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1

Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor.  

PubMed

The continuing threat to biodiversity lends urgency to the need of identification of sustainable source of natural products. This is not so much trouble if there is a microbial source of the compound. Herein, violacein, a natural indolic pigment extracted from Chromobacterium violaceum, was evaluated for its antitumoral potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Evaluation of violacein cytotoxicity using different endpoints indicated that EAT cells were twofold (IC(50)=5.0 microM) more sensitive to the compound than normal human peripheral blood lymphocytes. In vitro studies indicated that violacein cytotoxicity to EAT cells is mediated by a rapid (8-12h) production of reactive oxygen species (ROS) and a decrease in intracellular GSH levels, probably due to oxidative stress. Additionally, apoptosis was primarily induced, as demonstrated by an increase in Annexin-V positive cells, concurrently with increased levels of DNA fragmentation and increased caspase-2, caspase-9 and caspase-3 activities up to 4.5-, 6.0- and 5.5-fold, respectively, after 72 h of treatment. Moreover, doses of 0.1 and 1.0 microg kg(-1) violacein, administered intraperitoneally (i.p.) to EAT-bearing mice throughout the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. In view of these results, a 35-day toxicity study was conducted in vivo. Complete hematology, biochemistry (ALT, AST and creatinine levels) and histopathological analysis of liver and kidney indicated that daily doses of violacein up to 1000 microg kg(-1) for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity when administered i.p. to mice. Altogether, these results indicate that violacein causes oxidative stress and an imbalance in the antioxidant defense machinery of cells culminating in apoptotic cell death. Furthermore, this is the first report of its antitumor activity in vivo, which occurs in the absence of toxicity to major organs. PMID:20416285

Bromberg, Natália; Dreyfuss, Juliana L; Regatieri, Caio V; Palladino, Marcelly V; Durán, Nelson; Nader, Helena B; Haun, Marcela; Justo, Giselle Z

2010-04-21

2

Ehrlich ascites tumor cells produce a transforming growth factor-? (TGF?)-like activity but lack receptors with TGF?-binding capacity  

Microsoft Academic Search

Ehrlich ascites tumor cells incorporate [methyl-3H]thymidine into DNA independently of exogenous growth factors or fetal calf serum. Using an acid\\/ethanol extraction procedure we have obtained from these tumor cells a fraction that induces both the proliferation and the formation of cell foci by Swiss 3T3 mouse fibroblasts in the presence of insulin; inhibits the proliferation of Mv1Lu mink lung epithelial

Ana Elexpuru; José Martín-Nieto; Amparo Jiménez; Carmen Gómez; Antonio Villalobo

1997-01-01

3

Inhibition of Ehrlich ascites carcinoma (EAC) growth by carbonyl iron  

Microsoft Academic Search

Summary Treatment of Ehrlich ascites carcinoma (EAC) cells with carbonyl iron (20 mg\\/ml) produces a significant decrease in growth rate of tumor inoculum both in Swiss and in C57BL\\/6 mice. Possible interaction of the carbonyl iron or Fe+++ions with cell surface is suggested.

A. Pessina; P. Brambilla; Daniela Balzarin

1978-01-01

4

Alfa-Lipoic Acid Controls Tumor Growth and Modulates Hepatic Redox State in Ehrlich-Ascites-Carcinoma-Bearing Mice  

PubMed Central

The effect of oral supplementation of ?-lipoic (LA) on growth of Ehrlich ascites carcinoma cells (EACs) and hepatic antioxidant state in mice was investigated. The results revealed that ?-lipoic (LA) acid at 50?mg/kg body wt reduced the viability and volume of EAC cells and increased the survival of the treated animals. In addition, LA normalized oxidative stress in liver of mice-bearing EAC cells evidenced by increasing the levels of total thiols, glutathione, glutathione-S-transferase, superoxide dismutase, and catalyse. On the other hand, significant decreases in the levels of malondialdehyde and protein carbonyl were demonstrated in liver indicating controlled oxidative stress in these animals. As a consequence, LA regulated liver enzymes, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The data also indicated the efficiency of LA as cancer inhibitor and therapeutic influence. In conclusion, the present data suggest LA as a potential therapeutic complement in the treatment or prevention of different pathologies that may be related to an imbalance of the cellular oxidoreductive status associated with malignancy.

AL Abdan, M.

2012-01-01

5

Alfa-lipoic acid controls tumor growth and modulates hepatic redox state in Ehrlich-ascites-carcinoma-bearing mice.  

PubMed

The effect of oral supplementation of ?-lipoic (LA) on growth of Ehrlich ascites carcinoma cells (EACs) and hepatic antioxidant state in mice was investigated. The results revealed that ?-lipoic (LA) acid at 50?mg/kg body wt reduced the viability and volume of EAC cells and increased the survival of the treated animals. In addition, LA normalized oxidative stress in liver of mice-bearing EAC cells evidenced by increasing the levels of total thiols, glutathione, glutathione-S-transferase, superoxide dismutase, and catalyse. On the other hand, significant decreases in the levels of malondialdehyde and protein carbonyl were demonstrated in liver indicating controlled oxidative stress in these animals. As a consequence, LA regulated liver enzymes, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The data also indicated the efficiency of LA as cancer inhibitor and therapeutic influence. In conclusion, the present data suggest LA as a potential therapeutic complement in the treatment or prevention of different pathologies that may be related to an imbalance of the cellular oxidoreductive status associated with malignancy. PMID:23002387

Al Abdan, M

2012-05-01

6

Platelet interaction with a pancreatic ascites tumor.  

PubMed Central

The mechanism leading to the hypercoagulability in pancreatic carcinoma is unclear. The rapid progress of the disease after its diagnosis and the inaccessibility of the tumor make studies on the mechanism difficult in man. With the successful induction of this malignancy and conversion of it into an ascites tumor in Syrian golden hamsters, interactions between isolated tumor cells and individual hemostatic components can be investigated. In this paper, studies on in vitro tumor cell-platelet interactions and some hemostatic changes in hamsters following intravenous injection of isolated tumor cells are described. Freshly isolated tumor cells and tumor-cell sonicates, but not those that had been kept at 4 or -70 C overnight, induced comparable aggregation of human platelets in both heparinized and citrated platelet-rich plasmas (hPRP and cPRP). The aggregation was not followed by clot formation; a specific synthetic thrombin inhibitor had no effect on the aggregation in either hPRP or cPRP. Washed and gel-filtered platelets, even in the presence of 5% of citrated or heparinized platelet-poor plasma (cPPP or hPPP) failed to be aggregated by tumor cells. Tumor-cell-induced platelet aggregation was accompanied by thromboxane formation and serotonin release, both of which were several orders of magnitude greater in cPPP than in hPRP. Aspirin, apyrase, and PGI2 all inhibited tumor-cell-induced platelet aggregation in both PRPs, but the inhibition by aspirin was minimal. Intravenous infusion of isolated tumor cells into normal hamsters resulted in a 50% reduction of platelet count and a 20-30% decline in antithrombin III and fibrinogen. Platelet aggregates and fibrin strands were seen in the lungs of these animals. Images Figure 1 Figure 3 Figure 6

Hamilton, J.; Subbarao, V.; Granack, K.; Ts'ao, C.

1986-01-01

7

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

PubMed

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 ?B (NF-?B) responsive genes in CD4+ T cells but not in CD8+ T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-?B 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-?B-mediated gene transcription in CD4+ T cells is implicated in its immunomodulatory activity. PMID:23578476

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

2013-04-09

8

Ascites  

MedlinePLUS

Sections Liver and Gallbladder Disorders Chapters Manifestations of Liver Disease Ascites Ascites is the accumulation of protein-containing ( ... and thus bypasses the liver (see Manifestations of Liver Disease: Treatment ). Last full review/revision August 2012 by ...

9

Ascites  

Microsoft Academic Search

Ascites, the accumulation of fluid in the peritoneal cavity, is the most common complication of cirrhosis and portal hypertension\\u000a (1). In a prospective study of patients with compensated cirrhosis of all etiologies, the cumulative probability of developing\\u000a ascites ranges from 35% to 50% in 5 yr (1,2). Although cirrhosis is the cause of ascites in more than 75% of patients,

Sakib Karim Kbalid; Guadalupe Garcia-Tsao

10

Phosphofructokinase C Isozyme from Ascites Tumor Cells: Cloning, Expression, and Properties  

Microsoft Academic Search

The phosphofructokinase C isozyme (PFK-C) from ascites tumor cells has been cloned and characterized to investigate the particular properties of PFK activity in this type of cells. The isolated cDNA encodes a protein of 784 amino acids and 85.5 kDa, whose expression was constant along tumor growth and markedly decreased when cell proliferation stops. The enzyme was functionally expressed in

Cristina Sánchez-Mart??nez; Antonio M. Estévez; Juan J. Aragón

2000-01-01

11

Antitumor effect of the seashell protein Haishengsu on Ehrlich ascites tumor: an experimental study.  

PubMed

The aim of the study was to investigate the in vivo effect of the seashell protein Haishengsu (HSS) on Ehrlich ascites tumor. Mice were inoculated with Ehrlich ascites tumor cells and randomly divided into three HSS groups and a control group. The survival times in the three HSS-treated groups was longer than in the control (P < 0.01) and the increased life span in the high-dose HSS group was greater than in the lower-dose groups (P < 0.05). In comparison with control group, the mice receiving pretreatment of HSS had longer survival times and greater life spans following inoculation of the ascites tumor (P < 0.05). HSS therefore prolongs survival times and increases the life spans of mice bearing Ehrlich ascites tumor. Pretreatment with HSS also diminishes the detrimental effect of Ehrlich ascites tumor on the prognosis of these animals. PMID:19536610

Liu, Ji-Zhu; Chen, Shou-Guo; Bin, Zhang; Wang, Chun-Bo; Li, Guang-Yao; Wang, Le-Xin

2009-06-18

12

In Vitro Production of Mouse Mammary Tumor Virus in a Mouse Mammary Tumor Ascites Line  

Microsoft Academic Search

An ascites line derived from a spontaneous mouse mammary carcinoma produces, on explantation and cultivation in vitro, large amounts of oncornavirus particles. The biochemical, biophysical, and electron microscopic characteristics of the virions are described. Molecular hybridization and immunological methods identify these virions as mouse mammary tumor virus.

Jafa Keydar; Zvee Gilead; Jacob R. Hartman; Yehuda Ben-Shaul

1973-01-01

13

Angiogenesis and inflammation in skeletal muscle in response to ascites tumor in mice  

Microsoft Academic Search

This study addresses the interaction between Ehrlich ascites tumor and skeletal abdominal muscle, presenting quantitative analysis of ascites-induced angiogenesis and inflammation in this tissue of mice bearing-tumor. Time-dependent changes in the muscle (cellular activity, angiogenesis, inflammation and cytokines production) were assessed by morphometric, functional, and biochemical parameters at days 1, 4 and 8 after i.p. inoculation of Ehrlich tumor cells

A. S. Teixeira; F. A. Araújo; M. A. N. D. Ferreira; L. S. Barcelos; M. M. Teixeira; S. P. Andrade

2006-01-01

14

Treatment of Walker ascites tumor cells by combination of photodynamic therapy with cyclophosphamide and interleukin-2 entrapped in liposomes  

NASA Astrophysics Data System (ADS)

The purpose of this study was to investigate the beneficial and adverse local effects of PDT associated with chemoimmunotherapy on rats bearing Walker ascites tumor cells. Experiments were performed on five batches of Wistar inbred rats with ascites tumor cells receiving intraperitoneally PDT (Photofrin II and 18 hrs later HeNe laser irradiation); Cyclophosphamide (CY); interleukin-2 (IL-2) or associated therapy (PDT+CY+IL-2). The control batch consisted of untreated rats (HBSS). The following results were noticed: (a) sole administration of PDT, IL-2 or CY reduced tumor growth, gave survival rates between 28.4 and 56.5% and cure rates ranging from 12.4 to 33.3%; (b) combined therapy (PDT+CY+IL-2) decreased tumor growth, increased survival rates (88.5%) and cure rates were 73.1% forty-two days post-transplantation. Summing up, in this study we noticed that PDT associated with chemoimmunotherapy reduced mortality as well as tumor volumes and increased cure rates in rats with ascites tumor cells. This approach points to the need for further evaluation in patients with peritoneal malignancies.

Dima, Vasile F.; Ionescu, Mircea D.; Balotescu, Carmen; Dima, V. S.

2003-12-01

15

Importance of viability and attachment to an ascites tumor in the release of plasminogen activator.  

PubMed Central

Tumor plasminogen activator (PA) has been alleged to play a role in the growth and metastasis of tumors. Before such a role can be realized, PA first must be released from tumor cells. Having determined intra- and extracellular PA and PA-inhibitor activities in an experimental pancreatic ascites tumor grown in hamsters, the release of PA from these cells was investigated. No PA activity was detected in the suspension medium of freshly isolated tumor cells; inclusion of plasminogen, fibrinogen, or collagen in the medium yielded similar negative results. On the other hand, PA activity was demonstrated to be released in a time-dependent manner from these tumor cells embedded in fibrin clots. Plasminogen activator activity also was not found in the suspension medium of frozen-thawed tumor cells, despite the fact that most of them had breaks on their cell membrane. Unlike freshly isolated tumor cells, PA was not released from frozen-thawed cells embedded in fibrin clots. Full PA activity was demonstrated in frozen-thawed cells treated with Triton X-100, however. Frozen-thawed cells exhibited signs of severe damage, and more than 80% of them failed to exclude trypan blue. Obviously PA is released from viable tumor cells embedded in fibrin clots but not suspended in artificial medium. The PA-release mechanism, not PA itself, is destroyed in cells rendered nonviable by freeze thawing. Images Figure 1 Figure 5 Figure 6 Figure 7

Dong, Q.; Zhou, M.; Subbarao, V.; Ts'ao, C.

1991-01-01

16

The glycolytic inhibitor 2-deoxy-D-glucose enhances the efficacy of etoposide in ehrlich ascites tumor-bearing mice.  

PubMed

Earlier studies have shown that 2-deoxy-D-glucose (2-DG), a glucose analogue and inhibitor of glycolytic ATP production significantly enhances the cytotoxic effects of anticancer agents like topoisomerase inhibitors (etoposide and camptothecin) and a radiomimetic drug (bleomycin) in established human tumor cell lines. Therefore, combination of 2-DG and DNA damage causing cytotoxic agents could be very useful in enhancing local tumor control. The purpose of the present studies was to investigate the therapeutic effects of etoposide and 2-DG in Ehrlich ascites tumor (EAT) bearing mice, grown as solid tumor as well as in the ascites form. Cell growth, cell cycle perturbations (flow cytometry), cytogenetic damage (micronuclei assay) and apoptosis (DNA content, morphological changes) were studied as parameters of cellular response, while delay in tumor growth and cure rate (tumor free survival) were evaluated as parameters of systemic response. Body weight and general condition as well as the damage to bone marrow and spleen was monitored to evaluate normal tissue toxicity. Intraperitoneal administration of etoposide (30 mg/Kg b. wt.) resulted in significant tumor growth delay and cure (approximately 11%) only in subcutaneous tumors leading to local tumor control. When etoposide was combined with 2-DG (2 g/Kg b. wt.; i.v./i.p.; 4 h after etoposide injection), these effects were further enhanced resulting in a cure rate of approximately 22% in case of subcutaneous tumors and 20% in ascites bearing mice. Analysis of cells obtained from ascitic fluid as well as solid tumors during follow up clearly showed that etoposide induced cell death was mainly due to apoptosis, which was enhanced further by 2-DG. Although, there was a significant level of toxicity revealed by reduced animal survival, decrease in body weight and damage to sensitive organ status like spleen and bone marrow at 60 mg/Kg b. wt. of etoposide, it was not significant at 30 mg/Kg b.wt. 2-DG, however, did not enhance the etoposide toxicity at both the doses. These results indicate that the administration of 2-DG can improve the local control of tumors without increasing normal tissue toxicity, thereby enhancing the therapeutic efficacy of topoisomerase inhibitor based anticancer drugs like etoposide. PMID:15711125

Gupta, Seema; Mathur, Rohit; Dwarakanath, B S

2005-01-15

17

Targeting Vascular Endothelial Growth Factor Blockade: Ascites and pleural effusion formation  

Microsoft Academic Search

Primary Purpose. Formation of ascites and pleural effusion (PE) is a common problem for patients with advanced-stage cancer. These fluid accumulations cause severe symptoms such as abdominal distention, shortness of breath, cachexia, anorexia, and fatigue. Preclinical models have demonstrated that vascular endothelial growth factor (VEGF) plays a pivotal role in the accu- mulation of malignant PE or ascites. This study

H. M. W. Verheul; K. Hoekman; A. S. Jorna; E. F. Smith; H. M. PINEDOa

2000-01-01

18

Anti-tumor and proapoptotic effect of novel synthetic benzophenone analogues in Ehrlich ascites tumor cells.  

PubMed

A series of substituted benzophenone analogues, (2-aroyl-4-methylphenoxy)acetamides 4a-e, have been synthesized via three-step synthesis sequence beginning with the 2-hydroxybenzophenones 1a-e in excellent yield. 1a-e on reaction with ethyl chloroacetate afford ethyl (2-aroyl-4-methylphenoxy)acetates 2a-e which on alkaline hydrolysis afforded (2-aroyl-4-methylphenoxy)ethanoic acid 3a-e. Compounds 3a-e on condensation with p-chloroaniline furnished benzophenone analogues 4a-e. In the present report, we investigated the anti-tumor and proapoptotic effect of benzophenones in Ehrlich ascites tumor (EAT) cells. Treatment of benzophenones in vivo resulted in inhibition of proliferation of EAT cells and ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells is mediated through activation of caspase-3. These results suggest a further possible clinical application of these synthetic compounds as potent anti-tumor and proapoptotic compounds. PMID:16214348

Prabhakar, B T; Khanum, Shaukath Ara; Jayashree, K; Salimath, Bharathi P; Shashikanth, S

2005-10-07

19

Effects of some fatty acid esters on the viability and transplant- ability of ehrlich ascites tumor cells  

Microsoft Academic Search

SUMMARY Fatty acids, monoglycerides, and some esters of fatty acids show antitumor activity against Ehrlich ascites tumor in mice. For investigation of the in vivo mode of action of these lipids, the effects of those fatty acid esters on animal cells in vitro were studied in sheep red blood cells and Ehrlich ascites tumor cells. Throughout these studies, we used

Akiko Kato; Kunio Ando; G Tamura; K Arima

1971-01-01

20

Virus inoculation in mice bearing Ehrlich ascitic tumors: antigen production and tumor regression.  

PubMed Central

Ehrlich ascitic carcinoma, as developed in albino mice, has been used as a source of hemagglutinating and complement-fixing antigens, and it proved to be suitable for one type of antigen, or both, for at least 12 viruses of 16 tested. Hemagglutinins were obtained with members of arbovirus groups A, B, and C; complement-fixing antigens were obtained for at least one member of each antigenic group tested. Ehrlich ascitic tumor was compared with sarcoma 180 as a source of antigens; although sarcoma 180 showed many advantages over Ehrlich tumor, the latter gave, in general, better results for complement-fixing antigens. Oncolytic effect with complete recovery of the mice was observed in some instances. The highest recovery rate resulted with Congo and UNA viruses (40%), and the second highest rate resulted with dengue 2, St. Louis, Hazara, and Uukuniemi viruses (20%). The best survival was observed, in decreasing order, with Congo, St. Louis, dengue 2, Tacaribe, Sindbis, Junin, and Amapari viruses.

Mettler, N E; Clarke, D H; Casals, J

1982-01-01

21

Virus inoculation in mice bearing Ehrlich ascitic tumors: antigen production and tumor regression.  

PubMed

Ehrlich ascitic carcinoma, as developed in albino mice, has been used as a source of hemagglutinating and complement-fixing antigens, and it proved to be suitable for one type of antigen, or both, for at least 12 viruses of 16 tested. Hemagglutinins were obtained with members of arbovirus groups A, B, and C; complement-fixing antigens were obtained for at least one member of each antigenic group tested. Ehrlich ascitic tumor was compared with sarcoma 180 as a source of antigens; although sarcoma 180 showed many advantages over Ehrlich tumor, the latter gave, in general, better results for complement-fixing antigens. Oncolytic effect with complete recovery of the mice was observed in some instances. The highest recovery rate resulted with Congo and UNA viruses (40%), and the second highest rate resulted with dengue 2, St. Louis, Hazara, and Uukuniemi viruses (20%). The best survival was observed, in decreasing order, with Congo, St. Louis, dengue 2, Tacaribe, Sindbis, Junin, and Amapari viruses. PMID:7107004

Mettler, N E; Clarke, D H; Casals, J

1982-07-01

22

Molecular mechanism of action of butyric acid in Ehrlich Ascites Tumor cells  

Microsoft Academic Search

We have shown that butyric acid (in vivo) decreased cell proliferation of Ehrlich Ascites Tumor (EAT) cells. This effect of butyric acid is attributed to induction of apoptosis in EAT cells, as evidenced by prevalent apoptotic morphology in EAT cells. Molecular effects of butyric acid (in vivo and in situ) included a dose dependent inhibition of generation of Reactive Oxygen

Bharathi. P. Salimath; Arshiya Tabassum; E. G. Anupama; Bindumalini; G. B. Preeti; Paramahans. V. Salimath

1999-01-01

23

Involvement of polyamines in evening primrose extract-induced apoptosis in Ehrlich ascites tumor cells.  

PubMed

We previously demonstrated that evening primrose extract (EPE) induced apoptosis and inhibited the DNA synthesis in Ehrlich ascites tumor cells (EATC) and suggested that EPE-induced inhibition of the growth of EATC are via at least two pathway differentially modulated by reactive oxygen species, notably intracellular peroxides. These are (a) the EPE-induced apoptosis pathway which is dependent on increases in hydrogen peroxide and (b) the EPE-induced inhibition of cell proliferation which is hydrogen peroxide independent. In this study, EPE brought about a significant decrease in intracellular polyamine levels. Furthermore, the addition of polyamines reversed the EPE-induced decrease in cell viability and suppressed the EPE-induced increase in intracellular hydrogen peroxides. However, the addition of polyamines did not reverse EPE-induced decrease in DNA synthesis and phosphorylation of Rb protein, and EPE-induced translocation of AIF. These results suggest the involvement of polyamines in the EPE-induced apoptosis pathway which is dependent on increase in hydrogen peroxide. PMID:15700107

Arimura, T; Kojima-Yuasa, A; Tatsumi, Y; Kennedy, D O; Matsui-Yuasa, I

2005-02-10

24

Membrane potential, anion and cation conductances in Ehrlich ascites tumor cell  

Microsoft Academic Search

Summary The fluorescence intensity of the dye 1,1'-dipropyloxadicarbocyanine (DiOC3-(5)) has been measured in suspensions of Ehrlich ascites tumor cells in an attempt to monitor their membrane potential (Vm) under different ionic conditions, after treatment with cation ionophores and after hypotonic cell swelling. Calibration is performed with gramicidin in Na+-free K+\\/choline+ media, i.e., standard medium in which NaCl is replaced by

Ian Henry Lambert; Else Kay Hoffmann; Finn Jørgensen

1989-01-01

25

The membrane potential of Ehrlich ascites tumor cells microelectrode measurements and their critical evaluation  

Microsoft Academic Search

Summary Intracellular potentials were measured, using a piezoelectric electromechanical transducer to impale Ehrlich ascites tumor cells with capillary microelectrodes. In sodium Ringer's, the potential immediately after the penetration was ?24±7 mV, and decayed to a stable value of about ?8 mV within a few msec. The peak potentials disappeared in potassium Ringer's and reappeared immediately after resuspension in sodium. Ringer's,

U. V. Lassen; A.-M. T. Nielsen; L. Pape; L. O. Simonsen

1971-01-01

26

Effect of a seashell protein Haishengsu on the immunological function of mice with Ehrlich ascites tumor.  

PubMed

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100 mg/kg, i.v., respectively), cyclophosphamide (10 mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100 mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P < 0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8 +/- 1.2, 16.9 +/- 3.9 and 25.3 +/- 2.9, respectively), was greater than in the control (7.3 +/- 1.4), or the cyclophosphamide group (0.33 +/- 0.4) (all P < 0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P < 0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor. PMID:19874239

Li, Guang-Yao; Liu, Ji-Zhu; Chen, Shou-Guo; Wang, Chun-Bo; Bin, Zhang; Wang, Le-Xin

2009-01-01

27

A comparative study on proliferation, macromolecular synthesis and energy metabolism of in vitro-grown ehrlich ascites tumor cells in the presence of glucosone, galactosone and methylglyoxal  

Microsoft Academic Search

Summary 1.Proliferation of in vitro grown Ehrlich ascites tumor cells is completely inhibited by 0.2–0.4 mM methylglyoxal and 1–2mM glucosone or galactosone without severely affecting viability (dye exclusion test); no phase-specific arrest of cell growth is observed.2.Incorporation of [14C] thymidine into the acid-insoluble fraction of the cells decreases within a few minutes to less than 50% of that in controls

K. A. Reiffen; F. Schneider

1984-01-01

28

Iron-induced lipid peroxidation and inhibition of proliferation in Ehrlich ascites tumor cells.  

PubMed

The purpose of this study was to find further experimental evidence for the postulated negative association between the extent of lipid peroxidation in tumor cells and their proliferative behavior. After incubation of Ehrlich ascites tumor cells at 37 degrees C for 30 min with increasing concentrations of Fe(II) histidinate (Fe/His) the following parameters were determined: the formation of lipid hydroperoxides was measured fluorimetrically after reaction with dichlorofluorescein; 4-hydroxynonenal was determined by reversed-phase high-pressure chromatography after derivatization with dinitrophenylhydrazine; as a third parameter of lipid peroxidation the formation of 2-thiobarbituric-acid-reactive substances was determined. The proliferative activity was determined by measuring the growth rate in vivo after reimplantation i.p. of the tumor cells into mice. Trypan-blue exclusion tests for viability were performed before reimplantation. The reliability of the trypan-blue exclusion tests was checked by comparing the results with another parameter of viability, the release of the cytosolic enzyme lactate dehydrogenase. The concentration both of lipid hydroperoxides and of 2-thiobarbituric-acid-reactive substances showed a biphasic dependence on the concentration of Fe/His with maximal increase at iron concentrations of 0.25 mM and 0.1 mM respectively. 4-Hydroxynonenal, in contrast, showed a continuous increase up to 41.1 nM (corresponding to 0.58 pmol/10(9) cells) with increasing iron concentration in the range from 0.1 mM to 0.6 mM. The total number of tumor cells, when determined 5 days after reimplantation, continuously decreased with increasing iron concentration, showing half-maximal inhibition at about 0.22 mM Fe. The exclusion of the trypan-blue dye was unaffected by the presence of iron at any concentration used. Similarly, iron had no influence on the release of lactate dehydrogenase. The results support the hypothesis that 4-hydroxynonenal may act as an inhibiting messenger between endogenic lipid peroxidation and proliferation. PMID:2921275

Tillian, H M; Hammer, A; Kink, E; Schaur, R J; Schauenstein, E

1989-01-01

29

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

SciTech Connect

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 /sup 14/CO/sub 2/ from /sup 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.

Magnani, B.

1984-01-01

30

Multiple effects of amobarbital on Ehrlich ascites tumor cells. Inhibition of pyruvate dehydrogenase.  

PubMed

The inhibition of the proliferation of hyperdiploid Ehrlich ascites tumor cells in suspension cultures by amobarbital is coupled to an increased glycolytic activity as shown by lactic acid production and glucose consumption; higher concentrations of amobarbital than 1 mM enhance the ATP/ADP ratio of the total cell. The actual activity of pyruvate dehydrogenase of intact cells is completely inhibited in the presence of 2 mM amobarbital as was shown by the 14CO2 evolution from [114C]pyruvate or the incorporation of 14CO2 into the total lipid fraction of the cells from [U-14C]lactate. The pyruvate dehydrogenase complex from Ehrlich ascites tumor cells is completely inhibited by 1 mM amobarbital in vitro. The activity of alpha-oxoglutarate dehydrogenase is inhibited by amobarbital, too, as well as shown by measuring the 14CO2 evolution from [1-14C]glutamate with intact cells. It is suggested that the inhibition of pyruvate dehydrogenase in the presence of amobarbital is the result of a direct action on the enzyme as well as the consequence of a change in the cellular redox state or its energy charge. PMID:146357

Postius, S; Schneider, F

31

The Acyl Dihydroxyacetone Phosphate Pathway for Glycerolipid Biosynthesis in Mouse Liver and Ehrlich Ascites Tumor Cells  

PubMed Central

The glycerol portion of lipids may be derived biosynthetically by reduction of dihydroxyacetone phosphate to glycerolphosphate, and then be acylated with fatty acids or, alternatively, dihydroxyacetone phosphate may first be acylated and then reduced to 1-acyl sn glcerol-3-phosphate. Since the former pathway utilizes NADH for reduction of the C-2 carbonyl, while the latter requires NADPH, we were able to compare the relative participation of the two pathways for phospholipid synthesis by measuring the incorporation of radioactivity from tritiumlabeled NADH and NADPH into C-2 of lipid glycerol. The acyl-dihydroxyacetone phosphate pathway plays a significant role in glycerolipid synthesis in mouse liver homogenates and a clearly dominant one in Ehrlich ascites tumor cell homogenates. This finding is related to a reported lack of glycerol-3-phosphate dehydrogenase in tumor cells and to their high glycerol ether lipid content.

Agranoff, Bernard W.; Hajra, Amiya K.

1971-01-01

32

Increase of Cholesterol Level in the Surface Membrane of Lymphoma Cells and Its Inhibitory Effect on Ascites Tumor Development  

PubMed Central

An ascites form of malignant transformed lymphoma cells were treated in vitro with liposomes of 1:1 lecithin-cholesterol in order to increase the cholesterol level of the cell-surface membranes and thereby to increase the rigidity of the lipid layer. This treatment was found to inhibit the rate of killing by ascites tumor after intraperitoneal inoculation into adult mice of 104 and 105 treated cells per animal. With 103 treated cells per animal, full survival was observed up to 90 days after inoculation, whereas with the same number of untreated cells all infected mice died within 30 days after inoculation. An analogous treatment of the malignant lymphoma cells with liposomes of pure lecithin did not result in any appreciable inhibitory effect on the ascites tumor development in vivo, as initiated by inoculation of 105, 104, or 103 cells per animal.

Inbar, M.; Shinitzky, M.

1974-01-01

33

Treatment of mice bearing a Krebs ascitic tumor by means of a protocol based on radioactive copper (64Cu). III. Efficiency of the anticancer treatment according to the stage of tumor development.  

PubMed

The treatment described previously (Anticancer Res 9:947-954,1989) was efficient when applied on day 1 or 6 after the injection of 5 x 10(5) Krebs ascitic cells in mice. Under our experimental conditions, all the untreated mice died within 12 to 25 days. The experiments described show that the treatment developed, is efficient when applied on day 11 but not on day 16. To understand the difference in the treatment efficiency between these two days, we tested the 64Cu incorporation inside the ascitic cells. It was observed that 64Cu incorporation exists on day 11 but no longer on day 16. On day 16, the inefficiency of the treatment must be correlated with the non-incorporation of 64Cu inside the ascitic cells. As the tumor growth is also arrested on day 16, an irreversible stage is reached. A model was developed to explain the results obtained. In this model, cancer develops in 3 successive stages. In the first stage, the cellular functioning is under the control of the malignant tumor cells and the number of cells with the "cancer functioning" is increasing with time, but decreasing after removal of the malignant tumor; in the second stage, tumor and cancer both develop independently, meaning that the number of cells with the "cancer functioning" will continue to increase after the removal of the malignant tumor; in the third stage, each cell of the organism has the "cancer functioning" and the characteristics of malignancy will by retroaction. PMID:2817821

Apelgot, S; Guillé, E

34

Volume-induced increase of K + and Cl ? permeabilities in Ehrlich ascites tumor cells. Role of internal Ca 2+  

Microsoft Academic Search

Summary Ehrlich ascites tumor cells resuspended in hypotonic medium initially swell as nearly perfect osmometers, but subsequently recover their volume within 5 to 10 min with an associated KCl loss. 1. The regulatory volume decrease was unaffected when nitrate was substituted for Cl?, and was insensitive to bumetanide and DIDS. 2. Quinine, an inhibitor of the Ca2+-activated K+ pathway, blocked

Else K. Hoffmann; Lars Ole Simonsen; Ian H. Lambert

1984-01-01

35

Cellular thiols status and cell death in the effect of green tea polyphenols in Ehrlich ascites tumor cells  

Microsoft Academic Search

Epidemiological studies suggest that the consumption of green tea may help prevent cancers in humans, and also breast and prostate cancers in animal models are reduced by green tea, and several mechanisms have been proposed for these effects. In this study the relationship between cellular sulfhydryl (SH) groups and the cytotoxicity of green tea polyphenols in Ehrlich ascites tumor cells

David Opare Kennedy; Miho Matsumoto; Akiko Kojima; Isao Matsui-Yuasa

1999-01-01

36

Detection of 4-hydroxynonenal as a product of lipid peroxidation in native Ehrlich ascites tumor cells.  

PubMed

4-Hydroxynonenal, which is a major product of lipid peroxidation in rat liver microsomes, was detected in native Ehrlich ascites tumor cells. Its formation was stimulated either by ferrous ions or by Fe(II)-histidinate. The identification was based on chromatographic (TLC/HPLC) and ultraviolet-spectroscopic evidence using synthetic 4-hydroxynonenal as reference. Highest values of 4-hydroxynonenal concentration (about 0.1 microM in the cell suspension) after 30 min of incubation were observed with Fe(II)-histidinate as stimulant. Saturation was already reached after an incubation period of 10 min. The results confirm the expectation by Schauenstein and Esterbauer (in Submolecular Biology and Cancer, Ciba Foundation Series 67 (1979) pp. 225-244, Excerpta Medica, Amsterdam) that endogenous lipid peroxidation gives rise to a distinct intracellular level of alpha, beta-unsaturated aldehydes. A simple hypothetical mechanism for the formation of 4-hydroxynonenal from n-6-polyunsaturated fatty acids is presented. PMID:6548932

Winkler, P; Lindner, W; Esterbauer, H; Schauenstein, E; Schaur, R J; Khoschsorur, G A

1984-12-01

37

Apoptosis-inducing effects of Morinda citrifolia L. and doxorubicin on the Ehrlich ascites tumor in Balb-c mice.  

PubMed

Morinda citrifolia L. (Noni) is a herbal remedy with promising anti-cancer properties. However, its effects on various cancers are to be investigated to make a firm conclusion before implementing it into the clinical practice. Therefore, we investigated the cytotoxic potential of noni on Ehrlich ascites tumor grown in female Balb-c mice and also combined it with a potent anti-cancer agent, doxorubicin. One group received noni only (n = 8), another one doxorubicin (n = 8), and the other one noni + doxorubicin (n = 8) for 14 days after the inoculation of cells. The control group (n = 7) received 0.9% NaCl only. We found that short and long diameters of the tumor tissues were about 40-50% smaller, compared to those in control group. This anti-growth effect resulted from the induction of apoptosis, which was confirmed by the positive results from the Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) analysis and the active caspase-3 cells in tissues. Apoptosis also confirmed by caspase-cleaved cytokeratin 18 elevation in serum of the treated groups. Further, the proliferation was decreased, which was immunohistochemically shown by the PCNA staining. We conclude that noni may be useful in the treatment of breast cancer either on its own or in combination with doxorubicin. Further studies are warranted to assess the dosage and safety of using noni fruit juice in conjuction with anti-cancer drugs against breast cancer. PMID:19908222

Ta?kin, Elif Ilkay; Akgün-Dar, Kadriye; Kapucu, Ay?egül; Osanç, Esma; Do?ruman, Hüsniye; Eraltan, Hakan; Ulukaya, Engin

2009-12-01

38

An investigation of the stability of messenger RNAs in cell-free, translational systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells  

Microsoft Academic Search

The stabilities and translation of Ehrlich ascites tumor cell poly(A)-containing mRNA and mengovirus RNA in fractionated cell-free protein synthesizing systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells were studied. During incubation of the systems about 20% of the input RNA is reduced in size and associated with ribosomes engaged in polypeptide synthesis; the remainder is rapidly degraded by RNases.

P. B. Hackett; E. Egberts; P. Traub

1977-01-01

39

Design, synthesis and antitumor evaluation of novel thalidomide dithiocarbamate and dithioate analogs against Ehrlich ascites carcinoma-induced solid tumor in Swiss albino mice.  

PubMed

A series of 16 novel thalidomide sulfur analogs containing one and two sulfur atoms 2 and 4-18, respectively, were designed and synthesized. These compounds were screened for in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cell line and exhibited potent cytotoxic activity. On the bases of the obtained results for in vitro cytotoxic activity, thalidomide sulfur analogs containing two sulfur atoms 8, 9, 13 and 14 were selected and tested in vivo against EAC-induced solid tumor in female mice compared to thalidomide 1 as well as its analog 2 and exhibited a highly significant reduction in tumor volume (TV). Results illustrated the antioxidative activity of these compounds as the level of hepatic lipid peroxidation decreased and levels of antioxidant enzymes like superoxide dismutase (SOD) and catalase were elevated. The histopathological investigations revealed that thalidomide sulfur analogs 2, 8, 9, 13 and 14 have antimitotic, apoptotic and necrotic activities against solid tumor. These compounds lead to increase of Fas-L expression. The immunohistochemical studies showed a decrease in Ki67 and vascular endothelial growth factor (VEGF) staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate and angiogenic process associated with tumor growth. Compounds 9 and 13 were the most potent compounds in tumor necrosis without liver necrosis. At the same time, treatment with compound 9 resulted in liver degeneration. PMID:18951804

Zahran, Magdy A-H; Salem, Tarek A-R; Samaka, Rehab M; Agwa, Hussein S; Awad, Ayman R

2008-10-02

40

Chylous ascites after nephrectomy without lymphadenectomy for malignant rhabdoid tumor of the kidney: A rare occurrence and literature review  

PubMed Central

Chylous ascites (CA) is an extremely rare complication of abdominal surgery in children. This report describes a 4-month-old girl with malignant rhabdoid tumor of the kidney (MRTK), who developed CA after left nephrectomy without lymphadenectomy, and who was successfully treated conservatively with enteral therapy. The literature on CA after nephrectomy without lymphadenectomy for MRTK is reviewed herein, and the clinical problems of postoperative CA are discussed.

Einama, Takahiro; Okada, Tadao; Sasaki, Fumiaki; Todo, Satoru

2009-01-01

41

Secretion and hydrolysis of ATP by Ehrlich ascites tumor cells during centrifugation. Dependence on calcium and temperature  

Microsoft Academic Search

Precipitation of Ehrlich ascites tumor cells (EATC) by centrifugation causes ATP secretion. ATP secretion is accompanied by\\u000a an increase of calcium concentration in the cytosol and persists for a long time (minutes) after centrifugation during the\\u000a storage of cells at a low temperature. During prolonged storage (for more than 1.5 h), the concentration of extracellular\\u000a ATP decreases to the level

A. M. Krasnyi; A. I. Sergeev; L. P. Dolgacheva; E. L. Nikiforov; V. P. Zinchenko

2010-01-01

42

Comparing cell kinetic studies of the effect of ftorafur and 5-fluorouracil on the L 1210 ascites tumor  

Microsoft Academic Search

Ftorafur (FT), a 2-tetrahydrofuryl derivative of 5-fluorouracil (5-FU) was introduced into cancer chemotherapy with the hope to obtain a therapeutic effect comparable to 5-FU with a smaller dose and less side effects. A comparison of the effect of FT and 5-FU on the proliferation of L 1210 ascites tumor cells in the present work has shown that both drugs result

B. Schultze; W. Jellinghaus; G. Weis; V. Müller; W. Maurer

1981-01-01

43

Validation of the use of the lipophilic thiocyanate anion for the determination of membrane potential in Ehrlich ascites tumor cells  

Microsoft Academic Search

Summary The utility of the lipophilic anion thiocyanate (SCN+) as a probe for the indirect estimation of the cell membrane potential (Vm) in Ehrlich ascites tumor cells has been evaluated by comparison to direct electrophysiological measurements. SCN accumulation is consisten with first-order uptake into a single kinetically-identifiable cellular compartement, achieving steadystate distribution in 20–30 min at 22°C. The steady-state distribution

Thomas C. Smith; Susan C. Robinson

1989-01-01

44

Effect of arachidonic acid, fatty acids, prostaglandins, and leukotrienes on volume regulation in Ehrlich ascites tumor cells  

Microsoft Academic Search

Summary Arachidonic acid inhibits the cell shrinkage observed in Ehrlich ascites tumor cells during regulatory volume decrease (RVD) or after addition of the Ca ionophore A23187 plus Ca. In Na-containing media, arachidonic acid increases cellular Na uptake under isotonic as well as under hypotonic conditions. Arachidonic acid also inhibits KCl and water loss following swelling in Na-free, hypotonic media even

Ian Henry Lambert

1987-01-01

45

TGF-? blockade controls ascites by preventing abnormalization of lymphatic vessels in orthotopic human ovarian carcinoma models  

PubMed Central

Purpose Ovarian cancer patients with malignant ascites have poor prognosis. The accumulation of ascites is caused by an imbalance between fluid extravasation from the blood vessels and reabsorption by lymphatic vessels. Whereas, the role of Transforming Growth Factor beta (TGF-?) in tumor progression has been well studied, the role of TGF-? in lymphatic vessel function is far from understood. Here, we sought to dissect the role of TGF-? blockade in the formation of ascites. Experimental Design We used soluble TGF-? Receptor II (sT?RII) to block TGF-? signaling in two orthotopic human ovarian carcinoma models: SKOV3ip1 and Hey-A8. We measured tumor proliferation, apoptosis, lymphangiogenesis and angiogenesis by immunohistochemical staining, and examined diaphragm lymphatic vessel network by intraperitoneal injection of a fluorescent dye. Diaphragm lymphatic vessel function was assessed by tracking fluorescent beads in the diaphragm and measuring their drainage rate. Results TGF-? blockade impaired tumor growth in both models, accompanied by a decreased tumor cell proliferation and angiogenesis. More strikingly, TGF-? blockade almost completely abolished ascites formation. TGF-? blockade significantly inhibited the expression of VEGF, which is the major contributor to ascites formation. At the same time, TGF-? blockade prevent ‘abnormalization’ of diaphragm lymphatic vessels and improved ascites drainage. Conclusions TGF-? blockade decreased ascites by both inhibiting ascites formation and improving ascites drainage. Based on our finding, it is reasonable to consider the use of TGF-? blockade as a palliative treatment for symptomatic ascites.

Liao, Shan; Liu, Jieqiong; Lin, Peichun; Shi, Tony; Jain, Rakesh K.; Xu, Lei

2011-01-01

46

Homogeneous uridine kinase from Ehrlich ascites tumor: substrate specificity and inhibition by bisubstrate analogs.  

PubMed

Uridine kinase has been purified to homogeneity from Ehrlich ascites tumor cells. For the phosphate acceptor site, the enzyme shows substrate specificity only for ribopyrimidine nucleosides and is active with various analogs that have limited structural alterations; both endocyclic and exocyclic substituents can be acceptable. Of nucleosides that have been used in the chemotherapy of cancer, 5-fluorouridine, 6-azauridine, and 3-deazauridine are good substrates, whereas arabinosylcytosine is a poor substrate. No analogs are better substrates than the physiological substrates uridine and cytidine. 5', 5''' -P1, P4-Bisnucleoside oligophosphate bisubstrate analogs (e.g., Ap4U, Ap5U) were synthesized and tested as inhibitors. The most effective compound was Ap4U; with a Ki of 197 microM, it bound more tightly than ATP but no better than uridine. Ap3A, Ap4A, and Ap5A were also tested, with the result that both Ap4A and Ap4U were most effective, suggesting that this size of bisubstrate analog most closely approaches the spacing of the catalytic site. PMID:3016499

Cheng, N; Payne, R C; Kemp, W E; Traut, T W

1986-08-01

47

Evidence for activation of an active electrogenic proton pump in Ehrlich ascites tumor cells during glycolysis  

SciTech Connect

The addition of glucose to a suspension of Ehrlich ascites tumor cells results in rapid acidification of the extracellular medium due to lactic acid production. The nature of the H+ efflux mechanism has been studied by measuring the time course of the acidification, the rate of proton efflux, the direction and relative magnitude of the H+ concentration gradient, and the voltage across the membrane. Using the pH-sensitive dye acridine orange, we have established that after addition of 10 mM glucose an outward-directed H+ concentration gradient develops. As the rate of glycolysis slows, the continued extrusion of H+ reverses the direction of the H+ concentration gradient. Changes in absorbance of the voltage-sensitive dye diethyloxadicarbocyanine iodide (DOCC), and changes in the distribution of the lipid permeant cation tetraphenyl phosphonium, showed a dramatic and persistent hyperpolarization of the membrane voltage after glucose addition. The hyperpolarization was prevented by the protonophore tetrachlorosalicylanalide (TCS) and by valinomycin, but not by the neutral-exchange ionophore nigericin. Inhibitors of lactate efflux were found to reduce the rate of acidification after glucose addition but they had no effect on the magnitude of the resulting hyperpolarization. On the basis of these and other data we suggest that an active electrogenic pump mechanism for H+ efflux may be activated by glucose and that this mechanism operates independently of the lactate carrier system.

Heinz, A.; Sachs, G.; Schafer, J.A.

1981-01-01

48

Uptake of ferrous iron histidinate, a promoter of lipid peroxidation, by Ehrlich ascites tumor cells.  

PubMed

The kinetics of the uptake of Fe(II)-histidinate, a known promoter of lipid peroxidation, into Ehrlich ascites tumor (EAT) cells and the intracellular binding of iron were studied in vitro. EAT cells (27.10(6)/ml) were incubated in Hanks' balanced salts solution at 37 degrees C for various time intervals in the presence of FeSO4 (1 mM) and L-histidine (10 mM). Total iron was determined by the 1,10-phenanthroline/ascorbate method and ferric iron by reaction with 5-sulfosalicylic acid; the difference was ascribed to ferrous iron. Total iron decreased rapidly in the medium (242 nmol within the first 10 min), and a corresponding increase of total iron (saturation value 376 nmol after 60 min) was determined within the cells, after the cellular proteins had been solubilized with 6 M urea. In the absence of EAT cells, Fe(II)-histidinate was readily oxidized to Fe(III)-histidinate by oxygen, but this reaction was strongly retarded by the tumor cells. The uptake of iron histidinate occurred in the oxidized state, while an uptake of ferrous iron could not be proven unambiguously. When EAT cells were saturated with iron, it was found that 93% of intracellular iron was bound to water-insoluble proteins and 7% was associated with soluble proteins, while no unbound iron was detectable by the method used. It was concluded that, despite the high uptake of total iron, only a very small portion of the intracellular iron was available as a redox catalyst for lipid peroxidation. PMID:3416005

Sharaf El Din, M; Schaur, R J; Schauenstein, E

1988-09-01

49

Disposition of 1,4,6,8-tetramethyl-furoquinolinone in normal and ascitic tumor bearing mice.  

PubMed

1,4,6,8-Tetramethyl-2H-furo[2,3h]quinolin-2-one (FQ) belongs to a series of furocoumarin isosters, designed to obtain new drugs for photochemotherapy. The objective of this study was to characterize the disposition of orally administered 3H-FQ in normal and ascitic tumor bearing mice and to evaluate the influence of UVA irradiation in control mice. This compound was rapidly absorbed and its decay in serum was biphasic. Binding to serum proteins, which was maximum at 30 min (74 %), time-dependently declined. FQ was distributed to all the studied tissues, primarily to the liver and kidneys. The administered radioactivity was excreted mostly in the urine (43 %) and was associated with polar metabolites. The unchanged compound was not present to any detectable extent in the urine. Elimination in the faeces, that may include FQ not absorbed, was low (14 % of administered radioactivity), emphasizing the quantitatively efficient gastrointestinal absorption of the drug. UVA irradiation of FQ-treated mice for 2 h caused a significant increase in radioactivity measured in serum as well as in the liver. In mice bearing Ehrlich ascitic tumor, serum and tissue concentrations were lower than in control animals, possibly due to the larger volume of body fluids (10+/-4 ml of ascitic fluid) available for drug distribution. PMID:17225567

Bevilacqua, Rita; Baccichetti, Francarosa; Gaion, Rosa Maria; Guiotto, Adriano

2006-01-01

50

Sequential degradation of interstitial collagen by metalloproteinases extracted from tumors of murine ascites hepatomas  

Microsoft Academic Search

Gelatinolytic and collagenolytic proteinases were separately isolated by different extraction methods from the mouse ascites hepatoma MH134, and from rat ascites hepatoma AH109A. The activities of two proteinases in each extract showed no significant differences, but after trypsin activation the activities of proteinases from the highly metastic MH134 were significantly increased compared to the emzyme activities in AH109A, which has

Hiroyuki Koita; Kazuki Nabeshima; Teruhiko Inoue; Masashi Koono

1991-01-01

51

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

PubMed Central

Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-?3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker ?-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

2012-01-01

52

Growth, carcass characteristics, and incidence of ascites in broilers exposed to environmental fluctuations and oiled litter.  

PubMed

The effects of diurnal temperature fluctuations and removal of respirable dust, by application of canola oil to straw litter, on growth, carcass traits, and the degree of ascites was evaluated with 1,200 male broilers studied in two replicated 6-wk trials. Each trial used four pens of 150 birds. The temperature treatment consisted of a fluctuation of 3 C in temperature above the required temperature during the day (0600 to 1800 h) and 3 C below the required temperature at night (1800 to 0600 h) for a 6 C change in daily temperature. The control temperature was constant. All pens had the same mean daily temperature. In each trial, one control temperature pen and one fluctuation temperature pen received bi-weekly applications of canola oil to the litter (1.1 L/m2 of oil over 6 wk). At 6 wk of age, 30 birds from each pen were killed for determination of breast muscle, fatpad, and heart weights. All birds were scored for lesions of ascites at time of processing. A score of 0 or 1 represented slight pericardial effusion, slight pulmonary congestion, and edema. A score of 4 represented birds with marked accumulation of ascitic fluid in one or more ceolomic cavities (other than the pericardium) and advanced liver lesions. A cross-sectional image of each 4-mm heart slice (cross-section of the ventricles) was digitally recorded, and with image analysis we determined the right ventricular area (RVA), left ventricular area (LVA), and total heart area (HA). The final BW of the broilers were significantly different, the oiled-litter treatment (2,249 g) had lower weight gain compared with the nonoiled litter treatment (2,293 g). There were no differences in fatpad weight, shank length, lung weight, and percentage breast muscle between the main treatments. The Pectoralis minor and Pectoralis major weight were significantly heavier in the temperature fluctuation treatment than in the control temperature treatment by 3.0 and 12.0 g, respectively. The birds subjected to the control temperature treatment had a lower RVW than the birds subjected to the fluctuating temperature treatment. Temperature fluctuations also resulted in a 1.4% increase in the incidence of mortality. Temperature fluctuations negatively impact broiler growth due to heat loss when litter oiling was excessive. PMID:10735197

McGovern, R H; Feddes, J J; Robinson, F E; Hanson, J A

2000-03-01

53

Urinary ascites  

PubMed Central

A middle-aged male presented with abdominal pain and ascites following a fall in alcoholic intoxicated state. Evaluation revealed microscopic hematuria and severe renal failure. Ascitic fluid analysis showed high urea and creatinine values suggesting it to be a urinary ascites. Retrograde cystography confirmed intraperitoneal bladder rupture. Following continuous bladder drainage ascites subsided and serum creatinine has reduced to 3 mg/dL. This case report highlights the importance of ascitic fluid analysis as a pointer to diagnose urinary ascites secondary to intraperitoneal bladder rupture.

Abirami, K.; Sivaramakrishna, G.; Lakshmi, A. Y.; Sivakumar, V.

2012-01-01

54

In vivo antitumoral effect of Plantago major L. extract on Balb/C mouse with Ehrlich ascites tumor.  

PubMed

The aim of this study is to investigate the antitumor activity of Plantago major L. extract in Ehrlich ascites tumor (EAT) bearing Balb/C mice in vivo. Thirty male Balb/C mice were divided into 5 groups: 3 treatment groups and 2 control groups (6 per group). Treatment groups and the negative control group were injected with EAT (1 x 10(6) cells) intraperitoneally to develop ascites tumor. P. major L. extract (1%, 2% and 3% concentration extracts, 0.1 ml/day/mouse) were given p.o. for 10 alternate days. The control group was treated with 0.9% NaCl solution (0.1 ml/day/mouse). The changes of body weight in animals were recorded. On the 11th day, all of the mice were sacrified and their tissues were stained with haematoxylen and eosin for pathological studies. Body weights of in 3 treatment groups and the negative control group were elevated because of tumor burden. The maximal weight gain was recorded in the negative control group and the minimal weight gain was recorded in Group I. Pathological studies showed that P. major L. extract (especially 1% concentration) has inhibitive effect on EAT. P. major has an inhibitory effect on EAT in a dose dependent manner. PMID:17963323

Ozaslan, Mehmet; Didem Karagöz, I; Kalender, M Emin; Kilic, I Halil; Sari, Ibrahim; Karagöz, Alper

2007-01-01

55

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

PubMed

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

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

1999-01-01

56

Effect of sucrose monostearate, an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells.  

PubMed

Sucrose esters of fatty acids have antitumor activity. We studied the effect of sucrose monostearate (SS), an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells. The activity of ornithine decarboxylase (ODC) was increased in the cells by changing the medium. This increase in the activity was inhibited by adding sucrose stearate, but not sucrose or stearate to the medium. The activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of polyamine biodegradation, was enhanced with the addition of SS in a time- and dose-dependent manner. The elevation of SAT activity was completely prevented when cycloheximide was added to the culture simultaneously. In in vitro studies, SS at various concentrations up to 1 mM hardly affected the activities of ODC or SAT. The incorporation of [3H]inositol into both fractions of inositolphospholipid and inositol phosphates was inhibited by SS. These results suggest that the perturbation of polyamine metabolism and phosphatidylinositol turnover is involved in the mechanism of antitumor activity of SS in Ehrlich ascites tumor cells. PMID:7803498

Matsui-Yuasa, I; Koike, N; Ohtani, K; Otani, S

1994-12-30

57

[Pancreatic ascites].  

PubMed

Two cases of pancreatic ascites have been presented. 1. A 29 year old man, heavy alcoholic, with fast growing ascites presented since long biochemic features of pancreatitis. The diagnosis of the pancreatic origin of ascites was made on the ground of the high level of amylase in the ascitic fluid. Conservative treatment was effectless. The patients refused surgical therapy. Then he died in septic shock. Autopsy confirmed the pancreatic origin of ascites. 2. A 43 year old man heavy alcoholic as well admitted because of fast growing ascites. As in the first case examination of the fluid confirmed the diagnosis of pancreatic origin of ascites. Again a high level of amylase and protein was found. After clinical treatment and parenteral nutrition the condition of the patient improved and he was dismissed 4 weeks later. PMID:7479248

Jasi?ski, A; Suchanek, W; Mitlener, S; Kryszewski, A

1995-03-01

58

Ca2+ Transport by Mitochondria from L1210 Mouse Ascites Tumor Cells  

Microsoft Academic Search

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

Baltazar Reynafarje; Albert L. Lehninger

1973-01-01

59

Immunologic Mechanism of the AntiTumor Immunity Responses Induced by the Altogether Culture Medium of Porcine Cartilage Polysaccharide and S180 Ascites Lump Cells as a Tumor Vaccine  

Microsoft Academic Search

It is well known that tumor vaccines induce protective humoral and cell-mediated immune responses in several animal models .In this study, we took the S180 ascites lump cells treated with polysaccharide isolated from porcine cartilage for 48h as a tumor vaccine. The goal of this study was to investigate whether this tumor vaccine is able to augment the antitumor immune

An-jun Liu; Ya Gao; Shan-jie Ma; Hong Zhang; Jing-jing Fang; Guo-qiang Zheng; Yin-chu Li

2011-01-01

60

Treatment of mice bearing a Krebs ascitic tumor by means of a protocol based on radioactive copper (64Cu). IV. Consequences of the nature of cancer: tumor-resistant mice.  

PubMed

In the efficient treatment described (Anticancer Research 9: 941-946, 1989) some compounds (64Cu and thioproline) act against the malignant genomes, and other components (metal ions, amino acids, vitamin D2, thyroxine and chelating substances) act against the functioning of the host cells having the cancer functioning (cancer cells). The experiments described show that this treatment developed with mice injected on day zero with 5 x 10(5) Krebs ascitic cells, is also efficient for mice bearing a spontaneous malignant tumor even if it is not an ascitic tumor. After the decrease in weight due to the loss of the tumor, a typical weight evolution was observed characterized by a second weight increase followed by a decrease leading to normal weight. This last weight remained stable. This typical weight evolution in tumor-free mice (after spontaneous tumor or experimental Krebs ascitic tumor) was related to the age of the tumor at the beginning of the treatment, that is, according to our hypothesis (Anticancer Res 9:955-960, 1989) to the cancer evolution emphasizing the great importance of all physiological phenomena related to this cancer course. To test the consequence of this treatment, some of these tumor-free mice were injected with 5 x 10(5) ascitic cells. No tumor developed in these tumor-free mice meaning that they also were tumor-resistant. This last result is in agreement with the forecast of the systemic analysis on which the efficient treatment was based. PMID:2334118

Guillé, E; Apelgot, S

61

Massive ascites as the only sign of ovarian juvenile granulosa cell tumor in an adolescent: a case report and a review of the literature.  

PubMed

Ovarian neoplasms are relatively rare in childhood and adolescence; only 5% to 8% of the cases are of sex cord stromal origin. Granulosa cell tumors are a group of estrogen producing sex cord stromal tumors of the ovary. They occur in 95% of the cases in adults, and only about 5% of the cases, which differ in histologic characteristics, are of juvenile type. A 13-year-old girl is reported who presented with massive abdominal distention and ascites. An abdominopelvic computed tomography scan showed a predominantly cystic mass lesion with septations arising from the left ovary. All tumor markers were normal, but serum inhibin level was increased. The patient underwent mass resection with salpingoophorectomy. Histopathology was compatible with the juvenile granulosa cell tumor. Interestingly, menarche was started in the patient soon after the surgery. To the best of our knowledge, massive ascites as the only clinical manifestation in the juvenile granulosa cell tumor has not reported as yet. PMID:23424695

Ashnagar, Azin; Alavi, Samin; Nilipour, Yalda; Azma, Roxana; Falahati, Farahnaz

2013-01-29

62

A Rare Case of Secondary Bacterial Peritonitis from Clostridium perfringens in an Adult Patient with Noncirrhotic Ascites and a Krukenberg Tumor: Report of a Case  

PubMed Central

Secondary bacterial peritonitis, in comparison to spontaneous, presents with a surgically treatable intraabdominal source for infection such as a gastrointestinal perforation or abscess and is nearly always polymicrobial. We present a rare case of secondary bacterial peritonitis from Clostridium perfringens in an adult patient with noncirrhotic ascites and a Krukenberg tumor.

Kelley, Scott R.; Kerlakian, George M.

2011-01-01

63

Humanized Mouse Model of Ovarian Cancer Recapitulates Patient Solid Tumor Progression, Ascites Formation, and Metastasis  

Microsoft Academic Search

Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are

Richard B. Bankert; Sathy V. Balu-Iyer; Kunle Odunsi; Leonard D. Shultz; Raymond J. Kelleher; Jennifer L. Barnas; Michelle Simpson-Abelson; Robert Parsons; Sandra J. Yokota; Sandra Orsulic

2011-01-01

64

Growth performance, carcass characteristics, and the incidence of ascites in broilers in response to feed restriction and litter oiling.  

PubMed

The effect of feed restriction and the application of canola oil to broiler straw litter to contain respirable dust on growth performance, carcass traits, and the incidence of ascites was evaluated with 800 male broilers studied in two 6-wk periods. Two pens of birds were feed restricted. Two pens of birds received feed ad libitum for the 6-wk trial. One restricted and one ad libitum pen received biweekly addition of canola oil to the litter. At 6 wk of age, 30 birds from each pen were killed for determination of breast muscle, fat pad, and heart weights. All birds were scored for the incidence of ascites at processing. A cross sectional image of each heart was digitally recorded and, using image analysis, the right ventricular area (RVA), left ventricular area (LVA), and total heart area (HA) were determined. The right ventricular wall was removed and its weight was expressed as a percentage of total heart weight (PRVW). The 40-d BW was significantly greater in the ad libitum birds (2.07 kg) than in the feed-restricted birds (1.86 kg). The right ventricular weight (RVW) (1.69 and 1.92 g) and the RVA (0.35 and 0.40 cm2) were also significantly different between the two feeding treatments. The ascites score was significantly correlated to the RVW (r = 0.50) and RVA (r = 0.52). The RVA was also correlated to the RVW (r = 0.63). Oiling the litter did not result in differences in carcass characteristics. Litter oiling significantly reduced the RVA of the ad libitum birds (0.36 cm2) compared to the ad libitum birds that did not have oiled litter (0.44 cm2). Feed restriction reduced the incidence of ascites, but also reduced gain. Litter oiling in the feed-restricted groups reduced the RVA, but did not reduce mortality. PMID:10230904

McGovern, R H; Feddes, J J; Robinson, F E; Hanson, J A

1999-04-01

65

Effect of Lawsonia inermis on tumor expression induced by Dalton's lymphoma ascites in Swiss albino mice.  

PubMed

The purpose of this study was investigating experimentally the possible antitumor effect of ethanol extract of root of Lawsonia inermis against Dalton's lymphoma ascites (DLA) bearing mice. Mice were administered with L. inermis at a dosage of 180 mg/kg of body weight for 15 days after 24 h of DLA inoculation. The ethanolic root extract of L. inermis reverted the increased number of the WBC count, platelets and lymphocytes and decreased the number of the RBC count, hemoglobin content and monocytes. The effect of root extract of L. inermis also increased the pathophysiological marker enzyme, lipid profile and decreased the enzymic and non enzymic antioxidants. A histopathological result shows the loss of liver hepatocytes and kidney architecture in DLA bearing mice. However, mice treatment with L. inermis extract improves the liver and kidney function and rearranges more or less normal architecture. The present work indicates that the ethanol extract of L. inermis exhibited significant antitumor activity. PMID:23961147

Priya, R; Ilavenil, S; Kaleeswaran, B; Srigopalram, S; Ravikumar, S

2011-04-18

66

Effect of Lawsonia inermis on tumor expression induced by Dalton's lymphoma ascites in Swiss albino mice  

PubMed Central

The purpose of this study was investigating experimentally the possible antitumor effect of ethanol extract of root of Lawsonia inermis against Dalton’s lymphoma ascites (DLA) bearing mice. Mice were administered with L. inermis at a dosage of 180 mg/kg of body weight for 15 days after 24 h of DLA inoculation. The ethanolic root extract of L. inermis reverted the increased number of the WBC count, platelets and lymphocytes and decreased the number of the RBC count, hemoglobin content and monocytes. The effect of root extract of L. inermis also increased the pathophysiological marker enzyme, lipid profile and decreased the enzymic and non enzymic antioxidants. A histopathological result shows the loss of liver hepatocytes and kidney architecture in DLA bearing mice. However, mice treatment with L. inermis extract improves the liver and kidney function and rearranges more or less normal architecture. The present work indicates that the ethanol extract of L. inermis exhibited significant antitumor activity.

Priya, R.; Ilavenil, S.; Kaleeswaran, B.; Srigopalram, S.; Ravikumar, S.

2011-01-01

67

When ascites is not ascites  

Microsoft Academic Search

The case is reported of a patient presenting with ascites and acute renal failure resulting from spontaneous rupture of the urinary bladder, 30 years after the successful initial treatment of childhood rhabdomyosarcoma. The delay in the presentation until the patient began to experience the symptoms due to urinary ascites, the diagnostic dilemma because of the rarity of the condition, and

A Sharma; B Teh; D J R Morgan; D Bell; C Woodhouse

2008-01-01

68

Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation.  

PubMed

This study investigated the functional interplay between vascular endothelial growth factor (VEGF) and metalloproteinases (MMPs) in ovarian carcinomas. Levels of MMP9 (pro and activated form) and proMMP2 in ascites correlated with VEGF and with the ascitic volume in nude mice bearing human ovarian carcinoma xenografts (HOC22 and HOC8). The MMP inhibitor batimastat (BB-94) reduced VEGF release and ascitic fluid formation. Exogenous, activated MMP9, and, to a lesser extent, MMP2, increased VEGF release by SKOV3 and OVCAR3 ovarian carcinoma cells. The effect was dose and time dependent and inhibited by BB-94. MMP9-released VEGF was biologically active, because it induced endothelial cell motility, and its activity was prevented by the VEGF inhibitor SU5416. Our results indicate that MMPs, mainly MMP9, play a role in the release of biologically active VEGF and consequently in the formation of ascites. PMID:14500349

Belotti, Dorina; Paganoni, Paola; Manenti, Luigi; Garofalo, Angela; Marchini, Sergio; Taraboletti, Giulia; Giavazzi, Raffaella

2003-09-01

69

Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis  

PubMed Central

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

Waterman, Ruth S.; Henkle, Sarah L.; Betancourt, Aline M.

2012-01-01

70

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

PubMed

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. PMID:9187119

Yamamoto, N; Naraparaju, V R

1997-06-01

71

Conditions supporting repair of potentially lethal damage cause a significant reduction of ultraviolet light-induced division delay in synchronized and plateau-phase Ehrlich ascites tumor cells  

SciTech Connect

Repair of potentially lethal damage (PLD) induced by uv light in synchronized and in plateau-phase cultures of Ehrlich ascites tumor cells was studied by measuring cell survival. In particlar the influence of conditions supporting repair of PLD on growth kinetics was investigated. In synchronized G/sub 1/, S, or G/sub 2/ + M cells as well as in plateau-phase cells, uv light induced, almost exclusively, delay in the next S phase. A significant decrease of this delay was observed when the cells were incubated for 24 hr in balanced salt solution. Repair of PLD after uv irradiation was found to occur in plateau-phase cells and in cells in different phases of the cell cycle provided that after irradiation these were kept under conditions inhibiting cell multiplication (incubation in balanced salt solution or in conditioned medium). The repair time constant t/sub 50/ was significantly higher than those found for X irradiation (5-10 hr compared to 2 hr), and repair was not significantly inhibited by either 20 ..mu..g/ml cycloheximide or 2 mM caffeine in 24 hr.

Iliakis, G.; Nusse, M.

1982-09-01

72

Na+,Cl- cotransport in Ehrlich ascites tumor cells activated during volume regulation (regulatory volume increase).  

PubMed

Ehrlich ascites cells were preincubated in hypotonic medium with subsequent restoration of tonicity. After the initial osmotic shrinkage the cells recovered their volume within 5 min with an associated KCl uptake. The volume recovery was inhibited when NO-3 was substituted for Cl-, and when Na+ was replaced by K+, or by choline (at 5 mM external K+). The volume recovery was strongly inhibited by furosemide and bumetanide, but essentially unaffected by DIDS. The net uptake of Cl- was much larger than the value predicted from the conductive Cl- permeability. The undirectional 36Cl flux, which was insensitive to bumetanide under steady-state conditions, was substantially increased during regulatory volume increase, and showed a large bumetanide-sensitive component. During volume recovery the Cl- flux ratio (influx/efflux) for the bumetanide-sensitive component was estimated at 1.85, compatible with a coupled uptake of Na+ and Cl-, or with an uptake via a K+,Na+,2Cl- cotransport system. The latter possibility is unlikely, however, because a net uptake of KCl was found even at low external K+, and because no K+ uptake was found in ouabain-poisoned cells. In the presence of ouabain a bumetanide-sensitive uptake during volume recovery of Na+ and Cl- in nearly equimolar amounts was demonstrated. It is proposed that the primary process during the regulatory volume increase is an activation of an otherwise quiescent, bumetanide-sensitive Na+,Cl- cotransport system with subsequent replacement of Na+ by K+ via the Na+/K+ pump, stimulated by the Na+ influx through the Na+,Cl- cotransport system. PMID:6100866

Hoffmann, E K; Sjøholm, C; Simonsen, L O

1983-01-01

73

Influence of glutaraldehyde and\\/or osmium tetroxide on cell volume, ion content, mechanical stability, and membrane permeability of ehrlich ascites tumor cells  

Microsoft Academic Search

Effects of fixation with glutaraldehyde (GA), glutaraldehyde-osmium tetroxide (GA-OsO4), and osmium tetroxide (OsO4) on ion and ATP content, cell volume, vital dye staining, and stability to mechanical and thermal stress were studied in Ehrlich ascites tumor cells (EATC). Among variables investigated were fxation time, fixative concentration, temperature, osmolality of the fixative agent and buffer, total osmolality of the fixative solution,

ANTTI PENTTILA; HANNU KALIMO; BENJAMIN F. TRUMP

1974-01-01

74

Effect of Arachidonic Acid on Conductive Na, K and Anion Transport in Ehrlich Ascites Tumor Cells under Isotonic and Hypotonic Conditions  

Microsoft Academic Search

Na and K transport provoked in Ehrlich ascites tumor cells by addition of arachidonic acid is via conductive ion channels and not via any Na+\\/H+ or K+\\/H+ exchange systems nor any Cl-dependent cotransport system. The effect of arachidonic acid on the Na conductance is partly mediated via cyclooxygenase metabolites, while the effect on the K conductance is dominantly a nonspecific

Ian Henry Lambert

1991-01-01

75

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

PubMed

The microenvironment is known to play a dominant role in cancer progression. Cells closely associated with tumoral cells, named hospicells, have been recently isolated from the ascites of ovarian cancer patients. Whilst these cells present no specific markers from known cell lineages, they do share some homology with bone marrow-derived or adipose tissue-derived human mesenchymal stem cells (CD9, CD10, CD29, CD146, CD166, HLA-1). We studied the role of hospicells in ovarian carcinoma progression. In vitro, these cells had no effect on the growth of human ovarian carcinoma cell lines OVCAR-3, SKOV-1 and IGROV-1. In vivo, their co-injection with adenocarcinoma cells enhanced tumor growth whatever the tumor model used (subcutaneous and intraperitoneally established xenografts in athymic mice). In addition, their injection increased the development of ascites in tumor-bearing mice. Fluorescent macroscopy revealed an association between hospicells and ovarian adenocarcinoma cells within the tumor mass. Tumors obtained by coinjection of hospicells and human ovarian adenocarcinoma cells presented an increased microvascularization indicating that the hospicells could promote tumorigenicity of ovarian tumor cells in vivovia their action on angiogenesis. This effect on angiogenesis could be attributed to the increased HIF1alpha and VEGF expression associated with the presence of the hospicells. Collectively, these data indicate a role for these ascite-derived stromal cells in promoting tumor growth by increasing angiogenesis. PMID:19739074

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

2010-05-01

76

Radiotherapeutic Response of Ehrlich Ascites Tumor Cells Perfused in Agarose Gel Threads and Implanted in Mice  

Microsoft Academic Search

Aim: In order to obtain better understanding of radiation-induced alterations in intracellular metabolism, a dynamic and non-invasive experimental model system is required. A serial study in cultured tumor cell line followed by verification in the in vivo samples may be of considerable value for non-invasive prediction and\\/or detection of tumor response to therapy. The present study was undertaken to evaluate

Rakesh Kumar Sharma; Viney Jain

2001-01-01

77

Purification of, and generation of antibodies against an actin-binding cell surface glycoprotein from ascites tumor cell microvilli  

SciTech Connect

Isolated microvilli from 13762 ascites tumor cells contain a transmembrane, cell surface glycoprotein (CAG - cytoskeleton associated glycoprotein) which binds to microfilaments. The authors have purified this protein from Triton X-100 extracts of microvilli by two consecutive sucrose density gradient centrifugation steps in the presence of sodium dodecyl sulfate (SDS). Under non-reducing conditions, CAG behaves as a 20 S species, and has a molecular weight of 1-2 x 10/sup 6/. The molecular weight of the reduced, SDS subunit is 80,000. The authors have demonstrated that the purified, non-reduced CAG molecule can bind /sup 125/I actin. Antibodies against CAG were raised in rabbits by injecting CAG which was eluted from preparative SDS gels run under reducing conditions. Interestingly, this antibody also reacts with the heavy chain of soluble rat IgM, another mulitmeric glycoprotein of similar molecular weight. This antibody will be useful for the localization of cross-reactive molecules in other cells and tissues.

Metcalf, T.N. III; Carraway, C.A.C.; Carraway, K.L.

1987-05-01

78

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

SciTech Connect

Three /sup 14/C-labeled 22-carbon polyunsaturated fatty acids, 7,10,13,16-(/sup 14/C)docosatetraenoic acid (22:4(n-6)), 7,10,13,16,19-(/sup 14/C)docosapentaenoic acid (22:5(n-3)), and 4,7,10,13,16,19-(/sup 14/C)docosahexaenoic acid (22:6(n-3)), were compared with (/sup 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.

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

1986-11-01

79

Circadian rhythms and tumor growth.  

PubMed

Hormone secretion, metabolism, and the cell cycle are under rhythmic control. Lack of rhythmic control has been predicted to lead to uncontrolled proliferation and cancer. Consistent with this prediction are findings that circadian disruption by dim light at night or chronic jet lag accelerates tumor growth in desynchronized animals. Circadian controlled factors such as insulin/IGF-1, glucocorticoids, catecholamines, and melatonin have be implicated in controlling tumor growth in the desynchronized animals. Recent attention has focused on the signaling pathways activated by the circadian controlled factors because these pathways hold the potential for the development of novel strategies for cancer prevention and treatment. PMID:22252116

Greene, Michael W

2012-01-15

80

Ascites produced by peritoneal seeding of neuroblastoma  

Microsoft Academic Search

Preoperative CT and ultrasound of a 16-month-old girl with abdominal mass demonstrated the calcified mass and a copious amount of ascites. Pathological examination of the tumor revealed neuroblastoma, a tumor not usually associated with peritoneal seeding or ascites.

S. K. Fernbach

1993-01-01

81

Ascites produced by peritoneal seeding of neuroblastoma.  

PubMed

Preoperative CT and ultrasound of a 16-month-old girl with abdominal mass demonstrated the calcified mass and a copious amount of ascites. Pathological examination of the tumor revealed neuroblastoma, a tumor not usually associated with peritoneal seeding or ascites. PMID:8309772

Fernbach, S K

1993-01-01

82

31P and 13C NMR spectroscopic study of wild type and multidrug resistant Ehrlich ascites tumor cells.  

PubMed

Steady-state 31P NMR spectra of wild type EHR2 Ehrlich ascites tumor cells and multidrug resistant EHR2/DNR+ cells, immobilized in agarose threads, and continuously perfused with medium, showed temperature-dependent differences in the levels of intracellular phosphate metabolites. At 37 degrees C, the EHR2/DNR+ cells contained four times more phosphocreatine (PCr) than the EHR2 cells. At 20 degrees C, the EHR2 cells contained 80% more of phosphodiesters (PDE), the levels of PCr being equal. The quantitative metabolite level data are based on T1 relaxation times data and are normalized for the protein content of the cells. Perfusion of the cells with azide, an inhibitor of mitochondrial respiration, had no effect on the ATP level, and caused no changes in glucose consumption and lactate production. Azide perfusion, combined with glucose depletion, caused rapid drop in the ATP content, which was reestablished after renewed perfusion with glucose. Similarly, perfusion with 2,4-dinitrophenol, an uncoupler of the respiration chain, had no effect on the phosphate metabolites. These results demonstrate that aerobic glycolysis is the main route by which glucose is metabolised under the conditions used (glucose concentration in medium 2 g/L). Rates of uptake and phosphorylation of 2-deoxy-D-glucose were measured by following the formation of intracellular [6-13C]2-deoxy-D-glucose-6-phosphate by 13C NMR; at 37 degrees C the observed rates for EHR2 and EHR2/DNR+ cells were equal, about 10 nmol/(min x mg protein), whereas at 20 degrees C the wild type cells produced the 6-phosphate at an approximately twice the rate found for the resistant cells [about 4 and 2 nmol/(min x mg protein), respectively].(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8260748

Rasmussen, J; Hansen, L L; Friche, E; Jaroszewski, J W

1993-01-01

83

Statistical mechanics model of angiogenic tumor growth.  

PubMed

We examine a lattice model of tumor growth where the survival of tumor cells depends on the supplied nutrients. When such a supply is random, the extinction of tumors belongs to the directed percolation universality class. However, when the supply is correlated with the distribution of tumor cells, which as we suggest might mimic the angiogenic growth, the extinction shows different critical behavior. Such a correlation affects also the morphology of the growing tumors and drastically raises tumor-survival probability. PMID:22400505

Ferreira, António Luis; Lipowska, Dorota; Lipowski, Adam

2012-01-10

84

PROTEIN METABOLISM IN TUMOR CELLS AT VARIOUS STAGES OF GROWTH IN VIVO  

PubMed Central

Protein metabolism of Yoshida ascites hepatoma cells was studied in the early phase of logarithmic proliferation and in the following stage in which cell mass remains constant (resting phase). The rate of protein synthesis was measured by a short-time incorporation of [8H]lysine, while degradation was concurrently assessed by following the decrease of specific activity of [14C]lysine-labeled proteins. Most of the labeled amino acid injected intraperitoneally into the animal was immediately available for the tumor cells, with only a minor loss towards the extra-ascitic compartment. It was thus possible to calculate the dilution of the isotope in the ascitic pool of the lysine, which increased concurrently with the ascitic plasma volume. Amino acid transport capacity did not change in the log vs. the resting cells. This fact permitted the correction of the specific activity of the proteins synthesized by tumors in the two phases, taking into account the dilution effect. Protein synthesis was found to proceed at a constant rate throughout each of the two phases, although it was 30% lower during the resting as compared to the log phase. When cell mass attained the steady-state, protein degradation occurred at such a level as to balance the synthesis. Throughout the resting phase the amount of lysine taken up by the cells and renewed from the blood remained unchanged. Protein turnover, as studied in subcellular fractions, exhibited a similar rate in nuclei and microsomes, where it proceeded at a higher level than in mitochondria. On the whole, the results encourage the use of the Yoshida ascites hepatoma as a suitable model for studying protein turnover in relation to cell growth in vivo.

Olivotto, Massimo; Paoletti, Francesco

1974-01-01

85

Study of Tumor Growth under Hyperthermia Condition  

PubMed Central

The new concept of keeping primary tumor under control in situ to suppress distant foci sheds light on the treatment of metastatic tumor. Hyperthermia is considered as one of the means for controlling tumor growth. To simulate the tumor growth, a continuum mathematical model has been introduced. The newest understanding of the Warburg effect on the cellular metabolism and diffusion of the nutrients in the tissue has been taken into consideration. The numerical results are compared with the in vivo experimental data by fitting the tumor cell doubling time/tumor cell growth rate under different thermal conditions. Both the tumor growth curve and corresponding average glucose concentration have been predicted. The numerical results have quantitatively illustrated the controlling effect on tumor growth under hyperthermia condition in the initial stage.

Zhu, Qing; Zhang, Aili; Liu, Ping; Xu, Lisa X.

2012-01-01

86

Role of intracellular reactive oxygen species and mitochondrial dysfunction in evening primrose extract-induced apoptosis in Ehrlich ascites tumor cells.  

PubMed

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. Evening primrose extract (EPE) is extracted from Oenothera biennis L., one species of evening primroses, which has been shown to have several pharmacological effects. However, anti-tumor activity in the extract of defatted seeds of O. biennis L. has not been defined thus far. In this study, we identified the major biochemical changes upon EPE treatment and investigated the functional relationship between these changes. We found that EPE-induced apoptosis in Ehrlich ascites tumor cells as evidenced by morphological changes. Furthermore, our results demonstrated rapid increase of intracellular peroxides levels, loss of mitochondrial membrane potential and the release of cytochrome c from mitochondria to cytosol. These results suggest that the rapid increase of intracellular peroxides levels after addition of EPE triggers off induction of apoptosis. PMID:12732460

Arimura, Tsutomu; Kojima-Yuasa, Akiko; Watanabe, Sanae; Suzuki, Mayu; Kennedy, David Opare; Matsui-Yuasa, Isao

2003-06-15

87

Comparison of glutathione reductase activity and the intracellular glutathione reducing effects of 13 derivatives of 1'-acetoxychavicol acetate in Ehrlich ascites tumor cells.  

PubMed

In a previous study, we showed that (1'S)-acetoxychavicol acetate ((S)-ACA) caused a rapid decrease in glutathione (GSH) levels less than 15 min after exposure. (S)-ACA-induced cell death was reversed by the addition of N-acetylcysteine. In the current study, we investigated the inhibitory activities of 13 derivatives of (S)-ACA on tumor cell viability, intracellular GSH level and GR activity. Correlations were found among a decrease in cell viability, intracellular GSH levels and the activity of GR in Ehrlich ascites tumor cells treated with the various ACA analogues. A test of the 13 derivatives revealed that the structural factors regulating activity were as follows: (1) the para or 1'-position of acetoxyl group (or other acyl group) was essential, (2) the presence of a C2'-C3' double or triple bond was essential, and (3) the S configuration of the 1'-acetoxyl group was preferable. PMID:20230805

Xu, Shenghui; Kojima-Yuasa, Akiko; Azuma, Hideki; Kennedy, David Opare; Konishi, Yotaro; Matsui-Yuasa, Isao

2010-03-15

88

Effect of Lawsonia inermis on tumor expression induced by Dalton’s lymphoma ascites in Swiss albino mice  

Microsoft Academic Search

The purpose of this study was investigating experimentally the possible antitumor effect of ethanol extract of root of Lawsonia inermis against Dalton’s lymphoma ascites (DLA) bearing mice.Mice were administered with L. inermis at a dosage of 180mg\\/kg of body weight for 15days after 24h of DLA inoculation. The ethanolic root extract of L. inermis reverted the increased number of the

R. Priya; S. Ilavenil; B. Kaleeswaran; S. Srigopalram; S. Ravikumar

2011-01-01

89

Modelling Early Tumor Growth with Diffusion Equation  

Microsoft Academic Search

Abstract This essay is aimed at forming a lecture series on the modelling of early tumor growth using diffusion equations. We present basic models for tumor growth and discuss the linear stability of their steady states. The models discussed predict the size of the proliferating layer, the size of the tumor, and the effects of the immune system response, on

Asha Saidi Kalula; Jacek Banasiak

90

A comparison of the growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian tumours.  

PubMed Central

The growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian malignancy, benign ovarian tumours and non-tumour related gynaecological conditions have been investigated using an ovarian carcinoma cell line (OAW 42), mesothelial cells (58MC) and rat kidney cells (NRK-49F). Colony stimulating activity (CSA) for tumour cells and transforming activity (TA) for mesothelial cells were weakly correlated, but whereas elevated TA was tumour-associated, CSA was not. However, TA was not cancer-associated and, although the difference between the mean TA values of benign and malignant cyst fluids was of borderline significance, some benign cyst fluids from cystadenomas showed high TA values. Higher levels of TA in the cystadenomas showed a significant correlation with the menopausal status of the patient and higher levels of TA in the malignant cyst fluid/peritoneal fluid groups were associated with more advanced disease. Results indicated that some fluids contained TGF-beta-like activity, but there was no direct evidence for the presence of TGF-alpha/EGF-like activity in the fluids. Heparin inhibited clonogenic growth of tumour cells but not mesothelial cells. The reduced CSA which was observed after treatment of fluids with both heparin and thrombin implicated coagulation factors in the manifestation of CSA. It was concluded that CSA in the fluids was due, at least partly, to fibrin coagulation, and TA was due to unknown growth factor(s) which may include TGF-beta-like activity. The results are discussed in the context of the aetiology of ovarian carcinoma, and the possible clinical significance of TA. Images Figure 1

Wilson, A. P.; Fox, H.; Scott, I. V.; Lee, H.; Dent, M.; Golding, P. R.

1991-01-01

91

Cancer Progression and Tumor Growth Kinetics  

NASA Astrophysics Data System (ADS)

We present and analyze tumor growth data from prostate and brain cancer. Scaling the data from different patients shows that early stage prostate tumors show non-exponential growth while advanced prostate and brain tumors enter a stage of exponential growth. The scaling analysis points to the existence of cancer stem cells and/or massive apoptosis in early stage prostate cancer and that late stage cancer growth is not dominated by cancer stem cells. Statistical models of these two growth modes are discussed.

Blagoev, Krastan; Kalpathy-Cramer, Jayashree; Wilkerson, Julia; Sprinkhuizen, Sara; Song, Yi-Qiao; Bates, Susan; Rosen, Bruce; Fojo, Tito

2013-03-01

92

Selective promotion of ferrous ion-dependent lipid peroxidation in Ehrlich ascites tumor cells by histidine as compared with other amino acids.  

PubMed

Among tumors in general, Ehrlich ascites tumor cells are particularly resistant to lipid peroxidation. In this study lipid peroxidation was measured in terms of the formation of malondialdehyde-equivalent material in Ehrlich tumor cells during incubation in vitro. It was shown that the high antioxidant potential of these cells could be overcome by a strong radical-promoting agent like ferrous ion. Various amino acids were tested for their capability to augment the effect of Fe(II). Histidine and its 3-methyl-derivative turned out to be the most effective pro-oxidants, whose action could be ascribed to the presence of the imidazole group. From studies with homogenized and denatured cells it was concluded that lipid peroxidation stimulated by Fe(II)-histidinate is an autoxidation process and that no carrier effect of iron by histidine is predominating. The stimulatory action of Fe(II)-histidinate could be completely suppressed by vitamin C, which was shown to be a potent anti-oxidant under the conditions used. The combined application of Fe(II)-histidinate and vitamin C may offer a means to study lipid peroxidation of Ehrlich tumor cells in a controlled manner. PMID:6509073

Winkler, P; Schaur, R J; Schauenstein, E

1984-12-01

93

Patients with spontaneous bacterial peritonitis, and malignant and cirrhotic ascites.  

PubMed Central

BACKGROUND: Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. METHOD AND PATIENTS: We studied tumor necrosis factor-alpha, tumor necrosis factor receptor and C-reactive protein levels in both ascitic fluid and serum in patients with spontaneous bacterial peritonitis (SBP) (n = 22), and in the malignant (n = 38) and cirrhotic (n = 32) ascites. RESULTS: C-reactive protein, tumor necrosis factor-alpha and tumor necrosis factor receptor levels in the ascitic fluid were found to be elevated in the SBP (p < 0.001) and malignant groups (p < 0.005) when compared with the sterile cirrhotic group. C-reactive protein levels in the serum were found to be elevated in the SBP group when compared with the sterile cirrhotic (p < 0.001) and malignant group (p < 0.005). Tumor necrosis factor-alpha in the serum was significantly elevated in the SBP when compared with the cirrhotic (p < 0.005) and malignant ascites (p < 0.001). Sensitivity and specificity of ascitic fluid CRP in discriminating malignant 84% and 67% and SBP from sterile ascites were 90% and 76%, respectively. Sensitivity and specificity of ascitic fluid TNF-alpha in discriminating malignant 77% and 60% and SBP from sterile ascites were 82% and 66%, respectively. Sensitivity and specificity of TNF-r p60 in discriminating malignant 74% and 70% and SBP from sterile ascites were 80% and 76%, respectively. CONCLUSION: The sensitivity and specificity of ascitic fluid CRP, TNF-alpha and TNF-r values were found to be similar. Ascitic fluid Creactive protein to differentiate SBP and malignant ascitic from cirrhotic ascites are cheap, practical and safe tests used in the differential diagnosis of ascites.

Yildirim, Bulent; Sari, Ramazan; Isci, Nuran

2005-01-01

94

CD73 promotes tumor growth and metastasis  

PubMed Central

Our recent data and that of others demonstrate that both tumor and host CD73-generated adenosine promote tumor growth and metastasis in a multifactorial manner. Results with small molecule inhibitors or monoclonal antibodies against CD73 in multiple tumor models suggest that CD73 is a previously unappreciated important target for effective cancer therapy.

Zhang, Bin

2012-01-01

95

A Multiscale Model for Avascular Tumor Growth  

Microsoft Academic Search

The desire to understand tumor complexity has given rise to mathematical models to describe the tumor microenvironment. We present a new mathematical model for avascular tumor growth and development that spans three distinct scales. At the cellular level, a lattice Monte Carlo model describes cellular dynamics (proliferation, adhesion, and viability). At the subcellular level, a Boolean network regulates the expression

Y. Jiang; Jelena Pjesivac-Grbovic; Charles Cantrell; James P. Freyer

2005-01-01

96

Curcumin, a natural product present in turmeric, decreases tumor growth but does not behave as an anticachectic compound in a rat model  

Microsoft Academic Search

Systemic administration of curcumin [1,7-bis(4-hydroxy-3-methoxyphenil)1,6-heptadiene-3,5-dione] (20 ?g\\/kg body weight) for 6 consecutive days to rats bearing the highly cachectic Yoshida AH-130 ascites hepatoma resulted in an important inhibition of tumor growth (31% of total cell number). Interestingly, curcumin was also able to reduce (24%) in vitro tumor cell content at concentrations as low as 0.5 ?M without promoting any apoptotic

S??lvia Busquets; Neus Carbó; Vanessa Almendro; Mar??a T Quiles; Francisco J López-Soriano; Josep M Argilés

2001-01-01

97

Inhibition of Vascularization in Tumor Growth  

NASA Astrophysics Data System (ADS)

The transition to a vascular phase is a prerequisite for fast tumor growth. During the avascular phase, the neoplasm feeds only from the (relatively few) existing nearby blood vessels. During angiogenesis, the number of capillaries surrounding and infiltrating the tumor increases dramatically. A model which includes physical and biological mechanisms of the interactions between the tumor and vascular growth describes the avascular-vascular transition. Numerical results agree with clinical observations and predict the influence of therapies aiming to inhibit the transition.

Scalerandi, M.; Sansone, B. Capogrosso

2002-11-01

98

Tumor growth dynamics: insights into evolutionary processes.  

PubMed

Identifying the types of event that drive tumor evolution and progression is crucial for understanding cancer. We suggest that the analysis of tumor growth dynamics can provide a window into tumor biology and evolution by connecting them with the types of genetic change that have occurred. Although fundamentally important, the documentation of tumor growth kinetics is more sparse in the literature than is the molecular analysis of cells. Here, we provide a historical summary of tumor growth patterns and argue that they can be classified into five basic categories. We then illustrate how those categories can provide insights into events that drive tumor progression, by discussing a particular evolutionary model as an example and encouraging such analysis in a more general setting. PMID:23816268

Rodriguez-Brenes, Ignacio A; Komarova, Natalia L; Wodarz, Dominik

2013-06-28

99

Early tumor effect on splenic Th lymphocytes in mice  

Microsoft Academic Search

Tumors are characterized by their ability to avoid the host immune system. Ehrlich ascites tumor cells were used to investigate the early alterations of the host immune system after tumor inoculation. The results show that frequencies of splenic Th lymphocytes were drastically reduced during tumor growth, reaching a minimum only two days after tumor inoculation. The frequency of splenic CD4+

Juan A Segura; Laura G Barbero; Javier Márquez

1997-01-01

100

Simulating tumor growth in confined heterogeneous environments  

NASA Astrophysics Data System (ADS)

The holy grail of computational tumor modeling is to develop a simulation tool that can be utilized in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies. In order to develop such a predictive model, one must account for many of the complex processes involved in tumor growth. One interaction that has not been incorporated into computational models of neoplastic progression is the impact that organ-imposed physical confinement and heterogeneity have on tumor growth. For this reason, we have taken a cellular automaton algorithm that was originally designed to simulate spherically symmetric tumor growth and generalized the algorithm to incorporate the effects of tissue shape and structure. We show that models that do not account for organ/tissue geometry and topology lead to false conclusions about tumor spread, shape and size. The impact that confinement has on tumor growth is more pronounced when a neoplasm is growing close to, versus far from, the confining boundary. Thus, any clinical simulation tool of cancer progression must not only consider the shape and structure of the organ in which a tumor is growing, but must also consider the location of the tumor within the organ if it is to accurately predict neoplastic growth dynamics.

Gevertz, Jana L.; Gillies, George T.; Torquato, Salvatore

2008-09-01

101

Involvement of protein tyrosine phosphorylation and reduction of cellular sulfhydryl groups in cell death induced by 1' -acetoxychavicol acetate in Ehrlich ascites tumor cells.  

PubMed

Elucidation of the mechanisms underlying potential anticancer drugs continues and unraveling these mechanisms would not only provide a conceptual framework for drug design but also promote use of natural products for chemotherapy. To further evaluate the efficacy of the anticancer activity of 1'-acetoxychavicol acetate (ACA), this study investigates the underlying mechanisms by which ACA induces death of Ehrlich ascites tumor cells. ACA treatment induced loss of cell viability, and Western blotting analysis revealed that the compound stimulated tyrosine phosphorylation of several proteins with 27 and 70 kDa proteins being regulated in both dose- and time-dependent manner prior to loss of viability. Protein tyrosine kinase inhibitor herbimycin A moderately protected cells from ACA-induced toxicity. In addition, cellular glutathione and protein sulfydryl groups were also significantly reduced both dose- and time-dependently during evidence of cell death. Replenishing thiol levels by antioxidant, N-acetylcysteine (NAC), an excellent supplier of glutathione and precursor of glutathione, substantially recovered the viability loss, but the recovery being time-dependent, as late addition of NAC (at least 30 min after ACA addition to cultures) was, however, ineffective. Addition of NAC to ACA treated cultures also abolished tyrosine phosphorylation of the 27 kDa protein. These results, at least partly, identify cellular sulfhydryl groups and protein tyrosine phosphorylation as targets of ACA cytotoxicity in tumor cells. PMID:11823008

Moffatt, Jerry; Kennedy, David Opare; Kojima, Akiko; Hasuma, Tadayoshi; Yano, Yoshihisa; Otani, Shuzo; Murakami, Akira; Koshimizu, Koichi; Ohigashi, Hajime; Matsui-Yuasa, Isao

2002-02-20

102

Leiomyomatosis peritonealis disseminata (LPD) with acute ascites induced by gonadotropin-releasing hormone (GnRH) agonist: a case report.  

PubMed

Leiomyomatosis peritonealis disseminata (LPD) is a rare disorder characterized by the development of numerous leiomyomata throughout the peritoneal cavity. We present a case of a 29-year-old woman who had LPD with acute ascites induced by a GnRH agonist (Supremon; buserelin acetate nasal solution 400 micrograms/per day). We found abdominal wall leiomyomata under the left rectus muscle. Because the disorder tended to recur with acute ascites in this patient, castration was performed to eliminate the hormonal stimulation of tumor growth. We suggest postponing hormone replacement therapy post-operatively for 6 months, and we recommend close follow-up to prevent tumor recurrence and hypoestrogenism. PMID:9041767

Tseng, C W; ChangChien, C C; Lin, J W; Hsu, T Y; Chang, S Y

1996-12-01

103

Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma  

PubMed Central

Background At least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements. The components of ascites and their effects on the tumor cell microenvironment remain poorly understood. This study aimed to isolate and characterize stromal progenitor cells from the ascites of patients with epithelial ovarian adenocarcinoma (EOA). Methods Seventeen ascitic fluid samples and 7 fresh tissue samples were collected from 16 patients with EOA. The ascites samples were then cultured in vitro in varying conditions. Flow cytometry and immunocytochemistry were used to isolate and characterize 2 cell populations with different morphologies (epithelial type and mesenchymal type) deriving from the ascites samples. The in vitro cell culture model was established using conditional culture medium. Results The doubling times of the epithelial type and mesenchymal type cells were 36 h and 48 h, respectively, indicating faster growth of the epithelial type cells compared to the mesenchymal type cells. Cultured in vitro, these ascitic cells displayed the potential for self-renewal and long-term proliferation, and expressed the typical cancer stem/progenitor cell markers CD44high, CD24low, and AC133+. These cells also demonstrated high BMP-2, BMP4, TGF-?, Rex-1, and AC133 early gene expression, and expressed EGFR, integrin ?2?1, CD146, and Flt-4, which are highly associated with tumorigenesis and metastasis. The epithelial type cells demonstrated higher cytokeratin 18 and E-cadherin expression than the mesenchymal type cells. The mesenchymal type cells, in contrast, demonstrated higher AC133, CD73, CD105, CD117, EGFR, integrin ?2?1, and CD146 surface marker expression than the epithelial type cells. Conclusion The established culture system provides an in vitro model for the selection of drugs that target cancer-associated stromal progenitor cells, and for the development of ovarian cancer treatments.

2012-01-01

104

FTY720 inhibits tumor growth and angiogenesis  

Microsoft Academic Search

De novo malignancies and recurrence of tumors are some of the biggest threats to allograft recipients subjected to chronic immunosuppression. FTY720, a synthetic myriocin analogue, is an immunosuppressant that induces apoptosis of activated lymphocytes and prevents infiltration of lymphocytes into allografts, thereby prolonging allograft survival in a dose-dependent manner. Additionally, FTY720 was shown to prevent tumor growth and metastasis. Therefore,

G. Schmid; M. Guba; A. Papyan; I. Ischenko; M. Brückel; C. J. Bruns; K.-W. Jauch; C. Graeb

2005-01-01

105

Decreased IL1 RA concentration in ascites is associated with a significant improvement in overall survival in ovarian cancer  

Microsoft Academic Search

Background: Cytokines play a major role in promoting the growth and metastatic spread of cancer cells. Interleukin-1 ? and ? (IL-1) and IL-1 RA are known to be critically involved in carcinogenesis and in various solid tumors. There are limited data on expression of IL-1 ?, ? and RA in serum and ascites in patients with advanced ovarian cancer. Objectives

A. Mustea; C. Pirvulescu; D. Könsgen; E. I. Braicu; S. Yuan; P. Sun; W. Lichtenegger; J. Sehouli

2008-01-01

106

Tumor Growth Rate Approximation-Assisted Estimation  

PubMed Central

From tumor to tumor, there is a great variation in the proportion of cancer cells growing and making daughter cells that ultimately metastasize. The differential growth within a single tumor, however, has not been studied extensively and this may be helpful in predicting the aggressiveness of a particular cancer type. The estimation problem of tumor growth rates from several populations is studied. The baseline growth rate estimator is based on a family of interacting particle system models which generalize the linear birth process as models of tumor growth. These interacting models incorporate the spatial structure of the tumor in such a way that growth slows down in a crowded system. Approximation-assisted estimation strategy is proposed when initial values of rates are known from the previous study. Some alternative estimators are suggested and the relative dominance picture of the proposed estimator to the benchmark estimator is investigated. An over-riding theme of this article is that the suggested estimation method extends its traditional counterpart to non-normal populations and to more realistic cases.

An, Lihua; Ahmed, S. Ejaz; Ali, Adnan

2007-01-01

107

Microfilament association of ASGP-2, the concanavalin A-binding glycoprotein of the cell-surface sialomucin complex of 13762 rat mammary ascites tumor cells  

SciTech Connect

Microfilament-associated proteins and membrane-microfilament interactions are being investigated in microvilli isolated from 13762 rat mammary ascites tumor cells. Phalloidin shift analyses on velocity sedimentation gradients of Triton X-100 extracts of ({sup 3}H)-glucosamine-labeled microvilli identified a 120-kDa cell-surface glycoprotein associated with the microvillar microfilament core. The identification was verified by concanavalin A (Con A) blots of one- and two-dimensional (2D) electrophoresis gels of sedimented microfilament cores. By 2D-electrophoresis and lectin analyses the 120-kDa protein appeared to be a fraction of ASGP-2, the major Con A-binding glycoprotein of the sialomucin complex of the 13762 cells. This identity was confirmed by immunoblot analyses using immunoblot-purified anti-ASGP-2 from anti-membrane serum prepared against microvillar membranes. Proteolysis of the microvilli with subtilisin or trypsin resulted in an increase in the amount of ASGP-2 associated with the microfilament cores. Proteolysis of isolated microvillar membranes, which contain actin but not microfilaments, also increased the association of ASGP-2 with a Triton-insoluble, actin-containing membrane fraction. Since the Triton-insoluble membrane residue is enriched in actin-containing transmembrane complex, which contains a different glycoprotein, the authors suggest that the ASGP-2 is binding indirectly via this complex to the microfilament core in the intact microvilli.

Vanderpuye, L.A.; Carraway, C.A.C.; Carraway, K.L. (Univ. of Miami School of Medicine, FL (USA))

1988-10-01

108

Apoptosis induced by 1'-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation.  

PubMed

The efficacy of the antitumor activity of 1'-acetoxychavicol acetate (ACA), reported to be a suppressor of chemically induced carcinogenesis, was evaluated in Ehrlich ascites tumor cells. ACA treatment resulted in changes in morphology and a dose-dependent suppression of cell viability. Apoptosis, characterized by nuclear condensation, membrane blebbing, cell shrinkage and a significant induction of caspase-3-like protease activity at 8 h in a time-course study were observed. Formation of apoptotic bodies was preceded by lowering of intracellular polyamines, particularly putrescine, and both dose- and time-dependent inhibitory and activation effect by ACA on ornithine decarboxylase (ODC) and spermidine/spermine N(1)-acetyltransferase (SSAT), respectively. Administration of exogenous polyamines prevented ACA-induced apoptosis represented by a reduction in the number of apoptotic bodies and also caused reduction in the induced caspase-3-like protease activity at 8 h. These findings suggest that the anticarcinogenic effects of ACA might be partly due to perturbation of the polyamine metabolic pathway and triggering of caspase-3-like activity, which result in apoptosis. PMID:11133803

Moffatt, J; Hashimoto, M; Kojima, A; Kennedy, D O; Murakami, A; Koshimizu, K; Ohigashi, H; Matsui-Yuasa, I

2000-12-01

109

Autocrine growth factors and solid tumor malignancy.  

PubMed Central

The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images

Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

1991-01-01

110

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

Microsoft Academic Search

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

Isabelle Matte; Claudine Rancourt; Alain Piché

2010-01-01

111

Chemotherapeutic effects of 13 nitrosoureas on the LSA lymphoma ascites tumor of the C57BL mouse.  

PubMed

The LSA lymphoma of the C57BL/ym mouse has been used to test 13 nitrosoureas for cure of advanced tumors and for induced tumor resistance (ITR) of surviving animals. Tumors were initiated by intraperitoneal inoculation of 10(6) LSA cells. Controls died in 8-9 days. Five-day old tumors were defined as advanced tumors, and treatment consisted of a single dose of a nitrosourea to groups of 10 male mice, 8-9 weeks old, for each compound. The nitrosoureas used were: BCNU (NSC-40992), CCNU (NSC-79037), MeCCNU (NSC-95441), chlorozotocin (CLZ) (NSC-178248), streptozotocin (STZN) (NSC-85998) CNU (NSC-47547), FCNU (NSC-87974), GANU (NSC-254174), ACNU (NSC-245382), PCNU (NSC-95466), cis-acid (NSC-153174), 153174), NSC-88104, and GCNU (NSC-114460). The major endpoint assessed was tumor cure and was grouped as follows: (1) high (greater than or equal to 80%), achieved with BCNU, MeCCNU, CCNU, CLZ, ACNU, FCNU, PCNU, and cis-acid; (2) medium (40- less than 80%), obtained with GANU, NSC-88104, and GCNU, and (3) low or nil (less than 40%), shown by CNU and STZN. The second endpoint was treatment-induced ITR. Cured mice, i.e., those surviving over 30 days after death of controls were challenged with 10(5) LSA live cells, and survivors from this challenge were challenged with 10(7) LSA cells 1 month later. Survivors from both inocula were considered highly immune (HI). High percentages of HI mice (greater than or equal to 80%) were obtained from mice cured with MeCCNU, CCNU, ACNU, FCNU, PCNU, and NSC-88104. STZN produced 0.0% cures; the other nitrosoureas showed 33.3-75% HI mice. Cure rates and ITR appeared to be agent- and structure-related. Cure alone did not lead to the resistant state. PMID:3808571

Feola, J M; Maruyama, Y

1986-01-01

112

Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra  

Microsoft Academic Search

Blood vessel plays a crucial role in solid tumor development. It has been suggested that blocking of angiogenesis and the action of the cytokine VEGF could be possible in cancer therapy. In a screen for naturally occurring angiogenic inhibitors, we have identified an extract from the roots of Glycyrrhiza glabra, which has potent antiangiogenic and antitumor activity. The aqueous extract

M. L. Sheela; M. K. Ramakrishna; Bharathi P. Salimath

2006-01-01

113

Ethyl pyruvate administration inhibits hepatic tumor growth  

Microsoft Academic Search

EP is a potent inhibitor of HMGB1 release that has sig- nificant anti-inflammatory activities and exerts a pro- tective effect in animal models of inflammation. As in- flammation is linked to cancer growth, we hypothesized that EP would have anti-tumor activity and explored its effects in a liver tumor model. Mice injected intrapor- tally with MC38 colorectal cancer cells led

Xiaoyan Liang; A. Romo de Vivar Chavez; Nicole E. Schapiro; Patricia Loughran; Stephen H. Thorne; Andrew A. Amoscato; Herbert J. Zeh; Donna Beer-Stolz; Michael T. Lotze; Michael E. de Vera

2009-01-01

114

Interaction of tritium-labeled H 2 DIDS (4,4?-diisothiocyano-1,2,diphenyl ethane-2,2?disulfonic acid) with the ehrlich mouse ascites tumor cell  

Microsoft Academic Search

Summary The experiments reported in this paper were undertaken to explore the interaction of tritiated H2DIDS (4,4'-diisothiocyano-1,2,diphenyl ethane-2,2'-disulfonic acid) with Ehrlich ascites tumor cells. Addition of (3H)H2DIDS to tumor cell suspension at 21°C, pH 7.3, resulted in: (i) rapid reversible binding which increased with time and (ii) inhibition of sulfate transport. Tightly bound H2DIDS, i.e., reagent not removed by cell

Charles Levinson; Rebecca J. Corcoran; Ellen H. Edwards

1979-01-01

115

Blood porphyrin luminescence and tumor growth correlation  

NASA Astrophysics Data System (ADS)

Fluorescence technique appears very important for the diagnosis of cancer. Fluorescence detection has advantages over other light-based investigation methods: high sensitivity, high speed, and safety. Renal cell carcinoma (RCC) accounts for approximately 3% of new cancer incidence and mortality in the United States. Unfortunately many RCC masses remain asymptomatic and nonpalpable until they are advanced. Diagnosis and localization of early carcinoma play an important role in the prevention and curative treatment of RCC. Certain drugs or chemicals such as porphyrin derivatives accumulate substantially more in tumors than normal tissues. The autofluorescence of blood porphyrin of healthy and tumor induced male SCID mice was analyzed using fluorescence and excitation spectroscopy. A significant contrast between normal and tumor blood could be established. Blood porphyrin fluorophore showed enhanced fluorescence band (around 630 nm) in function of the tumor growth. This indicates that either the autofluorescence intensity of the blood fluorescence may provide a good parameter for the "first approximation" characterization of the tumor stage.

Courrol, Lilia Coronato; Rodrigues de Oliveira Silva, Flávia; Bellini, Maria Helena; Mansano, Ronaldo Domingues; Schor, Nestor; Vieira, Nilson Dias, Jr.

2007-02-01

116

Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis.  

PubMed

Claudin-3 (CLDN3) is a tight junction protein that is overexpressed in 90% of ovarian tumors. Previous in vitro studies have indicated that CLDN3 overexpression promotes the migration, invasion, and survival of ovarian cancer cells. Here, we investigated the efficacy of lipidoid-formulated CLDN3 siRNA in 3 different ovarian cancer models. Intratumoral injection of lipidoid/CLDN3 siRNA into OVCAR-3 xenografts resulted in dramatic silencing of CLDN3, significant reduction in cell proliferation, reduction in tumor growth, and a significant increase in the number of apoptotic cells. Intraperitoneal injection of lipidoid-formulated CLDN3 siRNA resulted in a substantial reduction in tumor burden in MISIIR/TAg transgenic mice and mice bearing tumors derived from mouse ovarian surface epithelial cells. Ascites development was reduced in CLDN3 siRNA-treated mice, suggesting the treatment effectively suppressed metastasis. Toxicity was not observed after multiple i.p. injections. Importantly, treatment of mice with nonimmunostimulatory 2'-OMe modified CLDN3 siRNA was as effective in suppressing tumor growth as unmodifed siRNA. These results suggest that lipidoid-formulated CLDN3 siRNA has potential as a therapeutic for ovarian cancer. PMID:19208807

Huang, Yu-Hung; Bao, Yunhua; Peng, Weidan; Goldberg, Michael; Love, Kevin; Bumcrot, David A; Cole, Geoffrey; Langer, Robert; Anderson, Daniel G; Sawicki, Janet A

2009-02-10

117

Connective tissue growth factor in tumor pathogenesis  

PubMed Central

Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors.

2012-01-01

118

Ascites in poultry  

Microsoft Academic Search

Research on ascites occurring in meat?type chickens reared at moderate and low altitude has shown that the pathogenesis is similar to that of the high altitude disease. Pulmonary hypertension (PH) caused by increased blood flow or increased resistance to flow in the lung results in right ventricular hypertrophy (RVH), valvular insufficiency, increased venous pressure and ascites. The structure of the

Richard J. Julian

1993-01-01

119

Evidence that repair and expression of potentially lethal damage cause the variations in cell survival after x irradiation observed through the cell cycle in Ehrlich ascites tumor cells  

SciTech Connect

The survival of synchronously growing Ehrlich ascites tumor cells (EAT cells) was measured after x irradiation in various stages of the cell cycle. Cells at the beginning of S or in G2 + M phase showed a high level of killing, whereas cells irradiated in G1 or in the middle of S phase were more resistant. These changes resulted from a change in the survival curve shoulder width (D/sub q/) as cells passed through the cell cycle, and the mean lethal dose (D/sub 0/) remained practically unchanged (0.8 +- 0.05 Gy). When synchronization of the cell population was further sharpened using nocodazole, exponential survival curves were obtained at the beginning of S phase and at mitosis with a D/sub 0/ = 0.8 Gy. When cells (in all stages) were incubated in balanced salt solution for 6 h after irradiation, repair of potentially lethal damage (PLD) was observed, resulting in an increase in D/sub q/, while D/sub 0/ remained constant. Treatment of the cells after irradiation with either caffeine or ..beta..-arabinofuranosyladenine (..beta..-araA) or hypertonic medium resulted in an expression of PLD and reduced the D/sub q/ of the survival curve. We measured the rate of the loss of sensitivity of these treatments that we assume reflects the rate of repair of PLD. Results indicate that the shoulder width D/sub q/ of the survival curve in cells irradiated at various stages of the cell cycle results from repair of PLD. It is suggested that the variations observed in cell survival through the cell cycle might reflect variations in the final amount of PLD either repaired or expressed as the cells progress through stages of the cell cycle.

Iliakis, G.; Nuesse, M.

1983-07-01

120

Management of refractory ascites.  

PubMed

Ascites that does not respond or recurs after high-dose diuresis and sodium restriction should be considered refractory ascites. As cirrhosis advances, the escaping fluid overwhelms the lymphatic return. Decrease in renal plasma flow leads to increased sodium reabsorption at the proximal tubule leading to decreased responsiveness to loop diuretics and mineralocorticoid antagonists, which work distally. These complex hemodynamic alterations lead to refractory ascites. In refractory ascites, high-dose diuresis (400 mg of spironolactone and 160 mg of furosemide) and sodium restriction (<90 mmol/d) result in inadequate weight loss and sub optimal sodium excretion (<78 mmol/d). Further use of diuretics is limited by complications such as encephalopathy, azotemia, renal insufficiency, hyponatremia, and hyperkalemia. Therapy for refractory ascites is limited. The available therapies are repeated large volume paracentesis (LVP), transjugular intrahepatic portosystemic shunts, peritoneovenous shunts, investigational medical therapies, and liver transplantation. LVP with concomitant volume expanders is the initial treatment of choice. Transjugular intrahepatic portosystemic seems to be superior to LVP in reducing the need for repeated paracentesis and improves the quality of life. Several treatments that act at different steps in the pathogenesis of ascites are investigational, and some show promising results. Splanchnic and peripheral vasoconstrictors (Octreotide, Midodrine, and Terlipressin) increase effective arterial volume and decrease activation of the renin-angiotensin system with resultant increase in renal sodium excretion. Clonidine when given with spironolactone has been shown to cause rapid mobilization of ascites by significantly decreasing the sympathetic activity and renin-aldosterone levels. Natural aquaretics and synthetic V2 receptor antagonists (satavaptan) are being evaluated for mobilization of ascites by increasing the excretion of solute-free water. Liver transplantation remains the only definitive therapy for refractory ascites. Because refractory ascites is a poor prognostic sign, liver transplantation should be considered and incorporated early in the treatment plan. PMID:21192246

Singhal, Shashideep; Baikati, Kiran K; Jabbour, Ibrahim I; Anand, Sury

2012-03-01

121

Generation of lymphokine-activated killer cells in human ovarian carcinoma ascitic fluid: Identification of transforming growth factor-? as a suppressive factor  

Microsoft Academic Search

Summary The effect of cell-free ascitic fluid from patients with epithelial ovarian carcinoma on the generation of lymphokine-activated killer cells (LAK) was compared to the activity generated in control medium containing 10% fetal bovine serum, using Daudi target cells. Samples of ascitic fluid from nine different patients tested inhibited LAK generation. Suppressive activity was evident as early as 24 h

Hal Hirte; David A. Clark

1991-01-01

122

Ascites fluid containing monoclonal antibody (EGFR1) to the epidermal growth factor (EGF) receptor (EGFR) stimulates tyrosine phosphorylation in solubilized placental membranes  

SciTech Connect

Ascites fluid containing EGFR1 antibody precipitated EGFR prelabelled by phosphorylating human placental membranes with EGF and (..gamma..-/sup 32/P)ATP. The ascites fluid (at 1:100 dilution) was also found to stimulate phosphorylation of the solubilized placental membranes EGFR and the 35 kDa Ca/sup 2 +/-dependent substrate of the EGFR/kinase from placental membrane. In intact membranes, ascites fluid produced a small but noticeable stimulation of EGFR autophosphorylation. In solubilized membrane preparations, ascites fluid and EGF produced a comparable stimulation of phosphorylation both of the receptor and of pp35. The effect of EGF and ascites fluid appeared to be additive. Since EGFR1 does not inhibit the binding of EGF to the receptor, the data suggest that the antibody stimulates the receptor kinase activity by interacting with a site distinct from the EGF-binding site; the antibody effect is unmasked by receptor solubilization.

Michiel, D.F.; Hollenberg, M.D.

1986-03-05

123

Inhibition of tumor growth and leukocyte alterations in splenectomized mice treated with a PCj3 polysaccharide.  

PubMed

The effect of a polysaccharide (PCj3), isolated from the ascomycete "Cyttaria johowii" was studied on the growth of the ascitic Sarcoma 180 (S180) inoculated subcutaneously in BALB/c mice which had been previously splenectomized. The leukocyte alterations in peripheral blood were analyzed simultaneously, and the percentage of cells with C3b receptors in the population of peritoneal cavity was evaluated through the E (IgM)C rosette technique. A significant inhibition of tumor growth was observed in the splenectomized mice treated with PCj3 with respect to the untreated splenectomized and to the control group, which had not been splenectomized. It was also found that the first group acquired relative resistance to the later inocula of the ascitic S180 via i.p. On the day 8 after the tumor inoculation a marked lymphocytosis increased up to 224% in PCj3 treated mice and only to 59% in untreated splenectomized mice. The increase in the controls, that had not been splenectomized was 18%. With regard to the number of neutrophils a significant difference was found between both splenectomized groups on the 8 day, corresponding the highest values to the group treated with PCj3. No differences were observed on the 25 day even though the neutrophilia was maintained. The percentage of cells with C3b receptors in population of peritoneal cavity was significantly lower in mice treated with PCj3, although an increase in the number of E (IgM)C attached per cell and ingestion of system were observed. PMID:3843456

Rumi, L S; Chasseing, N A; Couto, A; de Lederkremer, R M

1985-01-01

124

Congenital chylous ascites  

PubMed Central

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

Romanska-Kita, Justyna; Borszewska-Kornacka, Maria Katarzyna; Dobrzanska, Anna; Rudzinska, Iwona; Czech-Kowalska, Justyna; Wawrzoniak, Tomasz

2011-01-01

125

Nonlinear simulation of the effect of microenvironment on tumor growth  

Microsoft Academic Search

In this paper, we present and investigate a model for solid tumor growth that incorporates features of the tumor microenvironment. Using analysis and nonlinear numerical simulations, we explore the effects of the interaction between the genetic characteristics of the tumor and the tumor microenvironment on the resulting tumor progression and morphology. We find that the range of morphological responses can

Paul Macklin; John Lowengrub

2007-01-01

126

INFLUENCE OF GLUTARALDEHYDE AND/OR OSMIUM TETROXIDE ON CELL VOLUME, ION CONTENT, MECHANICAL STABILITY, AND MEMBRANE PERMEABILITY OF EHRLICH ASCITES TUMOR CELLS  

PubMed Central

Effects of fixation with glutaraldehyde (GA), glutaraldehyde-osmium tetroxide (GA-OsO4), and osmium tetroxide (OsO4) on ion and ATP content, cell volume, vital dye staining, and stability to mechanical and thermal stress were studied in Ehrlich ascites tumor cells (EATC). Among variables investigated were fixation time, fixative concentration, temperature, osmolality of the fixative agent and buffer, total osmolality of the fixative solution, osmolality of the postfixation buffer, and time of postfixation treatment in buffer (Sutherland, R. M., et al. 1967. J. Cell Physiol. 69:185.). Rapid loss of potassium, exchangeable magnesium, and ATP, and increase of vital dye uptake and electrical conductivity occurred with all fixatives studied. These changes were virtually immediate with GA-OsO4 or OsO4 but slower with GA (in the latter case they were dependent on fixative temperature and concentration) (Foot, N. C. 1950. In McClung's Handbook of Microscopical Technique. 3rd edition. 564.). Total fixative osmolality had a marked effect on cell volume with OsO4 but little or no effect with GA or GA-OsO4. Osmolality of the buffer had a marked effect on cell volume with OsO4, whereas with GA or GA-OsO4 it was only significant at very hypotonic buffer osmolalities. Concentration of GA had no effect on cell volume. Osmolality of the postfixation buffer had little effect on cell volume, and duration of fixation or postfixation treatment had no effect with all fixatives. Freezing and thawing or centrifugal stress (up to 100,000 g) had little or no effect on cell volume after all fixatives studied. Mechanical stress obtained by sonication showed that OsO4 alone produced poor stabilization and that GA fixation alone produced the greatest stabilization. The results indicate that rapid membrane permeability changes of EATC follow fixative action. The results are consistent with known greater stabilizing effects of GA on model protein systems since cells were also rendered relatively stable to osmotic stress during fixation, an effect not noted with OsO4. After fixation with GA and/or OsO4 cells were stable to osmotic, thermal, or mechanical stress; this is inconsistent with several earlier reports that GA-fixed cells retain their osmotic properties.

Penttila, Antti; Kalimo, Hannu; Trump, Benjamin F.

1974-01-01

127

Ascites in chickens. Oxygen consumption and requirement related to its occurrence  

Microsoft Academic Search

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 ascites, during a growth period of approximately six weeks, nowadays vary between 2 and 10 percent. This depends

C. W. Scheele

1996-01-01

128

Malignant ascites: pathophysiology and treatment.  

PubMed

Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal tumors. It is a primary cause of morbidity and raises several treatment challenges. MA has several symptoms, producing a significant reduction in the patient's quality of life: loss of proteins and electrolyte disorders cause diffuse oedema, while the accumulation of abdominal fluid facilitates sepsis. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk. A Pubmed, Medline, Embase, and Cochrane Library review of medical, interventional and surgical treatments of MA has been performed. Medical therapy, primarily paracentesis and diuretics, are first-line treatments in managing MA. Paracentesis is widely adopted but it is associated with significant patient discomfort and several risks. Diuretic therapy is effective at the very beginning of the disease but efficacy declines with tumor progression. Intraperitoneal chemotherapy, targeted therapy, immunotherapy and radioisotopes are promising medical options but their clinical application is not yet completely elucidated, and further investigations and trials are necessary. Peritoneal-venous shunts are rarely used due to high rates of early mortality and complications. Laparoscopy and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed as palliative therapy. Literature on the use of laparoscopic HIPEC in MA includes only reports with small numbers of patients, all showing successful control of ascites. To date, none of the different options has been subjected to evidence-based clinical trials and there are no accepted guidelines for the management of MA. PMID:22460778

Cavazzoni, Emanuel; Bugiantella, Walter; Graziosi, Luigina; Franceschini, Maria Silvia; Donini, Annibale

2012-03-31

129

Growth patterns of microscopic brain tumors  

NASA Astrophysics Data System (ADS)

Highly malignant brain tumors such as glioblastoma multiforme form complex growth patterns in vitro in which invasive cells organize in tenuous branches. Here, we formulate a chemotaxis model for this sort of growth. A key element controlling the pattern is homotype attraction, i.e., the tendency for invasive cells to follow pathways previously explored. We investigate this in two ways: we show that there is an intrinsic instability in the model, which leads to branch formation. We also give a discrete description for the expansion of the invasive zone, and a continuum model for the nutrient supply. The results indicate that both strong heterotype chemotaxis and strong homotype chemoattraction are required for branch formation within the invasive zone. Our model thus can give a way to assess the importance of the various processes, and a way to explore and analyze transitions between different growth regimes.

Sander, Leonard M.; Deisboeck, Thomas S.

2002-11-01

130

Pancreatic cancers require autophagy for tumor growth.  

PubMed

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and cell lines show elevated autophagy under basal conditions. Genetic or pharmacologic inhibition of autophagy leads to increased reactive oxygen species, elevated DNA damage, and a metabolic defect leading to decreased mitochondrial oxidative phosphorylation. Together, these ultimately result in significant growth suppression of pancreatic cancer cells in vitro. Most importantly, inhibition of autophagy by genetic means or chloroquine treatment leads to robust tumor regression and prolonged survival in pancreatic cancer xenografts and genetic mouse models. These results suggest that, unlike in other cancers where autophagy inhibition may synergize with chemotherapy or targeted agents by preventing the up-regulation of autophagy as a reactive survival mechanism, autophagy is actually required for tumorigenic growth of pancreatic cancers de novo, and drugs that inactivate this process may have a unique clinical utility in treating pancreatic cancers and other malignancies with a similar dependence on autophagy. As chloroquine and its derivatives are potent inhibitors of autophagy and have been used safely in human patients for decades for a variety of purposes, these results are immediately translatable to the treatment of pancreatic cancer patients, and provide a much needed, novel vantage point of attack. PMID:21406549

Yang, Shenghong; Wang, Xiaoxu; Contino, Gianmarco; Liesa, Marc; Sahin, Ergun; Ying, Haoqiang; Bause, Alexandra; Li, Yinghua; Stommel, Jayne M; Dell'antonio, Giacomo; Mautner, Josef; Tonon, Giovanni; Haigis, Marcia; Shirihai, Orian S; Doglioni, Claudio; Bardeesy, Nabeel; Kimmelman, Alec C

2011-03-15

131

Switching between control and phytohaemagglutinin-containing diets affects growth of Krebs II ascites cells and produces differences in the levels of putrescine, spermidine and spermine  

Microsoft Academic Search

Almost twice as many ascites tumour cells were recovered from mice pre-fed for 3 days on a lactalbumin (La)-based control diet, injected with Krebs II ascites cells and then maintained on the same diet for a further 8 days, when compared with mice fed on a phytohaemagglutinin-containing (PHA) diet for the whole period. A dietary switch on the day of

Ian F. Pryme; Susan Bardocz; George Grant; Tracey J. Duguid; David S. Brown; Arpad Pusztai

1995-01-01

132

Disaggregation and invasion of ovarian carcinoma ascites spheroids  

PubMed Central

Background Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient. Methods Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test. Results Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype. Conclusion We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.

Burleson, Kathryn M; Boente, Matthew P; Pambuccian, Stefan E; Skubitz, Amy PN

2006-01-01

133

Study on the therapeutic effects of low-energy laser therapy combined with cyclophosphamide on the mouse ascites sarcoma  

NASA Astrophysics Data System (ADS)

By using the experimental model of mouse S180 ascites sarcoma, the feasibility and mechanism of low-energy laser therapy combined with the traditional antitumor drug of cyclophosphamide in the treatment of malignant tumors were discussed. The S180 ascites sarcoma suffering BALB/c mice were irradiated upon the Harder's glands with the dosages of 11.00, 14.67 and 22.00 J/cm2 respectively, and/or injected with CYT intraperitoneally to evaluate the therapeutic effects of CYT/LELT combination on malignant tumors. The three dosages of LELT combined with CYT all showed remarkably therapeutic effects on the mouse S180 ascites sarcoma. Comparatively, the dosage of 14.67J/cm2 LELT combined with CYT showed the most ideal therapeutic effects and the survival time was up to 20.80 days, and the life prolongation ratio was 33.33% which was remarkably higher than those of the CYT and tumor control groups. CYT/LELT combined therapy had remarkably inhibiting effects on the mice ascites growth because of the existence of CYT.

Wang, Hongbin; Huang, Baoxu; Liu, Huanqi; Qu, Zhina; Liu, Xifeng; Cheng, Shaohui

2004-07-01

134

Potential new way to suppress tumor growth  

Cancer.gov

Researchers at the University of California, San Diego School of Medicine (home of the Moores Comprehensive Cancer Center), with colleagues at the University of Rochester Medical Center, have identified a new mechanism that appears to suppress tumor growth, opening the possibility of developing a new class of anti-cancer drugs. Writing in this week’s online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), the team reports that a particular form of a signaling protein called STAT5A stabilizes the formation of heterochromatin (a form of chromosomal DNA), which in turn suppresses the ability of cancer cells to issue instructions to multiply and grow.

135

Properties of Tumor Spheroid Growth Exhibited by Simple Mathematical Models  

PubMed Central

Solid tumors, whether in vitro or in vivo, are not an undifferentiated mass of cells. They include necrotic regions, regions of cells that are in a quiescent state (either slowly growing or not growing at all), and regions where cells proliferate rapidly. The decision of a cell to become quiescent or proliferating is thought to depend on both nutrient and oxygen availability and on the presence of tumor necrosis factor, a substance produced by necrotic cells that somehow inhibits the further growth of the tumor. Several different models have been suggested for the basic growth rate of in vitro tumor spheroids, and several different mechanisms are possible by which tumor necrosis factor might halt growth. The models predict the trajectory of growth for a virtual tumor, including proportions of the various components during its time evolution. In this paper we look at a range of hypotheses about basic rates tumor growth and the role of tumor necrotic factor, and determine what possible tumor growth patterns follow from each of twenty-five reasonable models. Proliferating, quiescent and necrotic cells are included, along with tumor necrosis factor as a potential inhibitor of growth in the proliferating pool and two way exchange between the quiescent and proliferating pools. We show that a range of observed qualitative properties of in vitro tumor spheroids at equilibrium are exhibited by one particular simple mathematical model, and discuss implications of this model for tumor growth.

Wallace, Dorothy I.; Guo, Xinyue

2013-01-01

136

Hereditary pancreatitis presenting with ascites.  

PubMed Central

We report a case of an adolescent girl who presented with painless massive ascites secondary to chronic pancreatitis and a ductal fistula. The diagnosis was delayed and an unnecessary laparotomy was performed, as initial evaluation of ascites did not include measurement of serum and ascitic amylase. Evidence of pancreatic abnormalities in asymptomatic relatives suggested an underlying hereditary pancreatitis. Hereditary pancreatitis presenting as pancreatic ascites, to our knowledge, has not been described previously.

Rao, S. S.; Riley, S. A.; Foster, P. N.; Losowsky, M. S.; Stone, W. D.

1986-01-01

137

Diethylstilbestrol inhibits tumor growth and prolactin production in rat pituitary tumors.  

PubMed Central

Treatment of rats bearing transplantable MtT/W15 tumors with 10 mg of diethylstilbestrol (DES) for 3 weeks led to inhibition of tumor growth. The inhibition of tumor growth was reversible after removal of the DES. Histologic examination revealed decreased mitotic activity; however, DES did not produce cell necrosis. Concomitantly, the anterior pituitary glands of animals treated with DES became hyperplastic, with an increased number of prolactin (PRL)-producing cells. DES resulted in a decreased number of PRL cells in the tumor and decreased serum PRL/tumor weight, compared with that of control rats. There was also an increase in the number of growth hormone (GH) tumor cells and an increased serum GH/tumor weight. 17 beta-Estradiol had an effect similar to that of DES, while progesterone did not inhibit tumor growth or cause pituitary cell hyperplasia. Ovariectomy resulted in a decrease in the tumor growth rate, compared with that of control animals, suggesting that the MtT/W 15 tumors are relatively dependent on estrogens for optimal growth. These results indicate that DES inhibition of MtT/W 15 tumor growth is an excellent model for study of the mechanism of the inhibition of tumor growth and the modification of GH and PRL expression by the tumor cells. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

Lloyd, R. V.; Landefeld, T. D.; Maslar, I.; Frohman, L. A.

1985-01-01

138

Pea lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cycle arrest in vivo in mice.  

PubMed

Pea (Pisum sativum L.) lectin is known to have interesting pharmacological activities and of great interest on biomedical research. In the current research pea lectin was purified followed by ion exchange chromatography on DEAE column and affinity chromatography on glucose-sepharose column. The lectin shown 11.7-84% inhibitory effect against Ehrlich ascites carcinoma (EAC) cells at the concentration range of 8-120?g/ml in RPMI 1640 medium as determined by MTT assay. Pea lectin was also shown 63% and 44% growth inhibition against EAC cells in vivo in mice when administered 2.8mg/kg/day and 1.4mg/kg/day (i.p.) respectively for five consequent days. When Pea lectin injected into the EAC bearing mice for 10 days its significantly increased the hemoglobin and RBC with the decreased of WBC levels toward the normal. Apoptotic cell morphological change of the treated EAC cells of mice was determined by fluorescence and optical microscope. Interestingly, cell growth inhibition of the lectin was significantly reduced in the presence of caspase inhibitors. Treatment with the lectin caused the cell cycle arrest at G2/M phase of EAC cells which was determined by flow cytometry. The expression of apoptosis-related genes, Bcl-2, Bcl-X and Bax was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Intensive increase of Bax gene expression and totally despaired of Bcl-2 and Bcl-X gene expression were observed in the cells treated with Pea lectin for five consecutive days. PMID:23867650

Kabir, Syed Rashel; Nabi, Md Mahamodun; Haque, Ariful; Zaman, Rokon Uz; Mahmud, Zahid Hayat; Reza, Md Abu

2013-07-16

139

Isolated fetal and neonatal ascites: report of two cases.  

PubMed

Neonatal ascites is an uncommon problem that may be caused by a number of etiologies including diseases of genitourinary system and gastrointestinal system, cardiac disease, hepatic disease, systemic infection such as TORCH or parvovirus, chylous, ovarian cause, inborn error of metabolism and idiopathic. We reported two cases of neonatal ascites, one was caused by cytomegalovirus and no obvious causes could be detected in the second one. The ascites were diagnosed by prenatal ultrasound at the gestational age of 25 weeks and 37 weeks respectively and were resolved spontaneously after birth. One-year follow-up of both cases revealed normal growth and development. No recurrent ascites could be detected by abdominal sonography except for evidence of mild hepatomegaly that was noted in case 1. Thus, isolated fetal and neonatal ascites without other concomitant abnormalities were diagnosed, a separate entity from non-immune hydrops fetalis with excellent prognosis. PMID:11431863

Chou, Y Y; Huang, H C; Liu, H C; Chung, M Y; Huang, C B

140

Inhibition of tumor growth by elimination of granulocytes  

PubMed Central

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth.

1995-01-01

141

Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.  

PubMed

Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. PMID:10502827

Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K

1999-10-01

142

Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes  

Microsoft Academic Search

Exosomes are membrane vesicles that are released from many different cell types. Tumor derived-exosomes play a role in immune suppression. We hypothesized that in ovarian carcinoma patients exosomes initially produced at the local abdominal site may become systemic. We examined paired samples of ascites and blood from ovarian carcinoma patients for the presence of exosomes. We also studied the requirements

Sascha Keller; Anne-Kathleen König; Frederik Marmé; Steffen Runz; Silke Wolterink; Dominique Koensgen; Alexander Mustea; Jalid Sehouli; Peter Altevogt

2009-01-01

143

Fibroblast growth factors are required for efficient tumor angiogenesis.  

PubMed

Although the function of vascular endothelial growth factor in the induction of tumor angiogenesis is well understood, the role of a second group of angiogenic factors, the fibroblast growth factors (FGFs), remains elusive. We used a recombinant adenovirus expressing soluble FGF receptor (AdsFGFR) to interfere with FGF function in tumor angiogenesis. AdsFGFR repressed endothelial cell proliferation in vitro and inhibited tumor angiogenesis in an ex vivo bioassay, in which endothelial cells were cocultured with angiogenic tumor biopsies in a collagen gel. Moreover, AdsFGFR repressed tumor angiogenesis and hence tumor growth in vivo in allograft transplantation experiments. Whereas adenoviral expression of a soluble form of VEGF receptor 1 (AdsFlt) predominantly affected the initiation of tumor angiogenesis, soluble FGF receptor (sFGFR) appeared to impair the maintenance of tumor angiogenesis. The combination of sFGFR and soluble Flt exhibited a synergistic effect in the repression of tumor growth. Finally, i.v. injection of AdsFGFR resulted in a dramatic repression of tumor growth in a transgenic mouse model of pancreatic beta cell carcinogenesis. Similar to control infections with AdsFlt, tumor-associated vessel density was decreased, indicating that the expression of sFGFR impaired tumor angiogenesis. These data indicate that FGFs play a critical role in tumor angiogenesis. PMID:11156426

Compagni, A; Wilgenbus, P; Impagnatiello, M A; Cotten, M; Christofori, G

2000-12-15

144

Pancreatic ascites in childhood.  

PubMed

A case is reported of pancreatic ascites in a 14-year-old girl who had acute and chronic pancreatitis associated with pancreatic duct stones and a ruptured pancreatic duct. Abdominal erythema ab igne was considered to be an important physical sign of genuine severe abdominal pain. PMID:2144996

Mucklow, E S; Freeman, N V

1990-06-01

145

Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing rats supplemented with fish oil rich in EPA and DHA.  

PubMed

We investigated the effect of fish oil (FO) supplementation on tumor growth, cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma (PPAR?), 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 (3×107 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-??CT 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 PPAR? (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 PPAR?, 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. PMID:24036940

Borghetti, G; Yamazaki, R K; Coelho, I; Pequito, D C T; Schiessel, D L; Kryczyk, M; Mamus, R; Naliwaiko, K; Fernandes, L C

2013-08-30

146

Eradication of intractable malignant ascites by abdominocentesis, reinfusion of concentrated ascites, and adoptive immunotherapy with dendritic cells and activated killer cells in a patient with recurrent lung cancer: a case report  

PubMed Central

Introduction Malignant ascites is often a sign of a terminal stage in several malignant diseases. To control ascites, drainage and intra-abdominal chemotherapy are often used in those patients but eradication of ascites is difficult and prognosis is poor. Case presentation A 55-year-old woman was admitted to our hospital on 26 January 2007 with dyspnea, abdominal distention and oliguria. Abdominocentesis revealed peritoneal carcinomatosis resulting from abdominal recurrence from lung cancer. To alleviate the dyspnea and abdominal distention, we drained the ascites aseptically and infused them intravenously back into the patient after removal of tumor cells by centrifugation, and then concentration by apheresis. After the drainage of ascites, we intraperitoneally infused activated killer cells and dendritic cells from the patient's tumor-draining lymph nodes, together with 4.5 × 105U interleukin-2 in 50 ml saline by 2.1 ml/hour infuser balloon. Drastic decreases in the tumor cell count and in ascite retention were observed after several courses of ascites drainage, intravenous infusion and intraperitoneal immunotherapy. The plasma protein level was maintained during the treatment notwithstanding the repeated drainage of ascites. Cell surface marker analysis, cytotoxic activities against autologous tumor cells and interferon-gamma examination of ascites suggested the possibility that these effects were mediated by immunological responses of activated killer cells and dendritic cells infused intraperitoneally. Conclusion Combination of local administration of immune cells and infusion of concentrated cell free ascites may be applicable for patients afflicted with refractory ascites.

Kimura, Hideki; Iizasa, Toshihiko; Ishikawa, Aki; Yoshino, Mitsuru; Shingyouji, Masato; Kimura, Masaki; Hirata, Tetushi; Odaka, Akiko; Matsubayasi, Keiko

2008-01-01

147

Proinvasive properties of ovarian cancer ascites-derived membrane vesicles.  

PubMed

Malignant ovarian ascites are rich in cellular components, membrane-bound vesicles, and soluble proteins. This study focused on the structure of membrane-bound vesicles and their ability to promote invasion in cultured malignant ovarian epithelium. Membrane vesicles were derived from women with stage I-IV malignant ovarian ascites and from nonmalignant gynecologic ascites. Isolated vesicles were characterized by immunofluorescence and Western blot analysis. Using gel zymography for matrix metalloproteinase (MMP) detection and a colorimetric assay for urokinase-type plasminogen activator (uPA) analysis, we analyzed the proteinase activities of MMP-2, MMP-9, and uPA from the prepared vesicles, whole cells isolated from ascites, and the cell-free ultracentrifuged supernatant. The invasiveness of established cultured malignant ovarian epithelium on addition of ascites-derived vesicles was tested using a Matrigel-based invasion assay. Fractionation of malignant ascites revealed that extracellular matrix-degrading proteinases including MMPs and uPA are localized preferentially in membrane vesicles. All malignant vesicles tested, regardless of cancer stage, stimulated invasion. Furthermore, the combination of ovarian cancer cells and membrane vesicles resulted in greater uPA activation than that of cells or vesicles alone. Membrane vesicles from malignant ascites were also found to contain activated MMP-2, MMP-9, and uPA. Our data suggest that vesicle-stimulated proteinase activation leads to increased extracellular matrix degradation, which may facilitate tumor cell invasion and metastasis. PMID:15466198

Graves, Laura E; Ariztia, Edgardo V; Navari, Jason R; Matzel, Heather J; Stack, M Sharon; Fishman, David A

2004-10-01

148

Dna Content of Rat Ascites Hepatoma Cells with Hypo- and Hyper-Diploid Number of Chromosomes.  

National Technical Information Service (NTIS)

There is no exact parallelism between the chromosome number and DNA content per nucleus in malignant tumors, when studied with different tumors, though they are derivations from a common normal ancestry, the liver cell of rats. Ascites hepatoma cells, eve...

H. Isaka

1968-01-01

149

Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites?  

PubMed

Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth factor (VEGF) by tumor cells has been identified as a main factor promoting the i.p. secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. Here, we review preclinical and clinical data supporting this hypothesis. We show current evidence suggesting that the i.p. application of the anti-VEGF antibody bevacizumab, which is already in use as an i.v. therapeutic drug for a variety of tumors, might represent an effective way to prevent local fluid accumulation. Because such an effect would result in significant relief for patients, future clinical studies should stringently assess the effectiveness of this targeted therapy for the treatment of malignant i.p. effusions. PMID:20008305

Kobold, Sebastian; Hegewisch-Becker, Susanna; Oechsle, Karin; Jordan, Karin; Bokemeyer, Carsten; Atanackovic, Djordje

2009-12-11

150

Caloric restriction reduces growth of mammary tumors and metastases  

PubMed Central

We investigated the effects of caloric restriction (CR) on growth of tumors and metastases in the 4T1 mammary tumor model and found that CR, compared with normal diet, reduced the growth of mammary tumors and metastases and the total number of metastases that originated both spontaneously from the primary tumor and also experimentally from i.v. injection of the tumor cells. CR also decreased proliferation and angiogenesis and increased apoptosis in tumors. CR reduced levels of insulin, leptin, insulin-like growth factor 1, insulin-like growth factor binding protein 3 and increased adiponectin in tumors. We also demonstrated that tumors from CR mice possessed lower levels of transforming growth factor-?, lower intratumor deposition of collagen IV and reduced invasiveness due to a decrease in tumor secretion of active matrix metalloproteinase 9. Our results suggest that CR-induced metabolic and signaling changes affect the stroma and the tumor cells resulting in a microenvironment that prevents proliferation of breast tumors and their metastases.

De Lorenzo, Mariana S.; Baljinnyam, Erdene; Vatner, Dorothy E.; Abarzua, Patricio; Vatner, Stephen F.; Rabson, Arnold B.

2011-01-01

151

Caloric restriction reduces growth of mammary tumors and metastases.  

PubMed

We investigated the effects of caloric restriction (CR) on growth of tumors and metastases in the 4T1 mammary tumor model and found that CR, compared with normal diet, reduced the growth of mammary tumors and metastases and the total number of metastases that originated both spontaneously from the primary tumor and also experimentally from i.v. injection of the tumor cells. CR also decreased proliferation and angiogenesis and increased apoptosis in tumors. CR reduced levels of insulin, leptin, insulin-like growth factor 1, insulin-like growth factor binding protein 3 and increased adiponectin in tumors. We also demonstrated that tumors from CR mice possessed lower levels of transforming growth factor-?, lower intratumor deposition of collagen IV and reduced invasiveness due to a decrease in tumor secretion of active matrix metalloproteinase 9. Our results suggest that CR-induced metabolic and signaling changes affect the stroma and the tumor cells resulting in a microenvironment that prevents proliferation of breast tumors and their metastases. PMID:21665891

De Lorenzo, Mariana S; Baljinnyam, Erdene; Vatner, Dorothy E; Abarzúa, Patricio; Vatner, Stephen F; Rabson, Arnold B

2011-06-10

152

Tumor-derived Expression of Vascular Endothelial Growth Factor Is a Critical Factor in Tumor Expansion and Vascular Function1  

Microsoft Academic Search

There is considerable controversy concerning the importance of tumor- derived angiogenic factors to the neovascularization of solid tumors. Tumor, endothelial, and stromal expression of vascular endothelial growth factor (VEGF) have been hypothesized to be critical for tumor angiogenesis. To determine the relative contribution of tumor versus nontransformed tissue expression of VEGF to tumor growth, we used gene targeting and cre-loxP

Jeremy Grunstein; W. Gregory Roberts; Odile Mathieu-Costello; Douglas Hanahan; Randall S. Johnson

1999-01-01

153

Tumor growth inhibition by ammonium chloride-induced acidosis.  

PubMed

Ammonium chloride-induced metabolic acidosis decreases the growth of various experimental tumors. Spleen exhibits the same effects. There is a sex factor which seems to affect the growth of both tumor and spleen. The observed tumor inhibition appears to be related to a systemic impairment of the anabolic mechanisms. The decrease in tumor calcium suggests that this element may play a role in the tissue growth. The possible implication of cell membrane changes and of a block in glycolysis in the acidosis effects are discussed. PMID:51839

Anghileri, L J

1975-10-01

154

Fibroblast Growth Factors Are Required for Efficient Tumor Angiogenesis1  

Microsoft Academic Search

Although the function of vascular endothelial growth factor in the induction of tumor angiogenesis is well understood, the role of a second group of angiogenic factors, the fibroblast growth factors (FGFs), remains elusive. We used a recombinant adenovirus expressing soluble FGF re- ceptor (AdsFGFR) to interfere with FGF function in tumor angiogenesis. AdsFGFR repressed endothelial cell proliferation in vitro and

Amelia Compagni; Petra Wilgenbus; Maria-Antonietta Impagnatiello; Matt Cotten; Gerhard Christofori

155

Malignant ascites and small renal mass: an unusual presentation of advanced renal cell carcinoma.  

PubMed

Metastatic renal cell carcinoma (RCC) presenting with peritoneal involvement or ascites is rare and has been previously described clinically in the setting of large renal mass or other distant metastases. We report an unusual case of RCC presenting with ascites without large mass or other distant metastases. Advances in cytologic diagnosis of metastatic RCC in serous ascitic fluid is discussed, while a potential mechanism of tumor spread is presented. PMID:23987183

Boateng, Akwasi A; Vinson, Mohabe A; Mutema, George K; Kuhn, Eric J

2013-09-01

156

Treatment of Malignant Ascites  

Microsoft Academic Search

Opinion statement  The management of malignant ascites is a significant challenge in gastrointestinal medical oncology. Current treatment strategies\\u000a include diuretic therapy, paracentesis, peritoneal drains, and venous shunts. However, there are no established evidence-based\\u000a guidelines, and there is a lack of randomized controlled trials identifying optimal therapy. Newer therapies are emerging\\u000a and will need further study. By summarizing published studies, this review

Michael Chung; Peter Kozuch

2008-01-01

157

Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth In vivo  

PubMed Central

Purpose Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors (“adipokines”) is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic micro-environment.

Landskroner-Eiger, Shira; Qian, Binzhi; Muise, Eric S.; Nawrocki, Andrea R.; Berger, Joel P.; Fine, Eugene J.; Koba, Wade; Deng, Yingfeng; Pollard, Jeffrey W.; Scherer, Philipp E.

2011-01-01

158

Palliative treatment of malignant ascites: profile of catumaxomab  

PubMed Central

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.

Ammouri, Lila; Prommer, Eric E

2010-01-01

159

Palliative treatment of malignant ascites: profile of catumaxomab.  

PubMed

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. PMID:20531969

Ammouri, Lila; Prommer, Eric E

2010-05-25

160

Translocator Receptor Blockade Reduces Prostate Tumor Growth  

PubMed Central

Statement of Translational Relevance Although benzodiazepines have been used clinically for over 50 years, their application as a form of cancer therapy is largely unexplored. Here we show that lorazepam, a benzodiazepine commonly prescribed to treat anxiety disorders and acts on both central and peripheral receptors, inhibits prostate cancer cell growth and survival. Our studies further elucidate the mechanism by which Translocator Protein (TSPO) antagonists alter cancer cell function. Antagonists for TSPO are already used in the clinic for other indications and demonstrate very minor side effects. Because lorazepam is a commonly prescribed FDA-approved drug, the translation of our preclinical results to the prostate cancer patient population could be readily achieved. Our studies could lead to a significant change in the management of prostate cancer by providing a treatment option with minimal toxicity for use after failure of androgen-deprivation therapy and could ultimately prevent prostate cancer deaths. Purpose The transmembrane molecule, Translocator Protein (TSPO) has been implicated in the progression of epithelial tumors. TSPO gene expression is high in tissues involved in steroid biosynthesis, neurodegenerative disease and in cancer and overexpression has been shown to contribute to pathologic conditions including cancer progression in several different models. The goal of our study was to examine the expression and biological relevance of TSPO in prostate cancer and demonstrate that the commonly prescribed benzodiazepine lorazepam, a ligand for TSPO, exhibits anti-cancer properties. Experimental Design Immunohistochemical analysis using tissue microarrays was used to determine the expression profile of TSPO in human prostate cancer tissues. To demonstrate the effect of benzodiazepines (lorazepam and PK11195) in prostate cancer, we utilized cell proliferation assays, apoptosis ELISA, prostate cancer xenograft study, and immunohistochemistry. Results TSPO expression is increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared to normal prostate tissue and benign prostatic hyperplasia. Furthermore, TSPO expression correlates with disease progression, as TSPO levels increased with increasing Gleason sum and stage with prostate cancer metastases demonstrating the highest level of expression among all tissues examined. Functionally, we have demonstrated that lorazepam has anti-proliferative and pro-apoptotic properties in vitro and in vivo. Additionally, we have shown that TSPO overexpression in nontumorigenic cells conferred susceptibility to lorazepam-induced growth inhibition. Conclusion These data suggest that blocking TSPO function in tumor cells induces cell death and denotes a survival role for TSPO in prostate cancer and provide the first evidence for the use of benzodiazepines in prostate cancer therapeutics.

Fafalios, Arlee; Akhavan, Ardavan; Parwani, Anil V.; Bies, Robert R.; McHugh, Kevin J.; Pflug, Beth R.

2009-01-01

161

Inhibition of tumor growth and metastasis in association with modification of immune response by novel organic germanium compounds.  

PubMed

The effects of two novel organic germanium compounds, 1-phenyl-2-carbamoylethylgermanium sesquisulfide (PCAGeS) and 1-phenyl-2-carbamoylethylgermanium sequioxide (PCAGeO), on transplantable murine tumors and immune responses were studied. Both drugs showed low toxicity for mice. In culture, neither substance displayed significant cytotoxicity against murine tumor cells L1210 leukemia, L5178Y lymphoma, or IMC carcinoma. Growth of subcutaneously transplanted IMC carcinoma or Meth-A fibrosarcoma was markedly reduced by oral administration of PCAGeS. PCAGeO exhibited a similar but smaller effect on the tumor growth. Pulmonary metastasis of Lewis lung carcinoma was inhibited by oral or intraperitoneal treatment with PCAGeS. The activity of cyclophosphamide or Adriamycin against L1210 leukemia was significantly potentiated by oral administration of PCAGeS. PCAGeS enhanced the delayed-type hypersensitivity response to sheep red blood cells (SRBC) of mice or restored the response suppressed by ascitic IMC carcinoma, but did not significantly affect the formation of antibody to SRBC. PCAGeO similarly stimulated the DTH reaction. Phagocytic activity of peritoneal macrophages was enhanced by oral treatment of mice with PCAGeS. The results suggest that PCAGeS and PCAGeO display tumor-inhibitory activity by modification of the immune mechanism. PMID:3998767

Sato, I; Yuan, B D; Nishimura, T; Tanaka, N

1985-04-01

162

Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression.  

PubMed

Recurrence and spread of ovarian cancer is the 5th leading cause of death for women in the United States. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase located on chromosome 8q24.3 (gene is Ptk2), a site commonly amplified in serous ovarian cancer. Elevated FAK mRNA levels in serous ovarian carcinoma are associated with decreased (logrank P = 0.0007, hazard ratio 1.43) patient overall survival, but how FAK functions in tumor progression remains undefined. We have isolated aggressive ovarian carcinoma cells termed ID8-IP after intraperitoneal (IP) growth of murine ID8 cells in C57Bl6 mice. Upon orthotopic implantation within the peri-ovarian bursa space, ID8-IP cells exhibit greater tumor growth, local and distant metastasis, and elevated numbers of ascites-associated cells compared to parental ID8 cells. ID8-IP cells exhibit enhanced growth under non-adherent conditions with elevated FAK and c-Src tyrosine kinase activation compared to parental ID8 cells. In vitro, the small molecule FAK inhibitor (Pfizer, PF562,271, PF-271) at 0.1 uM selectively prevented anchorage-independent ID8-IP cell growth with the inhibition of FAK tyrosine (Y)397 but not c-Src Y416 phosphorylation. Oral PF-271 administration (30 mg/kg, twice daily) blocked FAK but not c-Src tyrosine phosphorylation in ID8-IP tumors. This was associated with decreased tumor size, prevention of peritoneal metastasis, reduced tumor-associated endothelial cell number, and increased tumor cell-associated apoptosis. FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer. PMID:23275034

Ward, Kristy K; Tancioni, Isabelle; Lawson, Christine; Miller, Nichol L G; Jean, Christine; Chen, Xiao Lei; Uryu, Sean; Kim, Josephine; Tarin, David; Stupack, Dwayne G; Plaxe, Steven C; Schlaepfer, David D

2012-12-30

163

Alpha feto-protein and albumin in ascitic fluid in hepatocellular carcinoma patients.  

PubMed

Alpha-feto-protein (AFP) is the most popular tumor marker for hepatocellular carcinoma (HCC). It is used in diagnosis and follow up of cases by estimating its rise in the serum. The aim of this work is to study the value of estimating AFP in ascitic fluid of HCC patients with ascites. This work is a case control study on 32 patients, including 22 cases with ascites and HCC and 10 control group with ascites due to liver cirrhosis without HCC. The level of AFP was estimated in serum and in ascitic fluid by Radio-immuno assay RIA. The serum ascites albumin gradient (SAAG) was assessed by measuring albumin in all samples using bromocresole green dye binding. Guided aspiration liver biopsy and ascitic fluid cytology was done, stained with H & E. It was found that, AFP level in serum was elevated in 72.7% of HCC patients, and in ascitic fluid was elevated 63.6% HCC patients. Also, there was a highly significant, direct positive correlation between elevation of AFP in serum and in ascitic fluid (r = 0.778). No elevation of AFP in serum and in ascitic fluid was detected in control group. Ascitic fluid cytology showed malignant cells in one case only. SAAG was significantly lower in the HCC group 0.83 gm/dl than the control group 2.43 gm/dl (p-value < 0.001). Elevation of AFP in ascitic fluid is of high importance in evaluation of HCC, and is as significant as serum and runs parallel to it. Estimation of AFP in ascitic fluid is much more significant in evaluation of HCC cases than ascitic fluid cytology. PMID:9257984

Sadek, A; Abdel Hady, A; el Ayyat, A; Hassan, M; Mostafa, I; Nouh, A

1997-08-01

164

ANALYSIS OF SOLID TUMOR GROWTH MODELS: MECHANISMS OF VOLUME LOSS AND SLOWED GROWTH RATE  

Microsoft Academic Search

Abstract Studies on the mathematical modeling of solid, avascular tumor growth have been prevalent since the 1960s, with pioneers such as Greenspan and Hill. As experimental studies have improved, the mathematical models have evolved in order to remain relevant. One important issue in modeling tumor growth is the assumed method of volume loss within the tumor. McElwain and Morris constructed

Lacey Huebel

2007-01-01

165

SDF-1, DC1/DC2, and Tumor Angiogenesis.  

National Technical Information Service (NTIS)

To examine tumor angiogenesis in the tumor microenvironment, we studied malignant ascites and tumors of patients with untreated ovarian carcinoma. We observed that malignant ascites fluid induced potent in vivo neovascularization in Matrigel assay. We det...

W. Zou

2005-01-01

166

Tumor growth modeling based on cell and tumor lifespans.  

PubMed

This paper deals with the lifespan modeling of heterogenous tumors treated by radiotherapy. A bi-scale model describing the cell and tumor lifespans by random variables is proposed. First- and second-order moments as well as the cumulative distribution functions and confidence intervals are expressed for the two lifespans with respect to the model parameters. One interesting result is that the mean value of the tumor lifespan can be approached by a logarithmic function of the initial cancer cell number. Moreover, we show that TCP and NTCP, used in radiotherapy to evaluate, optimize and compare treatment plans, can be derived from the tumor lifespan and the surrounding healthy tissue, respectively. Finally, we propose a ROC curve, entitled ECT (Efficiency-Complication Trade-off), suited to the selection by clinicians of the appropriate treatment planning. PMID:22820494

Keinj, R; Bastogne, T; Vallois, P

2012-07-20

167

Effect of Angiogenic Growth on Tumor Growth, Vascular Function, and the Development of Hypoxic Therapeutic Resistance.  

National Technical Information Service (NTIS)

The primary objectives of this grant were to determine the effects of either angiogenic growth factor overexpression or inhibition on mammary tumor pathophysiology. We evaluated four transfected human breast tumors and two murine mammary carcinoma lines b...

B. M. Fenton

2003-01-01

168

Brain tumor modeling: glioma growth and interaction with chemotherapy  

NASA Astrophysics Data System (ADS)

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

2011-10-01

169

A two-phase mixture model of avascular tumor growth  

NASA Astrophysics Data System (ADS)

Interactions with biological environment surrounding a growing tumor have major influence on tumor invasion. By recognizing that mechanical behavior of tumor cells could be described by biophysical laws, the research on physical oncology aims to investigate the inner workings of cancer invasion. In this study, we introduce a mathematical model of avascular tumor growth using the continuum theory of mixtures. Mechanical behavior of the tumor and physical interactions between the tumor and host tissue are represented by biophysically founded relationships. In this model, a solid tumor is embedded in inviscid interstitial fluid. The tumor has viscous mechanical properties. Interstitial fluid exhibits properties of flow through porous medium. Associated with the mixture saturation constraint, we introduce a Lagrange multiplier which represents hydrostatic pressure of the interstitial fluid. We solved the equations using Finite Element Method in two-dimensions. As a result, we have introduced a two-phase mixture model of avascular tumor growth that provided a flexible mathematical framework to include cells' response to mechanical aspects of the tumor microenvironment. The model could be extended to capture tumor-ECM interactions which would have profound influence on tumor invasion.

Ozturk, Deniz; Burcin Unlu, M.; Yonucu, Sirin; Cetiner, Ugur

2012-02-01

170

Getting to Know Ovarian Cancer Ascites: Opportunities for Targeted Therapy-Based Translational Research  

PubMed Central

More than one third of ovarian cancer patients present with ascites at diagnosis, and almost all have ascites at recurrence. The presence of ascites correlates with the peritoneal spread of ovarian cancer and is associated with poor disease prognosis. Malignant ascites acts as a reservoir of a complex mixture of soluble factors and cellular components which provide a pro-inflammatory and tumor-promoting microenvironment for the tumor cells. Subpopulations of these tumor cells exhibit cancer stem-like phenotypes, possess enhanced resistance to therapies and the capacity for distal metastatic spread and recurrent disease. Thus, ascites-derived malignant cells and the ascites microenvironment represent a major source of morbidity and mortality for ovarian cancer patients. This review focuses on recent advances in our understanding of the molecular, cellular, and functional characteristics of the cellular populations within ascites and discusses their contributions to ovarian cancer metastasis, chemoresistance, and recurrence. We highlight in particular recent translational findings which have used primary ascites-derived tumor cells as a tool to understand the pathogenesis of the disease, yielding new insights and targets for therapeutic manipulation.

Ahmed, Nuzhat; Stenvers, Kaye L.

2013-01-01

171

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

PubMed Central

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

Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

2013-01-01

172

Population Ecology Issues in Tumor Growth  

Microsoft Academic Search

Mathematical models developed from population ecology are applied to tumor-host interactions and demonstrate the importance of increased efficiency in substrate absorption as a mechanism enabling tumor cells to (a) proliferate despite inefficient energy production and (b) compete successfully for resources with the numerically superior host cells. As with many biological invasions observed in nature, success of the invaders can be

Robert A. Gatenby

1991-01-01

173

VEGF-integrin interplay controls tumor growth and vascularization  

NASA Astrophysics Data System (ADS)

Cross-talk between the major angiogenic growth factor, VEGF, and integrin cell adhesion receptors has emerged recently as a critical factor in the regulation of angiogenesis and tumor development. However, the molecular mechanisms and consequences of this intercommunication remain unclear. Here, we define a mechanism whereby integrin v3, through activation, clustering, and signaling by means of p66 Shc (Src homology 2 domain containing), regulates the production of VEGF in tumor cells expressing this integrin. Tumors with "activatable" but not "inactive" 3 integrin secrete high levels of VEGF, which in turn promotes extensive neovascularization and augments tumor growth in vivo. This stimulation of VEGF expression depends upon the ability of v3 integrin to cluster and promote phosphorylation of p66 Shc. These observations identify a link between 3 integrins and VEGF in tumor growth and angiogenesis and, therefore, may influence anti-integrin as well as anti-VEGF therapeutic strategies. activation | angiogenesis | Src homology 2 domain containing

de, Sarmishtha; Razorenova, Olga; McCabe, Noel Patrick; O'Toole, Timothy; Qin, Jun; Byzova, Tatiana V.

2005-05-01

174

Two new C3H mouse ascites tumor cell lines capable of proliferation in vivo and in suspension culture: Morphological, karyological, kinetic, and immunological properties  

Microsoft Academic Search

Summary  The establishment of mouse tumor cell lines capable of proliferating in vivo and in suspension culture was undertaken. The\\u000a MM-46 tumor line, initiated from primary mammary carcinoma arising in a C3H\\/He mouse, was maintained for over 100 generations\\u000a in the peritoneal cavities of syngenic mice. At the 50th generation of the tumor suspension, cultures were initiated. The\\u000a established cell lines,

Atsushi Tsuboi; Mieko Matsui; Isamu Hayata; Takehiko Tsuchiya

1980-01-01

175

Catumaxomab: in malignant ascites.  

PubMed

Catumaxomab is a rat/murine hybrid, trifunctional, bispecific (anti-human epithelial cell adhesion molecule [EpCAM]?×?anti-CD3) monoclonal antibody. Compared with paracentesis alone, paracentesis followed by catumaxomab therapy was associated with significant prolongation of paracentesis-free survival and time to repeat paracentesis in a randomized, open-label, multicentre, pivotal phase II/III trial in patients with recurrent symptomatic malignant ascites due to EpCAM-positive tumours who were resistant to conventional chemotherapy. The benefits of catumaxomab were seen across a broad range of epithelial ovarian and nonovarian cancers, and irrespective of whether or not catumaxomab recipients developed human anti-mouse antibodies. Combining catumaxomab with paracentesis also resulted in more pronounced and prolonged reductions in ascites signs and symptoms and a delayed deterioration in health-related quality of life compared with paracentesis alone. Despite the study not being designed or powered to evaluate overall survival, significant differences favouring the addition of catumaxomab to paracentesis were seen in analyses of the safety population and the subpopulation of patients with gastric cancer. Catumaxomab was generally well tolerated in the pivotal phase II/III trial. The most frequent adverse events attributed to catumaxomab treatment included cytokine-release-related symptoms, which were mostly of mild to moderate severity and manageable with standard symptomatic treatment. PMID:22676343

Frampton, James E

2012-07-01

176

Second hand smoke stimulates tumor angiogenesis and growth  

Microsoft Academic Search

Exposure to second hand smoke (SHS) is believed to cause lung cancer. Pathological angiogenesis is a requisite for tumor growth. Lewis lung cancer cells were injected subcutaneously into mice, which were then exposed to sidestream smoke (SHS) or clean room air and administered vehicle, cerivastatin, or mecamylamine. SHS significantly increased tumor size, weight, capillary density, VEGF and MCP-1 levels, and

Bo-qing Zhu; Christopher Heeschen; Richard E. Sievers; Joel S. Karliner; William W. Parmley; John P. Cooke

2003-01-01

177

Phase transition in tumor growth: I avascular development  

NASA Astrophysics Data System (ADS)

We propose a mechanism for avascular tumor growth based on a simple chemical network. This model presents a logistic behavior and shows a "second order" phase transition. We prove the fractal origin of the empirical logistics and Gompertz constant and its relation to mitosis and apoptosis rate. Finally, the thermodynamics framework developed demonstrates the entropy production rate as a Lyapunov function during avascular tumor growth.

Izquierdo-Kulich, E.; Rebelo, I.; Tejera, E.; Nieto-Villar, J. M.

2013-12-01

178

[Effects of parenteral nutrition on tumor growth: experimental aspects].  

PubMed

There still exist controversies about the effect of parenteral nutrition on cancer growth. For elucidation of this question the development of Walker 256 carcinosarcoma in rats submitted to parenteral nutrition (PN) was studied. Thirty-five Wistar rats were randomly distributed in three groups: OT group (11), tumor-bearing animals always under oral feeding for 14 days; PC group (14), tumor free animals under PN for 7 days; PT group (10), tumor-bearing rats under PT for 7 days. PT solution contained 15% glucose, 3% aminoacids and essential micronutrients. Body and tumor weight (in OT and PT groups) were evaluated daily. Carcass weight was obtained by the difference between the body and tumor weight. The rats of the PC group had an initial body weight loss that became stabilized afterwards at a lower plateau level. The rats of the PT group also presented an initial body weight loss recovered progressively afterwards. This difference is probably due to tumor mass expansion in PT animals, since PT rats carcass weight remained similar to that of body weight in PC group. The tumor growth has shown no difference between the oral and parenteral feeding groups, particularly when tumor weight/carcass weight ratio was considered. It is concluded that parenteral nutrition does not favor tumor growth in detriment to carcass weight development. PMID:2135817

Yamaguchi, N; Lima-Gonçalves, E; Waitzberg, D L; Diniz Filho, A M; Goffi, F S

179

Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System  

PubMed Central

To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug) and drug (mirtazapine), and four groups with tumors, i.e. never (no drug), always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment), and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The “psychiatric” conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interlukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after) as compared with that of never. In addition, interferon-? level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-? (TNF-?) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.

Fang, Chun-Kai; Chen, Hong-Wen; Chiang, I-Tsang; Chen, Chia-Chieh; Liao, Jyh-Fei; Su, Ton-Ping; Tung, Chieh-Yin; Uchitomi, Yosuke; Hwang, Jeng-Jong

2012-01-01

180

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

PubMed Central

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 (?2 = 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 (?2 = 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.

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

2013-01-01

181

Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability.  

PubMed

Vascular endothelial growth factor (VEGF)-induced vascular permeability (VP) is a hallmark of tumor growth and metastasis. Previous studies have shown a requirement for Src kinase in VEGF-mediated VP and signaling in blood vessels. In this study, we have examined the effect of Src-mediated reduced VP on tumor growth and metastasis. The growth and spontaneous metastasis of VEGF-expressing tumor cells were determined in Src-knockout (src(-/-)) or control mice (src(+/+) or src(+/-)). In comparison to control mice, src-null mice had a significant reduction in tumor-induced VP as well as a subsequent reduction in spontaneous metastasis. In contrast, primary tumor weight and vascular density were unchanged between src-null and control mice. Consistent with a role for Src in the extravasation of tumor cells from the circulation, direct intravenous injection of lung carcinoma cells resulted in a more than 2-fold reduction in lung tumor burden in src-null mice compared to control mice. The comparison of the results from the experimental metastasis and the spontaneous metastasis models suggests that there are defects in VP in the primary site of Src-deficient mice and that there may be an essential role for Src and Src-mediated VP in tumor metastasis to the lung. PMID:15486073

Criscuoli, Michele L; Nguyen, Mai; Eliceiri, Brian P

2004-10-14

182

Divalent cation-phospholipid complexes and tumor growth inhibition.  

PubMed

Growth inhibition of DS sarcomas provoked by calcitonin treatment is accompanied by an increase of calcium and magnesium in the phospholipid fraction. Changes in tumor cell membrane characteristics reflected in ionic or molecular transport modifications seem to be involved in the growth impairment phenomenon. PMID:520494

Anghileri, L J; Delbrück, H

1979-12-15

183

RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors  

PubMed Central

Purpose The purpose of this preclinical study was to determine the effectiveness of RAF265, a multi-kinase inhibitor, for treatment of human metastatic melanoma and to characterize traits associated with drug response. Experimental Design Advanced metastatic melanoma tumors from 34 patients were orthotopically implanted to nude mice. Tumors that grew in mice (17 of 34) were evaluated for response to RAF265 (40 mg/kg, every day) over 30 days. The relation between patient characteristics, gene mutation profile, global gene expression profile, and RAF265 effects on tumor growth, mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation, proliferation, and apoptosis markers was evaluated. Results Nine of the 17 tumors that successfully implanted (53%) were mutant BRAF (BRAFV600E/K), whereas eight of 17 (47%) tumors were BRAF wild type (BRAFWT). Tumor implants from 7 of 17 patients (41%) responded to RAF265 treatment with more than 50% reduction in tumor growth. Five of the 7 (71%) responders were BRAFWT, of which 1 carried c-KITL576P and another N-RASQ61R mutation, while only 2 (29%) of the responding tumors were BRAFV600E/K. Gene expression microarray data from nonimplanted tumors revealed that responders exhibited enriched expression of genes involved in cell growth, proliferation, development, cell signaling, gene expression, and cancer pathways. Although response to RAF265 did not correlate with pERK1/2 reduction, RAF265 responders did exhibit reduced pMEK1, reduced proliferation based upon reduced Ki-67, cyclin D1 and polo-like kinase1 levels, and induction of the apoptosis mediator BCL2-like 11. Conclusions Orthotopic implants of patient tumors in mice may predict prognosis and treatment response for melanoma patients. A subpopulation of human melanoma tumors responds to RAF265 and can be characterized by gene mutation and gene expression profiles.

Su, Yingjun; Vilgelm, Anna E.; Kelley, Mark C.; Hawkins, Oriana E.; Liu, Yan; Boyd, Kelli L.; Kantrow, Sara; Splittgerber, Ryan C.; Short, Sarah P.; Sobolik, Tammy; Zaja-Milatovic, Snjezana; Dahlman, Kimberly Brown; Amiri, Katayoun I.; Jiang, Aixiang; Lu, Pengcheng; Shyr, Yu; Stuart, Darrin D.; Levy, Shawn; Sosman, Jeffrey A.; Richmond, Ann

2013-01-01

184

Concentrated ascitic fluid reinfusion after cascade filtration in tense ascites  

Microsoft Academic Search

A new method for concentrated ascitic fluid reinfusion using a double ultrafiltration device is reported as 22 procedures in 20 cirrhotic patients (6 females, 14 males; median age 55 years, range 33–69) with tense, refractory ascites. Eight of the 20 patients had elevated creatinine levels. The mean time for each procedure was 189±82 min, during which a mean of 7.7

Lorenzo Rossaro; Agnese Graziotto; Stefano Bonato; Mario Plebani; David H. Van Thiel; Angelo Burlina; Remo Naccarato; Mario Salvagnini

1993-01-01

185

The use of blood gas parameters to predict ascites susceptibility in juvenile broilers.  

PubMed

Ascites syndrome is a metabolic disorder found in modern broilers that have insufficient pulmonary vascular capacity. Commercial breeding programs have heavily focused on high growth rate, which led to fast-growing chickens, but as a negative consequence, the incidence of ascites syndrome increased. However, not all birds with a high growth rate will suffer from ascites syndrome, which might indicate a genetic susceptibility to ascites. Information on blood gas parameters measured early in life and their relation to ascites susceptibility is expected to contribute to identification on the cause of ascites syndrome. In this study, several physiological parameters, such as blood gas parameters [pH, partial pressure of CO(2) in venous blood (pvCO(2)), and partial pressure of O(2) in venous blood], hematocrit, electrolytes (Na(+), Ca(2+), and K(+)), metabolites (lactate and glucose), were measured at d 11 to 12 of age from 100 female and 100 male broilers. From d 14 onward, the birds were challenged to provoke the development of ascites syndrome. Our results showed that high pvCO(2) values together with low pH values (males) or high pH values (females) in the venous blood of juvenile broilers coincided with ascites. Therefore, blood pvCO(2) and pH in both juvenile male and female broilers seem to be critical factors in ascites pathophysiology and can be used as phenotypic traits to predict ascites susceptibility in juvenile broilers at d 11 to 12. A prediction model was built on a subpopulation of the broilers without any loss in sensitivity (0.52) and specificity (0.78) when applied to the validation population. The parameter sex was included in the prediction model because levels of pvCO(2) and pH that associated with ascites susceptibility are different between males and females. Commercial breeders can include these phenotypic traits in their genetic selection programs to reduce the incidence of ascites syndrome. PMID:20634524

van As, P; Elferink, M G; Closter, A M; Vereijken, A; Bovenhuis, H; Crooijmans, R P M A; Decuypere, E; Groenen, M A M

2010-08-01

186

An unidentified lipid prevalent in tumors  

Microsoft Academic Search

An unidentified lipid was found in five different tumor sources. It was not found in liver, bone marrow or plasma from tumor-bearing\\u000a animals, nor in the extracellular fluid supporting growth of Ehrlich ascites cells. The polarity of the unidentified component\\u000a was similar to that of a glyceryl ether diester, and it was isolated in milligram amounts by preparative thinlayer chromatography.

Fred Snyder; Edgar A. Cress; Nelson Stephens

1966-01-01

187

Study on the effects of low-energy laser irradiation on the development of mouse S180 ascites sarcoma in vivo  

NASA Astrophysics Data System (ADS)

The antitumor effects of low-energy laser irradiation (LELI) are always the focus of scientific investigation. The purpose of this study was to test the effects of low-energy He-Ne laser irradiation on mouse S180 ascites sarcoma. After innoculating S180 sarcoma cells at the dosage of 1 x 106 cells per mouse, five group of BALB/c mice were irradiated at the spot of one Harder's glands of the mouse eye for six days with five different dosages of 7.33, 11.00, 14.67, 22.00 and 29.33 J/cm2 respectively. The antitumor effects were evaluated in two aspects: life prolongation ratio and ascites growth of tumor-bearing mice. The results showed that low energy He-Ne laser irradiation of 7.33, 11.00, 14.67, 22.00 and 29.33 J/cm2 could inhibit the proliferation speed of S180 ascites sarcoma in vivo, and therefore could prolong the survival time of the tumor bearing mice in some degree. Moreover, the dosage of 14.67 J/cm2 showed the most remarkable inhibiting effects among the four dosages, and the life prolongation ratio was up to 45.51%. On the contrary, the proliferation speed of S180 ascites sarcoma cells in vivo was accelerated by the large dosage of 29.33 J/cm2 LELI and the survival time of the tumor bearing mice were remarkably shortened. Low energy He-Ne laser irradiation with proper dosages can inhibit the development of the mouse S180 ascites sarcoma, while too large dosage shows promotive effects.

Huang, Baoxu; Wang, Hongbin; Liu, Huanqi; Qu, Zhina; Liu, Xifeng; Cheng, Shaohui

2004-07-01

188

ADAM12 Transmembrane and Secreted Isoforms Promote Breast Tumor Growth  

PubMed Central

Increased levels of ADAM12 have been reported in a variety of human cancers. We have previously reported that urinary ADAM12 is predictive of disease status in breast cancer patients and that ADAM12 protein levels in urine increase with progression of disease. On the basis of these findings, the goal of this study was to elucidate the contribution of ADAM12 in breast tumor growth and progression. Overexpression of both the ADAM12-L (transmembrane) and ADAM12-S (secreted) isoforms in human breast tumor cells resulted in a significantly higher rate of tumor take and increased tumor size. Cells expressing the enzymatically inactive form of the secreted isoform, ADAM12-S, had tumor take rates and tumor volumes similar to those of wild-type cells, suggesting that the tumor-promoting activity of ADAM12-S was a function of its proteolytic activity. Of the two isoforms, only the secreted isoform, ADAM12-S, enhanced the ability of tumor cells to migrate and invade in vitro and resulted in a higher incidence of local and distant metastasis in vivo. This stimulatory effect of ADAM12-S on migration and invasion was dependent on its catalytic activity. Expression of both ADAM12 isoforms was found to be significantly elevated in human malignant breast tissue. Taken together, our results suggest that ADAM12 overexpression results in increased tumor take, tumor size, and metastasis in vivo. These findings suggest that ADAM12 may represent a potential therapeutic target in breast cancer.

Roy, Roopali; Rodig, Scott; Bielenberg, Diane; Zurakowski, David; Moses, Marsha A.

2011-01-01

189

Congenital tuberculosis presenting as ascites.  

PubMed

Congenital tuberculosis is a rare disease of which the most common presentations include respiratory distress, fever, and organomegaly. We report a case of congenital tuberculosis presenting with ascites. PMID:21529114

Aelami, Mohammad Hassan; Qhodsi Rad, Mohammad Ali; Sasan, Mohammad Saeed; Ghazvini, Kiarash

2011-05-01

190

Deregulation of tumor angiogenesis and blockade of tumor growth in PPAR?-deficient mice  

PubMed Central

The peroxisome proliferator-activated receptor-? (PPAR?) has been implicated in tumorigenesis, but its precise role remains unclear. Here, we show that the growth of syngeneic Pparb wild-type tumors is impaired in Pparb?/? mice, concomitant with a diminished blood flow and an abundance of hyperplastic microvascular structures. Matrigel plugs containing pro-angiogenic growth factors harbor increased numbers of morphologically immature, proliferating endothelial cells in Pparb?/? mice, and retroviral transduction of Pparb triggers microvessel maturation. We have identified the Cdkn1c gene encoding the cell cycle inhibitor p57Kip2 as a PPAR? target gene and a mediator of the PPAR?-mediated inhibition of cell proliferation, which provides a possible mechanistic explanation for the observed tumor endothelial hyperplasia and deregulation of tumor angiogenesis in Pparb?/? mice. Our data point to an unexpected essential role for PPAR? in constraining tumor endothelial cell proliferation to allow for the formation of functional tumor microvessels.

Muller-Brusselbach, Sabine; Komhoff, Martin; Rieck, Markus; Meissner, Wolfgang; Kaddatz, Kerstin; Adamkiewicz, Jurgen; Keil, Boris; Klose, Klaus J; Moll, Roland; Burdick, Andrew D; Peters, Jeffrey M; Muller, Rolf

2007-01-01

191

Spontaneous peritonitis in cirrhotic ascites  

Microsoft Academic Search

In a ten-year retrospective study 15 cases of spontaneous bacterial peritonitis were identified. All patients had cirrhosis and ascites. Abdominal pain was present in all and abdominal tenderness in 11. Diagnosis was established by paracentesis with the finding of either an elevated ascitic fluid cell count (>300 WBC\\/mm3) in 13 cases or organisms and numerous neutrophiles on gram stain in

Noel Curry; Richard W. McCallum; Paul H. Guth

1974-01-01

192

Reaction-diffusion model for the growth of avascular tumor.  

PubMed

A nutrient-limited model for avascular cancer growth including cell proliferation, motility, and death is presented. The model qualitatively reproduces commonly observed morphologies for primary tumors, and the simulated patterns are characterized by its gyration radius, total number of cancer cells, and number of cells on tumor periphery. These very distinct morphological patterns follow Gompertz growth curves, but exhibit different scaling laws for their surfaces. Also, the simulated tumors incorporate a spatial structure composed of a central necrotic core, an inner rim of quiescent cells and a narrow outer shell of proliferating cells in agreement with biological data. Finally, our results indicate that the competition for nutrients among normal and cancer cells may be a determining factor in generating papillary tumor morphology. PMID:11863563

Ferreira, S C; Martins, M L; Vilela, M J

2002-01-23

193

Paracrine/autocrine growth mechanisms in tumor metastasis.  

PubMed

The successful growth of metastatic tumor cells is due to their responses to local paracrine growth factors and inhibitors and their production and responses to autocrine growth factors. At early stages of metastatic progression, there is a tendency for many common malignancies to metastasize and grow preferentially at particular sites, suggesting that paracrine growth mechanisms may dominate the growth signals affecting metastatic cells. At later stages of metastatic progression, where widespread dissemination to various tissues and organs occurs, autocrine growth mechanisms may dominate the growth signals affecting metastatic cells. The progression of malignant cells to completely autonomous (acrine) states can ultimately occur, and at this stage of metastatic progression cell growth can be completely independent of growth factors or inhibitors. Various strategies have been developed to treat cancer that are based on the responses of malignant cells to growth factor or inhibitor analogs, anti-receptor antibodies, or antibody- or growth factor-toxin conjugates. Since the responses and expression of growth factor receptors can change during malignant progression, the development of cancer treatments using analogs of specific growth inhibitors or antagonists of growth factors, such as monoclonal antibodies or other agents, to block growth signaling mechanisms may only be useful at the early stages of malignant cancer progression before widespread metastasis of acrine cells occurs. PMID:1292754

Nicolson, G L

1992-01-01

194

[Interference of inflammation caused by polyester with the growth of Yoshida ascite hepatoma. IV. Modifications of the sedimentation profile of the hepatoma cells].  

PubMed

It was previously shown that Yoshida's ascites-hepatoma cells (Y cells) intraperitoneally injected into rats carrying chronic inflammation caused by polyester thread rapidly disappear. In this paper the sedimentation rate in a continuous Percoll gradient at unit gravity (1 g) using the CELSEP apparatus (Sorvall), the mean diameter and volume of the Y cells harvested from the peritoneal cavity of untreated (NT) and polyester-treated (TM) animals were determined at 6-12-18-24 hours after the inoculum. At 6 hours a number of Y cells appeared enlarged both from TM and NT rats, while afterwards, and notably at 18 and 24 hours, their size was decreased and their sedimentation rate was reduced only in TM animals. It seems that the chronic inflammation causes alterations both in the size and in the density of the Y cells and probably one of the mechanisms of their death is through shrinkage and apoptosis. PMID:2757821

Torboli, M; Melandri, P; Ventrelli, I; Berti, G; Benassi, G

1989-01-01

195

Genetics of ascites resistance and tolerance in chicken: a random regression approach.  

PubMed

Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re-ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions. PMID:22670223

Kause, Antti; van Dalen, Sacha; Bovenhuis, Henk

2012-05-01

196

Genetics of Ascites Resistance and Tolerance in Chicken: A Random Regression Approach  

PubMed Central

Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re-ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions.

Kause, Antti; van Dalen, Sacha; Bovenhuis, Henk

2012-01-01

197

Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes.  

PubMed

Development and preclinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts illustrate the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for women with newly diagnosed breast cancer; orthotopic breast tumor grafting is a step toward individualized models for tumor growth, metastasis and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer. PMID:22019887

DeRose, Yoko S; Wang, Guoying; Lin, Yi-Chun; Bernard, Philip S; Buys, Saundra S; Ebbert, Mark T W; Factor, Rachel; Matsen, Cindy; Milash, Brett A; Nelson, Edward; Neumayer, Leigh; Randall, R Lor; Stijleman, Inge J; Welm, Bryan E; Welm, Alana L

2011-10-23

198

Pinning of Tumoral Growth by Enhancement of the Immune Response  

NASA Astrophysics Data System (ADS)

Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around 80% 90% of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox's model hazard ratio of 0.85; 95% confidence interval 0.76 0.95, p=0.004)], and even the total elimination of some tumors.

Brú, A.; Albertos, S.; García-Asenjo, J. A.; Brú, I.

2004-06-01

199

Protection of Ehrlich Ascites Tumor Cells against the Antiproliferative Effect of Mechlorethamine (Nitrogen Mustard) by 5-A^A^-Dimethylamiloride1  

Microsoft Academic Search

V,\\/V-l )inu't hylamiliiride protects Ehrlich uscite* tumor cells against the antiproliferative effect of nitrogen mustard. The drug reduces the frequency of DNA inu-rsl rand cross-links introduced by nitrogen mustard. Cells with a defective choline carrier are not protected against nitrogen mustard by dimethylamiloride. As nitrogen mustard is taken up by the choline carrier, it is concluded that the recently reported

Wolfgang Doppier; Johann Hofmann; Karl Maly; Hans H. Grunicke

200

Semiautomatic growth analysis of multicellular tumor spheroids.  

PubMed

Multicellular tumor spheroids (MCTS) are routinely employed as three-dimensional in vitro models to study tumor biology. Cultivation of MCTS in spinner flasks provides better growing conditions, especially with regard to the availability of nutrients and oxygen, when compared with microtiter plates. The main endpoint of drug response experiments is spheroid size. It is common practice to analyze spheroid size manually with a microscope and an ocular micrometer. This requires removal of some spheroids from the flask, which entails major limitations such as loss of MCTS and the risk of contamination. With this new approach, the authors present an efficient and highly reproducible method to analyze the size of complete MCTS populations in culture containers with transparent, flat bottoms. MCTS sediments are digitally scanned and spheroid volumes are calculated by computerized image analysis. The equipment includes regular office hardware (personal computer, flatbed scanner) and software (Adobe Photoshop, Microsoft Excel, ImageJ). The accuracy and precision of the method were tested using industrial precision steel beads with known diameter. In summary, in comparison with other methods, this approach provides benefits in terms of semiautomation, noninvasiveness, and low costs. PMID:21908797

Rodday, Bjoern; Hirschhaeuser, Franziska; Walenta, Stefan; Mueller-Klieser, Wolfgang

2011-09-09

201

Neuropilin-1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment  

PubMed Central

The tumor microenvironment, including stromal myofibroblasts and associated matrix proteins, regulates cancer cell invasion and proliferation. Here we report that neuropilin-1 (NRP-1) orchestrates communications between myofibroblasts and soluble fibronectin (FN) that promote ?5?1 integrin-dependent FN fibril assembly, matrix stiffness, and tumor growth. Tumor growth and FN fibril assembly was reduced by genetic depletion or antibody neutralization of NRP-1 from stromal myofibroblasts in vivo. Mechanistically, the increase in FN fibril assembly required glycosylation of serine 612 of the extracellular domain of NRP-1, an intact intracellular NRP-1 SEA domain, and intracellular associations between NRP-1, the scaffold protein GIPC, and the nonreceptor tyrosine kinase c-Abl, that augmented ?5?1 FN fibril assembly activity. Analysis of human cancer specimens established an association between tumoral NRP-1 levels and clinical outcome. Our findings indicate that NRP-1 activates the tumor microenvironment, thereby promoting tumor growth. These results not only identify new molecular mechanisms of FN fibril assembly but also have important implications for therapeutic targeting of the myofibroblast in the tumor microenvironment.

Yaqoob, Usman; Cao, Sheng; Shergill, Uday; Jagavelu, Kumaravelu; Geng, Zhimin; Yin, Meng; de Assuncao, Thiago M; Cao, Ying; Szabolcs, Anna; Thorgeirsson, Snorri; Schwartz, Martin; Yang, Ju Dong; Ehman, Richard; Roberts, Lewis; Mukhopadhyay, Debabrata; Shah, Vijay H.

2012-01-01

202

Peritoneal catheter for massive cardiac ascites.  

PubMed

Cardiac ascites represents 5% of all causes of ascites. Diuretics and salt restriction remain the cornerstone of management. Large volume paracentesis is needed among patients who do not respond to conservative management. The use of peritoneal catheters to continuously drain steady amounts of ascitic fluid has been generally used in malignant ascites. When the ascites of any other origin is massive and requires many consecutive days of large-volume paracentesis, the use of a catheter may represent a more convenient strategy. We present a patient with cardiac ascites that was successfully managed with a peritoneal catheter. PMID:23595184

Aisenberg, Gabriel M

2013-04-16

203

Growth of melanoma brain tumors monitored by photoacoustic microscopy  

NASA Astrophysics Data System (ADS)

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

204

Ricci Flow and Entropy Model for Avascular Tumor Growth and Decay Control  

Microsoft Academic Search

Prediction and control of cancer invasion is a vital problem in medical science. This paper proposes a modern geometric Ricci-flow and entropy based model for control of avascular multicellular tumor spheroid growth and decay. As a tumor growth\\/decay control tool, a monoclonal antibody therapy is proposed. Keywords: avascular tumor growth and decay, multicellular tumor spheroid, Ricci flow and entropy, nonlinear

Tijana T. Ivancevic

2008-01-01

205

P-selectin deficiency attenuates tumor growth and metastasis.  

PubMed

Selectins are adhesion receptors that normally recognize certain vascular mucin-type glycoproteins bearing the carbohydrate structure sialyl-Lewisx. The clinical prognosis and metastatic progression of many epithelial carcinomas has been correlated independently with production of tumor mucins and with enhanced expression of sialyl-Lewisx. Metastasis is thought to involve the formation of tumor-platelet-leukocyte emboli and their interactions with the endothelium of distant organs. We provide a link between these observations by showing that P-selectin, which normally binds leukocyte ligands, can promote tumor growth and facilitate the metastatic seeding of a mucin-producing carcinoma. P-selectin-deficient mice showed significantly slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases from intravenously injected cells. Three potential pathophysiological mechanisms are demonstrated: first, intravenously injected tumor cells home to the lungs of P-selectin deficient mice at a lower rate; second, P-selectin-deficient mouse platelets fail to adhere to tumor cell-surface mucins; and third, tumor cells lodged in lung vasculature after intravenous injection often are decorated with platelet clumps, and these are markedly diminished in P-selectin-deficient animals. PMID:9689079

Kim, Y J; Borsig, L; Varki, N M; Varki, A

1998-08-01

206

P-selectin deficiency attenuates tumor growth and metastasis  

PubMed Central

Selectins are adhesion receptors that normally recognize certain vascular mucin-type glycoproteins bearing the carbohydrate structure sialyl-Lewisx. The clinical prognosis and metastatic progression of many epithelial carcinomas has been correlated independently with production of tumor mucins and with enhanced expression of sialyl-Lewisx. Metastasis is thought to involve the formation of tumor-platelet-leukocyte emboli and their interactions with the endothelium of distant organs. We provide a link between these observations by showing that P-selectin, which normally binds leukocyte ligands, can promote tumor growth and facilitate the metastatic seeding of a mucin-producing carcinoma. P-selectin-deficient mice showed significantly slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases from intravenously injected cells. Three potential pathophysiological mechanisms are demonstrated: first, intravenously injected tumor cells home to the lungs of P-selectin deficient mice at a lower rate; second, P-selectin-deficient mouse platelets fail to adhere to tumor cell-surface mucins; and third, tumor cells lodged in lung vasculature after intravenous injection often are decorated with platelet clumps, and these are markedly diminished in P-selectin-deficient animals.

Kim, Young J.; Borsig, Lubor; Varki, Nissi M.; Varki, Ajit

1998-01-01

207

Oral DNA vaccines target the tumor vasculature and microenvironment and suppress tumor growth and metastasis.  

PubMed

Four novel oral DNA vaccines provide protection against melanoma, colon, breast, and lung carcinoma in mouse models. Vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and respectively target vascular endothelial growth factor receptor-2, transcription factor Fos-related antigen-1, anti-apoptosis protein survivin and Legumain, an asparaginyl endopeptidase specifically overexpressed on tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). These vaccines are all capable of inducing potent cell-mediated protective immunity against self-antigens, resulting in marked suppression of tumor growth and dissemination. Key mechanisms induced by these DNA vaccines include efficient suppression of angiogenesis in the tumor vasculature and marked activation of cytotoxic T cells, natural killer cells, and antigen-presenting dendritic cells. The vaccine targeting Legumain establishes the new paradigm whereby a reduction in the density of TAMs in the TME decreases the release of factors potentiating tumor growth and angiogenesis. This, in turn, remodels the TME and decreases its immunosuppressive milieu and thereby potentiates the DNA vaccine's ability to effectively suppress tumor cell proliferation, vascularization, and metastasis. It is anticipated that such research efforts will lead to novel DNA-based vaccines that will be effective for the treatment of cancer. PMID:18363997

Xiang, Rong; Luo, Yunping; Niethammer, Andreas G; Reisfeld, Ralph A

2008-04-01

208

Transforming growth factor-beta and breast cancer: Tumor promoting effects of transforming growth factor-?  

Microsoft Academic Search

The transforming growth factor (TGF)-?s are potent growth inhibitors of normal epithelial cells. In established tumor cell systems, however, the preponderant experimental evidence suggests that TGF-?s can foster tumor-host interactions that indirectly support the viability and\\/or progression of cancer cells. The timing of this 'TGF-? switch' during the progressive transformation of epithelial cells is not clear. More recent evidence also

Nancy Dumont; Carlos L Arteaga

2000-01-01

209

Mining Brain Tumors and Tracking their Growth Rates  

Microsoft Academic Search

Mining brain tumors and tracking their growth trends in the course of magnetic resonance imaging is an important task that assists medical professionals to describe the appropriate treatment. Nevertheless, applying conventional techniques to carry out this process manually is time-consuming and often unreliable and insufficiently accurate. Automating this process is a challenging task due to the fact of the fractal

Abdel-Halim Elamy; Maidong Hu

2007-01-01

210

Altered tumor cell growth and tumorigenicity in models of microgravity  

NASA Astrophysics Data System (ADS)

Spaceflight environment and microgravity (MG) causes immune dysfunction and is a major health risk to humans, especially during long-term space missions. The effects of microgravity environment on tumor growth and carcinogenesis are yet unknown. Hence, we investigated the effects of simulated MG (SMG) on tumor growth and tumorigenicity using in vivo and in vitro models. B16 melanoma cells were cultured in static flask (FL) and rotating wall vessel bioreactors (BIO) to measure growth and properties, melanin production and apoptosis. BIO cultures had 50% decreased growth (p<0.01), increased doubling time and a 150% increase in melanin production (p<0.05). Flow cytometric analysis showed increased apoptosis in BIO. When BIO cultured melanoma cells were inoculated sc in mice there was a significant increase in tumorigenicity as compared to FL cells. Thus SMG may have supported &selected highly tumorigenic cells and it is pos sible that in addition to decreased immune function MG may alter tumor cell characteristics and invasiveness. Thus it is important to study effects of microgravity environment and its stressors using experimental tumors and SMG to understand and evaluate carcinogenic responses to true microgravity. Further studies on carcinogenic events and their mechanisms will allow us develop and formulate countermeasures and protect space travelers. Additional results will be presented. (Supported by NASA NCC8-168 grant, ADK)

Yamauchi, K.; Taga, M.; Furian, L.; Odle, J.; Sundaresan, A.; Pellis, N.; Andrassy, R.; Kulkarni, A.

211

Lymphangiogenic growth factors as markers of tumor metastasis.  

PubMed

Understanding the complex process of tumor metastasis is a problem which has challenged both clinician and scientist for well over 100 years. Defining molecular markers which reflect the metastatic potential of a tumor has also proved elusive. Recently, members of the vascular endothelial growth factor (VEGF) family of glycoproteins have been demonstrated to be potent mediators of both blood vessel and lymphatic vessel formation in the context of tumor biology. Experimental studies in animal models combined with extensive clinicopathological data provide a compelling case indicating that members of the VEGF family play a key role in the formation of metastases in a broad range of solid tumors. The question of whether VEGF signaling pathways can now serve as therapeutic targets alone, or in combination with other forms of anti-cancer agents, needs to be addressed. PMID:15563315

Stacker, Steven A; Williams, Richard A; Achen, Marc G

212

Ketone body utilization drives tumor growth and metastasis  

PubMed Central

We have previously proposed that catabolic fibroblasts generate mitochondrial fuels (such as ketone bodies) to promote the anabolic growth of human cancer cells and their metastasic dissemination. We have termed this new paradigm “two-compartment tumor metabolism.” Here, we further tested this hypothesis by using a genetic approach. For this purpose, we generated hTERT-immortalized fibroblasts overexpressing the rate-limiting enzymes that promote ketone body production, namely BDH1 and HMGCS2. Similarly, we generated MDA-MB-231 human breast cancer cells overexpressing the key enzyme(s) that allow ketone body re-utilization, OXCT1/2 and ACAT1/2. Interestingly, our results directly show that ketogenic fibroblasts are catabolic and undergo autophagy, with a loss of caveolin-1 (Cav-1) protein expression. Moreover, ketogenic fibroblasts increase the mitochondrial mass and growth of adjacent breast cancer cells. However, most importantly, ketogenic fibroblasts also effectively promote tumor growth, without a significant increase in tumor angiogenesis. Finally, MDA-MB-231 cells overexpressing the enzyme(s) required for ketone re-utilization show dramatic increases in tumor growth and metastatic capacity. Our data provide the necessary genetic evidence that ketone body production and re-utilization drive tumor progression and metastasis. As such, ketone inhibitors should be designed as novel therapeutics to effectively treat advanced cancer patients, with tumor recurrence and metastatic disease. In summary, ketone bodies behave as onco-metabolites, and we directly show that the enzymes HMGCS2, ACAT1/2 and OXCT1/2 are bona fide metabolic oncogenes.

Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Whitaker-Menezes, Diana; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P.

2012-01-01

213

Ketone body utilization drives tumor growth and metastasis.  

PubMed

We have previously proposed that catabolic fibroblasts generate mitochondrial fuels (such as ketone bodies) to promote the anabolic growth of human cancer cells and their metastasic dissemination. We have termed this new paradigm "two-compartment tumor metabolism." Here, we further tested this hypothesis by using a genetic approach. For this purpose, we generated hTERT-immortalized fibroblasts overexpressing the rate-limiting enzymes that promote ketone body production, namely BDH1 and HMGCS2. Similarly, we generated MDA-MB-231 human breast cancer cells overexpressing the key enzyme(s) that allow ketone body re-utilization, OXCT1/2 and ACAT1/2. Interestingly, our results directly show that ketogenic fibroblasts are catabolic and undergo autophagy, with a loss of caveolin-1 (Cav-1) protein expression. Moreover, ketogenic fibroblasts increase the mitochondrial mass and growth of adjacent breast cancer cells. However, most importantly, ketogenic fibroblasts also effectively promote tumor growth, without a significant increase in tumor angiogenesis. Finally, MDA-MB-231 cells overexpressing the enzyme(s) required for ketone re-utilization show dramatic increases in tumor growth and metastatic capacity. Our data provide the necessary genetic evidence that ketone body production and re-utilization drive tumor progression and metastasis. As such, ketone inhibitors should be designed as novel therapeutics to effectively treat advanced cancer patients, with tumor recurrence and metastatic disease. In summary, ketone bodies behave as onco-metabolites, and we directly show that the enzymes HMGCS2, ACAT1/2 and OXCT1/2 are bona fide metabolic oncogenes. PMID:23082722

Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Whitaker-Menezes, Diana; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

2012-09-19

214

Review of catumaxomab in the treatment of malignant ascites  

PubMed Central

Malignant ascites is frequently found with various solid tumors, and no established treatment options exist, apart from symptomatic paracentesis. Catumaxomab, a trifunctional bispecific monoclonal antibody, has two binding specificities directed to epithelial cell adhesion molecule (EpCAM) and the T cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells, including dendritic cells, macrophages, and natural killer cells. The trifunctional approach thus leads to a major histocompatibility complex-unrestricted but specific killing of epithelial tumor cells without need for preactivation or external costimulation. Because EpCAM is expressed in most solid tumors, but not in tissue of mesothelial origin, intraperitoneal treatment with catumaxomab is tumor-specific. Intraperitoneal treatment with catumaxomab resulted in a significant prolongation of puncture-free survival in patients with malignant ascites due to epithelial cancer. Catumaxomab has been approved in Europe for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive epithelial tumors where standard therapy is not available or no longer feasible.

Sebastian, Martin

2010-01-01

215

Review of catumaxomab in the treatment of malignant ascites.  

PubMed

Malignant ascites is frequently found with various solid tumors, and no established treatment options exist, apart from symptomatic paracentesis. Catumaxomab, a trifunctional bispecific monoclonal antibody, has two binding specificities directed to epithelial cell adhesion molecule (EpCAM) and the T cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells, including dendritic cells, macrophages, and natural killer cells. The trifunctional approach thus leads to a major histocompatibility complex-unrestricted but specific killing of epithelial tumor cells without need for preactivation or external costimulation. Because EpCAM is expressed in most solid tumors, but not in tissue of mesothelial origin, intraperitoneal treatment with catumaxomab is tumor-specific. Intraperitoneal treatment with catumaxomab resulted in a significant prolongation of puncture-free survival in patients with malignant ascites due to epithelial cancer. Catumaxomab has been approved in Europe for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive epithelial tumors where standard therapy is not available or no longer feasible. PMID:21188120

Sebastian, Martin

2010-11-08

216

The autophagic tumor stroma model of cancer or "battery-operated tumor growth"  

PubMed Central

The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the “Autophagy Paradox.” We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm “The Autophagic Tumor Stroma Model of Cancer Cell Metabolism” or “Battery-Operated Tumor Growth.” In this sense, autophagy in the tumor stroma serves as a “battery” to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients—both effectively “starving” cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy by the upregulation of natural, endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a “lethal” aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia.

Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Trimmer, Casey; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka K; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G

2010-01-01

217

Matrix metalloprotease 1a deficiency suppresses tumor growth and angiogenesis.  

PubMed

Matrix metalloprotease-1 (MMP1) is an important mediator of tumorigenesis, inflammation and tissue remodeling through its ability to degrade critical matrix components. Recent studies indicate that stromal-derived MMP1 may exert direct oncogenic activity by signaling through protease-activated receptor-1 (PAR1) in carcinoma cells; however, this has not been established in vivo. We generated an Mmp1a knockout mouse to ascertain whether stromal-derived Mmp1a affects tumor growth. Mmp1a-deficient mice are grossly normal and born in Mendelian ratios; however, deficiency of Mmp1a results in significantly decreased growth and angiogenesis of lung tumors. Coimplantation of lung cancer cells with wild-type Mmp1a(+/+) fibroblasts completely restored tumor growth in Mmp1a-deficient animals, highlighting the critical role of stromal-derived Mmp1a. Silencing of PAR1 expression in the lung carcinoma cells phenocopied stromal Mmp1a-deficiency, thus validating tumor-derived PAR1 as an Mmp1a target. Mmp1a secretion is controlled by the ability of its prodomain to facilitate autocleavage, whereas human MMP1 is efficiently secreted because of stable pro- and catalytic domain interactions. Taken together, these data demonstrate that stromal Mmp1a drives in vivo tumorigenesis and provide proof of concept that targeting the MMP1-PAR1 axis may afford effective treatments of lung cancer.Oncogene advance online publication, 27 May 2013; doi:10.1038/onc.2013.157. PMID:23708660

Foley, C J; Fanjul-Fernández, M; Bohm, A; Nguyen, N; Agarwal, A; Austin, K; Koukos, G; Covic, L; López-Otín, C; Kuliopulos, A

2013-05-27

218

Vascular endothelial growth factor immunoneutralization in combination with cisplatin reduces EAC tumor growth  

Microsoft Academic Search

In the present study, we evaluated the effects of a neutralizing anti-Vascular Endothelial Growth Factor (VEGF) polyclonal antibody on murine EAC tumor growth both in vitro and in vivo. Furthermore, we investigated if in the presence of effective VEGF blockade, a conventional chemotherapeutic drug Cisplatin could be effective, and if so would there be an additive effect of the combination

Sonali Ghosh; Putul Maity

2006-01-01

219

Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis  

PubMed Central

Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited better overall survival. We found 66c14 cells in the lumen of tumor lymphatic vessels and in lymph nodes. FGFR-2DN-expressing tumors exhibited a decrease in VEGFR-3 (Vascular Endothelial Growth Factor Receptor-3) or podoplanin-positive lymphatic vessels, an increase in isolated intratumoral lymphatic endothelial cells and a reduction in VEGF-C (Vascular Endothelial Growth Factor-C) mRNA expression. FGFs may act in an autocrine manner as the inhibition of FGFR signaling in tumor cells suppresses VEGF-C expression in a COX-2 (cyclooxygenase-2) or HIF1-? (hypoxia-inducible factor-1 ?) independent manner. FGFs may also act in a paracrine manner on tumor lymphatics by inducing expression of pro-lymphangiogenic molecules such as VEGFR-3, integrin ?9, prox1 and netrin-1. Finally, in vitro lymphangiogenesis is impeded in the presence of FGFR-2DN 66c14 cells. These data confirm that both FGF and VEGF signaling are necessary for the maintenance of vascular morphogenesis and provide evidence that targeting FGFR signaling may be an interesting approach to inhibit tumor lymphangiogenesis and metastatic spread.

Larrieu-Lahargue, Frederic; Welm, Alana L.; Bouchecareilh, Marion; Alitalo, Kari; Li, Dean Y.; Bikfalvi, Andreas; Auguste, Patrick

2012-01-01

220

HDAC6 inhibition restores ciliary expression and decreases tumor growth.  

PubMed

Primary cilia are multisensory organelles recently found to be absent in some tumor cells, but the mechanisms of deciliation and the role of cilia in tumor biology remain unclear. Cholangiocytes, the epithelial cells lining the biliary tree, normally express primary cilia and their interaction with bile components regulates multiple processes, including proliferation and transport. Using cholangiocarcinoma as a model, we found that primary cilia are reduced in cholangiocarcinoma by a mechanism involving histone deacetylase 6 (HDAC6). The experimental deciliation of normal cholangiocyte cells increased the proliferation rate and induced anchorage-independent growth. Furthermore, deciliation induced the activation of mitogen-activated protein kinase and Hedgehog signaling, two important pathways involved in cholangiocarcinoma development. We found that HDAC6 is overexpressed in cholangiocarcinoma and overexpression of HDAC6 in normal cholangiocytes induced deciliation and increased both proliferation and anchorage-independent growth. To evaluate the effect of cilia restoration on tumor cells, we targeted HDAC6 by short hairpin RNA (shRNA) or by the pharmacologic inhibitor, tubastatin-A. Both approaches restored the expression of primary cilia in cholangiocarcinoma cell lines and decreased cell proliferation and anchorage-independent growth. The effects of tubastatin-A were abolished when cholangiocarcinoma cells were rendered unable to regenerate cilia by stable transfection of IFT88-shRNA. Finally, inhibition of HDAC6 by tubastatin-A also induced a significant decrease in tumor growth in a cholangiocarcinoma animal model. Our data support a key role for primary cilia in malignant transformation, provide a plausible mechanism for their involvement, and suggest that restoration of primary cilia in tumor cells by HDAC6 targeting may be a potential therapeutic approach for cholangiocarcinoma. PMID:23370327

Gradilone, Sergio A; Radtke, Brynn N; Bogert, Pamela S; Huang, Bing Q; Gajdos, Gabriella B; LaRusso, Nicholas F

2013-01-31

221

Dietary rice component, Oryzanol, inhibits tumor growth in tumor-bearing Mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

Scope: We investigated the effects of rice bran and components on tumor growth in mice. Methods and results: Mice fed standard diets supplemented with rice bran, '-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet fo...

222

Netrin-4 regulates angiogenic responses and tumor cell growth  

SciTech Connect

Netrin-4 is a 628 amino acid basement membrane component that promotes neurite elongation at low concentrations but inhibits neurite extension at high concentrations. There is a growing body of literature suggesting that several molecules, including netrins, are regulators of both neuronal and vascular growth. It is believed that molecules that guide neural growth and development are also involved in regulating morphogenesis of the vascular tree. Further, netrins have recently been implicated in controlling epithelial cell branching morphogenesis in the breast, lung and pancreas. Characterization of purified netrin-4 in in vitro angiogenesis assays demonstrated that netrin-4 markedly inhibits HMVEC migration and tube formation. Moreover, netrin-4 inhibits proliferation of a variety of human tumor cells in vitro. Netrin-4 has only modest effects on proliferation of endothelial and other non-transformed cells. Netrin-4 treatment results in phosphorylation changes of proteins that are known to control cell growth. Specifically, Phospho-Akt-1, Phospho-Jnk-2, and Phospho-c-Jun are reduced in tumor cells that have been treated with netrin-4. Together, these data suggest a potential role for netrin-4 in regulating tumor growth.

Nacht, Mariana; St Martin, Thia B.; Byrne, Ann; Klinger, Katherine W.; Teicher, Beverly A. [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Madden, Stephen L. [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)], E-mail: steve.madden@genzyme.com; Jiang, Yide [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)], E-mail: yide.jiang@genzyme.com

2009-03-10

223

Non-diffeomorphic registration of brain tumor images by simulating tissue loss and tumor growth  

PubMed Central

Although a variety of diffeomorphic deformable registration methods exist in the literature, application of these methods in the presence of space-occupying lesions is not straightforward. The motivation of this work is spatial normalization of MR images from patients with brain tumors in a common stereotaxic space, aiming to pool data from different patients into a common space in order to perform group analyses. Additionally, transfer of structural and functional information from neuroanatomical brain atlases into the individual patient's space can be achieved via the inverse mapping, for the purpose of segmenting brains and facilitating surgical or radiotherapy treatment planning. A method that estimates the brain tissue loss and replacement by tumor is applied for achieving equivalent image content between an atlas and a patient's scan, based on a biomechanical model of tumor growth. Automated estimation of the parameters modeling brain tissue loss and displacement is performed via optimization of an objective function reflecting feature-based similarity and elastic stretching energy, which is optimized in parallel via APPSPACK (Asynchronous Parallel Pattern Search). The results of the method, applied to 21 brain tumor patients, indicate that the registration accuracy is relatively high in areas around the tumor, as well as in the healthy portion of the brain. Also, the calculated deformation in the vicinity of the tumor is shown to correlate highly with expert-defined visual scores indicating the tumor mass effect, thereby potentially leading to an objective approach to quantification of mass effect, which is commonly used in diagnosis.

Zacharaki, Evangelia I.; Hogea, Cosmina S.; Shen, Dinggang; Biros, George; Davatzikos, Christos

2009-01-01

224

Application of Meal Feeding and Skip-A-Day Feeding With or Without Probiotics for Broiler Chickens Grown at High-Altitude to Prevent Ascites Mortality  

Microsoft Academic Search

Problem statement: Ascites is a common rapid-growth-related problem in broiler chickens grown at high altitude where the partial pressure o f oxygen is low and is marginally adequate to support the growth performance and ascites-related variables. A mismatch between the growth of oxygen supplying organs and the oxygen demanding organs causes ascites in broiler chickens. In the present study, broilers

Ali Saffar; Fariborz Khajali

225

Vascular Endothelial Growth Factor as a Marker of Tumor Endothelium1  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that is a primary stimulant of the vascularization of solid tumors. VEGF production is induced by oncogenic gene mutations in the tumor cells and by hypoxic conditions inside the tumor mass. Hypoxia and the locally increased concentration of VEGF lead to an up-regulation of VEGF receptor expression on tumor endothelial

Rolf A. Brekken; Xianming Huang; Steven W. King; Philip E. Thorpe

1998-01-01

226

Pharmacologic activation of PKM2 slows lung tumor xenograft growth.  

PubMed

Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small-molecule PKM2 activators. The compounds exhibited low nanomolar activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of multiple lung cancer cell lines when serine was absent from the cell culture media. In addition, PKM2 activators inhibited the growth of an aggressive lung adenocarcinoma xenograft. These findings show that PKM2 activation by small molecules influences the growth of cancer cells in vitro and in vivo, and suggest that such compounds may augment cancer therapies. PMID:23720766

Parnell, K Mark; Foulks, Jason M; Nix, Rebecca N; Clifford, Adrianne; Bullough, Jeremy; Luo, Bai; Senina, Anna; Vollmer, David; Liu, Jihua; McCarthy, Virgil; Xu, Yong; Saunders, Michael; Liu, Xiao-Hui; Pearce, Scott; Wright, Kevin; O'Reilly, Marc; McCullar, Michael V; Ho, Koc-Kan; Kanner, Steven B

2013-05-29

227

Inhibition of Chlamydia trachomatis growth by recombinant tumor necrosis factor.  

PubMed Central

Purified human recombinant tumor necrosis factor (rTNF) alpha inhibited the growth of Chlamydia trachomatis (L2/434/Bu) in HEp-2 cell cultures. The inhibition of C. trachomatis yield could be achieved even when the rTNF alpha (200 ng/ml) was added up to 12 h after infection. The effect of rTNF alpha on chlamydial infection was synergistic with that of gamma interferon. Images

Shemer-Avni, Y; Wallach, D; Sarov, I

1988-01-01

228

Dominant-Negative Inhibition of Flk-1 Suppresses the Growth of Many Tumor Types in Vivo  

Microsoft Academic Search

Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including em bryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume. Several growth factor receptor tyrosine kinases have been implicated in angiogenesis, including receptors

Birgit Millauer; Michael P. Longhi; Karl H. Plate; Laura K. Shawver; Werner Risau; Axel Ullrich; Laurie M. Strawn

229

Mitochondrial dysfunction in breast cancer cells prevents tumor growth  

PubMed Central

Metformin is a well-established diabetes drug that prevents the onset of most types of human cancers in diabetic patients, especially by targeting cancer stem cells. Metformin exerts its protective effects by functioning as a weak “mitochondrial poison,” as it acts as a complex I inhibitor and prevents oxidative mitochondrial metabolism (OXPHOS). Thus, mitochondrial metabolism must play an essential role in promoting tumor growth. To determine the functional role of “mitochondrial health” in breast cancer pathogenesis, here we used mitochondrial uncoupling proteins (UCPs) to genetically induce mitochondrial dysfunction in either human breast cancer cells (MDA-MB-231) or cancer-associated fibroblasts (hTERT-BJ1 cells). Our results directly show that all three UCP family members (UCP-1/2/3) induce autophagy and mitochondrial dysfunction in human breast cancer cells, which results in significant reductions in tumor growth. Conversely, induction of mitochondrial dysfunction in cancer-associated fibroblasts has just the opposite effect. More specifically, overexpression of UCP-1 in stromal fibroblasts increases ?-oxidation, ketone body production and the release of ATP-rich vesicles, which “fuels” tumor growth by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells. Hence, the effects of mitochondrial dysfunction are truly compartment-specific. Thus, we conclude that the beneficial anticancer effects of mitochondrial inhibitors (such as metformin) may be attributed to the induction of mitochondrial dysfunction in the epithelial cancer cell compartment. Our studies identify cancer cell mitochondria as a clear target for drug discovery and for novel therapeutic interventions.

Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E.; Lamb, Rebecca; Hulit, James; Howell, Anthony; Gandara, Ricardo; Sartini, Marina; Rubin, Emanuel; Lisanti, Michael P.; Sotgia, Federica

2013-01-01

230

Interfacial properties in a discrete model for tumor growth  

NASA Astrophysics Data System (ADS)

We propose and study, by means of Monte Carlo numerical simulations, a minimal discrete model for avascular tumor growth, which can also be applied for the description of cell cultures in vitro. The interface of the tumor is self-affine and its width can be characterized by the following exponents: (i) the growth exponent ?=0.32(2) that governs the early time regime, (ii) the roughness exponent ?=0.49(2) related to the fluctuations in the stationary regime, and (iii) the dynamic exponent z=?/??1.49(2), which measures the propagation of correlations in the direction parallel to the interface, e.g., ??t1/z, where ? is the parallel correlation length. Therefore, the interface belongs to the Kardar-Parisi-Zhang universality class, in agreement with recent experiments of cell cultures in vitro. Furthermore, density profiles of the growing cells are rationalized in terms of traveling waves that are solutions of the Fisher-Kolmogorov equation. In this way, we achieved excellent agreement between the simulation results of the discrete model and the continuous description of the growth front of the culture or tumor.

Moglia, Belén; Guisoni, Nara; Albano, Ezequiel V.

2013-03-01

231

Inhibition of Early Tumor Growth Requires J18-positive (Natural Killer T) Cells1  

Microsoft Academic Search

The role of natural killer T (NKT) cells in the immune response to tumor cells has been largely unexplored. As a model of adoptive tumor immunotherapy, cells from the draining lymph nodes of mice immunized with a tumor-specific or irrelevant antigen were transferred to naive recipients with established tumor. Inhibition of early tumor growth (day 4) required the transfer of

Trina J. Stewart; Mark J. Smyth; Germain J. P. Fernando; Ian H. Frazer; Graham R. Leggatt

232

In-vivo visualization of melanoma tumor microvessels and blood flow velocity changes accompanying tumor growth  

NASA Astrophysics Data System (ADS)

We demonstrate that using micro multipoint laser Doppler velocimetry (?-MLDV) for noninvasive in-vivo imaging of blood vessels is useful for diagnosing malignant melanomas by comparison with visual diagnosis by dermoscopy. The blood flow velocity in microvessels varied during growth of melanomas transplanted in mouse ears. Mouse ears were observed by ?-MLDV up to 16 days after transplantation. The blood flow velocity in the tumor increased with increasing time and reached maximum of 4.5 mm/s at 9 days, which is more than twice that prior to transplantation. After 12 days, when the lesion had grown to an area of 6.6 mm2, we observed the formation of new blood vessels in the tumor. Finally, when the lesion had an area of 18 mm2 after 16 days, the flow velocity in the tumor decreased to approximately 3.2 mm/s.

Ishida, Hiroki; Hachiga, Tadashi; Andoh, Tsugunobu; Akiguchi, Shunsuke

2012-11-01

233

Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target.  

PubMed

We have previously reported that FuEP2/Ex2, a soluble decoy receptor for PGE2, suppresses tumor growth in an orthotopic xenograft model. To examine whether it has further uses, we examined the effect of FuEP2/Ex2 in an intraperitoneal metastasis model of ovarian cancer cells. We established FuEP2/Ex2-expressing ovarian cancer cells (SKOV/ip-FuEP2/Ex2) and injected them intraperitoneally into female nude mice. Mice injected with SKOV/ip-FuEP2/Ex2 had no ascitic fluid and showed smaller tumor lesions compared to mice injected with vector control cells, with decreased microvessel density and M2 macrophages. To identify molecular targets for combination treatment, we conducted cDNA microarray analysis and found three genes encoding enzyme [matrix metalloproteinase-7 (MMP-7), transmembrane protease serin 4 (TMPRSS4) and cytocrome P450 1B1 (CYP1B1)] to be upregulated in SKOV/ip-FuEP2/Ex2-derived tumors. Administration of TMPRSS4 inhibitor further reduced tumor weight and decreased the number of Ki-67?positive cells in SKOV/ip-FuEP2/Ex2-injected mice. These data indicate a possible EP-targeting strategy using FuEP2/Ex2 in the treatment of ovarian cancer and suggest that dual targeting of EP-mediated signaling and TMPRSS4 may enhance therapeutic value. PMID:23708855

Takahashi, Tetsuyuki; Uehara, Hisanori; Izumi, Keisuke

2013-05-24

234

Effect of Prebiotic on Gut Development and Ascites Incidence of Broilers Reared in a Hypoxic Environment1  

Microsoft Academic Search

Modern broilers have been genetically se- lected for an increased growth rate and improved feed conversion, but they are also more susceptible to ascites. Ascites occurs when there is an imbalance between avail- able oxygen and the oxygen demand of the broiler. We hypothesized that promoting neonatal gut development with a prebiotic, such as Aspergillus meal (Prebiotic-AM), would enhance gut

F. Solis; M. B. Farnell; G. Tellez; J. M. Balog; N. B. Anthony; A. Torres-Rodriguez; S. Higgins; B. M. Hargis; A. M. Donoghue

235

Carbohydrate Metabolism in Ascites Tumor Cells  

Microsoft Academic Search

Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences) Find Similar Abstracts: Use: Authors Title Return: Query Results Return items starting with number Query Form Database: Astronomy Physics arXiv e-prints

Efraim Racker

1956-01-01

236

A novel fusicoccin derivative preferentially targets hypoxic tumor cells and inhibits tumor growth in xenografts.  

PubMed

Malignant cells in solid tumors survive under prolonged hypoxia and can be a source of resistance to current cancer therapies. Tumor hypoxia is also associated with a more malignant phenotype and poor survival in cancer patients. Recent progress in our understanding of the biology of tumor cells under hypoxia has led to increased attention on targeting hypoxia for cancer therapy. We report here that a novel fusicoccin derivative (ISIR-042), but not its parent or related compounds such as fusicoccin A and cotylenin A, is more cytotoxic to hypoxic cells than to normoxic cells. The hypoxia-induced accumulation of hypoxia-inducible factor (HIF)-1? and the phosphorylation of Akt were effectively inhibited by treatment with ISIR-042, suggesting that the preferential cytotoxicity toward hypoxic cells is associated with a reduction of HIF-1? and Akt activation. ISIR-042 inhibited the growth of human pancreatic cancer MIAPaCa-2 cells while sparing normal endothelial cells, and significantly inhibited the growth of MIAPaCa-2 cells as xenografts without apparent adverse effects. Pancreatic cancer cells expressing CD24 and CD44 exhibited characteristics of stem cells. Treatment with gemcitabine increased this stem cell-enriched population, and this effect was significantly inhibited by ISIR-042, suggesting that ISIR- 042 preferentially inhibits stem/progenitors in pancreatic cancer cell lines compared with chemotherapeutic agents. These results suggest that ISIR-042 may be a potential therapeutic agent for hypoxic tumors such as pancreatic cancer. PMID:22263802

Kawakami, Koshi; Hattori, Miho; Inoue, Takatsugu; Maruyama, Yuriko; Ohkanda, Junko; Kato, Nobuo; Tongu, Miki; Yamada, Takaya; Akimoto, Miho; Takenaga, Keizo; Sassa, Takeshi; Suzumiy, Junji; Honma, Yoshio

2012-09-01

237

Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis  

PubMed Central

Heparan sulfate glycosaminoglycans, present at the cell surface and in the extracellular matrix that surrounds cells, are important mediators of complex biological processes. Furthermore, it is now apparent that cells dynamically regulate the structure of their heparan sulfate “coat” to differentially regulate extracellular signals. In the present study, the importance of sequence information contained within tumor cell-surface heparan sulfate was investigated. Herein, we demonstrate that the heparan sulfate glycosaminoglycan coat present on tumor cells contains bioactive sequences that impinge on tumor-cell growth and metastasis. Importantly, we find that growth promoting as well as growth inhibiting sequences are contained within the polysaccharide coat. Furthermore, we find that the dynamic balance between these distinct polysaccharide populations regulates specific intracellular signal-transduction pathways. This study not only provides a framework for the development of polysaccharide-based anti-cancer molecules but also underscores the importance of understanding a cell's polysaccharide array in addition to its protein complement, to understand how genotype translates to phenotype in this postgenomic age.

Liu, Dongfang; Shriver, Zachary; Venkataraman, Ganesh; El Shabrawi, Yosuf; Sasisekharan, Ram

2002-01-01

238

Review of Growth Inhibitory Peptide as a Biotherapeutic agent for tumor growth, adhesion, and metastasis  

Microsoft Academic Search

This review surveys the biological activities of an alpha-fetoprotein (AFP) derived peptide termed the Growth Inhibitory Peptide (GIP), which is a synthetic 34 amino acid segment produced from the full length 590 amino acid AFP molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult terminally-differentiated cells. The mechanism of action

M. Muehlemann; K. D. Miller; M. Dauphinee; G. J. Mizejewski

2005-01-01

239

Update of Alpha Fetoprotein Growth-Inhibitory Peptides as Biotherapeutic Agents for Tumor Growth and Metastasis  

Microsoft Academic Search

The present update describes the biological activities of an alpha fetoprotein (AFP)-derived peptide termed the growth-inhibitory peptide (GIP), which is a synthetic 34-amino acid segment produced from the native molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult cells. Even though its mechanism of action has not been completely elucidated,

G. J. Mizejewski; M. Muehlemann; M. Dauphinee

2006-01-01

240

Management of ascites with hydrothorax  

SciTech Connect

Hydrothorax occurs in 5.3 percent of ascitic patients. Experience with 22 cases forms the basis of this report. Of the 22 cases, 21 were spontaneous and 1 was due to transdiaphragmatic incision. Usually fluid enters the chest through tiny defects in the diaphragm. These defects are often covered by pleuroperitoneum, but the high abdominal pressure raises a bleb on the superior surface of the diaphragm. Rupture produces hydrothorax. The ascites is often relieved with the onset of the hydrothorax. Blockage of the thoracic duct has produced chylous ascites. The thoracoabdominal communication is immediately confirmed by a scan of the chest and abdomen after intraperitoneal injection of technetium-99 colloid. The rate at which the technetium-99 enters the chest is related to the size of the defect in the diaphragm. A significant transfer should occur within 12 hours. Immediate transfer occurs with large defects. The ruptured blister on the diaphragm forms a one-way valve. Intrathoracic injection does not migrate into the peritoneal cavity. The valvular characteristics of the leak force ascitic fluid into the thorax because the differential pressure between the abdominal and pleural cavities is intensified by inspiration. If tension hydrothorax has occurred, urgent thoracocentesis and paracentesis may be required. A chest tube should not be introduced. The main principle of surgery is to supply a low resistance pathway for the return of fluid to the venous system and to eliminate the diaphragmatic defect by obliteration of the pleural space. A LeVeen peritoneovenous shunt is performed after emptying the abdomen of its fluid load. After completion of the shunt operation, the chest is emptied of fluid, and a sclerosing agent (tetracycline or nitrogen mustard) is injected into the pleural cavity. With this regime, the defect closed or was rendered insignificant in 18 of 22 patients.

LeVeen, H.H.; Piccone, V.A.; Hutto, R.B.

1984-08-01

241

Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a, iNOS, COX-2, IL-1?, IL-6, IFN-?, IL-2, GM-CSF) and pro-angiogenic growth factor- VEGF.  

PubMed

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/ kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (?-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-?) in animals with DLA induced solid tumours. Increase in CD4+ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent. PMID:23886206

Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

2013-01-01

242

(Accumulation of methyl-deficient rat liver messenger ribonucleic acid on ethionine administration). Progress report. [Methyltransferase activity in Ehrlich ascites tumor cells and effects of phorbol ester on methyltransferase activity  

SciTech Connect

Enzyme fractions were isolated from Ehrlich ascites cells which introduced methyl groups into methyl deficient rat liver mRNA and unmethylated vaccinia mRNA. The methyl groups were incorporated at the 5' end into cap 1 structures by the viral enzyme, whereas both cap 0 and cap 1 structures were formed by the Ehrlich ascites cell enzymes. Preliminary results indicate the presence of adenine N/sup 6/-methyltransferase activity in Ehrlich ascites cells. These results indicate that mRNA deficient in 5'-cap methylation and in internal methylation of adenine accumulated in rats on exposure to ethionine. The methyl-deficient mRNA isolated from the liver of ethionine-fed rats differed in its translational properties from mRNA isolated from control animals. Preliminary experiments indicate that single topical application of 17n moles of TPA to mouse skin altered tRNA methyltransferases. The extent of methylation was increased over 2-fold in mouse skin treated with TPA for 48 hours. These changes have been observed as early as 12 hours following TPA treatment. In contrast, the application of initiating dose of DMBA had no effect on these enzymes. It should be emphasized that the changes in tRNA methyltransferases produced by TPA are not merely an increase of the concentration of the enzyme, rather that they represent alterations of specificity of a battery of enzymes. In turn the change in enzyme specificity can produce alterations in the structure of tRNA. (ERB)

Borek, E.

1980-01-01

243

Reduced Survival of Rectal Cancer Patients With Increased Tumor Epidermal Growth Factor Receptor Levels  

Microsoft Academic Search

PURPOSE: The epidermal growth factor receptor and its various ligands (epidermal growth factor, transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, heregulin, and betacellulin) have been implicated in growth and regeneration of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. Although some studies have investigated levels of epidermal growth factor receptor by radioligand binding

Reinhard Kopp; Elisabeth Rothbauer; Elisabeth Mueller; FriedrichWilhelm Schildberg; Karl-Walter Jauch; Andreas Pfeiffer

2003-01-01

244

Adapting a transforming growth factor -related tumor protection strategy to enhance antitumor immunity  

Microsoft Academic Search

Transforming growth factor (TGF-), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhib- its tumor-specific cellular immunity. Tu- mors can avoid the differentiating and apoptotic effects of TGF- by expressing a nonfunctional TGF- receptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-specific cytotoxic T lymphocytes

Catherine M. Bollard; Claudia Rossig; M. Julia Calonge; M. Helen; Hans-Joachim Wagner Huls; Joan Massague; Malcolm K. Brenner; Helen E. Heslop; Cliona M. Rooney

2002-01-01

245

Identification of Sonic Hedgehog-Induced Stromal Factors That Stimulate Prostate Tumor Growth.  

National Technical Information Service (NTIS)

We will determine the mechanism by which Shh signaling accelerates prostate tumor growth, identify Shh targets in prostate tumor stroma, and test the effect of individual target genes on tumor growth. The purpose of the report is to evaluate the second ye...

A. Shaw W. Bushman

2007-01-01

246

Tumor-derived expression of vascular endothelial growth factor is a critical factor in tumor expansion and vascular function.  

PubMed

There is considerable controversy concerning the importance of tumor-derived angiogenic factors to the neovascularization of solid tumors. Tumor, endothelial, and stromal expression of vascular endothelial growth factor (VEGF) have been hypothesized to be critical for tumor angiogenesis. To determine the relative contribution of tumor versus nontransformed tissue expression of VEGF to tumor growth, we used gene targeting and cre-loxP recombination to generate embryonic stem cell lines in which VEGF can be conditionally deleted. These lines were used to derive mouse embryonic fibroblast lines with null mutations in both alleles of VEGF. Upon immortalization and H-ras transformation, we used these VEGF null fibroblasts to make fibrosarcomas in immunocompromised mice. We report that tumorigenic VEGF expression is critical for ras-mediated tumorigenesis, and the loss of tumorigenic expression causes dramatic decreases in vascular density and vascular permeability and increases in tumor cell apoptosis. PMID:10197634

Grunstein, J; Roberts, W G; Mathieu-Costello, O; Hanahan, D; Johnson, R S

1999-04-01

247

Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.  

PubMed Central

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis. Images

Connolly, D T; Heuvelman, D M; Nelson, R; Olander, J V; Eppley, B L; Delfino, J J; Siegel, N R; Leimgruber, R M; Feder, J

1989-01-01

248

Dynamic density functional theory of solid tumor growth: Preliminary models  

PubMed Central

Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT) extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth.

Chauviere, Arnaud; Hatzikirou, Haralambos; Kevrekidis, Ioannis G.; Lowengrub, John S.; Cristini, Vittorio

2012-01-01

249

Chronic stress promotes tumor growth through increased BDNF production and neo-innervation  

Microsoft Academic Search

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor

Julie K Allen

2012-01-01

250

Tumor-host interaction: Analysis of cytokines, growth factors, and tumorinfiltrating lymphocytes in ovarian carcinomas  

Microsoft Academic Search

The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients

Athir J Merogi; Aizen J Marrogi; Rajagopal Ramesh; William R Robinson; Cesar D Fermin; Scott M Freeman

1997-01-01

251

Squalamine Inhibits Angiogenesis and Solid Tumor Growth in Vivo and Perturbs Embryonic Vasculature1  

Microsoft Academic Search

The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cyto- toxic to tumor cells, does not alter mitogen production by tumor

Allen K. Sills; Jon I. Williams; Betty M. Tyler; Darin S. Epstein; Eric P. Sipos; John D. Davis; Michael P. McLane; Simon Pitchford; Kimberly Cheshire; Francis H. Gannon; William A. Kinney; Tessa L. Chao; Mark Donowitz; John Laterra; Michael Zasloff; Henry Brem

252

Notch1 and Notch2 Have Opposite Effects on Embryonal Brain Tumor Growth  

Microsoft Academic Search

The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene in some neoplasms, and a tumor suppressor in others. Here, we show that different Notch receptors can have opposite effects in a single tumor type. Expression of truncated, constitutively active Notch1 or Notch2 in embryonal brain tumor cell lines caused antagonistic effects on tumor growth. Cell

Xing Fan; Irina Mikolaenko; Ihab Elhassan; XingZhi Ni; Yunyue Wang; Douglas Ball; Daniel J. Brat; Arie Perry; Charles G. Eberhart

2004-01-01

253

Effect of dietary aspirin on ascites in broilers raised in a hypobaric chamber.  

PubMed

During the course of ascites development in broilers, many factors can interact to cause hypoxia. To counteract hypoxia, birds with ascites develop greatly increased hematocrit and red cell counts. Increasing hematocrits result in more viscous blood. Prostaglandins are involved in the regulation of constriction and dilation of pulmonary blood vessels and in the formation of blood clots. Dietary aspirin, a prostaglandin inhibitor, was used in an attempt to promote vasodilation and inhibit blood clotting in broilers, with the objective of determining the effect of aspirin on ascites progression. The experimental design consisted of two trials with a total of 1,360, 1-d-old male broiler chicks, which were placed at either local altitude (390 m above sea level) or in a hypobaric chamber that simulated an altitude of 2,900 m above sea level. At each elevation, five dietary treatments were employed: [control, 0.025% crystalline acetylsalicylic acid (aspirin), 0.05% aspirin, 0.10% aspirin, and 0.20% aspirin]. Bird and feed weights were recorded weekly. At the end of 5 wk, blood samples and organ weights were collected, and all birds were examined for signs of ascites. In both trials, birds raised at high altitudes were significantly lighter, had a higher incidence of ascites, and had differences in hematology, compared with birds raised at local elevation. Only in Trial 2, however, did dietary aspirin appear to have any effect on ascites incidence. At the 0.20% aspirin level, a reduction in ascites incidence approached significance compared with controls (34% vs. 56%, P < or = 0.06). Unfortunately, birds fed 0.20% aspirin also were significantly (P < or = 0.01) lighter than controls. Because slowing growth rate is known to reduce ascites, this decrease in BW may have been partially responsible for any beneficial effect on ascites development and progression obtained through feeding aspirin. PMID:10947177

Balog, J M; Huff, G R; Rath, N C; Huff, W E

2000-08-01

254

VCC-1, a novel chemokine, promotes tumor growth  

SciTech Connect

We have identified a novel human gene by transcriptional microarray analysis, which is co-regulated in tumors and angiogenesis model systems with VEGF expression. Isolation of cDNA clones containing the full-length VCC-1 transcript from both human and mouse shows a 119 amino acid protein with a 22 amino acid cleavable signal sequence in both species. Comparison of the protein product of this gene with hidden Markov models of all known proteins shows weak but significant homology with two known chemokines, SCYA17 and SCYA16. Northern analysis of human tissues detects a 1 kb band in lung and skeletal muscle. Murine VCC-1 expression can also be detected in lung as well as thyroid, submaxillary gland, epididymis, and uterus tissues by slot blot analysis. By quantitative real time RT-PCR 71% of breast tumors showed 3- to 24-fold up-regulation of VCC-1. In situ hybridization of breast carcinomas showed strong expression of the gene in both normal and transformed mammary gland ductal epithelial cells. In vitro, human microvascular endothelial cells grown on fibronectin increase VCC-1 expression by almost 100-fold. In addition, in the mouse angioma endothelial cell line PY4.1 the gene was over-expressed by 28-fold 6 h after induction of tube formation while quiescent and proliferating cells showed no change. VCC-1 expression is also increased by VEGF and FGF treatment, about 6- and 5-fold, respectively. Finally, 100% of mice injected with NIH3T3 cells over-expressing VCC-1 develop rapidly progressing tumors within 21 days while no growth is seen in any control mice injected with NIH3T3 cells containing the vector alone. These results strongly suggest that VCC-1 plays a role in angiogenesis and possibly in the development of tumors in some tissue types.

Weinstein, Edward J. [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Head, Richard [Department of Genomics and Biotechnology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Griggs, David W. [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Sun Duo [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Evans, Robert J. [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Swearingen, Michelle L. [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Westlin, Marisa M. [Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States); Mazzarella, Richard [Department of Genomics and Biotechnology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198 (United States)]. E-mail: richard.a.mazzarella@pfizer.com

2006-11-10

255

T model of growth and its application in systems of tumor-immune dynamics.  

PubMed

In this paper we introduce a new growth model called T growth model. This model is capable of representing sigmoidal growth as well as biphasic growth. This dual capability is achieved without introducing additional parameters. The T model is useful in modeling cellular proliferation or regression of cancer cells, stem cells, bacterial growth and drug dose-response relationships. We recommend usage of the T growth model for the growth of tumors as part of any system of differential equations. Use of this model within a system will allow more flexibility in representing the natural rate of tumor growth. For illustration, we examine some systems of tumor-immune interaction in which the T growth rate is applied. We also apply the model to a set of tumor growth data. PMID:23906156

Tabatabai, Mohammad A; Eby, Wayne M; Singh, Karan P; Bae, Sejong

2013-06-01

256

Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models.  

PubMed

Tumor growth and progression rely upon angiogenesis, which is regulated by pro- and antiangiogenic factors, including members of the semaphorin family. By analyzing 3 different mouse models of multistep carcinogenesis, we show here that during angiogenesis, semaphorin 3A (Sema3A) is expressed in ECs, where it serves as an endogenous inhibitor of angiogenesis that is present in premalignant lesions and lost during tumor progression. Pharmacologic inhibition of endogenous Sema3A during the angiogenic switch, the point when pretumoral lesions initiate an angiogenic phase that persists throughout tumor growth, enhanced angiogenesis and accelerated tumor progression. By contrast, when, during the later stages of carcinogenesis following endogenous Sema3A downmodulation, Sema3A was ectopically reintroduced into islet cell tumors by somatic gene transfer, successive waves of apoptosis ensued, first in ECs and then in tumor cells, resulting in reduced vascular density and branching and inhibition of tumor growth and substantially extended survival. Further, long-term reexpression of Sema3A markedly improved pericyte coverage of tumor blood vessels, something that is thought to be a key property of tumor vessel normalization, and restored tissue normoxia. We conclude, therefore, that Sema3A is an endogenous and effective antiangiogenic agent that stably normalizes the tumor vasculature. PMID:19809158

Maione, Federica; Molla, Fabiola; Meda, Claudia; Latini, Roberto; Zentilin, Lorena; Giacca, Mauro; Seano, Giorgio; Serini, Guido; Bussolino, Federico; Giraudo, Enrico

2009-10-05

257

Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models  

PubMed Central

Tumor growth and progression rely upon angiogenesis, which is regulated by pro- and antiangiogenic factors, including members of the semaphorin family. By analyzing 3 different mouse models of multistep carcinogenesis, we show here that during angiogenesis, semaphorin 3A (Sema3A) is expressed in ECs, where it serves as an endogenous inhibitor of angiogenesis that is present in premalignant lesions and lost during tumor progression. Pharmacologic inhibition of endogenous Sema3A during the angiogenic switch, the point when pretumoral lesions initiate an angiogenic phase that persists throughout tumor growth, enhanced angiogenesis and accelerated tumor progression. By contrast, when, during the later stages of carcinogenesis following endogenous Sema3A downmodulation, Sema3A was ectopically reintroduced into islet cell tumors by somatic gene transfer, successive waves of apoptosis ensued, first in ECs and then in tumor cells, resulting in reduced vascular density and branching and inhibition of tumor growth and substantially extended survival. Further, long-term reexpression of Sema3A markedly improved pericyte coverage of tumor blood vessels, something that is thought to be a key property of tumor vessel normalization, and restored tissue normoxia. We conclude, therefore, that Sema3A is an endogenous and effective antiangiogenic agent that stably normalizes the tumor vasculature.

Maione, Federica; Molla, Fabiola; Meda, Claudia; Latini, Roberto; Zentilin, Lorena; Giacca, Mauro; Seano, Giorgio; Serini, Guido; Bussolino, Federico; Giraudo, Enrico

2009-01-01

258

Growth of Human Tumor Xenografts Implanted under the Renal Capsule of Normal Immunocompetent Mice  

Microsoft Academic Search

The subrenal capsule technique proved effective in demonstrating that the growth of human tumors in normal, immunocompetent animals for 6 days was quantifiable in ocular micrometer units. Positive growth was demonstrable not only with human tumors that had been established in serial transplantation in athymic nude mouse hosts, but also with primary surgical explants. Growth rates of transplantation-established xenograft systems

Arthur E. Bogden; Paula M. Haskell; Doreen J. LePage; Diane E. Kelton; William R. Cobb; Henry J. Esber

1979-01-01

259

Emerging treatment options for management of malignant ascites in patients with ovarian cancer.  

PubMed

Malignant ascites affects approximately 10% of patients with recurrent epithelial ovarian cancer and is associated with troublesome symptoms, including abdominal pressure and distension, dyspnea, bloating, pelvic pain, and bowel/bladder dysfunction. To date, no effective therapy has been identified for the treatment of malignant ascites in patients with recurrent, advanced ovarian cancer. In this article, we discuss currently existing options for the treatment of ascites associated with ovarian cancer, and review the literature as it pertains to novel, targeted therapies. Specifically, preclinical and clinical trials exploring the use of the antiangiogenic agents, bevacizumab and vascular endothelial growth factor-trap, as well as the nonangiogenic agent, catumaxomab, will be reviewed. Despite current limitations in treatment, knowledge regarding management options in the palliation of ascites is critical to practicing physicians. Ultimately, as with all novel therapies, symptom relief and treatment goals must be weighed against patient discomfort and potentially significant adverse events. PMID:22927770

Eskander, Ramez N; Tewari, Krishnansu S

2012-08-03

260

Emerging treatment options for management of malignant ascites in patients with ovarian cancer  

PubMed Central

Malignant ascites affects approximately 10% of patients with recurrent epithelial ovarian cancer and is associated with troublesome symptoms, including abdominal pressure and distension, dyspnea, bloating, pelvic pain, and bowel/bladder dysfunction. To date, no effective therapy has been identified for the treatment of malignant ascites in patients with recurrent, advanced ovarian cancer. In this article, we discuss currently existing options for the treatment of ascites associated with ovarian cancer, and review the literature as it pertains to novel, targeted therapies. Specifically, preclinical and clinical trials exploring the use of the antiangiogenic agents, bevacizumab and vascular endothelial growth factor-trap, as well as the nonangiogenic agent, catumaxomab, will be reviewed. Despite current limitations in treatment, knowledge regarding management options in the palliation of ascites is critical to practicing physicians. Ultimately, as with all novel therapies, symptom relief and treatment goals must be weighed against patient discomfort and potentially significant adverse events.

Eskander, Ramez N; Tewari, Krishnansu S

2012-01-01

261

Growth hormone releasing hormone plasmid supplementation, a potential treatment for cancer cachexia, does not increase tumor growth in nude mice  

Microsoft Academic Search

Growth hormone releasing hormone (GHRH) is known to have multiple anabolic effects and immune-stimulatory effects. Previous studies suggest that treatment with anabolic hormones also has the potential to mitigate the deleterious effects of cancer cachexia in animals. We studied the effects of plasmid-mediated GHRH supplementation on tumor growth and the role of antitumor immune cells with two different human tumor

Amir S Khan; Louis C Smith; Ingrid W Anscombe; Kathleen K Cummings; Melissa A Pope; Ruxandra Draghia-Akli

2005-01-01

262

Antenatal Ultrasonographic Appearance of Isolated Fetal Ascites  

Microsoft Academic Search

Background: Isolated fetal ascites can be caused by many heterogeneous disorders and is associated with a variety of conditions. Cloacal anomalies are rare abnormalities with a highly variable array of sonographic symptoms, which make them difficult to diagnose antenatally. We present a case with isolated fetal ascites without hydronephrosis caused by a cloacal malformation. Case: A 28-year-old woman, gravida 2,

I. Staboulidou; J. Schauer; G. A. Rau; R. Hass; B. Hollwitz; A. Scharf

2006-01-01

263

Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF)  

Microsoft Academic Search

Tumor growth is associated with angiogenesis and inflammation and the endogenous lipid, platelet activating factor (PAF), is a pro-inflammatory and pro-angiogenic mediator. We therefore measured tumor growth, angiogenesis and inflammation in normal (WT) mice and those lacking the receptor for PAF, through gene deletion (PAFR-KO). Growth of solid tumors derived from colon 26 cells was not altered but that from

M. A. N. D. Ferreira; L. S. Barcelos; M. M. Teixeira; Y. S. Bakhle; S. P. Andrade

2007-01-01

264

Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models  

Microsoft Academic Search

Purpose  New research findings have revealed a key role for vascular endothelial growth factor (VEGF) in the stimulation of angiogenesis\\u000a in clear cell renal carcinoma (RCC) which is a highly vascularized and treatment-resistant tumor. Sorafenib (BAY 43-9006,\\u000a Nexavar®) is a multi-kinase inhibitor which targets receptor tyrosine and serine\\/threonine kinases involved in tumor progression and\\u000a tumor angiogenesis. The effect of sorafenib on

Yong S. Chang; Jalila Adnane; Pamela A. Trail; Joan Levy; Arris Henderson; Dahai Xue; Elizabeth Bortolon; Marina Ichetovkin; Charles Chen; Angela McNabola; Dean Wilkie; Christopher A. Carter; Ian C. A. Taylor; Mark Lynch; Scott Wilhelm

2007-01-01

265

Bone cancer pain: the effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis  

Microsoft Academic Search

Patients with metastatic breast, lung or prostate cancer frequently have significant bone cancer pain. In the present report we address, in a single in vivo mouse model, the effects the bisphosphonate alendronate has on bone cancer pain, bone remodeling and tumor growth and necrosis. Following injection and confinement of green fluorescent protein-transfected murine osteolytic tumor cells into the marrow space

Molly A. Sevcik; Nancy M. Luger; David B. Mach; Mary Ann C. Sabino; Christopher M. Peters; Joseph R. Ghilardi; Matthew J. Schwei; Heidi Röhrich; Carmen De Felipe; Michael A. Kuskowski; Patrick W. Mantyh

2004-01-01

266

Management of ascites due to gastrointestinal malignancy  

PubMed Central

Ascites is the pathological accumulation of fluid within the abdominal cavity. The most common cancers associated with ascites are adenocarcinomas of the ovary, breast, colon, stomach and pancreas. Symptoms include abdominal distension, nausea, vomiting, early satiety, dyspnea, lower extremity edema, weight gain and reduced mobility. There are many potential causes of ascites in cancer patients, including peritoneal carcinomatosis, malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome and peritoneal infections. Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually indicated as it will impact both prognosis and the treatment approach. Key tests include serum albumin and protein and a simultaneous diagnostic paracentesis, checking ascitic fluid, WBCs, albumin, protein and cytology. Median survival after diagnosis of malignant ascites is in the range of 1 to 4 months; survival is apt to be longer for ovarian and breast cancers if systemic anti-cancer treatments are available.

Saif, Muhammad W.; Siddiqui, Imran A. P.; Sohail, Muhammad A.

2009-01-01

267

Epidermal growth factor receptor expression in oligodendroglial tumors.  

PubMed Central

A series of 13 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) was studied for gene amplification and expression of the epidermal growth factor receptor gene (EGFR). EGFR gene amplification was found in only one case of anaplastic oligodendroglioma, which additionally showed a deletion/rearrangement at the 5' end of the gene. Northern blot analysis, however, revealed increases of EGFR mRNA expression relative to non-neoplastic control brain in 6 of 13 oligodendrogliomas and 10 of 18 anaplastic oligodendrogliomas. All cases with increased mRNA expression showed strong immunoreactivity for EGFR protein. Our findings thus indicate that increased expression of EGFR mRNA and protein is common in low-grade and high-grade oligodendroglial tumors and in the vast majority of cases is not caused by gene amplification. Images Figure 1 Figure 2 Figure 3

Reifenberger, J.; Reifenberger, G.; Ichimura, K.; Schmidt, E. E.; Wechsler, W.; Collins, V. P.

1996-01-01

268

Photoacoustic endoscopic imaging study of melanoma tumor growth in a rat colorectum in vivo  

NASA Astrophysics Data System (ADS)

We performed a photoacoustic endoscopic imaging study of melanoma tumor growth in a nude rat in vivo. After inducing the tumor at the colorectal wall of the animal, we monitored the tumor development in situ by using a photoacoustic endoscopic system. This paper introduces our experimental method for tumor inoculation and presents imaging results showing the morphological changes of the blood vasculature near the tumor region according to the tumor progress. Our study could provide insights for future studies on tumor development in small animals.

Li, Chiye; Yang, Joon-Mo; Chen, Ruimin; Zhang, Yu; Xia, Younan; Zhou, Qifa; Shung, K. Kirk; Wang, Lihong V.

2013-03-01

269

Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor  

PubMed Central

Growth of tumors and metastasis are processes known to require neovascularization. To ascertain the participation of the endogenous angiogenic inhibitor thrombospondin-1 (TSP1) in tumor progression, we generated mammary tumor-prone mice that either lack, or specifically overexpress, TSP1 in the mammary gland. Tumor burden and vasculature were significantly increased in TSP1-deficient animals, and capillaries within the tumor appeared distended and sinusoidal. In contrast, TSP1 overexpressors showed delayed tumor growth or lacked frank tumor development (20% of animals); tumor capillaries showed reduced diameter and were less frequent. Interestingly, absence of TSP1 resulted in increased association of vascular endothelial growth factor (VEGF) with its receptor VEGFR2 and higher levels of active matrix metalloproteinase-9 (MMP9), a molecule previously shown to facilitate both angiogenesis and tumor invasion. In vitro, enzymatic activation of proMMP9 was suppressed by TSP1. Together these results argue for a protective role of endogenous inhibitors of angiogenesis in tumor growth and implicate TSP1 in the in vivo regulation of metalloproteinase-9 activation and VEGF signaling.

Rodriguez-Manzaneque, Juan Carlos; Lane, Timothy F.; Ortega, Maria Asuncion; Hynes, Richard O.; Lawler, Jack; Iruela-Arispe, M. Luisa

2001-01-01

270

Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis.  

PubMed

Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory cells. We found that tumor-associated adipocytes also contribute to inflammation. We have analyzed peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in peritumoral versus counterpart adipose tissues. CD11b(+) macrophages contributed strongly to the inflammatory activity. These macrophages were isolated from peritumoral adipose tissue and found to over-express ARG1, NOS2, CD301, CD163, MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors implanted at a site distant from subcutaneous, anterior adipose tissue were strongly growth-delayed, had fewer blood vessels and were less populated by CD11b(+) macrophages. In contrast to normal adipose tissue, micro-dissected peritumoral adipose tissue explants launched numerous vascular sprouts when cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue fuels the growth of malignant cells by acting as a proximate source for vascular endothelium and activated pro-inflammatory cells, in particular macrophages. PMID:22614697

Wagner, Marek; Bjerkvig, Rolf; Wiig, Helge; Melero-Martin, Juan M; Lin, Ruei-Zeng; Klagsbrun, Michael; Dudley, Andrew C

2012-05-22

271

Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis  

PubMed Central

Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory cells. We found that tumor-associated adipocytes also contribute to inflammation. We have analyzed peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in peritumoral versus counterpart adipose tissues. CD11b+ macrophages contributed strongly to the inflammatory activity. These macrophages were isolated from peritumoral adipose tissue and found to overexpress ARG1, NOS2, CD301, CD163, MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors implanted at a site distant from subcutaneous, anterior adipose tissue were strongly growth-delayed, had fewer blood vessels and were less populated by CD11b+ macrophages. In contrast to normal adipose tissue, micro-dissected peritumoral adipose tissue explants launched numerous vascular sprouts when cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue fuels the growth of malignant cells by acting as a proximate source for vascular endothelium and activated pro-inflammatory cells, in particular macrophages.

Wagner, Marek; Bjerkvig, Rolf; Wiig, Helge; Melero-Martin, Juan M.; Lin, Ruei-Zeng; Klagsbrun, Michael

2013-01-01

272

Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging  

PubMed Central

Transplantation models using human brain tumor cells have served an essential function in neuro-oncology research for many years. In the past, the most commonly used procedure for human tumor xenograft establishment consisted of the collection of cells from culture flasks, followed by the subcutaneous injection of the collected cells in immunocompromised mice. Whereas this approach still sees frequent use in many laboratories, there has been a significant shift in emphasis over the past decade towards orthotopic xenograft establishment, which, in the instance of brain tumors, requires tumor cell injection into appropriate neuroanatomical structures. Because intracranial xenograft establishment eliminates the ability to monitor tumor growth through direct measurement, such as by use of calipers, the shift in emphasis towards orthotopic brain tumor xenograft models has necessitated the utilization of non-invasive imaging for assessing tumor burden in host animals. Of the currently available imaging methods, bioluminescence monitoring is generally considered to offer the best combination of sensitivity, expediency, and cost. Here, we will demonstrate procedures for orthotopic brain tumor establishment, and for monitoring tumor growth and response to treatment when testing experimental therapies.

Ozawa, Tomoko; James, C. David

2010-01-01

273

Preliminary investigation of the inhibitory effects of mechanical stress in tumor growth  

NASA Astrophysics Data System (ADS)

In the past years different models have been formulated to explain the growth of gliomas in the brain. The most accepted model is based on a reaction-diffusion equation that describes the growth of the tumor as two separate components- a proliferative component and an invasive component. While many improvements have been made to this basic model, the work exploring the factors that naturally inhibit growth is insufficient. It is known that stress fields affect the growth of normal tissue. Due to the rigid skull surrounding the brain, mechanical stress might be an important factor in inhibiting the growth of gliomas. A realistic model of glioma growth would have to take that inhibitory effect into account. In this work a mathematical model based on the reaction-diffusion equation was used to describe tumor growth, and the affect of mechanical stresses caused by the mass effect of tumor cells was studied. An initial tumor cell concentration with a Gaussian distribution was assumed and tumor growth was simulated for two cases- one where growth was solely governed by the reaction-diffusion equation and second where mechanical stress inhibits growth by affecting the diffusivity. All the simulations were performed using the finite difference method. The results of simulations show that the proposed mechanism of inhibition could have a significant affect on tumor growth predictions. This could have implications for varied applications in the imaging field that use growth models, such as registration and model updated surgery.

Garg, Ishita; Miga, Michael I.

2008-04-01

274

Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect  

Microsoft Academic Search

Background: The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells with increased glycolysis and decreased mitochondrial activity. However, ''aerobic glycolysis'' generates fewer ATP per glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how increasing a less efficient process provides tumors with a growth advantage. Methods\\/Findings:

Yijun Chen; Rob Cairns; Ioanna Papandreou; Albert Koong; Nicholas C. Denko

2009-01-01

275

Preventing Growth of Brain Tumors by Creating a Zone of Resistance  

Microsoft Academic Search

Glioblastoma multiforme (GBM) is a devastating form of brain cancer for which there is no effective treatment. Here, we report a novel approach to brain tumor therapy through genetic modification of normal brain cells to block tumor growth and effect tumor regression. Previous studies have focused on the use of vector-based gene therapy for GBM by direct intratumoral injection with

Casey A Maguire; Dimphna H Meijer; Stanley G LeRoy; Laryssa A Tierney; Marike LD Broekman; Fabricio F Costa; Xandra O Breakefield; Anat Stemmer-Rachamimov; Miguel Sena-Esteves

2008-01-01

276

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization  

SciTech Connect

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

Leung, F.L.; Park, J.F.; Dagle, G.E.

1993-06-01

277

Astatine-211-tellurium radiocolloid cures experimental malignant ascites  

SciTech Connect

An investigation of the efficacy of astatine-211-tellurium colloid for the treatment of experimental malignant ascites in mice reveals that this ..cap alpha..-emitting radiocolloid can be curative without causing undue toxicity to normal tissue. By comparison, negatron-emitting phosphorus-32 as colloidal chromic phosphate had no antineoplastic activity. The most compelling explanation for this striking difference is the dense ionization and short range of action associated with ..cap alpha..-emission. These results have important implications for the development and use of ..cap alpha..-emitters as radiocolloid therapy for the treatment of human tumors.

Bloomer, W.D. (Harvard Medical School, Boston, MA); McLaughlin, W.H.; Neirinckx, R.D.; Adelstein, S.J.; Gordon, P.R.; Ruth, T.J.; Wolf, A.P.

1981-04-17

278

Portal vein ligation accelerates tumor growth in ligated, but not contralateral lobes  

PubMed Central

AIM: To investigate the mechanisms of liver growth and atrophy after portal vein ligation (PVL) and its effects on tumor growth. METHODS: Mice were subjected to PVL, partial hepatectomy, or sham surgery. The morphological alterations, activation of transcription factors, and expression of cytokines and growth factors involved in liver regeneration were evaluated. In a separate set of experiments, murine colorectal carcinoma cells were injected via the portal vein and the effect of each operation on liver tumor growth was studied. RESULTS: Liver regeneration after PVL and partial hepatectomy were very similar. In ligated lobes, various cytokines, transcription factors and regulatory factors were significantly upregulated compared to non-ligated lobes after PVL. Atrophy in ligated lobes was a result of early necrosis followed by later apoptosis. Tumor growth was significantly accelerated in ligated compared to non-ligated lobes. CONCLUSION: Tumor growth was accelerated in ligated liver lobes and appeared to be a result of increased growth factor expression.

Sakai, Nozomu; Clarke, Callisia N; Schuster, Rebecca; Blanchard, John; Tevar, Amit D; Edwards, Michael J; Lentsch, Alex B

2010-01-01

279

Drugs which inhibit osteoclast function suppress tumor growth through calcium reduction in bone  

Microsoft Academic Search

Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important

Xin Li; Jinhui Liao; Amy J. Koh; William D. Sadler; Kenneth J. Pienta; Thomas J. Rosol; Laurie K. McCauley

2011-01-01

280

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization.  

National Technical Information Service (NTIS)

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were ...

F. L. Leung J. F. Park G. E. Dagle

1993-01-01

281

On the probability of random genetic mutations for various types of tumor growth.  

PubMed

In this work, we consider the problem of estimating the probability for a specific random genetic mutation to be present in a tumor of a given size. Previous mathematical models have been based on stochastic methods where the tumor was assumed to be homogeneous and, on average, growing exponentially. In contrast, we are able to obtain analytical results for cases where the exponential growth of cancer has been replaced by other, arguably more realistic types of growth of a heterogeneous tumor cell population. Our main result is that the probability that a given random mutation will be present by the time a tumor reaches a certain size, is independent of the type of curve assumed for the average growth of the tumor, at least for a general class of growth curves. The same is true for the related estimate of the expected number of mutants present in a tumor of a given size, if mutants are indeed present. PMID:22311065

Tomasetti, Cristian

2012-02-07

282

SDF-1 Stimulates Vasculogenesis and Enhances Ewing's Sarcoma Tumor Growth in the Absence of VEGF  

PubMed Central

Stromal cell-derived Factor-1? (SDF-1?) stimulates the migration of bone marrow (BM) cells, similar to Vascular Endothelial Growth Factor (VEGF). We previously demonstrated that inhibition of VEGF165 by small interfering RNA inhibited Ewing’s sarcoma tumor growth, tumor vessel formation and recruitment of BM cells to the tumor. To determine the importance of BM cells in tumor vessel development, we investigated the effects of SDF-1? on VEGF-inhibited TC/siVEGF7-1 Ewing’s tumor neovasculature formation and growth. The effect of SDF-1? on CD34+ progenitor cell chemotaxis was determined in vivo. Using a BM transplantation model with GFP+ transgenic mice as BM donors and nude mice as recipients, we evaluated the effect of SDF-1? on the recruitment of BM-derived cells to VEGF165-inhibited TC/siVEGF7-1 tumors, as well as its effect on neovasculature development, vessel morphology and tumor growth. SDF-1? stimulated the migration of CD34+ progenitor cells to Matrigel plugs in vivo and promoted the retainment of BM-derived pericytes in close association with perfused, functional tumor vessels. Intratumor inoculation of Ad-SDF-1? into TC/siVEGF7-1 tumors resulted in increased SDF-1 and PDGF-BB expression, augmented tumor growth, an increase in the number of large, lumen-bearing vascular structures, and enhanced vessel pericyte coverage, with no change in VEGF165. SDF-1? stimulates BM cell chemotaxis and the association of these cells with functional tumor vessels. Furthermore, SDF-1? enhances tumor neovascularization and growth with no alteration in VEGF165. Our work suggests that SDF-1-mediated vasculogenesis may represent an alternate pathway that could potentially be utilized by tumors to sustain growth and neovasculature expansion after anti-VEGF therapy.

Reddy, Krishna; Zhou, Zhichao; Jia, Shu-Fang; Lee, Tim H.; Morales-Arias, Jaime; Cao, Ying; Kleinerman, Eugenie S.

2008-01-01

283

Incidence and growth of methylcholanthrene-induced tumors in mice with altered immunological status.  

PubMed

BALB/c mice were treated s.c. with 3-methylcholanthrene (MCA), and tumor incidence and growth were followed for 9 months. Immunological status of mice was altered by various treatments. Thymectomized, lethally irradiated, bone marrow reconstituted mice served as T-cell deficient recipients. In order to suppress natural killer (NK)-cell/macrophage functions some mice were injected with silica particles; to enhance these functions some mice were given Corynebacterium parvum (CP). Silica and CP were given simultaneously with MCA to test their influence on the presumed function of surveillance of tumor incidence, and also 2 months after MCA to test their influence on the growth of greater numbers of transformed host cells. Almost all mice developed tumors at the inoculation site and at the end of the observation period there was no difference in tumor incidence among 9 experimental groups. However, in T-cell deficient mice we observed shorter tumor duration and earlier death than in normal mice. Silica particles appeared to enhance tumor growth but the differences compared to normal controls were not significant. A single injection of CP simultaneously with MCA caused earlier tumor appearance but also slowed its growth. In contrast, CP given 2 months after MCA significantly delayed the appearance of the tumors. In regard to the tumor growth immunosuppression had stronger effects in males than in females; the opposite was true for immunostimulation treatments. We concluded that immunological status does not influence long-term tumor incidence, but that both T-cell and NK-cell/macrophage compartments strongly influence the parameters of growth of chemically induced tumors, i.e., the immune and natural resistance mechanisms do not influence the frequency of de novo arising tumors but both can slow down tumor growth. PMID:3490910

Trutin-Ostovi?, C; Golubi?, M; Matovi?, M; Marusi?, M

1986-01-01

284

Inhibitions of Several Antineoplastic Drugs on Serum Sialic Acid Levels in Mice Bearing Tumors  

PubMed Central

Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement.

Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

2013-01-01

285

Inhibitions of several antineoplastic drugs on serum sialic Acid levels in mice bearing tumors.  

PubMed

Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement. PMID:23641340

Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

2012-11-14

286

Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model  

PubMed Central

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-?, 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 immunotherapy as effector cells seek and destroy areas of tumor growth and for testing strategies to improve clinical effectiveness.

Oflazoglu, Ezogelin; Elliott, Mark; Takita, Hiroshi; Ferrone, Soldano; Henderson, Robert A; Repasky, Elizabeth A

2007-01-01

287

Luteolin Inhibits Human Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis  

PubMed Central

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9. Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 in HUVECs. Proinflammatory cytokines such as IL-1?, IL-6, IL-8, and TNF-? level were significantly reduced by the treatment of luteolin in PC-3 cells. Luteolin (10 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that luteolin inhibited tumorigenesis by targeting angiogenesis. CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin. Moreover, luteolin reduced cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 expressions. Taken together, our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.

Pratheeshkumar, Poyil; Son, Young-Ok; Budhraja, Amit; Wang, Xin; Ding, Songze; Wang, Lei; Hitron, Andrew; Lee, Jeong-Chae; Kim, Donghern; Divya, Sasidharan Padmaja; Chen, Gang; Zhang, Zhuo; Luo, Jia; Shi, Xianglin

2012-01-01

288

mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis.  

PubMed

Kaposi sarcoma originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma-associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin. PMID:23382046

Roy, Debasmita; Sin, Sang-Hoon; Lucas, Amy; Venkataramanan, Raman; Wang, Ling; Eason, Anthony; Chavakula, Veenadhari; Hilton, Isaac B; Tamburro, Kristen M; Damania, Blossom; Dittmer, Dirk P

2013-02-04

289

Ohio State study shows how normal cells can fuel tumor growth:  

Cancer.gov

A new study published in the journal Nature Cell Biology has discovered how normal cells in mouse tumors can fuel tumor growth. Led by researchers at the Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, the study examines what happens when normal cells called fibroblasts in mouse mammary tumors lose an important tumor-suppressor gene called Pten.

290

Effect of Protein Intake on Tumor Growth and Cell Cycle Kinetics  

Microsoft Academic Search

Previous research has documented significant acceleration of tumor growth in animals receiving shorttern parenteral nutrition. This study was performed to determine the effect of long-term enteral protein intake on tumor cell cycle kinetics in the tumor-bearing host. Fifty Lewis\\/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive a standard protein diet (22.0% protein; 4.20 kcal\\/g) or protein-depleted

Michael H. Torosian

1995-01-01

291

Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats.  

PubMed

We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia. PMID:21981555

Iagher, Fabíola; de Brito Belo, Sérgio Ricardo; Naliwaiko, Katya; Franzói, Andressa Machado; de Brito, Gleisson Alisson Pereira; Yamazaki, Ricardo Key; Muritiba, Ana Lúcia; Muehlmann, Luis Alexandre; Steffani, Jovani Antonio; Fernandes, Luiz Cláudio

2011-10-07

292

Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth.  

PubMed

Mesenchymal stem cells (MSCs) have opposite effects on tumor growth, being able either to favor angiogenesis and tumor initiation or to inhibit progression of established tumors. Factors produced by MSCs within the tumor microenvironment may be relevant for their biological effects. Recent studies demonstrated that microvesicles (MVs) are an integral component of inter-cellular communication within the tumor microenvironment. In the present study, we evaluated whether MVs derived from human bone marrow MSCs may stimulate or inhibit in vitro and in vivo growth of HepG2 hepatoma, Kaposi's sarcoma, and Skov-3 ovarian tumor cell lines. We found that MVs inhibited cell cycle progression in all cell lines and induced apoptosis in HepG2 and Kaposi's cells and necrosis in Skov-3. The observed activation of negative regulators of cell cycle may explain these biological effects. In vivo intra-tumor administration of MVs in established tumors generated by subcutaneous injection of these cell lines in SCID mice significantly inhibited tumor growth. In conclusion, MVs from human MSCs inhibited in vitro cell growth and survival of different tumor cell lines and in vivo progression of established tumors. PMID:23034046

Bruno, Stefania; Collino, Federica; Deregibus, Maria Chiara; Grange, Cristina; Tetta, Ciro; Camussi, Giovanni

2012-11-19

293

Stromal impact on tumor growth and lymphangiogenesis in human carcinoma xenografts  

PubMed Central

Squamous cell carcinomas (SCCs) arising in the oral cavity are associated with poor survival, mainly due to metastatic disease. In contrast, skin SCCs rarely metastasize and are usually curable. To study influence of tongue and skin stroma on cancer growth and induction of lymphangiogenesis, xenograft tumors of human carcinoma cells were established either in tongue or skin of BALB/c nude mice. Two oral and two skin SCC cell lines were used, as well as an endometrial adenocarcinoma cell line. Tongue tumors established from all cell lines were larger than corresponding skin tumors. Peritumoral lymphatic vessel density was up to five times higher in tongue than in corresponding skin tumors, and mRNA level of the lymphangiogenic growth factor vascular endothelial growth factor (VEGF)-C was twice as high in tongue tumors compared with corresponding skin tumors. Contrary to lymphatic vessel density, blood vessel density was higher in skin tumors than in tongue tumors. In a cohort of patient samples, lymphatic vessel density was found to be higher in tongue SCCs compared with skin SCCs, supporting a clinical relevance of our findings. Our results show that the tumor stroma has a profound impact on cancer growth and induction of lymphangiogenesis and angiogenesis. The difference in lymphatic vessel density between tongue and skin tumors may be important in directing metastatic potential of tumors arising in these organs.

Wetting, Hilde Ljones; Rikardsen, Oddveig; Steigen, Sonja E.; Kanapathippillai, Premasany; Grenman, Reidar; Winberg, Jan-Olof; Svineng, Gunbj?rg; Uhlin-Hansen, Lars

2010-01-01

294

Dendritic Cell-Tumor Fusion Vaccine Prevents Tumor Growth in Vivo  

Microsoft Academic Search

Dendritic cells (DCs) are potent antigen presenting cells that are uniquely effective in generating primary immune responses. DCs that are manipulated to present tumor antigens induce antitumor immunity in animal models and preclinical human studies. A myriad of strategies have been developed to load tumor antigen effectively onto DCs. DC-tumor fusion presents a spec- trum of tumor-associated antigens to helper

Gi-Young KIM; Ho-Jin CHAE; Ki-Hyung KIM; Man-Soo YOON; Kyu-Sub LEE; Chang-Min LEE; Dong-Oh MOON; Jun-Sik LEE; Young-Il JEONG; Yung Hyun CHOI; Yeong-Min PARK

2007-01-01

295

Introduction of antisense CD44S CDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells.  

PubMed

We created antisense CD44 transfectants using LS174T, a colon adenocarcinoma cell line and assessed the effects of overall CD44 down-regulation on colorectal tumor growth and metastasis. The expression of antisense CD44s (the standard form of CD44) cDNA markedly inhibited the overall expression of CD44 variants. In vitro studies showed a significantly reduced ability of the stable antisense transfectants (LS174TAS1 and LS174TAS2) to bind hyaluronate and osteopontin, ligands for CD44. These cells developed tumors more slowly than controls (parental LS174T and mock transfectants) when the cells were subcutaneously injected into SCID mice. However, in vitro proliferation assays demonstrated no significant difference between the antisense transfectants and the controls on a hyaluronate-coated surface, suggesting the participation of ligands other than hyaluronate in tumor growth in vivo. Intrasplenic injection of parental LS174T cells produced colonies in the liver in 10 of 11 mice, whereas mice injected with the antisense transfectants were completely free of metastasis. In peritoneal dissemination, the weight of nodules and amount of ascites were significantly reduced in LS174TAS1 and AS2 compared with the controls. In vitro adhesion assays between the transfectants or controls and human peritoneal mesothelial cells revealed that the binding of LS174T cells to mesothelial cells was partly mediated by CD44-hyaluronate interaction. These data suggest that CD44-hyaluronate interaction plays a crucial role in peritoneal dissemination in colorectal carcinoma. The results of our study demonstrate the possible application of antisense CD44s to the treatment of colorectal carcinoma. PMID:11149422

Harada, N; Mizoi, T; Kinouchi, M; Hoshi, K; Ishii, S; Shiiba, K; Sasaki, I; Matsuno, S

2001-01-01

296

Inoculated mammary carcinoma-associated fibroblasts: contribution to hormone independent tumor growth  

PubMed Central

Background Increasing evidence has underscored the role of carcinoma associated fibroblasts (CAF) in tumor growth. However, there are controversial data regarding the persistence of inoculated CAF within the tumors. We have developed a model in which murine metastatic ductal mammary carcinomas expressing estrogen and progesterone receptors transit through different stages of hormone dependency. Hormone dependent (HD) tumors grow only in the presence of progestins, whereas hormone independent (HI) variants grow without hormone supply. We demonstrated previously that CAF from HI tumors (CAF-HI) express high levels of FGF-2 and that FGF-2 induced HD tumor growth in vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can induce HD tumor growth. Methods Purified EPI cells of HD and HI tumors were inoculated alone, or together with CAF-HI, into female BALB/c mice and tumor growth was evaluated. In another set of experiments, purified EPI-HI alone or combined with CAF-HI or CAF-HI-GFP were inoculated into BALB/c or BALB/c-GFP mice. We assessed whether inoculated CAF-HI persisted within the tumors by analyzing inoculated or host CAF in frozen sections of tumors growing in BALB/c or BALB/c-GFP mice. The same model was used to evaluate early stages of tumor development and animals were euthanized at 2, 7, 12 and 17 days after EPI-HI or EPI-HI+CAF-HI inoculation. In angiogenesis studies, tumor vessels were quantified 5 days after intradermal inoculation. Results We found that admixed CAF-HI failed to induce epithelial HD tumor growth, but instead, enhanced HI tumor growth (p < 0.001). Moreover, inoculated CAF-HI did not persist within the tumors. Immunofluorescence studies showed that inoculated CAF-HI disappeared after 13 days. We studied the mechanisms by which CAF-HI increased HI tumor growth, and found a significant increase in angiogenesis (p < 0.05) in the co-injected mice at early time points. Conclusions Inoculated CAF-HI do not persist within the tumor mass although they play a role during the first stages of tumor formation promoting angiogenesis. This angiogenic environment is unable to replace the hormone requirement of HD tumors that still need the hormone to recruit the stroma from the host.

2010-01-01

297

Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors  

PubMed Central

Introduction Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues. This behavior of MSCs has been exploited as a tumor-targeting strategy for cell-based cancer therapy. However, the effects of MSCs on tumor growth are controversial. This study was designed to determine the effect of MSCs on the growth of breast and prostate tumors. Methods Bone marrow-derived MSCs (BM-MSCs) were isolated and characterized. Effects of BM-MSCs on tumor cell proliferation were analyzed in a co-culture system with mouse breast cancer cell 4T1 or human prostate cancer cell DU145. Tumor cells were injected into nude mice subcutaneously either alone or coupled with BM-MSCs. The expression of cell proliferation and angiogenesis-related proteins in tumor tissues were immunofluorescence analyzed. The angiogenic effect of BM-MSCs was detected using a tube formation assay. The effects of the crosstalk between tumor cells and BM-MSCs on expression of angiogenesis related markers were examined by immunofluorescence and real-time PCR. Results Both co-culturing with mice BM-MSCs (mBM-MSCs) and treatment with mBM-MSC-conditioned medium enhanced the growth of 4T1 cells. Co-injection of 4T1 cells and mBM-MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Similar experiments using DU145 cells and human BM-MSCs (hBM-MSCs) instead of 4T1 cells and mBM-MSCs obtained consistent results. Compared with tumors induced by injection of tumor cells alone, the blood vessel area was greater in tumors from co-injection of tumor cells with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from hBM-MSCs alone and co-cultures of hBM-MSCs with DU145 cells were able to promote tube formation ability of human umbilical vein endothelial cells. When hBM-MSCs are exposed to the DU145 cell environment, the expression of markers associated with neovascularization (macrophage inflammatory protein-2, vascular endothelial growth factor, transforming growth factor-beta and IL-6) was increased. Conclusion These results indicate that BM-MSCs promote tumor growth and suggest that the crosstalk between tumor cells and BM-MSCs increased the expression of pro-angiogenic factors, which may have induced tumor cell proliferation and angiogenesis thereby increasing solid tumor growth.

2013-01-01

298

Effects of Epigallocatechin-3-gallate (EGCG) on A549 Lung Cancer Tumor Growth and Angiogenesis.  

PubMed

Epigallocatechin 3-gallate (EGCG) has cytotoxic effects in many cancer cells. It has been reported that A549 lung cancer cells are markedly resistant to cell death induced by EGCG. In the present study, the effects of EGCG on A549 lung cancer cell growth and angiogenesis were studied. We found that EGCG dose-dependently suppressed A549 cell growth, while A549 cells were markedly resistant to cell death in vitro. Next we found that EGCG increased endostatin expression and suppressed vascular endothelial growth factor (VEGF) expression. We further studied to determine whether EGCG would suppress A549 tumor growth in nude mouse and angiogenesis. EGCG in drinking water significantly suppressed A549 tumor growth in nude mice. Histological analysis revealed that the number of CD34 positive vessels had a tendency to decrease in the tumor. In sum, EGCG had anti-proliferative effects of A549 on tumor growth and showed a tendency to suppress angiogenesis. PMID:24018658

Sakamoto, Yuhi; Terashita, Nobuhiro; Muraguchi, Takashi; Fukusato, Toshio; Kubota, Shunichiro

2013-09-07

299

Screening and Identification of Biomarkers in Ascites Related to Intrinsic Chemoresistance of Serous Epithelial Ovarian Cancers  

PubMed Central

Objective The ability to predict responses to chemotherapy for serous epithelial ovarian cancer (EOC) would be valuable since intrinsically chemoresistant EOC patients (persistent or recurrent disease within 6 months) gain little benefit from standard chemotherapy. The aim of this study was to screen and identify distinctive biomarkers in ascites of serous EOC associated with intrinsic chemoresistance. Methods Protein samples from ascites of 12 chemosensitive and 7 intrinsically chemoresistant serous EOC patients were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Furthermore, the identified proteins were validated by ELISA in ascites samples from 19 chemosensitive and 9 intrinsically chemoresistant EOC patients. Results The number of spots detected in all 2-D DIGE gels ranged from 1523–1711 using DeCyder software analysis. Thirty-four spots were differentially expressed based on the criteria of an average ratio of more than 1.5 and a student t-test P value <0.05. After MALDI-TOF/TOF MS analysis, 11 differentially expressed proteins, including 3 up-regulated and 8 down-regulated proteins, in ascites of chemoresistant tumors were successfully identified. Of the four selected proteins (ceruloplasmin, apoliprotein A-IV, transthyretin and haptoglobin) in ascites tested by ELISA, only ceruloplasmin was present at significantly different levels between the chemoresistant and chemosensitive ascites samples with average concentrations of 192.2 µg/ml and 157.5 µg/ml, respectively (P?=?0.001). Conclusion The significantly up-regulated level of ceruloplasmin in the ascites fluid of intrinsic chemoresistant serous EOC patients suggests its potential as a prognostic biomarker for responses to chemotherapy. This finding prompts further investigation with a larger study in order to validate the clinical utility of ceruloplasmin.

Liu, Jihong; Zheng, Minghui; Feng, Yanling; Hu, Kunhua; Huang, Yongwen; Huang, Qidan

2012-01-01

300

Targeting Vascular Endothelial Growth Factor (VEGF) for Antitumor Therapy, by Anti-VEGF Neutralizing Monoclonal Antibodies or by VEGF Receptor Tyrosine-kinase Inhibitors  

Microsoft Academic Search

Vascular endothelial growth factor\\/vascular permeability factor (VEGF\\/VPF) is an important mediator of tumor-induced angiogenesis and represents a potential target for innovative anticancer therapy. In several animal models, neutralizing anti-VEGF\\/VPF antibodies have shown encouraging inhibitory effects on solid tumor growth, ascites formation and metastatic dissemination. Targeting the VEGF signaling pathway by means of VEGF receptor tyrosine-kinase inhibitors has shown similar efficacy

Jean-Marc Schlaeppi; Jeanette M. Wood

1999-01-01

301

Insulin like growth factor binding protein-7 reduces growth of human breast cancer cells and xenografted tumors  

Microsoft Academic Search

Previously, we have shown that insulin-like growth factor binding protein-7 (IGFBP-7) expression is inversely correlated with\\u000a disease progression in breast cancer and is associated with poor outcome. To further investigate the role of IGFBP-7 in the\\u000a growth and metastatic behavior of breast cancer, primary breast tumors and metastatic tumors derived from the same patients\\u000a were analyzed for IGFBP-7 expression. Immunohistochemical

Y. Amemiya; W. Yang; T. Benatar; S. Nofech-Mozes; A. Yee; H. Kahn; C. Holloway; Arun Seth

2011-01-01

302

Stimulation of tumor growth in adult rats in vivo during an acute fast.  

PubMed

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast. PMID:3708579

Sauer, L A; Nagel, W O; Dauchy, R T; Miceli, L A; Austin, J E

1986-07-01

303

T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor  

PubMed Central

The results of this paper are consistent with the hypothesis that progressive growth of the Meth A fibrosarcoma evokes the generation of a T-cell-mediated mechanism of immunosuppression that prevents this highly immunogenic tumor from being rejected by its immunocompetent host. It was shown that it is possible to cause the regression of large, established Meth A tumors by intravenous infusion of tumor- sensitized T cells from immune donors, but only if the tumors are growing in T-cell-deficient recipients. It was also shown that the adoptive T-cell-mediated regression of tumors in such recipients can be prevented by prior infusion of splenic T cells from T-cell-intact, tumor-bearing donors. The results leave little doubt that the presence of suppressor T cells in T-cell-intact, tumor-bearing mice is responsible for the loss of an earlier generated state of concomitant immunity, and for the inability of intravenously infused, sensitized T cells to cause tumor regression. Because the presence of suppressor T cells generated in response to the Meth A did not suppress the capacity of Meth A-bearing mice to generate and express immunity against a tumor allograft, it is obvious that they were not in a state of generalized immunosuppression.

1980-01-01

304

pH control mechanisms of tumor survival and growth.  

PubMed

A distinguishing phenotype of solid tumors is the presence of an alkaline cellular feature despite the surrounding acidic microenvironment. This phenotypic characteristic of tumors, originally described by Otto Warburg, arises due to alterations in metabolism of solid tumors. Hypoxic regions of solid tumors develop due to poor vascularization and in turn regulate the expression of numerous genes via the transcription factor HIF-1. Ultimately, the tumor microenvironment directs the development of tumor cells adapted to survive in an acidic surrounding where normal cells perish. The provision of unique pH characteristics in tumor cells provides a defining trait that has led to the pursuit of treatments that target metabolism, hypoxia, and pH-related mechanisms to selectively kill cancer cells. Numerous studies over the past decade involving the cancer-specific carbonic anhydrase IX have re-kindled an interest in pH disruption-based therapies. Although an acidification of the intracellular compartment is established as a means to induce normal cell death, the defining role of acid-base disturbances in tumor physiology and survival remains unclear. The aim of this review is to summarize recent data relating to the specific role of pH regulation in tumor cell survival. We focus on membrane transport and enzyme studies in an attempt to elucidate their respective functions regarding tumor cell pH regulation. These data are discussed in the context of future directions for the field of tumor cell acid-base-related research. PMID:20857482

Parks, Scott K; Chiche, Johanna; Pouyssegur, Jacques

2011-02-01

305

Cellular thiol status-dependent inhibition of tumor cell growth via modulation of p27(kip1) translocation and retinoblastoma protein phosphorylation by 1'-acetoxychavicol acetate.  

PubMed

1'-Acetoxychavicol acetate (ACA) has been shown to inhibit tumor cell growth, but there is limited information on its effects on cell signaling and the cell cycle control pathway. In this study, we sought to determine how ACA alters cell cycle and its related control factors in its growth inhibitory effect in Ehrlich ascites tumor cells (EATC). ACA caused an accumulation of cells in the G1 phase and an inhibition of DNA synthesis, which were reversed by supplementation with N-acetylcysteine (NAC) or glutathione ethyl ester (GEE). Furthermore, ACA decreased hyperphosphorylated Rb levels and increased hypophosphorylated Rb levels. NAC and GEE also abolished the decease in Rb phosphorylation by ACA. As Rb phosphorylation is regulated by G1 cyclin dependent kinase and CDK inhibitor p27(kip1), which is an important regulator of the mammalian cell cycle, we estimated the amount of p27(kip1) levels by western blotting. Treatment with ACA had virtually no effect on the amount of p27(kip1) levels, but caused a decrease in phosphorylated p27(kip1) and an increase in unphosphorylated p27(kip1) as well as an increase in the nuclear localization of p27(kip1). These events were abolished in the presence of NAC or GEE. These results suggest that in EATC, cell growth inhibition elicited by ACA involves decreases in Rb and p27(kip1) phosphorylation and an increase in nuclear localization of p27(kip1), and these events are dependent on the cellular thiol status. PMID:17031475

Unahara, Y; Kojima-Yuasa, A; Higashida, M; Kennedy, D O; Murakami, A; Ohigashi, H; Matsui-Yuasa, I

2006-10-10

306

IMP1 promotes tumor growth, dissemination and a tumor-initiating cell phenotype in colorectal cancer cell xenografts.  

PubMed

Igf2 mRNA binding protein 1 (IMP1, CRD-BP, ZBP-1) is a messenger RNA binding protein that we have shown previously to regulate colorectal cancer (CRC) cell growth in vitro. Furthermore, increased IMP1 expression correlates with enhanced metastasis and poor prognosis in CRC patients. In the current study, we sought to elucidate IMP1-mediated functions in CRC pathogenesis in vivo. Using CRC cell xenografts, we demonstrate that IMP1 overexpression promotes xenograft tumor growth and dissemination into the blood. Furthermore, intestine-specific knockdown of Imp1 dramatically reduces tumor number in the Apc (Min/+) mouse model of intestinal tumorigenesis. In addition, IMP1 knockdown xenografts exhibit a reduced number of tumor cells entering the circulation, suggesting that IMP1 may directly modulate this early metastatic event. We further demonstrate that IMP1 overexpression decreases E-cadherin expression, promotes survival of single tumor cell-derived colonospheres and promotes enrichment and maintenance of a population of CD24+CD44+ cells, signifying that IMP1 overexpressing cells display evidence of loss of epithelial identity and enhancement of a tumor-initiating cell phenotype. Taken together, these findings implicate IMP1 as a modulator of tumor growth and provide evidence for a novel role of IMP1 in early events in CRC metastasis. PMID:23764754

Hamilton, Kathryn E; Noubissi, Felicite K; Katti, Prateek S; Hahn, Christopher M; Davey, Sonya R; Lundsmith, Emma T; Klein-Szanto, Andres J; Rhim, Andrew D; Spiegelman, Vladimir S; Rustgi, Anil K

2013-06-12

307

Antibody-guided irradiation of malignant ascites in ovarian cancer: a new therapeutic method possessing specificity against cancer cells  

SciTech Connect

Immunocytology of ascitic fluid of a patient with ovarian cancer demonstrated reactivity with two tumor-associated monoclonal antibodies, AUA1 and HMFG2. AUA1 radiolabeled with 48.6 mCi /sup 131/I was given intraperitoneally. There was a reduction in the rate of reaccumulation of ascites. Cytology of recurrent ascites revealed reactivity with antibody HMFG2 but not AUA1. The patient was further treated intraperitoneally with 39.0 mCi /sup 131/I-labeled HMFG2. There has been no reaccumulation of ascites. It is concluded that antibody-guided irradiation may be an effective treatment of malignant ascites secondary to ovarian cancer. Furthermore, this case illustrates the specificity of antibody interactions in the mediation of therapeutic effect and the possibility of tumor selection after irradiation with a single monoclonal antibody. If specificity plays a role, all major specificities should be covered by an appropriate panel of radioactively labeled antibodies. It is recommended that for comprehensive therapy of malignant ascites secondary to ovarian cancer, a mixture of antibodies such as HMFG2 and AUA1 should be used.

Epenetos, A.A.; Hooker, G.; Krausz, T.; Snook, D.; Bodmer, W.F.; Taylor-Papadimitriou, J.

1986-09-01

308

Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro.  

PubMed

Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins have been identified as the main active principle of mistletoe extracts. They have been shown to exhibit cytotoxic effects as well as immunomodulatory activities. The latter is exemplified by induction of cytokine secretion and increased activity of natural killer cells. Recent reports, however, indicated possible tumor growth stimulation by mistletoe extracts. Therefore, the three aqueous mistletoe extracts (Iscador M special, Iscador Qu special and Iscador P) were evaluated for antiproliferative and/or stimulatory effects in a panel of 16 human tumor cell lines in vitro using a cellular proliferation assay. The results show no evidence of stimulation of tumor growth by any of the three Iscador preparations, comprising central nervous system, gastric, non-small cell lung, mammary, prostate, renal and uterine cancer cell lines, as well as cell lines from hematological malignancies and melanomas. On the contrary, Iscador preparations containing a high lectin concentration (Iscador M special and Iscador Qu special) showed antitumor activity in the mammary cancer cell line MAXF 401NL at the 15 microg/ml dose level with a more than 70% growth inhibition compared to untreated control cells. In addition, a slight antitumor activity (growth inhibition 30-70%) was found in three tumor cell lines for Iscador M special and in seven tumor cell lines for Iscador Qu special, respectively. Iscador P, which contains no mistletoe lectin I, showed no antiproliferative activity. PMID:11984083

Maier, Gerhard; Fiebig, Heinz-Herbert

2002-04-01

309

Induction of senescence-associated growth inhibitors in the tumor-suppressive function of retinoids.  

PubMed

Retinoids, physiological regulators of cell growth and differentiation, are used in the treatment or chemoprevention of several malignant diseases. This class of compounds can induce growth arrest or apoptosis in tumor cells. Permanent growth arrest of retinoid-treated cells is often assumed to result from retinoid-induced differentiation. Recent studies in breast carcinoma and neuroblastoma cells demonstrated that retinoids can stop tumor cell growth through the program of senescence rather than differentiation. Retinoid-induced tumor suppression is associated with the induction of multiple intracellular and secreted growth-inhibitory proteins. Most of these proteins were also found to be upregulated in senescent cells. The induction of senescence-associated growth inhibitors appears to be an indirect effect of retinoids. Elucidation of the mechanisms responsible for the induction of growth-inhibitory genes in retinoid-treated cells should help in developing agents that would mimic the antiproliferative effect of retinoids in retinoid-insensitive cancers. PMID:12461777

Roninson, Igor B; Dokmanovic, Milos

2003-01-01

310

Exploring Cancer with Gapminder: Modeling Tumor Growth with Excel - BioQUEST Summer Workshop  

NSDL National Science Digital Library

This session explores global health data from Gapminder and WHO. Participants will look at social, economic, and environmental development at local, national and global levels and interpret log transformations for graphical display. We will build a data driven phenomenological model of tumor growth with a minimal number of parameters in order to make predictions about tumor growth. By relating the volume of the tumor to time measured in days we will predict when a tumor started to grow and when it will reach a size that is lethal to the patient.

Claudia Neuhauser (University of Minnesota-Rochester;Health Sciences)

2010-06-18

311

Control of Tumor Growth in Animals by Infusion of an Angiogenesis Inhibitor  

NASA Astrophysics Data System (ADS)

Angiogenesis and tumor growth were inhibited in two different animal models by regional infusion of a partially purified cartilage extract. In rabbits bearing corneal implants of V2 carcinoma and receiving the inhibitor, vascular growth rates were <3% of those in control animals receiving either Ringer's solution or bovine trypsin inhibitor (Trasylol). Subconjunctival B16 melanoma implants in mice receiving the inhibitor weighed <2.5% of implants in mice receiving Ringer's solution, Trasylol, or albumin. Histologic study of major organs and standard blood tests revealed no toxic effects in any of the animals. The inhibitor did not retard the growth of either tumor cell type in tissue culture at concentrations as high as 1 mg/ml. These results suggest that the cartilage factor does not interfere with the growth of the tumor cell population directly but that it prevents tumor growth by inhibiting angiogenesis.

Langer, Robert; Conn, Howard; Vacanti, Joseph; Haudenschild, Christian; Folkman, Judah

1980-07-01

312

The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox.  

PubMed

The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a "lethal" aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy, and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia. PMID:21051947

Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

2010-11-30

313

Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice.  

PubMed

Macrophages are an abundant inflammatory cell type in the tumor microenvironment that can contribute to tumor growth and metastasis. Macrophage recruitment into tumors is mediated by multiple cytokines, including vascular endothelial growth factor (VEGF), which is thought to function primarily through VEGF receptor (VEGFR) 1 expressed on macrophages. Macrophage infiltration is affected by VEGF inhibition. We show that selective inhibition of VEGFR2 reduced macrophage infiltration into orthotopic pancreatic tumors. Our studies show that tumor-associated macrophages express VEGFR2. Furthermore, peritoneal macrophages from tumor-bearing animals express VEGFR2, whereas peritoneal macrophages from non-tumor-bearing animals do not. To our knowledge, this is the first time that tumor-associated macrophages have been shown to express VEGFR2. Additionally, we found that the cytokine pleiotrophin is sufficient to induce VEGFR2 expression on macrophages. Pleiotrophin has previously been shown to induce expression of endothelial cell markers on macrophages and was present in the microenvironment of orthotopic pancreatic tumors. Finally, we show that VEGFR2, when expressed by macrophages, is essential for VEGF-stimulated migration of tumor-associated macrophages. In summary, tumor-associated macrophages express VEGFR2, and selective inhibition of VEGFR2 reduces recruitment of macrophages into orthotopic pancreatic tumors. Our results show an underappreciated mechanism of action that may directly contribute to the antitumor activity of angiogenesis inhibitors that block the VEGFR2 pathway. PMID:18519694

Dineen, Sean P; Lynn, Kristi D; Holloway, Shane E; Miller, Andrew F; Sullivan, James P; Shames, David S; Beck, Adam W; Barnett, Carlton C; Fleming, Jason B; Brekken, Rolf A

2008-06-01

314

Intussusceptive Microvascular Growth in a Human Colon Adenocarcinoma Xenograft: A Novel Mechanism of Tumor Angiogenesis  

Microsoft Academic Search

Intussusceptive microvascular growth refers to vascular network formation by insertion of interstitial tissue columns, called tissue pillars or posts, into the vascular lumen and subsequent growth of these columns, resulting in partitioning of the vessel lumen. While intussusception has been reported in normal developing organs, its existence in solid tumors has not been previously documented. By observing the growth of

Sybill Patan; Lance L. Munn; Rakesh K. Jain

1996-01-01

315

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

PubMed Central

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.

Loue, Vedi Andre Serges; Gbary, Eleonore; Koui, Sylvanus; Akpa, Bedi; Kouassi, Adelaide

2013-01-01

316

Defined tumor cell-host interactions are necessary for malignant growth.  

PubMed

Analyzing the different steps of malignant growth (primary tumor, metastasizing tumor cells, secondary tumor), one recognizes an intense interaction between normal and malignant cells. Tumor cells not only induce activities of normal cells, which normally are rarely activated, but also they exploit properties of normal cells for their own purposes. The major mechanisms and processes of this "parasitism" are described in more detail and the results are discussed. Tumors cannot grow beyond a certain size without a supply of blood and lymph vessels by the host (angiogenesis). Metastasizing tumor cells cannot leave the vessel (extravasate) in which they are transported without the cooperation of the respective endothelial cells of the host. An appropriate environment formed by the host tissues is essential for the settlement of tumor cells at secondary sites. Historically, these are a few examples that show intense cooperation between host and tumor. More are given in the present contribution. PMID:7948109

Paweletz, N; Boxberger, H J

1994-01-01

317

Napsin A and Thyroid Transcription Factor-1-Positive Cerebellar Tumor with Epidermal Growth Factor Receptor Mutation  

PubMed Central

We present a very rare case of cerebellar metastasis of unknown origin, in which a primary lung adenocarcinoma was diagnosed by pathological examination of a cerebellar metastatic tumor, using immunohistochemical markers and epidermal growth factor receptor (EGFR) mutation of primary lung cancer. A 69-year-old woman was admitted to our hospital because of a hemorrhagic cerebellar tumor and multiple small brain tumors. She underwent cerebellar tumor resection. On pathological examination, the tumor was diagnosed as adenocarcinoma. However, the primary tumor site was unidentifiable even with several imaging inspections. On immunohistochemical analysis, the resected tumor was positive for napsin A and thyroid transcription factor-1. In addition, an EGFR mutation was detected in the tumor. Therefore, primary lung cancer was diagnosed and the patient was started on gefitinib (250 mg/day) therapy.

Kuwata, Taiji; Iwata, Teruo; Iwanami, Takashi

2011-01-01

318

An Analysis of Trends and Growth Factor Receptor Expression of GI Carcinoid Tumors  

PubMed Central

The purpose of our study was twofold: 1) to determine the incidence, patient and tumor characteristics, and outcome of patients with GI carcinoid tumors using the Surveillance, Epidemiology and End Results (SEER) database, and 2) to delineate the expression pattern of growth factor receptors (GFRs) in carcinoid tumors. The SEER database search provided information on patients diagnosed with carcinoid tumors from 1990–2002. Carcinoid tumor sections (n = 46) were stained for the GFRs: epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGFR), vascular endothelial growth factor receptor (VEGFR), and HER-2/neu. Over the 12 year analysis period, 18,180 patients were identified with carcinoid tumors of the foregut, midgut, and hindgut; the incidence of carcinoid tumors increased ~2-fold during this time period. Of the patients with carcinoid tumors, there was a trend of increased expression of VEGF-R and IGF-R, particularly in the foregut and midgut carcinoids. Analysis of the SEER database confirms that the incidence of carcinoid tumors is increasing with an approximate doubling in the number of carcinoid cases from 1990–2002. Furthermore, an increase in VEGF-R and IGF-R expression suggests that GFR inhibitors may be effective adjuvant therapy for carcinoid cancer.

Bowen, Kanika A.; Silva, Scott R.; Johnson, Jessica N.; Doan, Hung Q.; Jackson, Lindsey N.; Gulhati, Pat; Qiu, Suimin; Riall, Taylor S.; Evers, B. Mark

2009-01-01

319

Pharmacological Inhibition of Microsomal Prostaglandin E Synthase-1 Suppresses Epidermal Growth Factor Receptor-Mediated Tumor Growth and Angiogenesis  

PubMed Central

Background Blockade of Prostaglandin (PG) E2 production via deletion of microsomal Prostaglandin E synthase-1 (mPGES-1) gene reduces tumor cell proliferation in vitro and in vivo on xenograft tumors. So far the therapeutic potential of the pharmacological inhibition of mPGES-1 has not been elucidated. PGE2 promotes epithelial tumor progression via multiple signaling pathways including the epidermal growth factor receptor (EGFR) signaling pathway. Methodology/Principal Findings Here we evaluated the antitumor activity of AF3485, a compound of a novel family of human mPGES-1 inhibitors, in vitro and in vivo, in mice bearing human A431 xenografts overexpressing EGFR. Treatment of the human cell line A431 with interleukin-1beta (IL-1?) increased mPGES-1 expression, PGE2 production and induced EGFR phosphorylation, and vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expression. AF3485 reduced PGE2 production, both in quiescent and in cells stimulated by IL-1?. AF3485 abolished IL-1?-induced activation of the EGFR, decreasing VEGF and FGF-2 expression, and tumor-mediated endothelial tube formation. In vivo, in A431 xenograft, AF3485, administered sub-chronically, decreased tumor growth, an effect related to inhibition of EGFR signalling, and to tumor microvessel rarefaction. In fact, we observed a decrease of EGFR phosphorylation, and VEGF and FGF-2 expression in tumours explanted from treated mice. Conclusion Our work demonstrates that the pharmacological inhibition of mPGES-1 reduces squamous carcinoma growth by suppressing PGE2 mediated-EGFR signalling and by impairing tumor associated angiogenesis. These results underscore the potential of mPGES-1 inhibitors as agents capable of controlling tumor growth.

Bocci, Elena; Coletta, Isabella; Polenzani, Lorenzo; Mangano, Giorgina; Alisi, Maria Alessandra; Cazzolla, Nicola; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

2012-01-01

320

MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis.  

PubMed

Mitogen-activated protein kinase kinase kinase 3 (MEKK3) plays an essential role in embryonic angiogenesis, but its role in tumor growth and angiogenesis is unknown. In this study, we further investigated the role of MEKK3 in embryonic angiogenesis, tumor angiogenesis, and angiogenic factor production. We found that endothelial cells from Mekk3-deficient embryos showed defects in cell proliferation, apoptosis, and interactions with myocardium in the heart. We also found that MEKK3 is required for angiopoietin-1 (Ang1)-induced p38 and ERK5 activation. To study the role of MEKK3 in tumor growth and angiogenesis, we established both wild-type and Mekk3-deficient tumor-like embryonic stem cell lines and transplanted them subcutaneously into nude mice to assess their ability to grow and induce tumor angiogenesis. Mekk3-deficient tumors developed and grew similarly as control Mekk3 wild-type tumors and were also capable of inducing tumor angiogenesis. In addition, we found no differences in the production of VEGF in Mekk3-deficient tumors or embryos. Taken together, our results suggest that MEKK3 plays a critical role in Ang1/Tie2 signaling to control endothelial cell proliferation and survival and is required for endothelial cells to interact with the myocardium during early embryonic development. However, MEKK3 is not essential for tumor growth and angiogenesis. PMID:17687003

Deng, Yong; Yang, Jianhua; McCarty, Marya; Su, Bing

2007-08-08

321

Inhibition of Tumor Growth and Angiogenesis by Soluble EphB41  

PubMed Central

Abstract EphB receptors and their ephrinB ligands play a key role in the formation of a regular vascular system. Recent studies have also shown the involvement of Eph/ephrin interactions in malignant tumor progression and angiogenesis. We have generated soluble monomeric EphB4 (sEphB4)-expressing A375 melanoma cells to study the effect of dominant negatively acting sEphB4 on tumor growth and angiogenesis. Soluble EphB4-expressing A375 tumors grown subcutaneously in nude mice show dramatically reduced tumor growth compared to control tumors. The proliferative capacity of sEphB4-expressing cells in monolayer culture is not altered. Yet, sEphB4-expressing A375 cells cannot establish proper cell-cell contacts in three-dimensional spheroids. However, sEphB4 transfectants have reduced proliferation and apoptosis rates when grown in three-dimensional culture in vitro or in subcutaneous tumors in vivo. Analysis of the vascular phenotype of the tumors revealed a reduction of intratumoral microvessel density in sEphB4-expressing tumors. Corresponding to these mouse experiments, a matched pair analysis of EphB4 and ephrinB2 expression in human colon carcinomas revealed significantly upregulated levels of EphB4 expression compared to adjacent normal tissue. Taken together, the data identify dual effects of sEphB4 on the tumor and the vascular compartment that collectively inhibit tumor growth.

Martiny-Baron, Georg; Korff, Thomas; Schaffner, Florence; Esser, Norbert; Eggstein, Stefan; Marme, Dieter; Augustin, Hellmut G

2004-01-01

322

Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes.  

PubMed

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores. PMID:3815372

Sauer, L A; Dauchy, R T

1987-04-01

323

Initiation of Liver Growth by Tumor Necrosis Factor: Deficient Liver Regeneration in Mice Lacking Type I Tumor Necrosis Factor Receptor  

Microsoft Academic Search

The mechanisms that initiate liver regeneration after resection of liver tissue are not known. To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA synthesis after PH was severely impaired in these animals, and the expected

Yasuhiro Yamada; Irina Kirillova; Jacques J. Peschon; Nelson Fausto

1997-01-01

324

Complete Inhibition of Rhabdomyosarcoma Xenograft Growth and Neovascularization Requires Blockade of Both Tumor and Host Vascular Endothelial Growth Factor  

Microsoft Academic Search

Growth of the human rhabdomyosarcoma A673 cell line in nude mice is substantially reduced but not completely suppressed after systemic administration of the antihuman vascular endothelial growth factor (VEGF) monoclonal antibody (Mab) A.4.6.1. Potentially, such escape might be attributable to incomplete local penetration of the antibody because of a diffusion barrier associated with tumor growth. Alterna- tively, it might reflect

Hans-Peter Gerber; Joe Kowalski; Daniel Sherman; David A. Eberhard; Napoleone Ferrara

2000-01-01

325

Tumor growth in experimental animals: nutritional manipulation and chemotherapeutic response in the rat.  

PubMed Central

The effects of nutritional manipulation on host body weight dynamics, tumor growth patterns and host-tumor responses to chemotherapy were studied in Sprague-Dawley rats with Walker-256 carcinosarcomas. Group I maintained throughout on a regular diet (RD) gained carcass weight steadily. Group II lost carcass weight while fed a protein-free diet (PFD) but rapidly gained weight after switching to RD on day 15. Mean tumor volume increased 105% in Group I from day 15 to 21, 218% in Group II and 77% in Group III (continued on PFD p less than 0.05). From day 21 to day 33 tumor growth patterns were similar in Groups I and II, while mean tumor volume eventually plateaued in Group III. In Study B, Group II animals were given Methotrexate (MTX-20 mg/kg) two days and six days after switching from PFD to RD. The mean change in tumor volume in the MTX-treated rats was 1.31 +/- 0.1 cm3 compared with 8.14 +/- 0.1 cm3 (p less than 0.001) in the saline-treated control rats. MTX did not significantly affect tumor growth patterns in Group III (PFD) rats. In Study A, protein-calorie malnutrition resulted in host carcass weight loss and tumor growth retardation while nutritional repletion restored host carcass weight and stimulated tumor growth. In Study B, MTX was maximally effective in tumor-bearing rats that were switched from PFD to RD demonstrating that nutritional manipulation can improve host nutritional status and increase tumor response to chemotherapy.

Daly, J M; Reynolds, H M; Rowlands, B J; Dudrick, S J; Copeland, E M

1980-01-01

326

Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis.  

PubMed

Intussusceptive microvascular growth refers to vascular network formation by insertion of interstitial tissue columns, called tissue pillars or posts, into the vascular lumen and subsequent growth of these columns, resulting in partitioning of the vessel lumen. While intussusception has been reported in normal developing organs, its existence in solid tumors has not been previously documented. By observing the growth of the human colon adenocarcinoma (LS174T) in vivo for a period of 6 weeks, we demonstrate that intussusception is an important mechanism of tumor angiogenesis. At the leading edge of the tumor, vascular growth was found to occur by both intussusception and endothelial sprouting. In the stabilized regions, intussusception led to network remodeling and occlusion of vascular segments. The formation of some tissue pillars appears to depend on intravascular blood-flow patterns or changes in intravascular shear stress. The rapid vascular remodeling by intussusception could possibly contribute to intermittent blood flow in tumors. PMID:8778579

Patan, S; Munn, L L; Jain, R K

1996-03-01

327

A Generative Approach for Image-Based Modeling of Tumor Growth  

PubMed Central

Extensive imaging is routinely used in brain tumor patients to monitor the state of the disease and to evaluate therapeutic options. A large number of multi-modal and multi-temporal image volumes is acquired in standard clinical cases, requiring new approaches for comprehensive integration of information from different image sources and different time points. In this work we propose a joint generative model of tumor growth and of image observation that naturally handles multimodal and longitudinal data. We use the model for analyzing imaging data in patients with glioma. The tumor growth model is based on a reaction-diffusion framework. Model personalization relies only on a forward model for the growth process and on image likelihood. We take advantage of an adaptive sparse grid approximation for efficient inference via Markov Chain Monte Carlo sampling. The approach can be used for integrating information from different multi-modal imaging protocols and can easily be adapted to other tumor growth models.

Menze, Bjoern H.; Van Leemput, Koen; Honkela, Antti; Konukoglu, Ender; Weber, Marc-Andre; Ayache, Nicholas; Golland, Polina

2011-01-01

328

Functional analysis of tumor cell growth and clearance in living animals  

NASA Astrophysics Data System (ADS)

Evaluation of antineoplastic therapies would be enhanced by sensitive methods that noninvasively asses both tumor location and neoplastic growth kinetics in living animals. Since light is transmitted through mammalian tissues, it was possible to externally monitor growth and regression of luciferase labeled murine tumor cells engrafted into immunodeficient mice. External quantification of tumor burden revealed the biological impact of the chemotherapeutic agent cyclophosphamide on the kinetics of tumor growth in living animals. Therapeutic activity was apparent but this drug did not eliminate the NIH 3T3 cell signal over the 28 d time course. This novel, noninvasive system allowed sensitive, real time spatiotemporal analyses of neoplastic cell growth and may facilitate rapid optimization of effective therapeutic treatment regimes.

Sweeney, Thomas J.; Mailaender, V.; Tucker, Amanda A.; Olomu, A. B.; Zhang, Weisheng; Negrin, Robert S.; Contag, Christopher H.

1999-07-01

329

Transforming Growth Factor Beta Regulation of Tumor Progression in Metastatic Cancer.  

National Technical Information Service (NTIS)

During the metastatic tumor development, osteoclasts differentiate in the presence of high transforming growth factor beta (TGF-beta) concentrations. We hypothesize that TGF-beta is a survival factor for TGF-beta-induced osteoclasts. We tested our hypothe...

M. J. Oursler

2004-01-01

330

Substance-P-Mediated Immunomodulation of Tumor Growth in a Murine Model  

Microsoft Academic Search

Background\\/Objective: Substance P (SP) has been reported to have immunoregulatory properties including effects on many of the mediators involved in anti-tumor immunity. In this study, we investigated the effect of SP on tumor development in a murine model of melanoma. In addition, we examined the role of natural killer (NK) and T cells in SP-mediated modulation of tumor growth. Materials

Jill M. Manske; Summer E. Hanson

2005-01-01

331

Analysis, forecasting, and control of three-dimensional tumor growth and treatment.  

PubMed

The main point of this contribution is to show how ideas of control theory, automata theory and computer science can be applied to the field of cancer research. We are stressing the modelling of three-dimensional tumor growth and the simulation of different kinds of tumor therapy (surgery, radiation therapy, chemotherapy). In the future it will be possible to schedule the optimized methods and time of tumor treatment by computer simulation prior to clinical therapy. PMID:6512442

Düchting, W; Vogelsaenger, T

1984-10-01

332

Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect  

Microsoft Academic Search

BackgroundThe unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells with increased glycolysis and decreased mitochondrial activity. However, “aerobic glycolysis” generates fewer ATP per glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how increasing a less efficient process provides tumors with a growth advantage.Methods\\/FindingsWe carried out

Yijun Chen; Rob Cairns; Ioanna Papandreou; Albert Koong; Nicholas C. Denko; Mikhail V. Blagosklonny

2009-01-01

333

A Pilot Study of Long-Acting Octreotide for Symptomatic Malignant Ascites (N04C2)  

PubMed Central

Background Effective, non-invasive, palliative strategies for symptomatic malignant ascites unavailable. This trial explored whether octreotide, an inhibitor of vascular endothelial growth factor (VEGF), a putative mediator of ascites, prolongs the interval to next paracentesis. Methods After a baseline paracentesis and a test of short-acting agent, patients with symptomatic ascites were randomly assigned to long-acting octreotide (Sandostatin LAR®) depot 30 mg intramuscularly every month versus 0.9% sodium chloride administered similarly. Patients were then monitored for recurrent, symptomatic ascites. Results 33 patients were enrolled: 16 to the octreotide- and 17 to the control-arm. The median time to next paracentesis was 28 and 14 days in the octreotide- and placebo-arm, respectively (p=0.17). After adjustment for extracted ascites volume and abdominal girth change, no statistically significant difference between groups was observed (hazard ratio= 0.52 with a 95% confidence interval: 0.21, 1.28; p=0.15, per the Cox model). Octreotide-treated patients described less 1-month abdominal bloating (p=0.01), abdominal discomfort (p=0.02), and shortness of breath (p=0.007), although other quality of life symptoms were comparable between arms. Long-acting octreotide was reasonably well tolerated. Conclusion As prescribed in this trial, octreotide did not seem effective in prolonging the time to next paracentesis, although improvements in symptoms suggest that VEGF inhibition merits further investigation.

Jatoi, Aminah; Nieva, Jorge J.; Qin, Rui; Loprinzi, Charles L.; Wos, Edward J.; Novotny, Paul J.; Moore, Dennis F.; Mowat, Rex B.; Bechar, Naftali; Pajon, Eduardo R.; Hartmann, Lynn C.

2013-01-01

334

Naftopidil, a selective {alpha}1-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma.  

PubMed

In prostate cancer, tumor-stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha(1)-adrenoceptor (?(1)-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G(1) cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective ?(1)-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and ?(1)-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G(1) cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells. PMID:21205739

Hori, Yasuhide; Ishii, Kenichiro; Kanda, Hideki; Iwamoto, Yoichi; Nishikawa, Kohei; Soga, Norihito; Kise, Hideaki; Arima, Kiminobu; Sugimura, Yoshiki

2011-01-01

335

Cerebrospinal Fluid (Vascular Endothelial Growth Factor) and Serologic (Recoverin) Tumor Markers for Malignant Glioma  

Microsoft Academic Search

Background: Clinically useful tumor markers have yet to be identified for malignant glioma. We report on two potential novel tumor markers, vascular endothelial growth factor (VEGF) and recoverin (protein A). VEGF is a highly specific endothelial cell activator that induces angiogenesis both in vivo and in vitro. Our study was designed to assess whether VEGF could be measured in the

Prakash Sampath; Charles E. Weaver; Arno Sungarian; Selina Cortez; Lloyd Alderson; Edward G. Stopa

2004-01-01

336

Combination of Clinical Factors Predictive of Growth of Small Choroidal Melanocytic Tumors  

Microsoft Academic Search

Objective: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. Design: Retrospective analysis. Setting: Clinical practice of ocular oncology. Patients: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. Results: On multivariate analysis, the clinical risk factors

Carol L. Shields; Jacqueline Cater; Jerry A. Shields; Arun D. Singh; Maria Carmen; M. Santos; Cynthia Carvalho

2000-01-01

337

Pitt team finds protein that keeps balance between tumor cell growth and suppression  

Cancer.gov

Using an approach that combines molecular biology, genetics, cell biology and physiology, and pathology, researchers at the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine have identified a protein that governs a key molecule involved in orchestrating the balance between tumor growth and tumor suppression.

338

Preferential growth of metastatic tumors at the pleural surface of mouse lung  

Microsoft Academic Search

In an experimental model of lung metastasis we have observed that more metastatic tumors are located on the pleura of the lung than in the parenchyma. To study possible reasons for this differential pattern we have now related the initial distribution of injected tumor cells to the later location and growth rate of metastases in different regions of the lung

F. W. Orr; L. Young; G. M. King; I. Y. R. Adamson

1988-01-01

339

Increased primary tumor growth in mice null for ?3- or ?3/?5-integrins or selectins  

PubMed Central

Expression of ?v?3- or ?v?5-integrins and selectins is widespread on blood cells and endothelial cells. Here we report that human tumor cells injected s.c. into mice lacking ?3- or ?3/?5-integrins or various selectins show enhanced tumor growth compared with growth in control mice. There was increased angiogenesis in mice lacking ?3-integrins, but no difference in structure of the vessels was observed by histology or by staining for NG2 and smooth muscle actin in pericytes. Bone marrow transplants suggest that the absence of ?3-integrins on bone marrow-derived host cells contributes to the enhanced tumor growth in ?3-null mice, although few, if any, bone marrow-derived endothelial cells were found in the tumor vasculature. Tumor growth also was affected by bone marrow-derived cells in mice lacking any one or all three selectins, implicating both leukocyte and endothelial selectins in tumor suppression. Reduced infiltration of macrophages was observed in tumors grown in mice lacking either ?3-integrins or selectins. These results implicate cells of the innate immune system, macrophages or perhaps natural killer cells, in each case dependent on integrins and selectins, in tumor suppression.

Taverna, Daniela; Moher, Heather; Crowley, Denise; Borsig, Lubor; Varki, Ajit; Hynes, Richard O.

2004-01-01

340

Adiponectin Deficiency Promotes Tumor Growth in Mice by Reducing Macrophage Infiltration  

PubMed Central

Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of both tumors. Immunohistochemical analyses indicated that adiponectin deficiency reduced macrophage recruitment to the tumor, but did not affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In addition, treatment with recombinant adiponectin did not affect the proliferation of cultured B16F10 tumor cells. Importantly, the restoration of microphage infiltration at an early stage of tumorigenesis by means of co-injection of B16F10 cells and macrophages reversed the increased tumor growth in adiponectin knockout mice. Thus, we conclude that the enhanced tumor growth observed in adiponectin deficient mice is likely due to the reduction of macrophage infiltration rather than enhanced angiogenesis.

Sun, Yutong; Lodish, Harvey F.

2010-01-01

341

Increasing occurence of tumour cell — Tumour cell emperipolesis in the regenerating JB1 ascites tumour  

Microsoft Academic Search

During the investigation of JB-1 ascites tumour cells in recurrent growth several cases of emperipolesis were observed. Different types of emperipolesis are presented. Light microscopical serial sections, autoradiography and transmission electron microscopy indicate that the cells involved in emperipolesis are separate cells, and the authors suggest that cytophagocytosis is the initial mechanism in the development of emperipolesis.

J. Chemnitz; P. Skaaring; P. Bichel

1975-01-01

342

Uptake of cytosine arabinoside (Ara-C) by LSA lymphoma after irradiation in the stationary phase of growth.  

PubMed

An in vitro system was used to assess uptake of cytosine arabinoside by LSA ascites tumor cells growing in vivo. Changes in tumor uptake with aging after depopulation and perturbation of the cell population with 1,000 rad were studied. Both DNA synthesis and drug uptake were highest during early rapid tumor growth and decreased with aging and the stationary phase of growth. However, irradiation caused a second peak of cellular activity and drug uptake. These results indicate that irradiation stimulates regrowth of tumor. PMID:7063699

Young, J A; Maruyama, Y

1982-03-01

343

Diallyl disulfide suppresses the growth of human colon tumor cell xenografts in athymic nude mice.  

PubMed

The present studies examined the anti-proliferative effects of diallyl disulfide (DADS) on the growth of human colon tumor cell line, HCT-15, xenografts in 6-wk-old female NCr nu/nu mice with an initial body weight of 20-22 g. Intraperitoneal injection of 1 mg DADS thrice weekly reduced tumor volume by 69% (P < 0.05) without apparent ill consequences such as altered growth of the host. Providing this quantity of DADS intragastrically also inhibited growth of the HCT-15 tumor. At equivalent DADS dosages, intraperitoneal treatment was proportionately more effective (P < 0.05) in reducing tumor growth than gastric intubation. Tumor inhibition caused by DADS (0.5 mg thrice weekly) was similar to that occurring with 5-fluorouracil (5-FU) treatment (0.5 mg thrice weekly). Combining DADS and 5-FU was no more effective in inhibiting tumor growth than using either compound alone. However, concurrent DADS treatment significantly (P < 0.05) inhibited the depression in leukocyte counts and spleen weight and prevented the elevated plasma urea caused by 5-FU treatment. These data suggest that DADS, a constituent of garlic oil, reduces the toxicity of 5-FU and is an effective antitumorigenic agent against xenografts resulting from an established human colon tumor cell line. PMID:8618131

Sundaram, S G; Milner, J A

1996-05-01

344

A Quantitative Theory of Solid Tumor Growth, Metabolic Rate and Vascularization  

PubMed Central

The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

Herman, Alexander B.; Savage, Van M.; West, Geoffrey B.

2011-01-01

345

Zinc ligand-disrupted recombinant human Endostatin: Potent inhibition of tumor growth, safety and pharmacokinetic profile  

Microsoft Academic Search

Endostatin, a potent endogenous inhibitor of angiogenesis, inhibits the growth of primary tumors without induction of acquired\\u000a drug resistance in mice. We report that a soluble recombinant human (rh) Endostatin produced with characteristics of the native\\u000a Endostatin, effectively inhibited the growth of primary tumors and pulmonary metastases in a dose-dependent manner. We also\\u000a show that deletion of two of the

B. Kim Lee Sim; William E. Fogler; Xin Hua Zhou; Hong Liang; John W. Madsen; Kieu Luu; Michael S. O'Reilly; Joseph E. Tomaszewski; Anne H. Fortier

1999-01-01

346

Increased primary tumor growth in mice null for 3- or 3\\/5-integrins or selectins  

Microsoft Academic Search

Expression of v3- or v5-integrins and selectins is widespread on blood cells and endothelial cells. Here we report that human tumor cells injected s.c. into mice lacking 3- or 3\\/5-integrins or various selectins show enhanced tumor growth compared with growth in control mice. There was increased angiogenesis in mice lacking 3-integrins, but no difference in structure of the vessels was

Daniela Taverna; Heather Moher; Denise Crowley; Lubor Borsig; Ajit Varki; Richard O. Hynes

2004-01-01

347

Blocking CXCR4-Mediated Cyclic AMP Suppression Inhibits Brain Tumor Growth In vivo  

Microsoft Academic Search

The chemokine CXCL12 and its cognate receptor CXCR4 regulate malignant brain tumor growth and are potential chemotherapeutic targets. However, the molecular basis for CXCL12-induced tumor growth remains unclear, and the optimal approach to inhibiting CXCR4 function in cancer is unknown. To develop such a therapeutic approach, we investigated the signaling pathways critical for CXCL12 function in normal and malignant cells.

Lihua Yang; Erin Jackson; B. Mark Woerner; Arie Perry; David Piwnica-Worms; Joshua B. Rubin

2007-01-01

348

Targeted chemotherapy using a cytotoxic somatostatin conjugate to inhibit tumor growth and metastasis in nude mice.  

PubMed

The major problems of traditional chemotherapy are non-selectivity and non-specificity, resulting in severe toxic side effects. Peptides are a new-generation of drug-delivery vector to increase efficacy of this therapy and avoid the resulting damage. The cytotoxic somatostatin (SST) conjugate JF-10-81 was developed by coupling camptothecin (CPT) to the N-terminus of a SST analog (JF-07-69) using an activated carbamate linker. This conjugate selectively targets somatostatin receptor subtype 2 (SSTR2) and also retains high binding affinity and rapid internalization as well as anti-proliferative activity towards various tumor cells. JF-10-81 was tested for its inhibitory activity against the growth of human tumors which included neuroblastoma (IMR32), pancreatic cancer (CFPAC-1), leukemia (MOLT-4), pancreatic carcinoid (BON) and prostate cancer (PC-3). Both SSTR2 mRNAs and proteins were detected in all these tumor cell lines. The conjugate displayed potent in vivo inhibitory activity, although some of the potency measured in in vitro experiments was lost. JF-10-81 was found to significantly inhibit growth of these SSTR-positive tumors, resulting in 87% tumor reduction in neuroblastoma IMR32 and 97% in leukemia MOLT-4 bearing animals, even inducing regression of CFPAC-1 tumors. SSTR-overexpressing BON tumors were unfortunately relatively CPT-insensitive in vitro, however, JF-10-81 again exhibited in vivo potency presumably by specifically increasing CPT concentrations inside the tumor cells so that the inhibition rate for JF-10-81 was 85%. Also, JF-10-81 was used to treat highly invasive PC-3 tumors where s.c. injections inhibited both tumor growth (almost 60% reduction) and tumor metastasis (over 70%). This conjugate demonstrated its broad and excellent anti-tumor activity by targeting SSTR2-specific tumor tissues, supporting that short peptides and their analogs may be applied as ideal drug-delivery carriers to improve the traditional chemotherapy. PMID:21892324

Sun, Li-Chun; Mackey, L Vienna; Luo, Jing; Fuselier, Joseph A; Coy, David H

2008-08-19

349

The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C.  

PubMed

In clear-cell renal cell carcinoma (ccRCC), inactivation of the tumor suppressor von Hippel-Lindau (VHL) occurs in the majority of the tumors and is causal for the pathogenesis of ccRCC. Recently, a large-scale genomic sequencing study of ccRCC tumors revealed that enzymes that regulate histone H3 lysine 4 trimethylation (H3K4Me3), such as JARID1C/KDM5C/SMCX and MLL2, were mutated in ccRCC tumors, suggesting that H3K4Me3 might have an important role in regulating gene expression and tumorigenesis. In this study we report that in VHL-deficient ccRCC cells, the overall H3K4Me3 levels were significantly lower than that of VHL+/+ counterparts. Furthermore, this was hypoxia-inducible factor (HIF) dependent, as depletion of HIF subunits by small hairpin RNA in VHL-deficient ccRCC cells restored H3K4Me3 levels. In addition, we demonstrated that only loss of JARID1C, not JARID1A or JARID1B, abolished the difference of H3K4Me3 levels between VHL-/- and VHL+/+ cells, and JARID1C displayed HIF-dependent expression pattern. JARID1C in VHL-/- cells was responsible for the suppression of HIF-responsive genes insulin-like growth factor-binding protein 3 (IGFBP3), DNAJC12, COL6A1, growth and differentiation factor 15 (GDF15) and density-enhanced phosphatase 1. Consistent with these findings, the H3K4Me3 levels at the promoters of IGFBP3, DNAJC12, COL6A1 and GDF15 were lower in VHL-/- cells than in VHL+/+ cells, and the differences disappeared after JARID1C depletion. Although HIF2? is an oncogene in ccRCC, some of its targets might have tumor suppressive activity. Consistent with this, knockdown of JARID1C in 786-O VHL-/- ccRCC cells significantly enhanced tumor growth in a xenograft model, suggesting that JARID1C is tumor suppressive and its mutations are tumor promoting in ccRCC. Thus, VHL inactivation decreases H3K4Me3 levels through JARID1C, which alters gene expression and suppresses tumor growth. PMID:21725364

Niu, X; Zhang, T; Liao, L; Zhou, L; Lindner, D J; Zhou, M; Rini, B; Yan, Q; Yang, H

2011-07-04

350

Dietary treatment of chylous ascites in yellow nail syndrome.  

PubMed Central

Chylous ascites has rarely been reported in yellow nail syndrome. A case of chylous ascites in yellow nail syndrome is described which was treated successfully with dietary restriction of fat and supplements of medium chained triglycerides.

Tan, W C

1989-01-01

351

Mesenchymal stem cells promote growth and angiogenesis of tumors in mice.  

PubMed

Though the early integration of mesenchymal stem cells (MSCs) into tumor-associated stroma of cancer has been demonstrated, the functional contributions and underlying mechanisms of these cells to tumor growth and angiogenesis remain to be clarified. Using a xenograft model, human colorectal cancer cells, MSCs, and their cell mixture were introduced to a subcutaneous site of immunodeficient mice. The tumor growth rate and angiogenesis of each transplantation was then compared. We demonstrate that a variety of colorectal cancer cells, when mixed with otherwise non-tumorigenic MSCs, increase the tumor growth rate and angiogenesis more than that when mixed with carcinoma-associated fibroblasts or normal colonic fibroblasts. The secretion of interleukin-6 (IL-6) from MSCs increases the secretion of endothelin-1 (ET-1) in cancer cells, which induces the activation of Akt and ERK in endothelial cells, thereby enhancing their capacities for recruitment and angiogenesis to tumor. The IL-6/ET-1/Akt or ERK pathway of tumor-stroma interaction can be targeted by an antibody against IL-6 or Lentiviral-mediated RNAi against IL-6 in MSCs, by inhibition or knockdown of ET-1 in cancer cells, or by inhibition of ERK and Akt in host endothelial cells. These demonstrate that attempts to interrupt the interaction of MSCs and cancer cells help to abrogate angiogenesis and inhibit tumor growth in tumors formed by cancer cells admixed with MSCs. These data demonstrate that the tumor microenvironment, namely, MSCs-secreted IL-6, may enrich the proangiognic factors secreted by cancer cells to increase angiogenesis and tumor growth and that targeting this interaction may lead to novel therapeutic and preventive strategies. PMID:23085755

Huang, W-H; Chang, M-C; Tsai, K-S; Hung, M-C; Chen, H-L; Hung, S-C

2012-10-22

352

Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.  

PubMed

Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression. PMID:22407271

Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

2012-03-07

353

Protein Arginine Methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor Programmed Cell Death 4  

PubMed Central

Programmed Cell Death 4 (PDCD4) has been described as a tumor suppressor, with high expression correlating with better outcomes in a number of cancer types. Yet a substantial number of cancer patients with high PDCD4 in tumors have poor survival, suggesting that oncogenic pathways may inhibit or change PDCD4 function. Here, we explore the significance of PDCD4 in breast cancer and identify Protein Arginine Methyltransferase 5 (PRMT5) as a cofactor that radically alters PDCD4 function. Specifically, we find that co-expression of PDCD4 and PRMT5 in an orthotopic model of breast cancer causes accelerated tumor growth and that this growth phenotype is dependent on both the catalytic activity of PRMT5 and a site of methylation within the N-terminal region of PDCD4. In agreement with the xenograft model, elevated PDCD4 expression was found to correlate with worse outcome within the cohort of breast cancer patients whose tumors contain higher levels of PRMT5. These results reveal a new cofactor for PDCD4 that alters its tumor suppressor functions and point to the utility of PDCD4/PRMT5 status as both a prognostic biomarker and a potential target for chemotherapy.

Powers, Matthew A.; Fay, Marta M.; Factor, Rachel E.; Welm, Alana L.; Ullman, Katharine S.

2011-01-01

354

Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation.  

PubMed

Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14) induction at the edge of tumors expressing the FGFR4-R388 risk variant. Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas, where they were partially coexpressed at the tumor/stroma border and tumor invasion front. The strongest overall coexpression was found in prostate carcinoma. Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant, which has previously been associated with poor cancer prognosis, increased MT1-MMP-dependent collagen invasion. In this experimental model, knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen. This was coupled with impaired phosphorylation of FGFR substrate 2 and Src, upregulation of E-cadherin, and suppression of cadherin-11 and N-cadherin. These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing. In contrast, knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen. These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors. PMID:20876804

Sugiyama, Nami; Varjosalo, Markku; Meller, Pipsa; Lohi, Jouko; Hyytiäinen, Marko; Kilpinen, Sami; Kallioniemi, Olli; Ingvarsen, Signe; Engelholm, Lars H; Taipale, Jussi; Alitalo, Kari; Keski-Oja, Jorma; Lehti, Kaisa

2010-09-28

355

High serum albumin ascites gradient ascites--an atypical presentation of metastatic pancreatic cancer.  

PubMed

Pancreatic adenocarcinoma has less than a 5% 5-year survival rate, and metastatic disease is associated with a median survival of 4.5 months. A typical presentation often includes evidence of biliary obstruction, abdominal pain, jaundice, and weight loss. Significant ascites is not commonly seen at initial presentation and, when present, is typically associated with a low serum albumin ascites gradient (SAAG). We discuss a patient who presented with high-SAAG ascites as her initial presentation, only to be later diagnosed with metastatic pancreatic adenocarcinoma. PMID:23025146

Fincher, R Keith; Green, Roland H

2012-09-01

356

Inhibition of Tumor Angiogenesis and Growth by Nanoparticle-Mediated p53 Gene Therapy in Mice  

PubMed Central

Mutation of the p53 tumor suppressor gene, the most common genetic alteration in human cancers, results in more aggressive disease and increased resistance to conventional therapies. Aggressiveness may be related to the increased angiogenic activity of cancer cells containing mutant p53. To restore wild-type p53 function in cancer cells, we developed polymeric nanoparticles (NPs) for p53 gene delivery. Previous in vitro and in vivo studies demonstrated the ability of these NPs to provide sustained intracellular release of DNA, thus sustained gene transfection and decreased tumor cell proliferation. We investigated in vivo mechanisms involved in NP-mediated p53 tumor inhibition, with focus on angiogenesis. We hypothesize that sustained p53 gene delivery will help decrease tumor angiogenic activity and thus reduce tumor growth and improve animal survival. Xenografts of p53 mutant tumors were treated with a single intratumoral injection of p53NPs. We observed intratumoral p53 gene expression corresponding to tumor growth inhibition, over 5 weeks. Treated tumors showed upregulation of thrombospondin-1, a potent antiangiogenic factor, and a decrease in microvessel density vs. controls (saline, p53 DNA alone, and control NPs). Greater levels of apoptosis were also observed in p53NP-treated tumors. Overall, this led to significantly improved survival in p53NP-treated animals. NP-mediated p53 gene delivery slowed cancer progression and improved survival in an in vivo cancer model. One mechanism by which this is accomplished is disruption of tumor angiogenesis. We conclude that the NP-mediated sustained tumor p53 gene therapy can effectively be used for tumor growth inhibition.

Prabha, Swayam; Sharma, Blanka; Labhasetwar, Vinod

2012-01-01

357

Laparoscopic diagnosis of ascites in Lesotho.  

PubMed Central

In a prospective study of 98 consecutive patients with undiagnosed ascites examined by laparoscopy a correct immediate diagnosis was made in 76 (78%) and a final diagnosis in 92 (94%) of those who underwent laparoscopy. Visual diagnosis was highly accurate in patients with tuberculous peritonitis but only moderately accurate in those with carcinomatosis and liver disease. When the laparoscopic findings were compared with histological and microbiological results visual diagnosis was found to be the most accurate diagnostic method. Laparoscopy may readily be used in rural hospitals for diagnosing ascites.

Menzies, R I; Fitzgerald, J M; Mulpeter, K

1985-01-01

358

Divergent Selection for Ascites Incidence in Chickens  

Microsoft Academic Search

ABSTRACT Chicken lines that were either resistant or susceptible to ascites syndrome,were developed,by using a hypobaric,chamber,to induce,the disease. Birds were reared in a hypobaric,chamber,that simulated,high alti- tude by operating under a partial vacuum, which thereby lowered,the partial pressure,of oxygen. Ascites mortality data from,birds reared under,hypobaric,chamber,condi- tions were used to select siblings to be used for breeding. The response,to selection for

H. O. Pavlidis; J. M. Balog; L. K. Stamps; J. D. Hughes; W. E. Huff; N. B. Anthony

2007-01-01

359

Celecoxib prevents tumor growth in an animal model by a COX2 independent mechanism  

Microsoft Academic Search

Purpose  Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible\\u000a antineoplastic drugs are cyclooxygenase-2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were\\u000a evaluated in rats bearing Walker-256 (W256) tumor.\\u000a \\u000a \\u000a \\u000a Methods  W256 carcinosarcoma cells were inoculated subcutaneously (107 cells\\/rat) in rats submitted to treatment with celecoxib (25 mg kg?1) or vehicle for 14 days. Tumor growth,

Amanda Leite Bastos-Pereira; Daiana Lugarini; Adriana de Oliveira-Christoff; Thiago Vinicius Ávila; Simone Teixeira; Amanda do Rocio Andrade Pires; Sílvia Maria Suter Correia Cadena; Lucélia Donatti; Helena Cristina da Silva de Assis; Alexandra Acco

2010-01-01

360

Origin of the vasculature supporting growth of primary patient tumor xenografts  

PubMed Central

Background Studies of primary patient tumor xenografts grown in immunodeficient mice have shown that these tumors histologically and genetically closely resemble the original tumors. These patient xenograft models are becoming widely used for therapeutic efficacy studies. Because many therapies are directed at tumor stromal components and because the tumor microenvironment also is known to influence the response of a tumor to therapy, it is important to understand the nature of the stroma and, in particular, the vascular supply of patient xenografts. Methods Patient tumor xenografts were established by implanting undisrupted pieces of patient tumors in SCID mice. For this study, formalin fixed, paraffin embedded specimens from several types of solid tumors were selected and, using species-specific antibodies which react with formalin fixed antigens, we analyzed the species origin of the stroma and blood vessels that supported tumor growth in these models. Additionally, we investigated the kinetics of the vascularization process in a colon tumor and a mesothelioma xenograft. In mice bearing a head and neck xenograft, a perfusion study was performed to compare the functionality of the human and mouse tumor vessels. Results In patient tumors which successfully engrafted, the human stroma and vessels which were engrafted as part of the original tumor did not survive and were no longer detectable at the time of first passage (15–25 weeks). Uniformly, the stroma and vessels supporting the growth of these tumors were of murine origin. The results of the kinetic studies showed that the loss of the human vessels and vascularization by host vessels occurred more rapidly in a colon tumor (by 3 weeks) than in a mesothelioma (by 9 weeks). Finally, the perfusion studies revealed that while mouse vessels in the periphery of the tumor were perfused, those in the central regions were rarely perfused. No vessels of human origin were detected in this model. Conclusions In the tumors we investigated, we found no evidence that the human stromal cells and vessels contained in the original implant either survived or contributed in any substantive way to the growth of these xenografts.

2013-01-01

361

A hybrid cellular automaton model of solid tumor growth and bioreductive drug transport.  

PubMed

Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 \\mu {\\rm M} as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ. PMID:23221082

Kazmi, Nabila; Hossain, M A; Phillips, Roger M

362

PPAR? agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition  

PubMed Central

Angiogenesis and inflammation are central processes through which the tumor microenvironment influences tumor growth. We have demonstrated recently that peroxisome proliferator-activated receptor (PPAR)? deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of thrombospondin (TSP)-1 and prevents tumor growth. Hence, we speculated that pharmacologic activation of PPAR? would promote tumor growth. Surprisingly, the PPAR? agonist fenofibrate potently suppressed primary tumor growth in mice. This effect was not mediated by cancer-cell-autonomous antiproliferative mechanisms but by the inhibition of angiogenesis and inflammation in the host tissue. Although PPAR?-deficient tumors were still susceptible to fenofibrate, absence of PPAR? in the host animal abrogated the potent antitumor effect of fenofibrate. In addition, fenofibrate suppressed endothelial cell proliferation and VEGF production, increased TSP-1 and endostatin, and inhibited corneal neovascularization. Thus, both genetic abrogation of PPAR? as well as its activation by ligands cause tumor suppression via overlapping antiangiogenic pathways. These findings reveal the potential utility of the well tolerated PPAR? agonists beyond their use as lipid-lowering drugs in anticancer therapy. Our results provide a mechanistic rationale for evaluating the clinical benefits of PPAR? agonists in cancer treatment, alone and in combination with other therapies.

Panigrahy, Dipak; Kaipainen, Arja; Huang, Sui; Butterfield, Catherine E.; Barnes, Carmen M.; Fannon, Michael; Laforme, Andrea M.; Chaponis, Deviney M.; Folkman, Judah; Kieran, Mark W.

2008-01-01

363

Growth inhibition of ovarian tumor-initiating cells by niclosamide.  

PubMed

A recent hypothesis for cancer chemoresistance posits that cytotoxic survival of a subpopulation of tumor progenitors drives the propagation of recurrent disease, underscoring the need for new therapeutics that target such primitive cells. To discover such novel compounds active against drug-resistant ovarian cancer, we identified a subset of chemoresistant ovarian tumor cells fulfilling current definitions of cancer-initiating cells from cell lines and patient tumors using multiple stemness phenotypes, including the expression of stem cell markers, membrane dye efflux, sphere formation, potent tumorigenicity, and serial tumor propagation. We then subjected such stem-like ovarian tumor-initiating cells (OTIC) to high-throughput drug screening using more than 1,200 clinically approved drugs. Of 61 potential compounds preliminarily identified, more stringent assessments showed that the antihelmintic niclosamide selectively targets OTICs in vitro and in vivo. Gene expression arrays following OTIC treatment revealed niclosamide to disrupt multiple metabolic pathways affecting biogenetics, biogenesis, and redox regulation. These studies support niclosamide as a promising therapy for ovarian cancer and warrant further preclinical and clinical evaluation of this safe, clinically proven drug for the management of this devastating gynecologic malignancy. PMID:22576131

Yo, Yi-Te; Lin, Ya-Wen; Wang, Yu-Chi; Balch, Curt; Huang, Rui-Lan; Chan, Michael W Y; Sytwu, Huey-Kang; Chen, Chi-Kuan; Chang, Cheng-Chang; Nephew, Kenneth P; Huang, Tim; Yu, Mu-Hsien; Lai, Hung-Cheng

2012-05-10

364

Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma  

PubMed Central

Inappropriate kinase expression and subsequent promiscuous activity defines the transformation of many solid tumors including renal cell carcinoma (RCC). Thus, the expression of novel tumor-associated kinases has the potential to dramatically shape tumor cell behavior. Further, identifying tumor-associated kinases can lend insight into patterns of tumor growth and characteristics. Here, we report the identification of Ror2, a new tumor-associated kinase in RCC cell lines and primary tumors. Ror2 is an orphan receptor tyrosine kinase with physiological expression normally seen in the embryonic kidney. However, in RCC, Ror2 expression correlated with expression of genes involved at the extracellular matrix, including Twist and matrix metalloprotease-2 (MMP2). Expression of MMP2 in RCC cells was suppressed by Ror2 knockdown, placing Ror2 as a mediator of MMP2 regulation in RCC and a potential regulator of extracellular matrix remodeling. The suppression of Ror2 not only inhibited cell migration, but also inhibited anchorage independent growth in soft agar and growth in an orthotopic xenograft model. These findings suggest a novel pathway of tumor-promoting activity by Ror2 within a subset of renal carcinomas, with significant implications for unraveling the tumorigenesis of RCC.

Wright, Tricia M; Brannon, A Rose; Gordan, John D; Mikels, Amanda J; Mitchell, Cicely; Chen, Shufen; Espinosa, Inigo; van de Rijn, Matt; Pruthi, Raj; Wallen, Eric; Edwards, Lloyd; Nusse, Roel; Rathmell, W Kimryn

2009-01-01

365

A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors  

NASA Astrophysics Data System (ADS)

The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Gi protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.

Rubin, Joshua B.; Kung, Andrew L.; Klein, Robyn S.; Chan, Jennifer A.; Sun, Yanping; Schmidt, Karl; Kieran, Mark W.; Luster, Andrew D.; Segal, Rosalind A.

2003-11-01

366

Thyroid tumors with a follicular growth pattern: problems in differential diagnosis.  

PubMed

Tumors of the thyroid characterized by a follicular growth pattern constitute the most common type of lesion of this organ encountered by pathologists. The vast majority of such lesions do not pose difficulties for histopathologic interpretation. A subset of these tumors, however, can represent a serious challenge for diagnosis. Thyroid tumors with a follicular growth pattern include a broad range of lesions that range from benign, hyperplastic nodules to follicular adenomas to follicular carcinomas. In addition, other types of tumors belonging in separate diagnostic categories can also present histologically with a follicular growth pattern, including the follicular variant of papillary thyroid carcinoma and medullary carcinoma. The histologic features and diagnostic criteria used for distinguishing among these conditions can often be subtle and subjective. PMID:16831055

Suster, Saul

2006-07-01

367

Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice.  

PubMed

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast, all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors. PMID:12114691

Koyama, Chiaki; Matsumoto, Hirokazu; Sakai, Takafumi; Wakabayashi, Katsumi; Ito, Akihiro; Couch, Ernest F.; Inoue, Kinji

1995-01-01

368

Anti-VEGF antibody in experimental hepatoblastoma: Suppression of tumor growth and altered angiogenesis  

Microsoft Academic Search

Background: Hepatoblastoma is the most common primary hepatic malignancy of childhood, frequently presenting as advanced disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen and survival factor critical to growth and angiogenesis in many human cancers. Inhibition of VEGF effectively suppresses tumorigenesis in multiple experimental models. The authors hypothesized that anti-VEGF antibody would alter vascular architecture and impede tumor

Kimberly W. McCrudden; Benjamin Hopkins; Jason Frischer; Anna Novikov; Jianzhong Huang; Angela Kadenhe; Tamara New; Akiko Yokoi; Darrell J. Yamashiro; Jessica J. Kandel; William Middlesworth

2003-01-01

369

Image Guided Personalization of Reaction-Diffusion Type Tumor Growth Models Using Modified Anisotropic Eikonal Equations  

Microsoft Academic Search

Reaction-diffusion based tumor growth models have been widely used in the literature for modeling the growth of brain gliomas. Lately, recent models have started integrating medical images in their formulation. Including different tis sue types, geometry of the brain and the directions of white matter fiber tracts improved the spatial accuracy of reaction-diffusio n models. The adaptation of the general

Ender Konukoglu; Olivier Clatz; Bjoern H. Menze; Marc-Andre Weber; Bram Stieltjes; Emmanuel Mandonnet; Herve Delingette; Nicholas Ayache

2010-01-01

370

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses  

Microsoft Academic Search

BACKGROUND: Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed

Luis E Bergues Cabrales; J Godina Juan Nava; Andrés Ramírez Aguilera; Javier A González Joa; Héctor M Camué Ciria; Maraelys Morales González; Miriam Fariñas Salas; Manuel Verdecia Jarque; Tamara Rubio González; Miguel A O'Farril Mateus; Soraida C Acosta Brooks; Fabiola Suárez Palencia; Lisset Ortiz Zamora; María Quevedo; Sarah Edward Seringe; Vladimir Crombet Cuitié; Idelisa Bergues Cabrales; Gustavo Sierra González

2010-01-01

371

The epidermal growth factor receptor–tyrosine kinase: A promising therapeutic target in solid tumors  

Microsoft Academic Search

The overexpression and aberrant function of the epidermal growth factor receptor (EGFR) and its ligands in several human carcinomas have provided a rationale for targeting this signaling network with novel treatment approaches. The epidermal growth factor receptor–tyrosine kinase (EGFR-TK) is a selective target for inhibiting cancer because it is activated in many tumor cells, yet is strictly controlled in normal

Christoph A Ritter; Carlos L Arteaga

2003-01-01

372

Receptor tyrosine kinase inhibition suppresses growth of pediatric renal tumor cells in vitro  

Microsoft Academic Search

Purpose: Children who undergo standard therapy for renal tumors are at an increased risk for treatment sequelae such as congestive heart failure, abnormal trunk development, and secondary malignancies. Therefore, research on the use of novel chemotherapeutic agents with fewer side effects is justified. Recent experimental evidence suggests that growth factor receptors such as epidermal growth factor receptor (EGFR) and platelet-derived

Shalizeh Naraghi; Sami Khoshyomn; Joseph A DeMattia; Dennis W Vane

2000-01-01

373

Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice  

PubMed Central

Membrane-bound proteases have recently emerged as critical mediators of tumorigenesis, angiogenesis, and metastasis. However, the mechanisms by which they regulate these processes remain unknown. As the cell surface serine protease fibroblast activation protein (FAP) is selectively expressed on tumor-associated fibroblasts and pericytes in epithelial tumors, we set out to investigate the role of FAP in mouse models of epithelial-derived solid tumors. In this study, we demonstrate that genetic deletion and pharmacologic inhibition of FAP inhibited tumor growth in both an endogenous mouse model of lung cancer driven by the K-rasG12D mutant and a mouse model of colon cancer, in which CT26 mouse colon cancer cells were transplanted into immune competent syngeneic mice. Interestingly, growth of only the K-rasG12D–driven lung tumors was also attenuated by inhibition of the closely related protease dipeptidyl peptidase IV (DPPIV). Our results indicate that FAP depletion inhibits tumor cell proliferation indirectly, increases accumulation of collagen, decreases myofibroblast content, and decreases blood vessel density in tumors. These data provide proof of principle that targeting stromal cell–mediated modifications of the tumor microenvironment may be an effective approach to treating epithelial-derived solid tumors.

Santos, Angelica M.; Jung, Jason; Aziz, Nazneen; Kissil, Joseph L.; Pure, Ellen

2009-01-01

374

Intratumoral Heterogeneity for Expression of Tyrosine Kinase Growth Factor Receptors in Human Colon Cancer Surgical Specimens and Orthotopic Tumors  

PubMed Central

The design of targeted therapy, particularly patient-specific targeted therapy, requires knowledge of the presence and intratumoral distribution of tyrosine kinase receptors. To determine whether the expression of such receptors is constant or varies between and within individual colon cancer neoplasms, we examined the pattern of expression of the ligands, epidermal growth factor, vascular endothelial growth factor, and platelet-derived growth factor-B as well as their respective receptors in human colon cancer surgical specimens and orthotopic human colon cancers growing in the cecal wall of nude mice. The expression of the epidermal growth factor receptor and the vascular endothelial growth factor receptor on tumor cells and stromal cells, including tumor-associated endothelial cells, was heterogeneous in surgical specimens and orthotopic tumors. In some tumors, the receptor was expressed on both tumor cells and stromal cells, and in other tumors the receptor was expressed only on tumor cells or only on stromal cells. In contrast, the platelet-derived growth factor receptor was expressed only on stromal cells in both surgical specimens and orthotopic tumors. Examination of receptor expression in both individual surgical specimens and orthotopic tumors revealed that the platelet-derived growth factor receptor was expressed only on stromal cells and that the patterns of epidermal growth factor receptor and vascular endothelial growth factor receptor 2 expression differed between tumor cells. This heterogeneity in receptor expression among different tumor cells suggests that targeting a single tyrosine kinase may not yield eradication of the disease.

Kuwai, Toshio; Nakamura, Toru; Kim, Sun-Jin; Sasaki, Takamitsu; Kitadai, Yasuhiko; Langley, Robert R.; Fan, Dominic; Hamilton, Stanley R.; Fidler, Isaiah J.

2008-01-01

375

Interleukin10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth  

Microsoft Academic Search

BACKGROUND: Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like,

Aline Bolpetti; João S Silva; Luisa L Villa; Ana Paula Lepique

2010-01-01

376

Reinforcement learning based control of tumor growth with chemotherapy  

Microsoft Academic Search

In this paper, optimal drug schedule for patients in progressive cancer phase who take the drug through infusion pump is obtained. An objective of control is reducing tumor cell numbers effectively while minimizing total amount of drug regimen. This is done because of the known serious side effects and major damages resulting from chemotherapy. Chemotherapy brings about weakness of the

Amin Hassani; M. B. Naghibi

2010-01-01

377

Antiangiogenic Therapy of Transgenic Mice Impairs de novo Tumor Growth  

Microsoft Academic Search

Angiogenesis is activated during multistage tumorigenesis prior to the emergence of solid tumors. Using a transgenic mouse model, we have tested the proposition that treatment with angiogenesis inhibitors can inhibit the progression of tumorigenesis after the switch to the angiogenic phenotype. In this model, islet cell carcinomas develop from multifocal, hyperproliferative nodules that show the histological hallmarks of human carcinoma

Sareh Parangi; Michael O'Reilly; Gerhard Christofori; Lars Holmgren; Jeffrey Grosfeld; Judah Folkman; Douglas Hanahan

1996-01-01

378

Cotargeting tumor and stroma in a novel chimeric tumor model involving the growth of both human prostate cancer and bone stromal cells  

Microsoft Academic Search

Stromal–epithelial interaction contributes to local prostate tumor growth, androgen-independent progression and distant metastasis. We have established in vitro coculture and in vivo chimeric tumor models to evaluate the roles of stromal cells isolated from either osteosarcoma or normal bone, a site where prostate cancer cells frequently metastasize, in contributing to the growth and survival of human prostate cancer cells. We

Chia-Ling Hsieh; Thomas A Gardner; Li Miao; Gary Balian; Leland W K Chung; Leland WK Chung

2004-01-01

379

Ascites syndrome and related pathologies in feed restricted broilers raised in a hypobaric chamber.  

PubMed

It has been demonstrated that the incidence of ascites can be significantly reduced through feed restriction. This method is thought to have an effect by slowing the growth rate of the birds. Interestingly, when birds are grown in a hypobaric chamber, ascites incidence increases while the overall growth rate of the birds is decreased. Unfortunately, the restriction programs practiced also have a detrimental effect on growth characteristics. An experiment was conducted to determine if the timing and duration of feed restriction can be used to reduce the incidence of ascites for broilers reared under high altitude and local elevation without having a negative impact on growth. A total of 600 commercial broiler males were used. Birds were divided, placing 360 birds in the hypobaric chamber at a simulated 2900 m (9,500 ft) above sea level, and 240 birds were placed at local elevation [390 m (1,300 ft) above sea level]. At each altitude there were four treatments: 1) fully fed controls; 2) feed available for 8 h/d for 6 wk (the duration of the study); 3) feed available for 8 h/d during the first 3 wk, then full feed for the remaining 3 wk; and 4) full feed for the first wk, then 3 wk of 8 h of feed availability, then 2 wk of full feed. Birds and feed were weighed weekly, and mortalities were necropsied to determine the cause of death. At the end of 6 wk, blood samples were taken, and the birds were weighed, necropsied, and scored for ascites, and organ weights were recorded. All feed restriction treatments significantly reduced ascites incidence, when compared with the fully fed controls. Treatment 2 birds were significantly lighter than any other group at both altitudes. The fully fed controls at local elevation were heavier than the fully fed controls at simulated high altitude, as seen in past experiments. PMID:10735196

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

2000-03-01

380

Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin.  

PubMed

Capsaicin, the pungent ingredient of hot chilli pepper, has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. Here, we investigated the role of the vanilloid capsaicin in the death regulation of the human cancer androgen-resistant cell line PC-3. Capsaicin inhibited the growth of PC-3 with an IC(50) of 20 microM cells and induced cell apoptosis, as assessed by flow cytometry and nuclei staining with DAPI. Capsaicin induced apoptosis in prostate cells by a mechanism involving reactive oxygen species generation, dissipation of the mitochondrial inner transmembrane potential (DeltaPsi(m)) and activation of caspase 3. Capsaicin-induced apoptosis was not reduced by the antagonist capsazepine in a dose range from 0.1 microM to 20 microM, suggesting a receptor-independent mechanism. To study the in vivo effects of capsaicinoids, PC-3 cells were grown as xenografts in nude mice. Subcutaneous injection of either capsaicin or capsazepine (5 mg/kg body weight) in nude mice suppressed PC-3 tumor growth in all tumors investigated and induced apoptosis of tumor cells. Our data show a role for capsaicin against androgen-independent prostate cancer cells in vitro and in vivo and suggest that capsaicin is a promising anti-tumor agent in hormone-refractory prostate cancer, which shows resistance to many chemotherapeutic agents. PMID:16374544

Sánchez, A M; Sánchez, M G; Malagarie-Cazenave, S; Olea, N; Díaz-Laviada, I

2006-01-01

381

Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs  

SciTech Connect

The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using {sup 125}I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

Leung, F.C.; Bohn, L.R.; Dagle, G.E. (Pacific Northwest Lab., Richland, WA (USA))

1991-04-01

382

Modeling tumor growth in a complex evolving confinement using a diffuse domain approach  

NASA Astrophysics Data System (ADS)

Understanding the spatiotemporal evolution of tumor growth represents an essential step towards engineering effective treatment for cancer patients. At the macroscopic scale, various biophysical models describing tumors as continuum fluids have been constructed, particularly on a Cartesian grid, where efficient numerical schemes are available to analyze the model for general tumor behaviors in a relatively unconfined space. For practical problems, however, tumors are often found in a confined sub-domain, which can even be dilated and distorted by the growing tumor within. To study such tumors, we adopt a novel diffuse domain approach that enables us to adapt a model to an evolving sub-domain and formulate the modified problem on a Cartesian grid to utilize existing numerical schemes. To demonstrate this approach, we adapt a diffuse-interface model presented in Wise et al. [2008, Three-dimensional multispecies nonlinear tumor growth - I Model and numerical method, J. Theor. Biol. 253, 524-543] to simulate lymphoma growth in a lymph node structure.

Chuang, Yao-Li; Lowengrub, John; Chen, Ying; Li, Xiangrong; Frieboes, Hermann; Cristini, Vittorio

2011-11-01

383

Non-invasive optical imaging of tumor growth in intact animals  

NASA Astrophysics Data System (ADS)

We describe here a system for rapidly visualizing tumor growth in intact rodent mice that is simple, rapid, and eminently accessible and repeatable. We have established new rodent tumor cell line -- SP2/0-GFP cells that stably express high level of green fluorescent protein (GFP) by transfected with a plasmid that encoded GFP using electroporation and selected with G418 for 3 weeks. 1 x 104 - 1x107 SP2/0-GFP mouse melanoma cells were injected s.c. in the ears and legs of 6- to 7-week-old syngeneic male BALB/c mice, and optical images visualized real-time the engrafted tumor growth. The tumor burden was monitored over time by cryogenically cooled charge coupled device (CCD) camera focused through a stereo microscope. The results show that the fluorescence intensity of GFP-expressing tumor is comparably with the tumor growth and/or depress. This in vivo optical imaging based on GFP is sensitive, external, and noninvasive. It affords continuous visual monitoring of malignant growth within intact animals, and may comprise an ideal tool for evaluating antineoplastic therapies.

Lu, Jinling; Li, Pengcheng; Luo, Qingming; Zhu, Dan

2003-12-01

384

Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: tumor-tropic potential and inhibition of ovarian cancer cell growth.  

PubMed

Recent studies have shown that genetically engineered stem cells (GESTECs) to produce suicide enzymes that convert non-toxic prodrugs to toxic metabolites selectively migrate toward tumor sites and reduce tumor growth. In the present study, we evaluated whether these GESTECs were capable of migrating to human ovarian cancer cells and examined the potential therapeutic efficacy of the gene-directed enzyme prodrug therapy against ovarian cancer cells in vitro. The expression of cytosine deaminase (CD) or carboxyl esterase (CE) mRNA of GESTECs was confirmed by RT-PCR. A modified transwell migration assay was performed to determine the migratory capacity of GESTECs to ovarian cancer cells. GESTECs (HB1.F3.CD or HB1.F3.CE cells) engineered to express a suicide gene (CD or CE) selectively migrated toward ovarian cancer cells. A [(3)H] thymidine incorporation assay was conducted to measure the proliferative index. Treatment of human epithelial ovarian cancer cell line (SKOV-3, an ovarian adenocarcinoma derived from the ascites of an ovarian cancer patient) with the prodrugs 5-fluorocytosine (5-FC) or camptothecin-11 (CPT-11) in the presence of HB1.F3.CD or HB1.F3.CE cells resulted in the inhibition of ovarian cancer cell growth. Based on the data presented herein, we suggest that GESTECs expressing CD/CE may have a potent advantage to selectively treat ovarian cancers. PMID:20704576

Kim, Ki-Yon; Kim, Seung U; Leung, Peter C K; Jeung, Eui-Bae; Choi, Kyung-Chul

2010-04-01

385

A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth  

PubMed Central

We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords “immunotherapy” AND “cancer” for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5–121 mm3 in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm3 was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm3, and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm3, and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth.

Wen, Frank T.; Thisted, Ronald A.; Rowley, Donald A.; Schreiber, Hans

2012-01-01

386

Morphology and growth characteristics of epithelial cells from classic Wilms' tumors.  

PubMed Central

The ability to establish cell cultures representing the epithelial component of Wilms' tumor was determined for 18 cases of classic Wilms' tumors. From these 18 cases only two resulted in the culture of epithelial cells. Although the tumors from both cases were composed of a prominent epithelial component, other classic tumors not producing epithelial cell cultures also possessed appreciable epithelial components. Likewise, heterotransplants of these two primary tumors failed to give rise to epithelial cell cultures, although cultures of the blastemal element were produced. This suggests that Wilms' tumors may be prone to differentiate in different directions at varying times during tumor growth, possibly dependent on local tumor environment. Epithelial cells from these two classic cases were grown in culture in basal medium composed of a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium, supplemented with selenium, insulin, transferrin, hydrocortisone, tri-iodothyronine, and epidermal growth factor, on a collagen type I matrix with absorbed fetal calf serum proteins. One of the two cases also required the addition of bovine pituitary extract, ethanolamine, prostaglandin E1, and putrescine for optimum growth. Morphological analysis disclosed that the cultured cells were very similar to normal renal tubular cells in culture, except that the cells displayed little evidence for differentiated active ion transport and tended to grow in a multilayered arrangement. The culture of the epithelial cells from classic Wilms' tumors provides a model system for the study of tumor differentiation and progression. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12

Hazen-Martin, D. J.; Garvin, A. J.; Gansler, T.; Tarnowski, B. I.; Sens, D. A.

1993-01-01

387

Granulocyte Macrophage Colony-Stimulating Factor Inhibits Breast Cancer Growth and Metastasis by Invoking an Anti-Angiogenic Program in Tumor-Educated Macrophages  

Microsoft Academic Search

Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granulocyte macrophage colony-stimulating factor (GM-CSF) blocked macrophages vascular endothelial growth factor (VEGF) activity by produc- ing soluble VEGF receptor-1 (sVEGFR-1) and determined the effect on tumor-associated macrophage behavior and tumor growth. We show GM-CSF treatment of murine mammary tumors slowed tumor growth and slowed metastasis. These tumors had more macrophages,

Tim D. Eubank; Ryan D. Roberts; Mahmood Khan; Jennifer M. Curry; Gerard J. Nuovo; Periannan Kuppusamy; Clay B. Marsh

2009-01-01

388

Inhibition of tumor cell growth in the liver by RNA interference-mediated suppression of HIF-1? expression in tumor cells and hepatocytes  

Microsoft Academic Search

Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of ? and ? subunits. HIF-1 activates transcription of various genes including those involved in metastatic tumor growth. In the present study, HIF-1? expression in tumor-bearing mouse liver was examined after inoculation of tumor cells into portal vein. We found that tumor-bearing liver showed greatly increased HIF-1? expression. Plasmid

Y Takahashi; M Nishikawa; Y Takakura

2008-01-01

389

Inhibition of tumor growth and metastasis by chronic intravenous infusion of prostaglandin E1.  

PubMed Central

The role of prostaglandins and their synthesis inhibitors in malignant disease is undefined. The following studies were done to determine the effects of continuous intravenous prostaglandin E1 (PGE1) or a prostaglandin synthesis inhibitor, indomethacin, on tumor growth and metastasis in mice bearing Lewis lung carcinoma. Male B6D2F1 mice underwent tumor implantation in the right axilla on day 0. After 10 days of tumor growth, mice underwent intravenous (IV) catheterization and were infused with either PGE1 at 3 micrograms/kg/minute (PG-LOW), PGE1 at 6 micrograms/kg/minute (PG-HIGH), indomethacin (INDO) at 1 microgram/kg/minute, or normal saline (NS). After 10 days of infusion, tumor volume, tumor weight, and the number of metastases greater than 2 mm in diameter were significantly decreased, and tumor doubling time was significantly prolonged in the PG-HIGH group compared to NS controls. None of the other experimental groups showed differences in these parameters. A second experiment with a similar experimental design was done infusing PGE1 at 6 micrograms/kg/minute and at 12 micrograms/kg/minute to determine the maximum dose response of IV PGE1. Again a decrease in tumor volume, tumor weight, and metastatic rates were identified when compared to saline control, but there were no significant difference between the two doses of PGE1.

Ellis, L M; Copeland, E M; Bland, K I; Sitren, H S

1990-01-01

390

Impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1-null mice  

PubMed Central

Despite 2 decades of research, no clear function for annexin A1 (AnxA1) has been established. Using AnxA1-KO mice, we show that tumor growth and metastasis are significantly decreased, whereas rodent survival and tumor necrosis are greatly increased when tumors grow in AnxA1-KO mice. Systems analysis of gene expression in these tumors specifically implicates 2 related vascular functions, angiogenesis and wound healing, in this impairment. Both tumor vascular development and wound healing are greatly retarded in KO tissues. Aortic ring assays reveal induced AnxA1 expression on sprouting endothelial cells of normal mice whereas KO aortas exhibit impaired endothelial cell sprouting that is rescued by adenoviral expression of AnxA1. Key differences in specific gene regulation may define new molecular pathways mediating angiogenesis, including a reset profile of pro- versus anti-angiogenic factors, apparently distinct for physiological versus pathological angiogenesis. These studies establish novel pro-angiogenic functions for AnxA1 in vascular endothelial cell sprouting, wound healing, and tumor growth and metastasis, thereby uncovering a new functional target for repairing damaged tissue and treating diseases such as cancer. They also provide critical new evidence that the tumor stroma and its microenvironment can greatly affect tumor progression and metastasis.

Yi, Ming; Schnitzer, Jan E.

2009-01-01

391

Thymidine Phosphorylase is Angiogenic and Promotes Tumor Growth  

Microsoft Academic Search

Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). The effect of TP on [methyl-^3H]thymidine uptake does not arise from de novo DNA synthesis and the molecule is not a growth factor. Despite this, TP is strongly angiogenic in a rat sponge and freeze-injured

Amir Moghaddam; Hua-Tang Zhang; Tai-Ping D. Fan; De-En Hu; Vivien C. Lees; Helen Turley; Stephen B. Fox; Kevin C. Gatter; Adrian L. Harris; Roy Bicknell

1995-01-01

392

CD200-expressing human basal cell carcinoma cells initiate tumor growth  

PubMed Central

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.

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.

2013-01-01

393

Characterization of Human Kallikreins 6 and 10 in Ascites Fluid from Ovarian Cancer Patients  

Microsoft Academic Search

Objectives: Human kallikreins 6 (hK6) and 10 (hK10) are secreted serine proteases. We previously found that hK6 and hK10 are highly overexpressed in epithelial ovarian tumors and demonstrated that serum levels of hK6 and hK10 are valuable biomarkers for ovarian cancer diagnosis and prognosis. Our aim is to purify and characterize these two kallikreins from ascites fluid of ovarian cancer

Liu-Ying Luo; Antoninus Soosaipillai; Linda Grass; Eleftherios P. Diamandis

2006-01-01

394