell death that combined features of both apoptosis and necrosis in GD2-positive tumor cells and did not affect GD2-negative tumors. Anti-GD2 mAbs directly induced cell death, which included alteration of mitochondrial membrane potential, induction of apoptotic volume decrease and cell membrane permeability. This cytotoxic effect was mediated exclusively by specific binding of anti-GD2 antibodies with ganglioside GD2 but not with other molecules. Moreover, the level of GD2 expression correlated with

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

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available 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.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.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.

  18. Ovarian granulosa cell tumors : histopathology, immunopathology and prognosis

    NARCIS (Netherlands)

    S. Chadha-Ajwani (Savi)

    1987-01-01

    textabstractGranulosa cell tumors (GCT) of the ovary account for 2% of all ovarian tumors. As the name indicates, they are composed of granulosa cells but may also contain an admixture of theca cells. They are potentially malignant but, except for extraovarian spread, which is generally agreed

  19. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2011-01-01

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163 + cells were significantly increased based on the pathological grade. CD163 + cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163 + cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4 + and CD8 + T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163 + TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC

  20. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  1. Solid KHT tumor dispersal for flow cytometric cell kinetic analysis

    International Nuclear Information System (INIS)

    Pallavicini, M.G.; Folstad, L.J.; Dunbar, C.

    1981-01-01

    A bacterial neutral protease was used to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not obseved with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required

  2. 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. Copyright © 2016. Published by Elsevier GmbH.

  3. Human breast tumor cells are more resistant to cardiac glycoside toxicity than non-tumorigenic breast cells.

    Directory of Open Access Journals (Sweden)

    Rebecca J Clifford

    Full Text Available Cardiotonic steroids (CTS, specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer therapies.

  4. A contribution of glutathione to interphase death of dividing cells

    International Nuclear Information System (INIS)

    Rybina, V.V.; Korystov, Yu.N.; Degtyareva, O.V.; Dobrovinskaya, O.R.; Ehjdus, L.Kh.

    1988-01-01

    A study was made of a change in the content of reduced glutathionine (GSH) in Ehrlich ascites tumor (EAT) cells after irradiation with doses evoking their interphase death (ID). GSH content was determined in a suspension of EAT cells fixed by hot ethanol. The postirradiation decrease in the GSH content of the suspension was due to its oxidation by hydrogen peroxide resulting from radiochemical reactions after releasing thereof from cells upon fixation. In the absence of an irradiated medium no changes occurred in the GSH content of EAT cells. It is concluded that ID of EAT cells is not associated with the radiation-induced decrease in the content of GSH, an endogenous antioxidant

  5. Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

    Science.gov (United States)

    McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

    2016-07-01

    Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

    Directory of Open Access Journals (Sweden)

    Sebastian Diegeler

    2017-06-01

    Full Text Available Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  7. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities.

    Science.gov (United States)

    Diegeler, Sebastian; Hellweg, Christine E

    2017-01-01

    Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  8. The effect of ascitic fluid hydrostatic pressure on albumin extravasation rate in patients with cirrhosis of the liver

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Parving, H H; Lassen, N A

    1981-01-01

    and pigs with posthepatic portal hypertension and intraperitoneally instilled fluid were studied before and after abdominal paracentesis in order to evaluate the effect of ascitic fluid hydrostatic pressure on the transvascular escape rate of albumin. TERalb of the ascitic patients (n = 6) were on average......, TERalb rose significantly to an average of 24.3% IVMalb.h-1. The increased albumin extravasation rate after removal of ascites is best explained by an increased sinusoidal-tissue pressure difference caused by a decreased hydrostatic fluid pressure in the liver interstitium (portal and subcapsular spaces......) due to the hydrostatic effect of the removed ascitic fluid....

  9. Accumulation of sup(99m)Tc-MDP in pleural effusions and ascites

    International Nuclear Information System (INIS)

    Yokomizo, Yu; Ichiya, Yuichi; Kuwabara, Yasuo; Wada, Makoto; Shiozaki, Hiroshi

    1983-01-01

    In 1500 cases bone scintigraphy was performed. sup(99m)Tc-MDP accumulation were revealed on bone scintigraphy in pleural effusion in 5 cases and that in ascitic effusion in 2 cases. The sensitivity of sup(99m)Tc-MDP accumulation was 5.5% for pleural effusion and 10.0% for ascites. It was noticed that the sup(99m)Tc-MDP accumulation was often associated with retention of a large amount of pleural effusion. (Ueda, J.)

  10. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  11. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  12. Innate immune cell-derived microparticles facilitate hepatocarcinoma metastasis by transferring integrin α(M)β₂ to tumor cells.

    Science.gov (United States)

    Ma, Jingwei; Cai, Wenqian; Zhang, Yi; Huang, Chunmei; Zhang, Huafeng; Liu, Jing; Tang, Ke; Xu, Pingwei; Katirai, Foad; Zhang, Jianmin; He, Wei; Ye, Duyun; Shen, Guan-Xin; Huang, Bo

    2013-09-15

    Mechanisms by which tumor cells metastasize to distant organs still remain enigmatic. Immune cells have been assumed to be the root of metastasis by their fusing with tumor cells. This fusion theory, although interpreting tumor metastasis analogically and intriguingly, is arguable to date. We show in this study an alternative explanation by immune cell-derived microparticles (MPs). Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell migration in vitro and metastasis in vivo. The underlying molecular basis was involved in integrin α(M)β₂ (CD11b/CD18), which could be effectively relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking either CD11b or CD18 led to significant decreases in MP-mediated tumor cell metastasis. This MP-mediated transfer of immune phenotype to tumor cells might also occur in vivo. These findings suggest that tumor cells may usurp innate immune cell phenotypes via MP pathway for their metastasis, providing new insight into tumor metastatic mechanism.

  13. Ascites due to anastomotic stenosis after liver transplantation using the piggyback technique: Treatment with endovascular prosthesis

    International Nuclear Information System (INIS)

    Bilbao, Jose Ignacio; Herrero, Jose Ignacio; Martinez-Cuesta, Antonio; Quiroga, Jorge; Pueyo, Jesus Ciro; Vivas, Isabel; Delgado, Carlos; Pardo, Fernando

    2000-01-01

    Liver transplantation preserving the retrohepatic interior vena cava, the so-called piggyback technique, is becoming more frequently used because it avoids caval cross-clamping during the anhepatic phase of surgery. However, hepatic venous outflow blockade causing ascites seems to be less infrequent after piggyback than with cavo-caval anastomosis. We report a 62-year-old patient who underwent liver transplantation using the piggyback technique and developed a stenosis in the anastomosis between the hepatic veins and the inferior vena cava leading to severe postoperative ascites. Ascites was unresponsive to diuretic therapy and was associated with renal function impairment. Since the etiology of the stenosis was mechanical (torsion), percutaneous transluminal angioplasty was unsuccessful. Finally, an autoexpandable prosthesis was placed across the anastomosis resulting in rapid and permanent (3 years of follow-up) resolution of ascites.

  14. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

    International Nuclear Information System (INIS)

    Samoszuk, Michael; Kanakubo, Emi; Chan, John K

    2005-01-01

    The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7), a powerful, heparin-binding growth factor for breast epithelial cells. Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors

  15. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

    Directory of Open Access Journals (Sweden)

    Kanakubo Emi

    2005-09-01

    Full Text Available Abstract Background The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. Methods We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7, a powerful, heparin-binding growth factor for breast epithelial cells. Results Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Conclusion Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors.

  16. Tumor-associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells.

    Science.gov (United States)

    Ghosh, Tithi; Barik, Subhasis; Bhuniya, Avishek; Dhar, Jesmita; Dasgupta, Shayani; Ghosh, Sarbari; Sarkar, Madhurima; Guha, Ipsita; Sarkar, Koustav; Chakrabarti, Pinak; Saha, Bhaskar; Storkus, Walter J; Baral, Rathindranath; Bose, Anamika

    2016-11-01

    Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naïve CD4(+) and CD8(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naïve T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment. © 2016 UICC.

  17. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    International Nuclear Information System (INIS)

    Garbe, Yvette; Klier, Ulrike; Linnebacher, Michael

    2011-01-01

    Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4 + , activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed. Cellular fusions of MSI + carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and

  18. Radiation Therapy of Suprasellar Germ Cell Tumors

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Choi, Doo Ho; Choi, Eun Kyung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il

    1988-01-01

    A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10 patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delivered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain, The tumor was not controlled and he had spinal recurrence. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available

  19. Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a 'real-world' UK health economic evaluation.

    Science.gov (United States)

    Parker, Matthew J; Guha, Neil; Stedman, Brian; Hacking, Nigel; Wright, Mark

    2013-07-01

    To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. Secondary care. Cirrhotic patients with refractory ascites. We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.

  20. Serum and Ascitic Fluid Superoxide Dismutase and Malondialdehyde Levels in Patients with Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ugur Coskun

    2008-01-01

    Full Text Available Serum and ascitic fluid superoxide dismutase (SOD and malondialdehyde (MDA levels were measured in 43 patients with cirrhosis and in a 10 healthy control group. Compensated cirrhotic patients had no clinically detectable ascites, but decompensated patients had massive ascites. Cirrhotic patients were divided into three groups: patients with compensated cirrhosis (n = 16, patients with decompensated cirrhosis with Spontaneous bacterial peritonitis (SBP (n = 14, and patients with decompensated cirrhosis without SBP (n = 13. All cirrhotic patients in the experimental group had significantly higher serum SOD (p 0.05. These results suggest that the increase in serum SOD and MDA levels are not related to the presence of SBP and the status of liver cirrhosis. To sum up, clarifying the impact of increased serum SOD and MDA levels in cirrhotic patients needs further investigation.