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1

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

SciTech Connect

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

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

2014-01-15

2

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

PubMed

Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC50=25 ± 0.38) when compared to reference compound PTER (IC50=65 ± 0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. PMID:24216289

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

2014-01-15

3

Antiangiogenic and growth inhibitory effects of synthetic novel 1, 5-diphenyl-1,4 pentadiene-3-one-3-yl-ethanone pyridine curcumin analogues on Ehrlich ascites tumor in vivo  

Microsoft Academic Search

In the present investigation we have synthesized novel substituted dienone pyridine ethanone curcumin analogues 3a and 3b by nucleophilic substitution reactions with 2-bromo-1-pyridine-3-yl ethanone and characterized by 1H nuclear magnetic resonance (NMR), infrared IR, mass, and CHNS analysis. The compounds demonstrated tumor growth inhibition\\u000a and antiangiogenic effects against mouse Ehrlich ascites tumor in vivo and suppressed neovascularization in a chorio

H. Chandru; A. C. Sharada; C. S. Ananda Kumar; K. S. Rangappa

2008-01-01

4

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 PMID:3510553

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

1986-01-01

5

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

SciTech Connect

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. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-?B activity in CD4 + T cells.

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

2013-06-15

6

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

2013-06-15

7

Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells.  

PubMed Central

Human ovarian cancer, the leading cause of death from gynecologic malignancy, tends to remain localized to the peritoneal cavity until late in the disease. In established disease, ascitic fluid accumulates in the peritoneal cavity. We have previously demonstrated that this ascitic fluid is a potent source of in vitro mitogenic activity including at least one unique growth factor. We now report that the human ovarian adenocarcinoma line, HEY, can be induced to grow intraperitoneally in immunodeficient nude mice in the presence (23/28 mice), but not absence (0/21 mice) of ascitic fluid from ovarian cancer patients. Ascitic fluid from patients with benign disease did not have similar effects on intraperitoneal growth of HEY cells (1/15 mice). Once tumors were established by injections of exogenous ascitic fluid, they could progress in the absence of additional injections of ascitic fluid. The mice eventually developed ascitic fluid which contained potent growth factor activity, suggesting that the tumors eventually produced autologous growth factors. This nude mouse model provides a system to study the action of ovarian cancer growth factors on tumor growth in vivo and to evaluate preclinically, therapeutic approaches designed to counteract the activity of these growth factors. PMID:2394835

Mills, G B; May, C; Hill, M; Campbell, S; Shaw, P; Marks, A

1990-01-01

8

Ascites  

MedlinePLUS

... patients with ascites due to cirrhosis: Update 2012. American Association for the Study of Liver Diseases. 2013. Mehta G, Rothstein KD. Health maintenance issues in cirrhosis. Med Clin North Am. 2009;93:901-915. Garcia-Tsao G. ...

9

Ursolic acid inhibits tumor angiogenesis and induces apoptosis through mitochondrial-dependent pathway in Ehrlich ascites carcinoma tumor.  

PubMed

Ursolic acid (UA) is a pentacyclic triterpene naturally occurring in many plant foods. In the present study, we investigated anti-cancer activity of UA in vivo in Ehrlich ascites carcinoma (EAC) tumor. 15 × 10(6) EAC cells were implanted intraperitoneally (i.p., ascitic tumor) and subcutaneous (s.c., solid tumor) in Swiss albino mice. Mice with established tumors received UA i.p. at 25, 50 and 100mg/kg bw for 14 d in ascitic and 100mg/kg bw in solid tumor for 30 d. On day 15, blood samples were collected for hematological assessment of hemoglobin (Hb%), RBCs, WBCs and PCV. Tumor volume, cell viability, angiogenic, anti-angiogenic, anti-inflammatory factors and antioxidant parameters were determined. Immunohistochemistry analysis for VEGF, iNOS, CD31, caspase-3 and Bax were also performed. UA significantly inhibited tumor growth, cell viability, in both ascites and solid tumor model in vivo (p<0.001). The anti-angiogenic effects were accompanied with decreased VEGF, iNOS, TNF-? and increased IL-12 levels. UA at 100mg/kg bw dose significantly increased SOD and CAT activity (p<0.01). GSH and TBARS were increased as compared to control group (p<0.001). Furthermore, UA increased total RBCs, WBCs as well as Hb% significantly (p<0.05) compared to cyclophosphamide (CP). Histopathological examination of tumor cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. Decreased peritoneal angiogenesis showed the anti-angiogenic potential. UA downregulated VEGF & iNOS expression whereas bax and caspase-3 expressions were upregulated suggesting drug induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3 and downregulation of VEGF. The present study sheds light on the potent antitumor property of the UA and can be extended further to develop therapeutic protocols for treatment of cancer. PMID:24051192

Saraswati, Sarita; Agrawal, S S; Alhaider, Abdulqader A

2013-11-25

10

Immunogenicity of ascites tumor cells following in vitro hyperthermia  

SciTech Connect

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

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

1982-06-01

11

Gracilaria edulis extract induces apoptosis and inhibits tumor in Ehrlich Ascites tumor cells in vivo  

PubMed Central

Background Marine environment is inestimable for their chemical and biological diversity and therefore is an extraordinary resource for the discovery of new anticancer drugs. Recent development in elucidation of the mechanism and therapeutic action of natural products helped to evaluate for their potential activity. Methods We evaluated Gracilaria edulis J. Ag (Brown algae), for its antitumor potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Cytotoxicity evaluation of Ethanol Extract of Gracilaria edulis (EEGE) using EAT cells showed significant activity. In vitro studies indicated that EEGE cytotoxicity to EAT cells is mediated through its ability to produce reactive oxygen species (ROS) and therefore decreasing intracellular glutathione (GSH) levels may be attributed to oxidative stress. Results Apoptotic parameters including Annexin-V positive cells, increased levels of DNA fragmentation and increased caspase-2, caspase-3 and caspase-9 activities indicated the mechanism might be by inducing apoptosis. Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity. Conclusion Comprehensive antitumor analysis in animal model and in Ehrlich Ascites Tumor cells was done including biochemical, and pathological evaluations indicate antitumor activity of the extract and non toxic in vivo. It was evident that the mechanism explains the apoptotic activity of the algae extract. PMID:24274337

2013-01-01

12

Ascites analysis by a microfluidic chip allows tumor-cell profiling  

E-print Network

Ascites tumor cells (ATCs) represent a potentially valuable source of cells for monitoring treatment of ovarian cancer as it would obviate the need for more invasive surgical biopsies. The ability to perform longitudinal ...

Peterson, Vanessa M.

13

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

2005-01-01

14

Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH130)  

Microsoft Academic Search

The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of

S Dessí; B Batetta; C Anchisi; P Pani; P Costelli; L Tessitore; FM Baccino

1992-01-01

15

Growth rate of ascites-resistant versus ascites-susceptible broilers in commercial and experimental lines.  

PubMed

The high growth rate (GR) of contemporary broilers is driven by high rate of feed intake and metabolism. Because of the consequent high oxygen demand, especially when coupled with exposure to high altitude or low temperatures, some broilers fail to regulate oxygen supply and develop the ascites syndrome (AS), which leads to mortality and economic losses. Because of the association between high GR, oxygen demand, and AS, it has been suggested that AS is induced by high GR. If true, further GR enhancement should be avoided because it will increase the proportion of AS-susceptible individuals in contemporary stocks. An alternative hypothesis claims that AS is associated with high actual GR only because the latter increases oxygen demand and that there are genetically AS-resistant broilers that do not develop AS, even when exhibiting high GR. These hypotheses were tested in trials in the years 2002 and 2006, with broilers differing in potential GR: contemporary fast-growing commercial lines and an experimental line derived from commercial broilers in 1986, and (in 2002 only) divergently selected AS-susceptible and AS-resistant lines. A protocol of high-challenge ascites-inducing conditions (AIC) from d 19 was used to distinguish between AS-susceptible and AS-resistant individuals and to determine their GR up to this age. The difference in AS incidence between the divergent lines (93.9 vs. 9.5%) was not explained by the 5% difference in their GR, thus indicating a lack of genetic correlation. In the broiler lines, AS incidence was 31 and 47% in 2002 and 2006, respectively, and 32% in the 1986 slow-growing line. Most broilers that remained healthy under the high-challenge AIC exhibited the same early GR and BW as those that later developed AS. These results, and the relatively high incidence of AS in the slow-growing line, indicate that there is very little, if any, direct genetic association between AS and genetic differences in potential GR, and suggest that AS-resistant broilers can be selected for higher GR and remain healthy even under AIC. PMID:18420980

Druyan, S; Hadad, Y; Cahaner, A

2008-05-01

16

Synergism between propolis and hyperthermal intraperitoneal chemotherapy with cisplatin on ehrlich ascites tumor in mice.  

PubMed

We investigated antitumor, genotoxic, chemopreventive, and immunostimulative effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse-bearing Ehrlich ascites tumor (EAT). Mice were treated with water-soluble derivative of propolis (WSDP) at a dose of 50 mg kg(-1) , 7 and 3 days before implantation of EAT cells, whereas cisplatin (5 or 10 mg kg(-1) ) was injected 3 days after implantation of EAT cells at 37°C and 43°C. The following variables were analyzed: the total number of cells, differential count of the cells present in the peritoneal cavity, functional activity of macrophages, comet assay, and micronucleus assay. The combination of WSDP + CIS 5 mg kg(-1) at 37°C resulted in tumor growth inhibition and increased the survival of mice by additional 115.25%. WSDP with HIPEC increased the survival of mice by additional 160.3% as compared with HIPEC. WSDP reduced cisplatin toxic and genotoxic effect to normal cells without affecting cisplatin cytotoxicity on EAT cells. In addition, WSDP with HIPEC increased the cytotoxic actions of macrophages to tumor cells. Water-soluble derivative of propolis increases macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin toxicity to normal cells. PMID:24136132

Oršoli?, Nada; Car, Nikola; Lisi?i?, Duje; Benkovi?, Vesna; Kneževi?, Anica Horvat; Diki?, Domagoj; Petrik, József

2013-12-01

17

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

PubMed

Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR). AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125), epithelial cell adhesion molecule (EpCAM) and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p.) injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC) markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions. PMID:23056490

Latifi, Ardian; Luwor, Rodney B; Bilandzic, Maree; Nazaretian, Simon; Stenvers, Kaye; Pyman, Jan; Zhu, Hongjian; Thompson, Erik W; Quinn, Michael A; Findlay, Jock K; Ahmed, Nuzhat

2012-01-01

18

Isolation and Characterization of Tumor Cells from the Ascites of Ovarian Cancer Patients: Molecular Phenotype of Chemoresistant Ovarian Tumors  

PubMed Central

Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR). AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125), epithelial cell adhesion molecule (EpCAM) and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12–14 weeks after intraperitoneal (i.p.) injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC) markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions. PMID:23056490

Latifi, Ardian; Luwor, Rodney B.; Bilandzic, Maree; Nazaretian, Simon; Stenvers, Kaye; Pyman, Jan; Zhu, Hongjian; Thompson, Erik W.; Quinn, Michael A.; Findlay, Jock K.; Ahmed, Nuzhat

2012-01-01

19

Rapid growth problems: ascites and skeletal deformities in broilers.  

PubMed

Over the last 40 yr, genetic selection for rapid growth and improved feed efficiency has been very effective in meat-type poultry. Combined with changes in the feed that have increased both the nutritional and physical density to encourage a high nutrient intake, growth rate has more than doubled. The effect of genetic selection for high muscle to bone ratio and high calorie intake of a ration that supplies all nutritional requirements causes significant mortality from cardiovascular disease. In the chicken, sudden death syndrome (flip-over) and pulmonary hypertension syndrome resulting in ascites are the most important. Ruptured aorta, spontaneous turkey cardiomyopathy (round heart), and cardiomyopathy causing sudden death produce high mortality in turkeys. Rapid growth induced by high nutrient intake alone can cause severe lameness, bone defects, and deformity, as these problems are seen in animals that have not been selected for rapid growth: dogs, horses, pigs, ratites and wild birds kept in zoologic gardens. In meat-type poultry, growth-related disease can be reduced or eliminated by reducing feed intake without affecting final body weight. Rapid growth alone may not be the pathogenic mechanism that results in cardiovascular or musculoskeletal defects. Metabolic imbalance induced by high nutrient intake may cause some of the conditions. These metabolic problems might be corrected without reducing growth rate. PMID:9872578

Julian, R J

1998-12-01

20

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

PubMed Central

Doxorubicin (Dox) treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001), isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications. PMID:25389448

Joseph, Manu M.; Aravind, S.R.; George, Suraj K.; Pillai, Raveendran K.; Mini, S.; Sreelekha, T.T.

2014-01-01

21

Co-encapsulation of Doxorubicin with galactoxyloglucan nanoparticles for intracellular tumor-targeted delivery in murine ascites and solid tumors.  

PubMed

Doxorubicin (Dox) treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001), isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton's lymphoma ascites and Ehrlich's ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications. PMID:25389448

Joseph, Manu M; Aravind, S R; George, Suraj K; Pillai, Raveendran K; Mini, S; Sreelekha, T T

2014-10-01

22

Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model  

PubMed Central

Nanomedicine concerns the use of precision-engineered nanomaterials to develop novel therapeutic and diagnostic modalities for human use. The present study demonstrates the efficacy of biologically synthesized silver nanoparticles (AgNPs) as an antitumor agent using Dalton’s lymphoma ascites (DLA) cell lines in vitro and in vivo. The AgNPs showed dose- dependent cytotoxicity against DLA cells through activation of the caspase 3 enzyme, leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation. Acute toxicity, ie, convulsions, hyperactivity and chronic toxicity such as increased body weight and abnormal hematologic parameters did not occur. AgNPs significantly increased the survival time in the tumor mouse model by about 50% in comparison with tumor controls. AgNPs also decreased the volume of ascitic fluid in tumor-bearing mice by 65%, thereby returning body weight to normal. Elevated white blood cell and platelet counts in ascitic fluid from the tumor-bearing mice were brought to near-normal range. Histopathologic analysis of ascitic fluid showed a reduction in DLA cell count in tumor-bearing mice treated with AgNPs. These findings confirm the antitumor properties of AgNPs, and suggest that they may be a cost-effective alternative in the treatment of cancer and angiogenesis-related disorders. PMID:21042421

Sriram, Muthu Irulappan; Kanth, Selvaraj Barath Mani; Kalishwaralal, Kalimuthu; Gurunathan, Sangiliyandi

2010-01-01

23

Mechanism of inhibition of polypeptide chain initiation in calcium- depleted Ehrlich ascites tumor cells  

PubMed Central

Protein synthesis in Ehrlich ascites tumor cells is inhibited when cellular calcium is depleted by the addition of EGTA to the growth medium. This inhibition is at the level of polypeptide chain initiation as evidenced by a disaggregation of polyribosomes accompanied by a significant elevation in 80-S monomers. To identify direct effects of calcium on the protein synthesis apparatus we have developed a calcium- dependent, cell-free protein-synthesizing system from the Ehrlich cells by using 1,2-bis(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), a recently developed chelator with a high (greater than 10(5)) selectivity for calcium (pKa = 6.97) over magnesium (pKa = 1.77). BAPTA inhibits protein synthesis by 70% at 1 mM and 90% at 2 mM. This effect was reversed by calcium but not by other cations tested. The levels of 43-S complexes (i.e., 40-S subunits containing bound methionyl- tRNAf.eIF-2.GTP) were significantly lower in the calcium-deprived incubations, indicating either inhibition of the rate of formation or decreased stability of 43-S complexes. Analysis of 43-S complexes on CsCl gradients showed that in BAPTA-treated lysates, 40-S subunits containing eIF-3, completely disappeared and the residual methionyl- tRNA-containing complexes were bound to 40-S subunits lacking eIF-3. Our results demonstrate a direct involvement of Ca2+ in protein synthesis and we have localized the effect of calcium deprivation to decreased binding of eIF-2 and eIF-3 to 40-S subunits. PMID:2500444

1989-01-01

24

Action of Tumor-inhibitory Gum Tragacanth on Potassium Permeability of Ascites Tumor Cells and Partial Characterization of the Cytotoxic Componentl  

Microsoft Academic Search

SUMMARY Electrolyte balance was examined in ascites tumor cells treated with the surface-combining mitotic inhibitor gum tragacanth. Potassium and sodium levels remained normal during treatment with physiological doses of the agent, thus precluding imbalance of these ions as an explanation of the tumor-inhibitory effect. Incorporation of amino acids into protein also remained unaffected. Washing and centrifugation of treated cells resulted

E. M. F. Roe; Honor Smyth; Eleanor Flahavan

1972-01-01

25

Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130).  

PubMed Central

The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed. PMID:1419621

Dessí, S.; Batetta, B.; Anchisi, C.; Pani, P.; Costelli, P.; Tessitore, L.; Baccino, F. M.

1992-01-01

26

Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130).  

PubMed

The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed. PMID:1419621

Dessí, S; Batetta, B; Anchisi, C; Pani, P; Costelli, P; Tessitore, L; Baccino, F M

1992-11-01

27

Intracellular compartmentation of Na + , K + and Cl ? in the Ehrlich ascites tumor cell: Correlation with the membrane potential  

Microsoft Academic Search

Summary The intracellular distribution of Na+, K+, Cl- and water has been studied in the Ehrlich ascites tumor cell. Comparison of the ion and water contents of whole cells with those of cells exposed to La3+ and mechanical stress indicated that La3+ treatment results in selective damage to the cell membrane and permits evaluation of cytoplasmic and nuclear ion concentrations.

Thomas C. Smith; Ramona Adams

1977-01-01

28

Mechanism of potentiation of endosulfan cytotoxicity by thiram in Ehrlich ascites tumor cells.  

PubMed

Cytotoxicity of the two pesticides, thiram and endosulfan, have been studied in Ehrlich ascites tumor cells. Thiram cytotoxicity was much lower than that of endosulfan with LC(50) (1h exposure) of 4.02 and 1.12mM, respectively. The cytotoxic action of the pesticides on the cells were characterised by glutathione depletion, induction of reactive oxygen species (ROS). The cell death induced by the pesticides was of necrotic type as confirmed by lactate dehydrogenase (LDH) leakage. At non-cytotoxic concentration, thiram potentiated the cytotoxicity of endosulfan when cells were exposed to a mixture of both chemicals. The mechanisms involved in the potentiation of cytotoxicity include excessive glutathione depletion and induction ROS which were higher than the additive effects of individual chemicals. The study demonstrates the importance of pesticide interactions in toxicity risk assessment. PMID:19781625

Rana, Indrajeetsinh; Shivanandappa, T

2010-02-01

29

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth  

Microsoft Academic Search

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with

Paola Costelli; Marta Llovera; Joaquín López-Soriano; Neus Carbó; Luciana Tessitore; Francisco J. López-Soriano; Francesco M. Baccino; Josep M. Argilés

1995-01-01

30

Rapid Growth Problems: Ascites and Skeletal Deformities in Broilers  

Microsoft Academic Search

Over the last 40 yr, genetic selection for rapid growth and improved feed efficiency has been very effective in meat-type poultry. Combined with changes in the feed that have increased both the nutritional and physical density to encourage a high nutrient intake, growth rate has more than doubled. The effect of genetic selection for high muscle to bone ratio and

R. J. JULIAN

31

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

SciTech Connect

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

Edwards, E.H.

1984-01-01

32

Characterization of Lin?ALDH (bright) population using Ehrlich ascites tumor cells in mice.  

PubMed

Cancer stem cells (CSCs)/tumor initiating cells have been shown to exist in recent studies; however, it is challenging to isolate these cells. The latest evidence suggests that elevated aldehyde dehydrogenase (ALDH) activity is a hallmark of CSCs. In this study, mice implanted with Ehrlich ascites tumor (EAT) cells were used to isolate cancer stem cells. Femoral bone marrow aspirations were performed 15 days after the injection of EAT cells and Lin(-)ALDH(bright) and Lin(-)ALDH(low) cell populations were isolated. Lin(-)ALDH(bright) cells isolated from EAT-bearing mice accounted for 11.08?±?10.52 % of all the Lin(-) cell population. Analysis of hematopoietic stem cell markers showed that Sca-1, c-kit, and CD38 were expressed higher in the Lin(-)ALDH(bright) population compared with Lin(-)ALDH(low). The Lin(-)ALDH(bright) population expressed P-glycoprotein, a product of the multidrug resistance (MDR) gene. P-gp activity measured by rhodamine 123 (Rh123) and blocked by verapamil. Among the cells treated with doxorubicin for 48 h, the Lin(-)ALDH(bright) cell groups were more resistant and had higher overexpression of Bcl-2 protein than Lin(-)ALDH(low). PMID:25048967

Yalçintepe, Leman; Altinel, Pinar; Albeniz, I?il; Yilmaz, Abdullah; Nurten, Rustem

2014-10-01

33

Role of metallothionein in the zinc metabolism of Ehrlich ascites tumor cells  

SciTech Connect

The reactions of zinc and zinc, cadmium metallothioneins with apocarbonic anhydrase have been studied. Apo-carbonic anhydrase abstracts zinc from zinc metallothionein and zinc, cadmium metallothionein in second-order processes which are two to three orders of magnitude more rapid than those of EDTA abstraction of zinc and are similar to the rate of reconstitution of the apo-enzyme by unligated Zn. In comparison with other proteins, zinc metallothionein contains unusually reactive metal binding sites suggesting this protein may be a physiological donor of Zn to zinc requiring sites in cells. When limiting amounts of dietary zinc stimulate the deficient cells to divide, zinc is not observed in metallothionein. A non-limiting amount of dietary zinc supports both proliferation and the steady state presence of zinc in this protein. Zinc metallothionein is shown to be the principal donor of zinc to added apo-carbonic anhydrase in Ehrlich cell cytosol. Treatment of cells with a copper ligand known to possess anti-tumor activity, with the toxic metal Cd, or with cis-dichlorodiamine Pt(II) which is another anti-tumor agent, all cause cells to cease proliferation at levels of each agent which result in the displacement of zinc from metallothionein. These results are used to construct a model of zinc metabolism in which Zn metallothionein is a central, biochemically active form of zinc. The finding in a number of tumors other than Ehrlich ascites carcinoma of the existence of metal binding protein with characteristics similar to metallothionein suggests that the significantly elevated levels of metallothionein-like protein may be a general feature of many tumors and that it may play a vital role in rapidly proliferating tissue in general.

Kraker, A.J.

1983-01-01

34

The influence of 630nm semiconductor laser irradiation on rat s180 ascitic tumor cells without photosensitizers  

NASA Astrophysics Data System (ADS)

Objective: To study the influence of 630nm semiconductor laser irradiation on rat ascetic tumor cells without photosensitizers. Methods: In this work, rat ascitic tumor cells (s180) were incubation with no photosensitizers.630nm light (total output 2W) was delivered to tumor cells at different fluence rate:100?200?250mw/cm2 . According to each fluence rate, S180 tumor cells were divided into 5 groups, which were irradiated with various time periods: 20?15?10?5?3min. In all cases, S180 tumor cells were taken photos. We use the morphology and flow cytometry technique to investigate the apoptosis of tumor cells during the experiment. Results: 1?No obvious morphological difference between test groups and control groups at various time periods during the experiment. 2?No obvious cell apoptosis difference between test groups and control groups using FCM. Conclusion: After irradiated with 630nm semiconductor laser light, rat ascitic tumor cells (s180) with no photosensitizers incubation were not obviously killed or induced apoptosis.

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

2005-07-01

35

Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model.  

PubMed

We assessed the antitumor efficacy of KRN951, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptors, using a rat colon cancer RCN-9 syngeneic model in which the tumor cells are transplanted into the peritoneal cavity of F344 rats. KRN951 treatments that commenced 4 days after tumor transplantation (day 4) significantly inhibited tumor-induced angiogenesis, the formation of tumor nodules in the mesenteric windows, and the accumulation of malignant ascites. Moreover, KRN951 treatments initiated on day 14, by which time angiogenesis and malignant ascites have already been well established, resulted in the regression of newly formed tumor vasculatures with aberrant structures and also in the apparent loss of malignant ascites by the end of the study period. Quantitative analysis of the vessel architecture on mesenteric windows revealed that KRN951 not only regressed, but also normalized the tumor-induced neovasculature. Continuous daily treatments with KRN951 significantly prolonged the survival of rats bearing both early stage and more advanced-stage tumors, compared with the vehicle-treated animals. The results of our current study thus show that KRN951 inhibits colon carcinoma progression in the peritoneal cavity by blocking tumor angiogenesis, ascites formation, and tumor spread, thereby prolonging survival. Moreover, these studies clearly demonstrate the therapeutic effects of KRN951 against established tumors in the peritoneal cavity, including the regression and normalization of the tumor neovasculature. Our findings therefore suggest that KRN951 has significant potential as a future therapeutic agent in the treatment of peritoneal cancers with ascites. PMID:18201272

Taguchi, Eri; Nakamura, Kazuhide; Miura, Toru; Shibuya, Masabumi; Isoe, Toshiyuki

2008-03-01

36

Long-Term Treatment with Aqueous Garlic and/or Tomato Suspensions Decreases Ehrlich Ascites Tumors.  

PubMed

We evaluated the preventive and therapeutic effects of aqueous suspensions of garlic, tomato, and garlic + tomato in the development of experimental Ehrlich tumors in mice. The aqueous suspensions (2%) were administered over a short term for 30 days before tumor inoculation and 12 days afterward, and suspensions at 6% were administered for 180 days before inoculation and for 12 days afterward. The volume, number, and characteristics of the tumor cells and AgNOR counts were determined to compare the different treatments. Aqueous 6% suspensions of garlic, tomato, and garlic + tomato given over the long term significantly reduced tumor growth but when given over the short term, they did not alter tumor growth. PMID:25093026

Bom, Jenifer; Gunutzmann, Patrícia; Hurtado, Elizabeth C Pérez; Maragno-Correa, Jussara M R; Kleeb, Silvia Regina; Lallo, Maria Anete

2014-01-01

37

Aquaporin 5 expression is altered in ovarian tumors and ascites-derived ovarian tumor cells in the chicken model of ovarian tumor.  

PubMed

BackgroundAquaporin 5 (AQP5), a member of the aquaporin family of transmembrane channel proteins, is involved in water transport and cellular proliferation in various tumors. The objective of this study was to determine cellular localization of aquaporin 5 (AQP5) in the ovarian tumors of chicken, a preclinical model for human ovarian tumor and to determine if AQP5 mRNA and protein expression levels in cancerous chicken ovaries and in ascites-derived chicken ovarian cancer (COVCAR) cell lines are different from normal ovaries and normal ovarian surface epithelial (NOSE) cells, respectively.MethodsImmunohistochemical staining was performed to determine the localization of AQP5-immunoreactive (ir) cells in normal and cancerous ovaries. To determine AQP5 mRNA and protein concentrations in cancerous ovaries and COVCAR cell lines, quantitative real time PCR and Western blotting analysis were performed, respectively. Studentżs t-test was performed to compare the levels of AQP5 mRNA or protein in cancerous ovaries and COVCAR cell lines with that of normal ovaries and NOSE cells, respectively.ResultsAQP5-ir cells were localized in granulosa and theca layers of normal ovarian follicles whereas cancerous ovaries showed AQP5 immunostaining in the surface epithelium, fibroblast cells of the stroma, and in the cells lining tumor cysts and acini. AQP5 mRNA concentration were significantly lesser while AQP5 protein concentrations were significantly greater in cancerous ovaries compared to that in normal ovaries (Pż<ż0.05). Whereas AQP5 mRNA concentrations were significantly greater while AQP5 protein concentrations were lesser (Pż<ż0.05) in COVCAR cell lines compared with that in NOSE cells.ConclusionAQP5 is differentially expressed in ovarian tumor and in COVCAR cell lines suggesting a potential involvement of AQP5 in ovarian tumorigenesis, metastasis, and survival of ovarian tumor cells in ascites. PMID:25344048

Tiwari, Anupama; Hadley, Jill A; Ramachandran, Ramesh

2014-10-25

38

Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution. 1. Alterations in the CD4/CD8 distribution in thymocytes.  

PubMed

We have previously shown that the progressive ascitic growth of a transplantable T cell lymphoma of spontaneous origin in a murine host, designated as Dalton's lymphoma (DL), induces the inhibition of various immune responses. In a quest to understand the mechanism(s) of tumor-growth-dependent immunosuppression, we were interested to investigate if the thymus, the center for the differentiation of immunocompetent T cells, undergoes any alteration concomitant with the growth of DL. Thus, DL was grown as an ascitic tumor in BALB/c mice for a period of 4 or 17 days, designated as the early and late tumor stages, respectively, and the thymuses were examined immediately after sacrifice of the animals on the 4th or 17th day of tumor transplantation. Progressive growth of DL was observed to be associated with thymic atrophy, as well as an involution of thymic organization and a depletion of cell mass. Histological sections of thymus from DL-bearing mice revealed a complete disintegration of the thymic architecture with a massive depletion of the cortical region and disappearance of the corticomedullary junctions. Flow cytometric analysis of alterations in the distribution of thymocytes revealed a decrease in CD4+CD8-, CD4-CD8+ and CD4+CD8+ cell populations, whereas the CD4-CD8- population showed an increase, suggesting an impairment in thymocyte differentiation at an early T cell maturation stage. Furthermore, tumor growth was shown to suppress the proliferation ability of thymocytes. Moreover, an increase in thymocytes of smaller size was also found with the progression of DL, which is an indication that a large fraction of thymocytes of a small, abnormal size could be apoptotic cells. Furthermore, the paper discusses the immunological implications of thymic atrophy in a host bearing a T cell lymphoma. PMID:10940825

Shanker, A; Singh, S M; Sodhi, A

2000-01-01

39

Addition of propolis to irinotecan therapy prolongs survival in ehrlich ascites tumor-bearing mice.  

PubMed

We investigated possible synergistic action of anticancer drug Irinotecan (IRI) combined with ethanolic (EEP) and water-soluble (WSDP) derivate of propolis on Swiss albino mice injected with Ehrlich ascites tumor (EAT). For survival analysis mice were administered WSDP and EEP (100?mg/kg) daily for 3 consecutive days, beginning on 3rd day after EAT cell (1×10?) injection. IRI was administered at a dose of 50?mg/kg on days 1, 13, and 19. We simultaneously studied peripheral white blood cell count, cell types washed from the peritoneal cavity, functional activity of macrophages from peritoneal cavity, and the level of primary DNA damage in leukocytes, kidney, and liver cells using the alkaline comet assay. Three out of 9 mice per group survived the entire duration of the experiment (90 days) in groups treated with IRI combined with WSDP and EEP. All test components increased survival of mice by 7.53% to 231.54%. Combined treatment with IRI and/or WSDP and EEP significantly decreased percentage of tumor cells in the peritoneal cavity as compared to nontreated EAT-injected mice. All treated animals had significantly higher percentage of neutrophils in the peritoneal cavity in comparison to nontreated EAT-injected mice. We observed significantly higher value of DNA damage in leukocytes of mice treated with IRI and combination of IRI and/or WSDP and EEP as compared to nontreated EAT-injected mice, while the same treatment decreased DNA damage in kidney. Our results showed that addition of propolis to IRI treatment enhanced antitumor activity of IRI and prolongs survival in EAT-bearing mice, which definitely deserve further studies to clarify the possible mechanisms of antitumor actions of combined herb-drug treatments. PMID:24383762

Lisi?i?, Duje; Benkovi?, Vesna; Điki?, Domagoj; Blaževi?, Ana Sofia; Mihaljevi?, Josipa; Oršoli?, Nada; Kneževi?, Anica Horvat

2014-03-01

40

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

41

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

Microsoft Academic Search

Summary 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. 1. The volume recovery was inhibited when NO3- was substituted for Cl-, and when Na+ was replaced by K+, or by choline (at 5mm external K+). 2. The

Else K. Hoffmann; Carsten Sjřholm; Lars Ole Simonsen

1983-01-01

42

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

PubMed

Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells. PMID:20306700

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

2008-01-01

43

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

SciTech Connect

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

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

1980-12-01

44

Evaluation of pharmacokinetics of 111In-labeled VNB-PEGylated liposomes after intraperitoneal and intravenous administration in a tumor/ascites mouse model.  

PubMed

Nanoliposomes are important drug carriers that can passively target tumor sites by the enhanced permeability and retention (EPR) effect in neoplasm lesions. This study evaluated the biodistribution and pharmacokinetics of 111In-labeled vinorelbine (VNB)-encapsulated PEGylated liposomes (IVNBPL) after intraperitoneal (i.p.) and intravenous (i.v.) administration in a C26/tk-luc colon carcinoma ascites mouse model. IVNBPL was prepared by labeling VNB-encapsulated PEGylated liposomes with 111In-oxine. BALB/c mice were i.p. inoculated with 2 x 10(5) C26/tk-luc cells in 500 muL of phosphate-buffered saline. Peritoneal tumor lesions were confirmed by 124I-FIAU/micro-PET (positron emission tomography) and bioluminescence imaging. Ascites production was examined by ultrasound imaging on day 10 after tumor cell inoculation. The pharmacokinetics and biodistribution studies of IVNBPL in a tumor/ascites mouse model were conducted. The labeling efficiency was more than 90%. The in vitro stability in human plasma at 37 degrees C for 72 hours was 83% +/- 3.5%. For i.p. administration, the areas under curves (AUCs) of ascites and tumor were 6.78- and 1.70-fold higher, whereas the AUCs of normal tissues were lower than those via the i.v. route. This study demonstrates that i.p. administration is a better approach than i.v. injection for IVNBPL, when applied to the treatment of i.p. malignant disease in a tumor/ascites mouse model. PMID:19694580

Lin, Yi-Yu; Li, Jia-Je; Chang, Chih-Hsien; Lu, Yi-Ching; Hwang, Jeng-Jong; Tseng, Yun-Long; Lin, Wuu-Jyh; Ting, Gann; Wang, Hsin-Ell

2009-08-01

45

Characteristics of the accumulation of methotrexate polyglutamate derivatives in Ehrlich ascites tumor cells and isolated rat hepatocytes  

SciTech Connect

The intracellular synthesis and retention of polygammaglutamyl derivatives of methotrexate and their interactions with H/sub 2/ folate reductase was evaluated. Methotrexate polyglutamates were detected within 15 minutes in hepatocytes exposed to 1 microM methotrexate, and continued to accumulate for at least 60 minutes producing a large transmembrane gradient. These derivatives appeared to be preferentially retained within the cell. In studies with the Ehrlich ascites tumor accumulation of methotrexate polyglutamates was increased over 5-fold by the addition of 5 mM L-glutamine or L-glutamate and exhibited a positive correlation with the extracellular concentration of methotrexate. When Ehrlich ascites tumor cells were exposed to 10 microM methotrexate and 5 mM L-glutamine intracellular polyglutamates were detected within 10 minutes and their levels increased linearly over 4 hours. As these derivatives accumulated, there was a decline in intracellular methotrexate due at least in part to a replacement of methotrexate on H/sub 2/ folate reductase by polyglutamates and subsequent efflux of the previously bound methotrexate from the cell. When polyglutamate derivatives were in excess of the H/sub 2/ folate reductase binding capacity and extracellular methotrexate removed, methotrexate rapidly exited the cell whereas the majority of its metabolites were retained and eventually saturated the major portion of the enzyme. These studies indicate that (1) intracellular methotrexate is rapidly converted to polygammaglutamyl derivatives, (2) these metabolites effectively compete with methotrexate for binding sites on H/sub 2/ folate reductase, (3) these derivatives are retained within the cell more effectively than methotrexate, and (4) vincristine and probenecid may be potentially useful for selectively increasing methotrexate polyglutamates in tumor cells.

Fry, D.W.; Gewirtz, D.A.; Yalowich, J.C.; Goldman, I.D.

1983-01-01

46

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. PMID:23029122

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

2012-01-01

47

Mechanics in Tumor Growth 1 Mechanics in Tumor Growth  

E-print Network

the extracellular matrix. As will be described in the following this process is affected by the stress applied some of the main feature of tumor growth and in particular the phenomena involving stress description, one can say that the cells forming a compact tumor, like other cells in the body, live

Preziosi, Luigi

48

A rare cause of ascites: myxoedema ascites.  

PubMed

The case report describes an 88-year-old patient who presented with new-onset ascites. After excluding frequent causes of ascites, he was diagnosed with myxoedema ascites. Myxoedema ascites is rare. Analysis of ascitic fluid shows a high serum-ascites albumin gradient and a high protein level. Myxoedema ascites resolves completely after starting thyroid hormone replacement therapy. PMID:24579248

Stinkens, K; Vermeyen, E; De Hondt, G

2013-01-01

49

Effects of ascites syndrome in broilers on their growth performances and the availability of energy and nutrients  

Microsoft Academic Search

An experiment was carried out to investigate the effects of ascites syndrome (AS) on the growth performance and availability\\u000a of dietary energy and nutrients in broilers. One hundred and twenty one-day-old avian broilers were randomly allotted into\\u000a two groups (control group and test group) with six replications of ten birds. In the test group, the addition of 3,3,5-triiodothyronine\\u000a (T3, 1.5

Bin Sun; Keying Zhang; Qiufeng Zeng; Cairong Wang

2007-01-01

50

Enhanced antitumor immunity contributes to the radio-sensitization of ehrlich ascites tumor by the glycolytic inhibitor 2-deoxy-D-glucose in mice.  

PubMed

Two-deoxy-D-glucose (2-DG), an inhibitor of glycolysis differentially enhances the radiation and chemotherapeutic drug induced cell death in cancer cells in vitro, while the local tumor control (tumor regression) following systemic administration of 2-DG and focal irradiation of the tumor results in both complete (cure) and partial response in a fraction of the tumor bearing mice. In the present studies, we investigated the effects of systemically administered 2-DG and focal irradiation of the tumor on the immune system in Ehrlich ascites tumor (EAT) bearing Strain "A" mice. Markers of different immune cells were analyzed by immune-flow cytometry and secretary cytokines by ELISA, besides monitoring tumor growth. Increase in the expression of innate (NK and monocytes) and adaptive CD4+cells, and a decrease in B cells (CD19) have been observed after the combined treatment, suggestive of activation of anti-tumor immune response. Interestingly, immature dendritic cells were found to be down regulated, while their functional markers CD86 and MHC II were up regulated in the remaining dendritic cells following the combination treatment. Similarly, decrease in the CD4(+) naďve cells with concomitant increase in activated CD4+ cells corroborated the immune activation. Further, a shift from Th2 and Th17 to Th1 besides a decrease in inflammatory cytokines was also observed in the animals showing complete response (cure; tumor free survival). This shift was also complimented by respective antibody class switching followed by the combined treatment. The immune activation or alteration in the homeostasis favoring antitumor immune response may be due to depletion in T regulatory cells (CD4(+)CD25(+)FoxP3(+)). Altogether, these results suggest that early differential immune activation is responsible for the heterogenous response to the combined treatment. Taken together, these studies for the first time provided insight into the additional mechanisms underlying radio-sensitization by 2-DG in vivo by unraveling its potential as an immune-modulator besides direct effects on the tumor. PMID:25248151

Farooque, Abdullah; Singh, Niharika; Adhikari, Jawahar Singh; Afrin, Farhat; Dwarakanath, Bilikere Srinivasa Rao

2014-01-01

51

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

52

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

2012-05-28

53

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

54

Inhibition ATP of the Growth-inhibitory Effect of Synkavit (2-methyl-1,4-naphthaquinol Bis Disodium Phosphate) on Mouse Ascites Tumour Cells  

PubMed Central

Ehrlich ascites cells or another strain derived from a spontaneous mouse mammary carcinoma (DiVita's ascites cells) were incubated in vitro at 37° C. at cell concentrations of 1-2 × 107 cells/ml. with 10-4M Synkavit in Spinner-medium under various conditions. The cells were then inoculated under standard conditions into mice, and the growth of ascites tumour was determined. On this basis, Synkavit has been shown to retard the growth of ascites tumour provided that the cells were incubated in vitro at pH 7.4 for 30 minutes. This retardation of tumour growth was not dependent on the presence of glucose in the incubation medium and could be observed in the presence of about 5% ascitic fluid. However, the retardation appeared to be considerably less marked (though readily detectable) when the incubation with Synkavit was performed anaerobically. The retardation of tumour growth by Synkavit was abolished completely by simultaneous incubation with excess ATP or partially by equimolar ATP. Simultaneous incubation with excess ADP also abolished the retardation by Synkavit of the growth of tumour. Moreover, ATP addition to the medium at a later period appeared to be partially successful in abolishing the Synkavit effect on tumour growth. The mechanism by which ATP reduced the growth-inhibitory effect of Synkavit has been partially clarified by investigating the effect of ATP on the incorporation of a tritiated derivative of Synkavit, TRK 219. The results show that in Ehrlich ascites cells, simultaneous incubation in Spinner-medium with excess, or equimolar, ATP reduced the incorporation of labelled metabolites of Synkavit by 78% or 14% respectively. On the other hand, in a continuous cell line of human epithelial cells (HEp/2), excess ATP reduced the incorporation of metabolites of labelled Synkavit very slightly. These results have been discussed in the light of other evidence to consider the mechanism whereby ATP reduced the growth-inhibitory effects of Synkavit.

Harrison, P. R.

1970-01-01

55

Interaction of the fluorescent probe, 1-anilino-8-napthalene sulfonate, with the sulfate transport system of Ehrlich ascites tumor cells.  

PubMed

The addition of the fluorescent dye, ANS, to intact ascites tumor cells results in an enhancement of fluorescence intensity. The increase in fluorescence intensity as a function of time is biphasic which suggests that at least two processes occur. The first associated with the rapid initial rise in fluorescence represents binding to the cell surface while the second or slower phase reflects entrance of ANS into the intracellular phase. The relationship between bound and free ANS in 0.50 mM sulfate medium was used to calculate the apparent dissociation constant of ANS-membrane complex (Kd = 6.53 times 10(-5) M) and the total number of ANS binding sites (4.49 nmoles/mg dry weight). Kinetic analysis of steady state sulfate transport in the presence and absence of ANS suggests that (1) sulfate exchange can be described by Michaelis Menten type kinetics (Km = 2.05 times 10(-3) M), (2) a small fraction of surface associated ANS competitively inhibits sulfate exchange (Ki = 4.28 times 10(-6) M) and (3) the transport system has a higher affinity for ANS than for sulfate. These data are consistent with the hypothesis that inhibition of sulfate exchange is related to the direct, reversible interaction of the negatively charged sulfonate group of ANS with superficial positively charged membrane sites. PMID:1176539

Levinson, C; Villereal, M L

1975-08-01

56

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

PubMed

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

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

2014-01-01

57

Role of chemokines in tumor growth  

Microsoft Academic Search

Chemokines play a paramount role in the tumor progression. Chronic inflammation promotes tumor formation. Both tumor cells and stromal cells elaborate chemokines and cytokines. These act either by autocrine or paracrine mechanisms to sustain tumor cell growth, induce angiogenesis and facilitate evasion of immune surveillance through immunoediting. The chemokine receptor CXCR2 and its ligands promote tumor angiogenesis and leukocyte infiltration

Dayanidhi Raman; Paige J. Baugher; Yee Mon Thu; Ann Richmond

2007-01-01

58

Nerve Growth Factor from Cobra Venom Inhibits the Growth of Ehrlich Tumor in Mice  

PubMed Central

The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved. PMID:24577582

Osipov, Alexey V.; Terpinskaya, Tatiana I.; Kryukova, Elena V.; Ulaschik, Vladimir S.; Paulovets, Lubov V.; Petrova, Elena A.; Blagun, Ekaterina V.; Starkov, Vladislav G.; Utkin, Yuri N.

2014-01-01

59

Nerve growth factor from cobra venom inhibits the growth of Ehrlich tumor in mice.  

PubMed

The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved. PMID:24577582

Osipov, Alexey V; Terpinskaya, Tatiana I; Kryukova, Elena V; Ulaschik, Vladimir S; Paulovets, Lubov V; Petrova, Elena A; Blagun, Ekaterina V; Starkov, Vladislav G; Utkin, Yuri N

2014-03-01

60

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. PMID:4369083

Olivotto, Massimo; Paoletti, Francesco

1974-01-01

61

Cimetidine inhibits angiogenesis and suppresses tumor growth.  

PubMed

Cimetidine, a histamine type-2 receptor antagonist, has been reported to improve survival of patients with cancers. However, the exact mechanisms by which cimetidine suppresses development of cancers remain to be elucidated. Solid tumors require neovascularization for their growth. Here, we investigated the effects of cimetidine on tumor growth and angiogenesis. Syngeneic colon cancer cells, CMT93 cells, were inoculated into the subcutaneous space of C57BL/6 mice. Mice were treated with either saline or cimetidine. Tumor size was measured everyday and angiogenesis was evaluated histologically. Cimetidine markedly suppressed tumor growth with reduced neovascularization in the tumor. Cimetidine had no effect on proliferation of CMT93 cells in vitro. Vascular endothelial growth factor production by cancer cells was not affected by cimetidine, while vascular-like tube formation by endothelial cells in vitro was significantly impaired in the presence of cimetidine. Our findings suggest that cimetidine suppresses tumor growth, at least in part, by inhibiting tumor-associated angiogenesis. PMID:15740937

Natori, Takeshi; Sata, Masataka; Nagai, Ryozo; Makuuchi, Masatoshi

2005-01-01

62

Cancer-derived VEGF plays no role in malignant ascites formation in the mouse  

PubMed Central

AIM: Vascular endothelial growth factor (VEGF) is a potent mediator of peritoneal fluid accumulation following tumor progression. This study investigated the role of VEGF secreted by cancerous cells in the formation of malignant ascites. METHODS: VEGF expression was eliminated by knockdown in the pancreas cancer cell-line PancO2 using vector-based short-hairpin type RNA interference (RNAi). Malignant ascites formation in the mouse was analyzed by intraperitoneal injection of PancO2 cells expressing VEGF or with expression knockdown. RESULTS: The VEGF knockdown PancO2 cell was successfully established. Knockdown of VEGF did not affect cancer cell proliferation in vitro or in vivo. The volume of ascites following peritoneal expansion of the tumor in VEGF knockdown cells and control cells did not differ statistically in this in vivo study. Moreover, the VEGF concentration in the ascites did not differ statistically. CONCLUSION: Malignant ascites formation might be mediated by VEGF production in noncancerous tissues, such as stromal compartments. An anti-VEGF strategy against malignant ascites could be applied to various tumors regardless of whether they secrete VEGF. PMID:16222736

Guleng, Bayasi; Tateishi, Keisuke; Kanai, Fumihiko; Jazag, Amarsanaa; Ohta, Miki; Asaoka, Yoshinari; Ijichi, Hideaki; Tanaka, Yasuo; Imamura, Jun; Ikenoue, Tsuneo; Fukushima, Yasushi; Morikane, Keita; Miyagishi, Makoto; Taira, Kazunari; Kawabe, Takao; Omata, Masao

2005-01-01

63

Host response in tumor growth and progression.  

PubMed

Tumor growth and progression result from complex controls that appear to be facilitated by the growth factors (GFs) which emerge from the tumor and find responsive targets both within the tumor and in the surrounding host. For example, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are both angiogenic signals which appear to emerge from upregulated genetic messages in the proliferating rim of a solid tumor in response to tumor-wide hypoxia. If these signals are generated in response to unfavorable environmental conditions, i.e. a tumor-wide decrease in oxygen tension, then the tumor may be playing a role in manipulating its own environment. Two questions are raised in this paper: (1) How does the host respond to such signals? (2) Is there a linkage between the host's response and the ultimate growth of the tumor? To answer these questions, we have idealized these adaptive signals within a mathematical model of tumor growth. The host response is characterized by a function which represents the host's carrying capacity for the tumor. If the function is constant, then environmental control is strictly limited to tumor shape and mitogenic signal processing. However, if we assume that the response of the local stroma to these signals is an increase in the host's ability to support an ever larger tumor, then the model describes a positive feedback controller. In this paper, we summarize our previous results and ask the question: What form of host response is reasonable, and how will it affect ultimate tumor growth? We examine some specific candidate response functions, and analyze them for system stability. In this model, unstable states correspond to 'infinite' tumor growth. We will also discuss countervailing negative feedback signals and their roles in maintaining tumor stability. PMID:9311388

Michelson, S; Leith, J T

1996-01-01

64

Effect of two aliphatic aldehydes, methylglyoxal and 4-hydroxypentenal, on the growth of Yoshida ascites hepatoma AH-130.  

PubMed

The influence of a ketoaldehyde, methylglyoxal (MG), and a hydroxyalkenal, 4-hydroxypentenal (HPE), on the growth of a highly-deviated tumour has been investigated. MG and HPE, administered intraperitoneally, strongly depressed in rats the proliferative activity of the Yoshida ascites hepatoma AH-130, reducing its mitotic and labelling indices as well as the proportion of cycling cells (growth fraction). Monitoring the effects on the cell cycle by the labelled mitoses method showed that the percentage of labelled mitoses was markedly lowered after either aldehyde, which is indicative for a blocking effect in the S phase. In addition, the mean cell cycle time was slightly prolonged by MG, probably due to accumulation of cells in G1, whereas HPE delayed the first mitotic peak and increased the mean DNA synthetic period without modifying the overall cycle time. The effects of HPE on the cell cycle were prevented by pretreatment with polyamines. Repeated doses of MG significantly increased the fraction of tumour-bearing rats surviving at 90 days ('indefinite' survivors) as well as the survival time of those which succumbed, implying that the carcinostatic effect of MG persisted over several cell cycles. By contrast, HPE did not significantly modify the survival of AH-130-bearing rats, suggesting that its influence on tumour growth was rapidly reversible. PMID:2525964

Tessitore, L; Bonelli, G; Costelli, P; Matera, L; Pileri, A; Baccino, F M; Dianzani, M U

1989-01-01

65

Phenotypic and functional analysis of tumor-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and peripheral blood lymphocytes in patients with advanced ovarian cancer.  

PubMed

To investigate and compare the phenotype and function of lymphocytes collected from patients harboring advanced ovarian cancer, leukocytes from peripheral blood (n = 18), ascitic fluid (n = 13) and tumor tissues (n = 13) were evaluated for the relative proportions of lymphocyte subsets, including CD3+, CD4+, CD8+, CD19+, CD56 and the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells. The ability to synthesize type 1 cytokines (IFN-gamma and IL-2) and a type 2 cytokine (IL-4) was assessed by flow cytometry. In all patients, T cells (CD3+) were the major leukocyte population detected in each tissue, with CD4+ T cells being dominant in peripheral blood lymphocytes (PBL) and tumor-associated lymphocytes (TAL) but not in tumor-infiltrating lymphocytes (TIL) (CD4:CD8 ratios: 3.0 vs. 2.0 vs. 1.0, respectively). CD19+ lymphocytes (B cells) and CD56+ lymphocytes (NK cells) were significantly higher in PBL compared to TAL and TIL (p < 0.05). TAL and TIL had a higher proportion of T cells expressing the late activation marker HLA-DR compared to PBL. In contrast, no significant differences were detected in PBL, TAL and TIL in the expression of the early activation marker CD25. Type 1 cytokines were the dominant type produced by in vitro stimulated T cells for each population, with a greater proportion of IFN-gamma+ T cells in TAL and TIL compared to PBL (p < 0.01), and a higher proportion of IL-2+ T cells in PBL compared with TAL and TIL (p < 0.05). Low percentages of IL-4+ T cells (i.e. Th2) were detected in each tissue. Taken together, these data demonstrate the recruitment and accumulation of high concentrations of antigen-experienced T lymphocytes in TAL and TIL compared to PBL. However, low surface expression of IL-2 receptor (i.e. CD25), as well as depressed intracellular IL-2 production in chronically stimulated TAL and TIL suggests that the impaired antitumor function commonly detected in these lymphocyte populations may be secondary to an acquired dysregulation of the IL-2 pathway. PMID:11408737

Santin, A D; Hermonat, P L; Ravaggi, A; Bellone, S; Roman, J J; Smith, C V; Pecorelli, S; Radominska-Pandya, A; Cannon, M J; Parham, G P

2001-01-01

66

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

PubMed Central

Background Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P?ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-?B survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. PMID:24761768

2014-01-01

67

Strange Attractor in Immunology of Tumor Growth  

E-print Network

The time delayed cytotoxic T-lymphocyte response on the tumor growth has been developed on the basis of discrete approximation (2-dimensional map). The growth kinetic has been described by logistic law with growth rate being the bifurcation parameter. Increase in the growth rate results in instability of the tumor state and causes period-doubling bifurcations in the immune+tumor system. For larger values of tumor growth rate a strange attractor has been observed. The model proposed is able to describe the metastable-state production when time series data of the immune state and the number of tumor cells are irregular and unpredictable. This metastatic disease may be caused not by exterior (medical) factors, but interior density dependent ones.

Margarita Voitikova

1997-08-21

68

Metabolic changes in the liver of mice with Ehrlich ascites carcinoma.  

PubMed

The dynamics of NADP-dependent dehydrogenase activity and malonic dialdehyde content in the liver were studied in mice with Ehrlich ascites carcinoma. Tumor growth was accompanied by the development of conditions for an increase in the intensity of energy metabolism and amphibolic role of the tricarboxylic acid cycle in LPO activation in liver cells. PMID:25342485

Inzhevatkin, E V; Savchenko, A A

2014-10-01

69

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

NASA Astrophysics Data System (ADS)

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

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

2005-07-01

70

Ascites associated with uterine leiomyoma in a 22-year-old woman with systemic lupus erythematosus.  

PubMed

Ascites in systemic lupus erythematosus (SLE) patients has a variety of etiologies, which usually require different treatment options. Our case was a 22-year-old patient with an unusual combination of ascites, uterine leiomyoma and SLE. The patient presented with painless ascites of an inflammatory nature. However, the ascites was not related to peritonitis and SLE disease activity. The ascites disappeared following laparotomy and tumor resection without additional medication. Gynecologic benign tumors including uterine leiomyoma can be the cause of ascites in SLE patients. Clinicians should be aware of that possibility in case painless ascites occurs in females with SLE. PMID:24972898

Seo, M R; Sung, J Y; Cho, H J; Ryu, H J; Choi, H-J; Park, C-Y; Baek, H J

2014-10-01

71

Fibroblast-mediated acceleration of human epithelial tumor growth in vivo.  

PubMed Central

Transformed fibroblasts coinoculated with epithelial cells accelerated the growth and shortened the latency period of human epithelial tumors in athymic mice. Addition of NbF-1 fibroblasts caused epithelial tumors to grow from five marginally tumorigenic or "nontumorigenic" (nontumor-forming) human tumor cell lines or strains: PC-3 (prostate), WH (bladder), MDA-436 (breast), and cells derived from the ascites fluids of patients with metastatic renal pelvic or prostate cancers. Evidence for the human and epithelial nature of these experimental tumors was provided by histologic, immunohistochemical, Southern and dot-blot hybridization, and cytogenetic analyses. Transformed fibroblasts induced predominantly carcinosarcomas, whereas nontumorigenic fibroblasts (NIH 3T3) and lethally irradiated transformed fibroblasts induced exclusively carcinomas. The fibroblast-epithelial interaction appears to occur bidirectionally and does not result from cell fusion. Because coculture experiments in vitro did not demonstrate an increased cell proliferation, it appears that undefined host factors can influence tumor growth. This tumor model may be useful in drug-screening programs and in mechanistic studies of factors regulating human tumor growth and progression. Images PMID:2296606

Camps, J L; Chang, S M; Hsu, T C; Freeman, M R; Hong, S J; Zhau, H E; von Eschenbach, A C; Chung, L W

1990-01-01

72

[Immunomodulating effect of electromagnetic waves on production of tumor necrosis factor in mice with various rates of neoplasm growth].  

PubMed

The effects of low-density centimeter waves (8.15-18 GHz, 1 microW/cm2, 1 h daily for 14 days; MW) on tumor necrosis factor production in macrophages of mice with different growth rate of a cancer solid model produced after hypodermic injection of Ehrlich carcinoma ascites cells into hind legs were studied. After irradiation, an increase in the concentration of tumor necrosis factor in immunocompetent cells of healthy and, specially, of tumor-bearing animals was observed; and the effect of stimulation was higher upon exposure of mice carrying rapidly growing tumors. We suggest that the significant immunomodulating effect of low-density microwaves can be utilized for tumor growth suppression. PMID:11969180

Glushkova, O V; Novoselova, E G; Sinotova, O A; Vrublevskaia, V V; Fesenko, E E

2002-01-01

73

The impact of the Uighur medicine abnormal savda munziq on antitumor and antioxidant activity in a S180 and Ehrlich ascites carcinoma mouse tumor model  

PubMed Central

Aim: This study was designed to study the antitumor and antioxidant activity of Uighur medicine abnormal savda munziq (ASMq) in the S180 and Ehrlich ascites carcinoma mice tumor model. Materials and Methods: The serum levels of superoxide dismutase (SOD), malonaldehyde (MDA), and glutathione-catalase (GSH-PX) were analyzed, and the mice were also subjected to a hypoxia tolerance test. Their climbing ability was also analyzed. Results: The findings of the study revealed that ASMq-treatment leads to an increase in blood serum SOD and GSH-PX levels but a decrease in blood serum MDA levels. Moreover, ASMq-treatment enhanced the survival time of mice maintained under hypoxic conditions and improved their mice climbing ability. Conclusions: The results of this study indicate that ASMq has obvious antitumor and antioxidative effects. PMID:22701288

Aikemu, Ainiwaer; Yusup, Abdiryim; Umar, Anwar; Berké, Bénédicte; Moore, Nicholas; Upur, Halmurat

2012-01-01

74

Neuronal transcription factor Brn-3a(l) is over expressed in high-grade ovarian carcinomas and tumor cells from ascites of patients with advanced-stage ovarian cancer  

Microsoft Academic Search

OBJECTIVES: In view of the recent association of Brn-3 transcription factors with neuroblastomas, cervical, breast, and prostate cancers we examined the expression of Brn-3a(l) in normal ovaries and in different histological grades of ovarian tumors. The expression of Brn-3a(l) was also evaluated in normal ovarian and cancer cell lines and tumor cells isolated from the ascites of advanced-stage ovarian cancer

Nuzhat Ahmed; Ardian Latifi; Clyde B Riley; Jock K Findlay; Michael A Quinn

2010-01-01

75

ROLE OF CHEMOKINES IN TUMOR GROWTH  

PubMed Central

Chemokines play a paramount role in the tumor progression. Chronic inflammation promotes tumor formation. Both tumor cells and stromal cells elaborate chemokines and cytokines. These act either by autocrine or paracrine mechanisms to sustain tumor cell growth, induce angiogenesis and facilitate evasion of immune surveillance through immunoediting. The chemokine receptor CXCR2 and its ligands promote tumor angiogenesis and leukocyte infiltration into the tumor microenvironment. In harsh acidic and hypoxic microenvironmental conditions tumor cells up-regulate their expression of CXCR4, which equips them to migrate up a gradient of CXCL12 elaborated by carcinoma associated fibroblasts (CAFs) to a normoxic microenvironment. The CXCL12-CXCR4 axis facilitates metastasis to distant organs and the CCL21-CCR7 chemokine ligand-receptor pair favors metastasis to lymph nodes. These two chemokine ligand-receptor systems are common key mediators of tumor cell metastasis for several malignancies and as such provide key targets for chemotherapy. In this paper, the role of specific chemokines/chemokine receptor interactions in tumor progression, growth and metastasis and the role of chemokine/chemokine receptor interactions in the stromal compartment as related to angiogenesis, metastasis, and immune response to the tumor are reviewed. PMID:17629396

Raman, Dayanidhi; Baugher, Paige J.; Thu, Yee Mon; Richmond, Ann

2007-01-01

76

Effects of Dietary L-carnitine Supplementation on Growth Performance, Organ Weight, Biochemical Parameters and Ascites Susceptibility in Broilers Reared Under Low-temperature Environment  

PubMed Central

The objective of this study was to investigate the effects of L-carnitine on growth performance, organ weight, biochemical parameters of blood, heart and liver, and ascites susceptibility of broilers at different ages reared under a low-temperature environment. A total of 420 1-d-old male Ross 308 broilers were randomly assigned to two dietary treatments with fifteen replicates of fourteen broilers each. Treatment diets consisted of L-carnitine supplementation at levels of 0 and 100 mg/kg. At 11-d of age, low temperature stress was used to increase ascites susceptibility. Blood, heart and liver samples were collected at different ages for analysis of boichemical parameters. The results showed that, there was no significant difference in growth performance with L-carnitine supplementation, but the mortality due to ascites was significantly decreased. Dietary L-carnitine supplementation significantly reduced heart index (HI) and ascites heart index (AHI) on d 21, lung index (LUI) on d 35 and liver index (LI) on d 42. The broilers fed diets containing L-carnitine had significantly lower red blood cell counts (RBC), hemoglobin (HGB) concentration and hematocrit (HCT) on d 42. Dietary L-carnitine supplementation significantly reduced malondialdehyde (MDA) content of heart tissue on d 21 and 35, and significantly increased total superoxide dismutase (T-SOD) and Glutathione peroxidase (GSH-Px) activity of the heart on d 21 and 42. L-carnitine supplementation significantly reduced serum triglyceride (TG) content on d 28 and 35 and serum glucose (GLU) on d 35 and 42, and significantly increased serum total protein (TP) and globulin (GLO) content on d 42. L-carnitine supplementation significantly enhanced liver succinodehydrogenase (SDH), malic dehydrogenase (MDH) and Na+-K+-ATPase activity on d 28, and tended to reduce the lactic acid (LD) level of liver on d 35 (p = 0.06). L-carnitine supplementation significantly reduced serum uric acid (UA) content on d 28, 35 and 42. Based on the current results, it can be concluded that dietary L-carnitine supplementation reduced organ index, red blood cell counts and hematocrit, enhanced antioxidative capacity of the heart, enhanced liver enzymes activity involved in tricarboxylic acid cycle, and reduced serum glucose and triglyceride. Therefore, it is suggested that L-carnitine can potentially reduce susceptibility and mortality due to ascites. PMID:25049781

Wang, Y. W.; Ning, D.; Peng, Y. Z.; Guo, Y. M.

2013-01-01

77

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth.  

PubMed

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect. PMID:7585474

Costelli, P; Llovera, M; López-Soriano, J; Carbó, N; Tessitore, L; López-Soriano, F J; Baccino, F M; Argilés, J M

1995-10-20

78

Tumor growth influences skeletal muscle protein turnover in the pregnant rat.  

PubMed

The implantation of a fast growing tumor (the Yoshida AH-130 ascites hepatoma) to mid-pregnant rats resulted in no changes in fetus weight, in spite of an important body weight decrease observed in the mother. Tumor-bearing pregnant rats showed an accelerated muscle protein degradation that resulted in decreases in both gastrocnemius and soleus muscle weight and protein content. Although very slight changes were observed in liver protein turnover after tumor implantation, muscle protein degradation and ubiquitin gene expression were increased (in relation with the non-tumor-bearing pregnant rats) in the first postimplantation period (0-4 d), whereas it remained lower in the second studied period (4-7 d), compensating for the initial differences when the whole period (0-7 d) was considered. Similar results were observed when muscle protein synthesis was studied. On the whole, tumor growth resulted in a slightly decreased protein accumulation rate. The results presented suggest that the implantation of this tumor in the pregnant rat has little or no consequences in fetal growth but results in an important muscle waste in the mother. PMID:9475293

Carbó, N; Costelli, P; López-Soriano, F J; Argilés, J M

1998-02-01

79

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 PMID:1926844

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

1991-01-01

80

Prophylactic action of lipoic acid on oxidative stress and growth performance in broilers at risk of developing ascites syndrome  

Microsoft Academic Search

The objective of this study was to assess the effects of dietary supplementation with lipoic acid (LA) on broilers maintained at 2235 m above sea level with high risk to develop ascites syndrome (AS). A total of 2040 chicks were fed under commercial conditions with water and specific diets ad libitum during 7 weeks in two consecutive experiments. Mortality and

Antonio Díaz-cruz; Maurilio Serret; Guadalupe Ramírez; Ernesto Ávila; Raquel Guinzberg; Enrique Pińa

2003-01-01

81

Angiogenin antagonists prevent tumor growth in vivo.  

PubMed Central

A noncytotoxic neutralizing monoclonal antibody (mAb), 26-2F, to human angiogenin (Ang), a potent inducer of neovascularization, has been reported to prevent or delay the establishment of HT-29 human tumor xenografts in athymic mice. In the present study the tumor model was modified to increase sensitivity to Ang antagonists to facilitate further investigations and comparisons of their capacity to inhibit tumor growth. An increase in the percentage of tumor-free mice from 10-25% to 65% is observed in this modified model after treatment with mAb 26-2F. An additional neutralizing mAb, 36u, that interacts with a different epitope on Ang similarly prevents the appearance of tumors, both alone and in combination with mAb 26-2F. In those tumors that develop in mice treated with these agents, the number of vascular elements is reduced. Actin, an Ang antagonist that unlike the mAbs binds both human and mouse Ang, also prevents the establishment of tumors while exhibiting no toxic effects at daily doses > 50 times the molar amount of circulating mouse Ang. Ang antagonists also inhibit the appearance of tumors derived from two other Ang-secreting human tumor cell lines--i.e., A549 lung adenocarcinoma and HT-1080 fibrosarcoma. These results demonstrate that inhibition of the action of Ang is an effective therapeutic approach for the treatment of malignant disease. Images Fig. 2 PMID:7831307

Olson, K A; Fett, J W; French, T C; Key, M E; Vallee, B L

1995-01-01

82

[Bacterial phagelysates and malignant tumor growth].  

PubMed

Anti-tumor preventive efficacy of E.coli phagelysate has been studied. Investigations were conducted on 2-3 months 48 male mice. Regimen of preventive vaccinations were: single - 0,25 ml phagelysate intraperitoneal injection, 3 days before Ehrlich carcinoma inoculation (1x10(6) tumor cells); 3 times vaccinations (0,25 ml, with 3 day intervals) 3, 6, and 9 days before inoculation of carcinoma; and 10 times (during 10 days, before inoculation of carcinoma). Treatment efficacy was evaluated according to the indices of cancer growth (development of cancer tissue, cancer growth inhibition percent, lifespan and survival percent). Experiments have shown that single and 3 times preventive vaccinations inhibited tumor development and delayed malignant growth, while, 10 times permanent vaccinations had no effects on cancer growth. Cancer growth inhibition percent in single and 3 times vaccinated animals were 58% on the average. Maximal lifespan in control group mice consisted 59 days. By the 125th day of cancer growth, at single vaccination 17% of mice were alive, while in 3 times vaccinated mice the survival percent was 25%. Anti-tumor potential of E.coli pagelysate supposedly could be explained by immunoregulatory properties of the preparation. PMID:24743131

Gambashidze, K; Bejitashvili, N; Azaladze, T; Pkhaladze, M; Azaladze, A

2014-03-01

83

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. PMID:23259759

2012-01-01

84

Investigation of Combined Action of Food Supplement's and Ionizing Radiation on the Cytogenetic Damage Induction and Ehrlich Ascite Carcinoma Growth on Mice in Vivo  

NASA Astrophysics Data System (ADS)

In recent ten years one of the major problems of modern radiobiology is the study of radiation protective mechanisms with the help of different substances as well as activation of internal resources of the organism. Internal resources mean such phenomena as hormesis and adaptive response which represent cell or body reaction on low doses of inducing factors and predetermine their further high dose effect resistance. At present special interest is attracted by studies of biological effects of low-dose-rate high-LET radiation because of searching for new types of radiation for more effective cancer therapy and searching for new methods of radiation protection. Since natural biologically active substances have low toxicity and are capable of affecting physiological processes taking place in human’s organism and increasing organism’s natural defense system, the interest to protective means of vegetal origin and search of special food supplements intensifies every year. The purpose of this study is to investigate the combined influence of food supplement, low dose rate high-LET radiation simulating high-altitude flight conditions and X-ray radiations on radiosensitivity, induction of radiation adaptive response (RAR) and growth of Ehrlich ascite carcinoma as well. Experiments were performed with males of SHK mice at the age of two months. The animals were being irradiated with low-dose-rate high-LET radiation with the dose of 11,6 cGy (0,5 cGy/day) behind the concrete shield of the 70 GeV protons accelerator (Protvino). The X-ray irradiation was carried out on the RTH device with a voltage of 200 kV (1 Gy/min; Pushchino). The diet composition included products containing big amount of biologically active substances, such as: soybeam meat, buckwheat, lettuce leaves and drug of cod-liver oil. Four groups of mice were fed with selected products mentioned above during the whole irradiation period of 22 days. The control groups received the same food without irradiation. The relation of the amount of the food supplement to the quantity of standard food was selected experimentally. In order to determine the level of radiosensitivity all groups of mice were subjected to X-radiation with the dose of 1,5 Gy and for induction of RAR the animals were irradiated according to the standard scheme (10 cGy+1,5 Gy). The influence of food supplement on the growth of solid tumor was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells s.c. into the femur. The percent of polychromatic erythrocytes (PCE) with micronucleus (MN) in marrow served as definition criteria of cytogenetic level of damage. The results of the study indicate that: 1) Due to influence of high-LET radiation with the dose of 11,6 Gy, mice who had dietary supplement demonstrated reduction of PCE with MN to the level of natural background radiation comparing with mice who had only standard food; 2) Diet containing soybeam, buckwheat or greens unlike cod-liver oil reduces the sensitivity of mice to X-radiation with the dose of 1,5 Gy and causes significant slowdown in growth of Ehrlich carcinoma; 3) The combined effect of high-LET radiation and the food supplements (except for cod-liver oil) reduces the sensitivity of mice to irradiation with the dose of 1,5 Gy, which demonstrate ability of RAR induction unlike the mice only irradiated with high-LET radiation and causes the slowdown in growth speed of Ehrlich carcinoma in contrast to the mice only irradiated with high-LET with the dose of 11,6 Gy; 4) The combined effect of high-LET radiation and the food supplements (except for cod-liver oil) does not influence the quantity of RAR according to the standard scheme (10 cGy+1,5 Gy).

Sorokina, Svetlana; Zaichkina, Svetlana; Dyukina, Alsu; Rozanova, Olga; Balakin, Vladimir; Peleshko, Vladimir; Romanchenko, Sergey; Smirnova, Helena; Aptikaeva, Gella; Shemyakov, Alexander

85

Three phase flow dynamics in tumor growth  

NASA Astrophysics Data System (ADS)

Existing tumor models generally consider only a single pressure for all the cell phases. Here, a three-fluid model originally proposed by the authors is further developed to allow for different pressures in the host cells (HC), the tumor cells (TC) and the interstitial fluid (IF) phases. Unlike traditional mixture theory models, this model developed within the thermodynamically constrained averaging theory contains all the necessary interfaces. Appropriate constitutive relationships for the pressure difference among the three fluid phases are introduced with respect to their relative wettability and fluid-fluid interfacial tensions, resulting in a more realistic modeling of cell adhesion and invasion. Five different tumor cases are studied by changing the interfacial tension between the three liquid phases, adhesion and dynamic viscosity. Since these parameters govern the relative velocities of the fluid phases and the adhesion of the phases to the extracellular matrix significant changes in tumor growth are observed. High interfacial tensions at the TC-IF and TC-HC interface support the lateral displacement of the healthy tissue in favor of a rapid growth of the malignant mass, with a relevant amount of HC which cannot be pushed out by TC and remain in place. On the other hand, lower TC-IF and TC-HC interfacial tensions tend to originate a more compact and dense tumor mass with a slower growth rate of the overall size. This novel computational model emphasizes the importance of characterizing the TC-HC interfacial properties to properly predict the temporal and spatial pattern evolution of tumor.

Sciumč, G.; Gray, W. G.; Hussain, F.; Ferrari, M.; Decuzzi, P.; Schrefler, B. A.

2014-03-01

86

Dual effects of indoleamine 2,3-dioxygenase inhibitors on the therapeutic effects of cyclophosphamide and cycloplatam on Ehrlich ascites tumor in mice.  

PubMed

Ethyl pyruvate, an inhibitor of indoleamine 2,3-dioxygenase, slightly suppressed the growth of transplantable Ehrlich tumor in mice and significantly potentiated the therapeutic effect of cyclophosphamide. Another inhibitor amidoxime produced a similar effect. However, both ethyl pyruvate and amidoxime significantly reduced the effect of cycloplatam therapy. The observed changes can be stipulated by different effects of cyclophosphamide and cycloplatam on the subpopulations of lymphoid cells taking part in the formation of antitumor immunity and resistance to tumors. PMID:25110094

Bogdanova, L A; Morozkova, T S; Amitina, S A; Mazhukin, D G; Nikolin, V P; Popova, N A; Kaledin, V I

2014-08-01

87

FTY720 inhibits tumor growth and angiogenesis.  

PubMed

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, we examined the effect of FTY720 on angiogenesis in a HUVEC spheroid model. To substantiate our in vitro findings the effect of FTY720 was also tested in C57/B16 mice subcutaneously injected with Lewis Lung Carcinoma (LLC1) cells. After establishment of a palpable tumor the animals were treated daily with either saline or 1, 5, or 10 mg/kg FTY720. Subsequently, the tumor size was measured, periodically. In our experiments FTY720 showed a strong antiangiogenic effect, overcoming the stimulating effect of VEGF (20 ng/mL) even at subnanomolar concentrations. In vivo, FTY720 showed a dose-dependent inhibition of subcutaneous tumors, and the tumor size of animals treated with 10 mg/kg FTY720 was less than half of the size of tumors in control animals. In conclusion, FTY-720 demonstrated a strong antiangiogenic effect in vitro and a substantial antitumor effect in vivo. Presumably, the stabilizing effect of surrounding pericytes limits the effect of FTY720 in our mouse model. Therefore, a combination of FTY720 with an mTOR inhibitor might be the most favorable immunosuppressive drug combination for allograft recipients at risk for tumor development. PMID:15808563

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

2005-01-01

88

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

89

The bradykinin B1 receptor antagonist R-954 inhibits Ehrlich tumor growth in rodents.  

PubMed

The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B(1) antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE(2) production (82%), and TNF? release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84-94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B(1) receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats. PMID:21835216

Fernandes, Patricia Dias; Gomes, Niele de Matos; Sirois, Pierre

2011-09-01

90

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

Microsoft Academic Search

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

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

2010-01-01

91

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

92

Ascites syndrome in broilers: physiological and nutritional perspectives.  

PubMed

Broiler chickens are intensively selected for productive traits. The management of these highly productive animals must be optimal to allow their full genetic potential to be expressed. If this is not done, inefficient production and several metabolic diseases such as ascites become apparent. The causes of the ascites are multifactorial but diet and, particularly, interactions between diet, other environmental and genetic factors play an important role. The relatively high heritability estimates for ascites-related traits and the significance of maternal genetic effects for most of the traits indicate that direct and maternal genetic effects play an important role in development of the ascites syndrome. An imbalance between oxygen supply and the oxygen required to sustain rapid growth rates and high food efficiencies causes ascites in broiler chickens. Because of the relationship to oxygen demand, ascites is affected and/or precipitated by factors such as growth rate, altitude (hypoxia) and environmental temperature. As the high metabolic rate (fast growth) is a major factor contributing to the susceptibility of broilers to ascites, early-age feed or nutrient restriction (qualitative or quantitative) or light restriction in order to slow down the growth rate seem practically viable methods, since final body weight is not compromised. Manipulation of the diet composition and/or feed allocation system can have a major effect on the incidence of ascites. Optimization of the house temperature and ventilation in cold weather seem helpful practices to decrease ascites incidence. PMID:18393088

Baghbanzadeh, A; Decuypere, E

2008-04-01

93

TUSC1, a Putative Tumor Suppressor Gene, Reduces Tumor Cell Growth In Vitro and Tumor Growth In Vivo  

PubMed Central

We previously reported the identification of TUSC1 (Tumor Suppressor Candidate 1), as a novel intronless gene isolated from a region of homozygous deletion at D9S126 on chromosome 9p in human lung cancer. In this study, we examine the differential expression of TUSC1 in human lung cancer cell lines by western blot and in a primary human lung cancer tissue microarray by immunohistochemical analysis. We also tested the functional activities and mechanisms of TUSC1 as a tumor suppressor gene through growth suppression in vitro and in vivo. The results showed no expression of TUSC1 in TUSC1 homozygously deleted cells and diminished expression in some tumor cell lines without TUSC1 deletion. Interestingly, the results from a primary human lung cancer tissue microarray suggested that higher expression of TUSC1 was correlated with increased survival times for lung cancer patients. Our data demonstrated that growth curves of tumor cell lines transfected with TUSC1 grew slower in vitro than those transfected with the empty vector. More importantly, xenograph tumors in nude mice grew significantly slower in vivo in cells stably transfected with TUSC1 than those transfected with empty vector. In addition, results from confocal microscopy and immunohistochemical analyses show distribution of TUSC1 in the cytoplasm and nucleus in tumor cell lines and in normal and tumor cells in the lung cancer tissue microarray. Taken together, our results support TUSC1 has tumor suppressor activity as a candidate tumor suppressor gene located on chromosome 9p. PMID:23776618

Shan, Zhihong; Shakoori, Abbas; Bodaghi, Sohrab; Goldsmith, Paul; Jin, Jen; Wiest, Jonathan S.

2013-01-01

94

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

95

Shrinkage-induced Activation of the Na + \\/H + Exchanger in Ehrlich Ascites Tumor Cells: Mechanisms Involved in the Activation and a Role for the Exchanger in Cell Volume Regulation  

Microsoft Academic Search

.   Amiloride-sensitive, Na+-dependent, DIDS-insensitive cytoplasmic alkalinization is observed after hypertonic challenge in Ehrlich ascites tumor cells.\\u000a This was assessed using the fluorescent pH-sensitive probe 2?,7?-bis-(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). A parallel\\u000a increase in the amiloride-sensitive unidirectional Na+ influx is also observed. This indicates that hypertonic challenge activates a Na+\\/H+ exchanger. Activation occurs after several types of hypertonic challenge, is a graded function of

S. F. Pedersen; B. Kramhřft; N. K. Jřrgensen; E. K. Hoffmann

1996-01-01

96

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. PMID:7807024

1995-01-01

97

Cellular Potts Modeling of Tumor Growth, Tumor Invasion, and Tumor Evolution  

PubMed Central

Despite a growing wealth of available molecular data, the growth of tumors, invasion of tumors into healthy tissue, and response of tumors to therapies are still poorly understood. Although genetic mutations are in general the first step in the development of a cancer, for the mutated cell to persist in a tissue, it must compete against the other, healthy or diseased cells, for example by becoming more motile, adhesive, or multiplying faster. Thus, the cellular phenotype determines the success of a cancer cell in competition with its neighbors, irrespective of the genetic mutations or physiological alterations that gave rise to the altered phenotype. What phenotypes can make a cell “successful” in an environment of healthy and cancerous cells, and how? A widely used tool for getting more insight into that question is cell-based modeling. Cell-based models constitute a class of computational, agent-based models that mimic biophysical and molecular interactions between cells. One of the most widely used cell-based modeling formalisms is the cellular Potts model (CPM), a lattice-based, multi particle cell-based modeling approach. The CPM has become a popular and accessible method for modeling mechanisms of multicellular processes including cell sorting, gastrulation, or angiogenesis. The CPM accounts for biophysical cellular properties, including cell proliferation, cell motility, and cell adhesion, which play a key role in cancer. Multiscale models are constructed by extending the agents with intracellular processes including metabolism, growth, and signaling. Here we review the use of the CPM for modeling tumor growth, tumor invasion, and tumor progression. We argue that the accessibility and flexibility of the CPM, and its accurate, yet coarse-grained and computationally efficient representation of cell and tissue biophysics, make the CPM the method of choice for modeling cellular processes in tumor development. PMID:23596570

Szabó, András; Merks, Roeland M. H.

2013-01-01

98

HYPOBARIC HYPOXIA IN ASCITES RESISTANT AND SUSCEPTIBLE BROILER GENETIC LINES INFLUENCES GUT MORPHOLOGY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Genetic selection based on rapid growth rates, improved feed conversion and increased body weights has led to a predisposition to ascites in broiler populations. Sire-family selection was applied to a commercial elite line to produce divergent lines of ascites resistant (26.0% ascites mortality, RES...

99

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

100

Prophylactic action of lipoic acid on oxidative stress and growth performance in broilers at risk of developing ascites syndrome.  

PubMed

The objective of this study was to assess the effects of dietary supplementation with lipoic acid (LA) on broilers maintained at 2235 m above sea level with high risk to develop ascites syndrome (AS). A total of 2040 chicks were fed under commercial conditions with water and specific diets ad libitum during 7 weeks in two consecutive experiments. Mortality and indicators of performance and oxidative stress were compared weekly in broilers fed a basal diet plus 0, 10, 20, or 40 parts/10(6) LA. The effects of LA at 40 parts/10(6) were also studied during the initial 3 weeks or the last 4 weeks of the production cycle. Diets supplemented with 40 parts/10(6) of LA during 7 weeks significantly improved feed conversion, decreased general mortality and mortality attributable to AS, and lowered thiobarbituric acid reactive substances and hydroxyl radicals in liver, and increased total glutathione pool. Smaller doses or shorter periods of exposure to LA were partially effective. In conclusion, LA under our experimental conditions has a prophylactic action in broilers with high risk to develop AS due to oxygen availability limitation. PMID:14676017

Díaz-Cruz, Antonio; Serret, Maurilio; Ramírez, Guadalupe; Avila, Ernesto; Guinzberg, Raquel; Pińa, Enrique

2003-12-01

101

Rare cancers yield potential source of tumor growth  

Cancer.gov

Researchers at the National Institutes of Health have discovered a genetic mutation that appears to increase production of red blood cells in tumors. The discovery, based on analysis of tissue from rare endocrine tumors, may help clarify how some tumors generate a new blood supply to sustain their growth, the researchers explained.

102

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

103

Inhibition of rate of tumor growth by creatine and cyclocreatine.  

PubMed

Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors. PMID:8475072

Miller, E E; Evans, A E; Cohn, M

1993-04-15

104

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 2.8 mg/kg/day and 1.4 mg/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; Rokon Uz Zaman; Mahmud, Zahid Hayat; Reza, Md Abu

2013-11-15

105

Vascular Endothelial Growth Factor C–Induced Lymphangiogenesis DecreasesTumor Interstitial Fluid Pressure and Tumor Growth1  

PubMed Central

Characteristically, most solid tumors exhibit an increased tumor interstitial fluid pressure (TIFP) that directly contributes to the lowered uptake of macromolecular therapeutics into the tumor interstitium. Abnormalities in the tumor-associated lymph vessels are a central brick in the development and prolonged sustaining of an increased TIFP. In the current study, vascular endothelial growth factor C (VEGF-C) was used to enhance tumor-associated lymphangiogenesis as a new mechanism to actively reduce the TIFP by increased lymphatic drainage of the tumor tissue. Human A431 epidermoid vulva carcinoma cells were inoculated in NMRI nu/nu mice to generate a xenograft mouse model. Seven days after tumor cell injection, VEGF-C was peritumorally injected to induce lymphangiogenesis. Tumor growth and TIFP was lowered significantly over time in VEGF-C-treated tumors in comparison to control or VEGF-A-treated animals. These data demonstrate for the first time that actively induced lymphangiogenesis can lower the TIFP in a xenograft tumor model and apparently reduce tumor growth. This model represents a novel approach to modulate biomechanical properties of the tumor interstitium enabling a lowering of TIFP in vivo. PMID:23908682

Hofmann, Matthias; Pflanzer, Ralph; Zoller, Nadja Nicole; Bernd, August; Kaufmann, Roland; Thaci, Diamant; Bereiter-Hahn, Jurgen; Hirohata, Satoshi; Kippenberger, Stefan

2013-01-01

106

Dermatomyositis with massive ascites.  

PubMed

There have been few reports of dermatomyositis causing ascites. Here we report a case of a 63-year-old man complaining of general fatigue and gastromegaly. Abdominal examination revealed distension without tenderness. Serum myogenic enzyme was elevated. Electromyographic investigation indicated low amplitude signs, which were compatible with muscle disorder. Abdominal paracentesis on the fifth day yielded 2,500 ml clear, serous fluid. The specific gravity was 1.026 (range 1.005-1.015), with a positive Rivalta reaction, 3.4 g/dl total protein, and 1.59 g/dl albumin, suggesting exudate. Excluding the other causes of exudative ascites, we considered that the ascites was caused by dermatomyositis. PMID:17287935

Ota, Seisuke; Kasahara, Akinori; Yamada, Taku; Tanimoto, Mitsune

2007-07-01

107

Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor.  

PubMed

Characteristically, most solid tumors exhibit an increased tumor interstitial fluid pressure (TIFP) that directly contributes to the lowered uptake of macromolecular therapeutics into the tumor interstitium. Abnormalities in the tumor-associated lymph vessels are a central brick in the development and prolonged sustaining of an increased TIFP. In the current study, vascular endothelial growth factor C (VEGF-C) was used to enhance tumor-associated lymphangiogenesis as a new mechanism to actively reduce the TIFP by increased lymphatic drainage of the tumor tissue. Human A431 epidermoid vulva carcinoma cells were inoculated in NMRI nu/nu mice to generate a xenograft mouse model. Seven days after tumor cell injection, VEGF-C was peritumorally injected to induce lymphangiogenesis. Tumor growth and TIFP was lowered significantly over time in VEGF-C-treated tumors in comparison to control or VEGF-A-treated animals. These data demonstrate for the first time that actively induced lymphangiogenesis can lower the TIFP in a xenograft tumor model and apparently reduce tumor growth. This model represents a novel approach to modulate biomechanical properties of the tumor interstitium enabling a lowering of TIFP in vivo. PMID:23908682

Hofmann, Matthias; Pflanzer, Ralph; Zoller, Nadja Nicole; Bernd, August; Kaufmann, Roland; Thaci, Diamant; Bereiter-Hahn, Jurgen; Hirohata, Satoshi; Kippenberger, Stefan

2013-08-01

108

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

109

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

110

Effects of Trypanosoma brucei gambiense infections in Microtus montanus on susceptibility to Ehrlich's tumors.  

PubMed

Trypanosoma brucei gambiense infections in the field vole Microtus montanus increased susceptibility to Ehrlich's tumor growth. Whereas uninfected voles were totally resistant to intraperitoneal Ehrlich's ascites tumor cell challenge, over 78% of the animals infected with the trypanosomes developed tumors after challenge. Likewise, when Ehrlich's ascites cells were injected subcutaneously to induce solid tumor formation, only 7% of uninfected controls developed tumors, whereas over 82% of trypanosome-infected animals exhibited malignancies after Ehrlich's cell challenge. Finally, when solid tumors grown in albino CD-1 mice were implanted subcutaneously into uninfected voles, the tumor mass rapidly diminished in size and could not be found when animals were examined 2 weeks postimplant. However, in trypanosome-infected voles, implanted tumors exhibited pronounced expansion, and viable, solid tumors were recovered from over 70% of the challenged voles at 2 weeks postimplant. The implications of trypanosome-induced immunosuppression, especially toward susceptibility to neoplastic growth, are discussed. PMID:770326

Ackerman, S B; Seed, J R

1976-02-01

111

Antitumor effect of nuclear factor-?B decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites.  

PubMed

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor-?B (NF-?B) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF-?B decoy into TAMs by ultrasound (US)-responsive, mannose-modified liposome/NF-?B decoy complexes (Man-PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF-?B decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-?B decoy into TAMs effectively. When the NF-?B decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor necrosis factor-?, and IL-6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF-?B decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF-?B decoy efficiently by Man-PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. PMID:24850474

Kono, Yusuke; Kawakami, Shigeru; Higuchi, Yuriko; Maruyama, Kazuo; Yamashita, Fumiyoshi; Hashida, Mitsuru

2014-08-01

112

Treatment for Malignant Ascites  

Cancer.gov

In this trial, researchers will randomly assign patients with malignant ascites to receive either octreotide or a placebo once a month for up to two years. The investigators will see whether octreotide can delay, or even eliminate, the need for paracentesis and assess side effects and quality of life of patients undergoing this treatment.

113

Oncogenes and Angiogenesis: Signaling Three-Dimensional Tumor Growth  

Microsoft Academic Search

Three-dimensional tumor growth is dependent on the perpetual recruitment of host blood vessels to the tumor site. This recruitment process (mainly via angiogenesis) is thought to be triggered, at least in part, by the very same set of genetic alterations (activated oncogenes, inactivated\\/lost tumor suppressor genes) as those responsible for other aspects of malignant transformation (e.g., aberrant mitogenesis, resistance to

Janusz Rak; Joanne L. Yu; Giannoula Klement; Robert S. Kerbel

2000-01-01

114

IL18-producing Salmonella inhibit tumor growth  

Microsoft Academic Search

Previous studies have shown that intravenously applied bacteria can accumulate in tumors and lead to sporadic tumor regression. Recently, systemic administration of attenuated Salmonella typhimurium was demonstrated to generate no significant side effects in humans, but also no antitumor responses. We report the enhanced antitumor activity in preclinical mouse cancer models of nonvirulent S. typhimurium engineered to synthesize the cytokine

M Loeffler; G Le'Negrate; M Krajewska; J C Reed

2008-01-01

115

Evaluation of growth rate, body weight, heart rate, and blood parameters as potential indicators for selection against susceptibility to the ascites syndrome in young broilers.  

PubMed

The continuous selection for rapid growth has been accompanied by an increasing occurrence of ascites syndrome (AS), which develops in broilers failing to supply the increasing demand for O(2) in their bodies. Moderate heritability has been reported for AS in broiler populations, suggesting that selection against AS is feasible. However, direct selection based on AS mortality requires exposure of candidate birds to AS-inducing conditions (AIC), which hinder selection for performance traits. Noninvasive indicators of AS, expressed under standard husbandry, may facilitate the integration of selection against AS into breeding programs. This study was designed to look for differences in heart rate, hematocrit, O(2) saturation of hemoglobin in arterial blood (SaO(2)), BW, and weight gain, all measured at early ages under standard brooding conditions, between birds that later developed AS and those that remained healthy under AIC, and to estimate the heritability of these AS-related parameters and their genetic correlation with the tendency of broilers to develop AS. The experimental population was derived from a broiler dam line. Male progeny of 34 half-sib sire families were reared under standard brooding conditions to 19 d of age, then under an AIC protocol consisting of housing in individual cages, cool air high-speed ventilation, and growth enhancement using high-energy pelleted feed and 23 h/d of light. Birds were necropsied upon mortality or at the end of the trials and were recorded as being susceptible, with manifestations of AS (SUS), or resistant and healthy (RES). About 44% developed AS, confirming the efficacy of the novel AIC protocol. The SUS and RES chicks did not differ in BW and weight gain up to 19 d of age, suggesting that there was no association between AS susceptibility and rapid early growth. The SUS chicks exhibited lower SaO(2) and heart rate than the RES chicks. Moderate heritability was estimated for all traits, but only SaO(2) exhibited consistently significant genetic correlation (-0.5) with AS, suggesting that it may serve as an early indicator for selection against AS, albeit with a limited efficacy. PMID:17369531

Druyan, S; Shlosberg, A; Cahaner, A

2007-04-01

116

Insulin-like growth factors inhibit dendritic cell-mediated anti-tumor immunity through regulating ERK1/2 phosphorylation and p38 dephosphorylation.  

PubMed

Insulin-like growth factors (IGFs) can promote tumorigenesis via inhibiting the apoptosis of cancer cells. The relationship between IGFs and dendritic cell (DC)-mediated immunity were investigated. Advanced-stage ovarian carcinoma patients were first evaluated to show higher IGF-1 and IGF-2 concentrations in their ascites than early-stage patients. IGFs could suppress DCs' maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8(+) T cell. IGF-treated DCs also secreted higher concentrations of IL-10 and TNF-?. IGF-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The percentages of matured DCs in the ascites were significantly lower in the IGF-1 or IGF-2 highly-expressing WF-3 tumor-bearing mice. The IGF1R inhibitor - NVP-AEW541, could block the effects of IGFs to rescue DCs' maturation and to restore DC-mediated antigen-specific immunity through enhancing ERK1/2 phosphorylation and p38 dephosphorylation. IGFs can inhibit DC-mediated anti-tumor immunity through suppressing maturation and function and the IGF1R inhibitor could restore the DC-mediated anti-tumor immunity. Blockade of IGFs could be a potential strategy for cancer immunotherapy. PMID:25592043

Huang, Ching-Ting; Chang, Ming-Cheng; Chen, Yu-Li; Chen, Tsung-Ching; Chen, Chi-An; Cheng, Wen-Fang

2015-04-01

117

Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma  

PubMed Central

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment. PMID:24980821

Zhu, Li Ming; Shi, Dong Mei; Dai, Qiang; Cheng, Xiao Jiao; Yao, Wei Yan; Sun, Ping Hu; Ding, Yan Fei; Qiao, Min Min; Wu, Yun Lin; Jiang, Shi Hu; Tu, Shui Ping

2014-01-01

118

Understanding the Mechanisms of Tumor Growth | Physical Sciences in Oncology  

Cancer.gov

Though cancer is certainly a disease caused by changes in a cell's genes, it has become clear over the past few years that cancer is also a disease of biomechanical malfunctions. Indeed, research has shown that interactions between the mechanical properties of tumors and the tissues that surround them play a critical role in the development and growth of tumors.

119

Association Between Weight Gain, Blood Parameters, and Thyroid Hormones and the Development of Ascites Syndrome in Broiler Chickens1  

Microsoft Academic Search

The present study examined the associa- tion between thyroid hormones and the development of ascites on one hand and the ability to predict ascites from growth rate and hematocrit on the other hand. Ascites syndrome was induced in broiler chickens in two trials by exposing the chicks to low ambient temperature (Ta) and by supplying a pellet form of diet.

D. Luger; D. Shinder; V. Rzepakovsky; M. Rusal; S. Yahav

120

Host Stromal Bradykinin B2 Receptor Signaling Facilitates Tumor-Associated Angiogenesis and Tumor Growth  

Microsoft Academic Search

We evaluated the significance of the host kallikrein-kinin system in tumor angiogenesis and tumor growth using two rodent models geneti- cally deficient in a kallikrein-kinin system. Inoculation of Walker 256 carcinoma cells into the s.c. tissues of the back of normal Brown Norway Kitasato rats (BN-Ki rats) resulted in the rapid development of solid tumors with marked angiogenesis. By contrast,

Yasuhiro Ikeda; Izumi Hayashi; Emi Kamoshita; Akira Yamazaki; Hirahito Endo; Keiko Ishihara; Shohei Yamashina; Yoshiaki Tsutsumi; Hiroaki Matsubara; Masataka Majima

2004-01-01

121

Comparison of Three Lines of Broilers Differing in Ascites Susceptibility or Growth Rate. 2. Egg Weight Loss, Gas Pressures, Embryonic Heat Production, and Physiological Hormone Levels  

Microsoft Academic Search

Ascites is a metabolic disorder that ac- counts for over 25% of overall mortality in the broiler industry. This disorder is manifested between wk 5 and 6 posthatch, but there are previous indications that pre- disposition may be identified during embryonic develop- ment. In this current study, we determined embryonic physiological and metabolic parameters that may be asso- ciated with

L. De Smit; K. Tona; V. Bruggeman; O. Onagbesan; M. Hassanzadeh; L. Arckens; E. Decuypere

122

VEGF is a target molecule for peritoneal metastasis and malignant ascites in gastric cancer: prognostic significance of VEGF in ascites and efficacy of anti-VEGF monoclonal antibody  

PubMed Central

Background In gastric cancer, poor prognosis is associated with peritoneal dissemination, which often accompanies malignant ascites. We searched for a target molecule in peritoneal metastasis and investigated its clinical utility as a biomarker. Methods Biopsy specimens from both primary lesions and peritoneal metastasis, and if possible, malignant ascites, were obtained from 40 patients with gastric cancer. Vascular endothelial growth factor (VEGF) expression was analyzed by immunohistochemical staining and enzyme-linked immunosorbent assay. Results VEGF expression was seen in 70% of peritoneal samples. Of the 40 patients, 35 had malignant ascites. These 35 patients were divided into two groups: 15 with ascites found beyond the pelvic cavity (large group) and 20 whose ascites were within the pelvic cavity (small group). The two groups did not significantly differ by serum VEGF levels, but ascites VEGF levels in the large group were significantly higher than in the small group (P < 0.0001). Serum VEGF and ascites VEGF levels were highly correlated in the large group (r = 0.686). A high ascites VEGF level was found to be a risk factor for survival (P = 0.045). We include a report of a patient with chemoresistant refractory gastric cancer and symptomatic ascites who obtained 8 months of palliation from systemic bevacizumab. Conclusion Anti-VEGF therapies are promising, and the ascites VEGF level is an important marker in managing patients with gastric cancer and peritoneal metastasis. PMID:24204159

Fushida, Sachio; Oyama, Katsunobu; Kinoshita, Jun; Yagi, Yasumichi; Okamoto, Kouichi; Tajima, Hidehiro; Ninomiya, Itasu; Fujimura, Takashi; Ohta, Tetsuo

2013-01-01

123

Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumors  

PubMed Central

Tumor endothelial marker 1 (Tem1; endosialin) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of Tem1, we disrupted the Tem1 gene in mice by targeted homologous recombination. Tem1?/? mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.c. sites. However, there was a striking reduction in tumor growth, invasiveness, and metastasis after transplantation of tumors to abdominal sites in mice without functional Tem1 genes. These data indicate that the stroma can control tumor aggressiveness and that this control varies with anatomic site. Therefore, they have significant implications for the mechanisms underlying tumor invasiveness and for models that evaluate this process. PMID:16492758

Nanda, Akash; Karim, Baktiar; Peng, Zhongsheng; Liu, Guosheng; Qiu, Weiping; Gan, Christine; Vogelstein, Bert; St. Croix, Brad; Kinzler, Kenneth W.; Huso, David L.

2006-01-01

124

Homeostatic competition drives tumor growth and metastasis nucleation  

E-print Network

in epithelial tissues from where they invade through the basal membrane into the connective tissue. At some a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show data. In addition, it potentially explains the observed preferential growth of metastases on tissue

Turner, Matthew

125

A multiphase model for three-dimensional tumor growth  

NASA Astrophysics Data System (ADS)

Several mathematical formulations have analyzed the time-dependent behavior of a tumor mass. However, most of these propose simplifications that compromise the physical soundness of the model. Here, multiphase porous media mechanics is extended to model tumor evolution, using governing equations obtained via the thermodynamically constrained averaging theory. A tumor mass is treated as a multiphase medium composed of an extracellular matrix (ECM); tumor cells (TCs), which may become necrotic depending on the nutrient concentration and tumor phase pressure; healthy cells (HCs); and an interstitial fluid for the transport of nutrients. The equations are solved by a finite element method to predict the growth rate of the tumor mass as a function of the initial tumor-to-healthy cell density ratio, nutrient concentration, mechanical strain, cell adhesion and geometry. Results are shown for three cases of practical biological interest such as multicellular tumor spheroids (MTSs) and tumor cords. First, the model is validated by experimental data for time-dependent growth of an MTS in a culture medium. The tumor growth pattern follows a biphasic behavior: initially, the rapidly growing TCs tend to saturate the volume available without any significant increase in overall tumor size; then, a classical Gompertzian pattern is observed for the MTS radius variation with time. A core with necrotic cells appears for tumor sizes larger than 150 ?m, surrounded by a shell of viable TCs whose thickness stays almost constant with time. A formula to estimate the size of the necrotic core is proposed. In the second case, the MTS is confined within a healthy tissue. The growth rate is reduced, as compared to the first case—mostly due to the relative adhesion of the TCs and HCs to the ECM, and the less favorable transport of nutrients. In particular, for HCs adhering less avidly to the ECM, the healthy tissue is progressively displaced as the malignant mass grows, whereas TC infiltration is predicted for the opposite condition. Interestingly, the infiltration potential of the tumor mass is mostly driven by the relative cell adhesion to the ECM. In the third case, a tumor cord model is analyzed where the malignant cells grow around microvessels in a three-dimensional geometry. It is shown that TCs tend to migrate among adjacent vessels seeking new oxygen and nutrients. This model can predict and optimize the efficacy of anticancer therapeutic strategies. It can be further developed to answer questions on tumor biophysics, related to the effects of ECM stiffness and cell adhesion on TC proliferation.

Sciumč, G.; Shelton, S.; Gray, W. G.; Miller, C. T.; Hussain, F.; Ferrari, M.; Decuzzi, P.; Schrefler, B. A.

2013-01-01

126

MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis.  

PubMed

MerTK, a receptor tyrosine kinase (RTK) of the TYRO3/AXL/MerTK family, is expressed in myeloid lineage cells in which it acts to suppress proinflammatory cytokines following ingestion of apoptotic material. Using syngeneic mouse models of breast cancer, melanoma, and colon cancer, we found that tumors grew slowly and were poorly metastatic in MerTK-/- mice. Transplantation of MerTK-/- bone marrow, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice (a model of metastatic breast cancer) decreased tumor growth and altered cytokine production by tumor CD11b+ cells. Although MerTK expression was not required for tumor infiltration by leukocytes, MerTK-/- leukocytes exhibited lower tumor cell-induced expression of wound healing cytokines, e.g., IL-10 and growth arrest-specific 6 (GAS6), and enhanced expression of acute inflammatory cytokines, e.g., IL-12 and IL-6. Intratumoral CD8+ T lymphocyte numbers were higher and lymphocyte proliferation was increased in tumor-bearing MerTK-/- mice compared with tumor-bearing wild-type mice. Antibody-mediated CD8+ T lymphocyte depletion restored tumor growth in MerTK-/- mice. These data demonstrate that MerTK signaling in tumor-associated CD11b+ leukocytes promotes tumor growth by dampening acute inflammatory cytokines while inducing wound healing cytokines. These results suggest that inhibition of MerTK in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies. PMID:23867499

Cook, Rebecca S; Jacobsen, Kristen M; Wofford, Anne M; DeRyckere, Deborah; Stanford, Jamie; Prieto, Anne L; Redente, Elizabeth; Sandahl, Melissa; Hunter, Debra M; Strunk, Karen E; Graham, Douglas K; Earp, H Shelton

2013-08-01

127

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. PMID:24093089

Ahmed, Nuzhat; Stenvers, Kaye L.

2013-01-01

128

Thermographic assessment of tumor growth in mouse xenografts.  

PubMed

In human breast tumors, a 1-2 degrees C increase in skin surface temperature is usually observed at the periphery; it has been proposed that this change is due to the hypervascularity and increased blood flow resulting from tumor-associated angiogenesis. Here we tested the hypothesis that thermal imaging might represent a useful adjunctive technique in monitoring the growth dynamics of human tumor xenografts. Xenografts were established in immunocomprised nude mice using MDA-MB-231 or MCF7 breast cancer cells. We exploited the inherent noncontact and noninvasive advantages of infrared thermography to detect skin surface temperature changes. Continuous thermographic investigation was performed to detect and monitor tumor growth in vivo and high resolution digital images were analyzed to measure the tumor temperature dynamics. In contrast to the skin temperature increases associated with human breast cancer, a consistent temperature decrease was found in the xenograft mice. In one case, a smaller secondary tumor, otherwise undetectable, was clearly evident by thermal imaging. The tumors were cooler than the surrounding tissue with a maximum temperature reduction of 1.5 degrees C for MDA-MB-231 tumor and 3 degrees C for MCF7 tumors observed on day 14. In addition, the temperature of the xenograft tumors decreased progressively as they grew throughout the observation period. It was demonstrated that thermographic imaging could detect temperature changes as small as 0.1 degrees C on the skin surface at an early stage of tumor development. The findings of the study indicate that thermographic imaging might have considerable potential in monitoring human tumor xenografts and their response to anticancer drugs. PMID:17487841

Song, Chengli; Appleyard, Virginia; Murray, Karen; Frank, Tim; Sibbett, Wilson; Cuschieri, Alfred; Thompson, Alastair

2007-09-01

129

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

PubMed Central

Objective: The present investigation was performed to evaluate the antiproliferative and antioxidant activity of Aegle marmelos leaves in Dalton's Lymphoma Ascites (DLA)-bearing mice. Materials and Methods: The DLA cells maintained in vivo in Swiss albino mice were used for developing ascitic tumor in mice by intraperitoneal transplantation. The standardized 50% ethanolic extract of A. marmelos leaves (AMEE) was administered intraperitoneally in dose levels 200 and 400 mg/kg, after 24 hours of tumor inoculation in mice for two weeks. Results: The AMEE treatment significantly prevented (P<0.001) the increase in body weight due to tumor cell growth and increased the mean survival time of the tumor-bearing mice as compared to the untreated DLA control mice. The treatment of DLA-bearing mice brought down the Alanine Aminotransferase (ALAT), Aspartate Aminotransferase (ASAT), and alkaline phosphatase to normal levels. The extract decreased the levels of hepatic lipid peroxidation and increased the levels of hepatic antioxidants Glutathione, Superoxide Dismutase (SOD), and catalase. All the changes observed with AMEE treatment were dose dependent. Conclusion: The hydroalcoholic extract of A. marmelos exhibits strong antitumor and antioxidant activities in DLA-bearing mice. PMID:22529480

Chockalingam, Vijaya; Kadali, SDV Suryakiran; Gnanasambantham, Pratheesh

2012-01-01

130

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. PMID:21493715

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

2011-01-01

131

Acellular fraction of ovarian cancer ascites induce apoptosis by activating JNK and inducing BRCA1, Fas and FasL expression in ovarian cancer cells  

PubMed Central

Acellular fraction of ascites might play an active role in tumor development. Nevertheless the mechanisms involved in the tumor-modulating properties are still controversial. Here, we demonstrate that malignant ascites from 8 patients with epithelial ovarian cancer did not influence proliferative or invasive properties of ovarian cancer cells, but promoted H2O2-induced apoptosis and increased sensitivity to paclitaxel. Malignant ascites induced BRCA1, Fas and FasL expression and phosphorylation of JNK, but not the activation of caspase pathway. Ascites-induced apoptosis of ovarian cancer cells was strongly inhibited by a JNK inhibitor suggesting a critical role of JNK pathway in ascite-induced apoptosis. The use of siRNA JNK confirmed the importance of JNK in ascites-induced Fas and FasL expression. These results demonstrate that malignant ascites induce apoptosis of ovarian cancer cells and encourage us to think about the clinical management of ovarian cancer patients with malignant ascites. PMID:25594018

Cohen, Marie; Pierredon, Sandra; Wuillemin, Christine; Delie, Florence; Petignat, Patrick

2014-01-01

132

Three-Dimensional Multispecies Nonlinear Tumor Growth–II: Tumor Invasion and Angiogenesis  

PubMed Central

We extend the diffuse interface model developed in Wise et al. (2008) to study nonlinear tumor growth in 3D. Extensions include the tracking of multiple viable cell species populations through a continuum diffuse-interface approach, onset and aging of discrete tumor vessels through angiogenesis, and incorporation of individual cell movement using a hybrid continuum-discrete approach. We investigate disease progression as a function of cellular-scale parameters such as proliferation and oxygen/nutrient uptake rates. We find that heterogeneity in the physiologically complex tumor microenvironment, caused by non-uniform distribution of oxygen, cell nutrients, and metabolites, as well as phenotypic changes affecting cellular-scale parameters, can be quantitatively linked to the tumor macro-scale as a mechanism that promotes morphological instability. This instability leads to invasion through tumor infiltration of surrounding healthy tissue. Models that employ a biologically-founded, multiscale approach, as illustrated in this work, could help to quantitatively link the critical effect of heterogeneity in the tumor microenvironment with clinically observed tumor growth and invasion. Using patient tumor-specific parameter values, this approach may provide a predictive tool to characterize the complex in vivo tumor physiological characteristics and clinical response, and thus lead to improved treatment modalities and prognosis. PMID:20303982

Frieboes, H.B.; Jin, F.; Chuang, Y.-L.; Wise, S.M.; Lowengrub, J.S.; Cristini, V.

2010-01-01

133

Inhibition of melanoma tumor growth in vivo by survivin targeting.  

PubMed

A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr(34)-->Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr(34)-->Ala inhibited tumor growth by 60-70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy. PMID:11149963

Grossman, D; Kim, P J; Schechner, J S; Altieri, D C

2001-01-16

134

Inhibition of melanoma tumor growth in vivo by survivin targeting  

PubMed Central

A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr34?Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr34?Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr34?Ala inhibited tumor growth by 60–70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy. PMID:11149963

Grossman, Douglas; Kim, Paul J.; Schechner, Jeffrey S.; Altieri, Dario C.

2001-01-01

135

Genetic parameters of ascites-related traits in broilers: effect of cold and normal temperature conditions  

Microsoft Academic Search

1. Ascites syndrome is a growth-related disorder of broilers that occurs more often in fast-growing birds and at low temperatures. The objective of this study was to estimate genetic and phenotypic correlations among ascites-related traits measured either under cold or under normal temperature conditions, and to estimate genetic correlations between ascites-related traits measured under cold and normal conditions.2. Several traits

A. Pakdel; J. A. M. van Arendonk; A. L. J. Vereijken; H. Bovenhuis

2005-01-01

136

Liposome targeting to tumors using vitamin and growth factor receptors  

Microsoft Academic Search

Liposome-encapsulated anticancer drugs reveal their potential for increased therapeutic efficacy and decreased nonspecific toxicities due to their ability to enhance the delivery of chemotherapeutic agents to solid tumors. Advances in liposome technology have resulted in the development of ligand-targeted liposomes capable of selectively increasing the efficacy of carried agents against receptor-bearing tumor cells. Receptors for vitamins and growth factors have

Daryl C. Drummond; Keelung Hong; John W. Park; Christopher C. Benz; Dmitri B. Kirpgtin

2000-01-01

137

Multiscale models for the growth of avascular tumors  

NASA Astrophysics Data System (ADS)

In the past 30 years we have witnessed an extraordinary progress on the research in the molecular biology of cancer, but its medical treatment, widely based on empirically established protocols, still has many limitations. One of the reasons for that is the limited quantitative understanding of the dynamics of tumor growth and drug response in the organism. In this review we shall discuss in general terms the use of mathematical modeling and computer simulations related to cancer growth and its applications to improve tumor therapy. Particular emphasis is devoted to multiscale models which permit integration of the rapidly expanding knowledge concerning the molecular basis of cancer and the complex, nonlinear interactions among tumor cells and their microenvironment that will determine the neoplastic growth at the tissue level.

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

2007-06-01

138

Ursolic acid-induced changes in tumor growth, O2 consumption, and tumor interstitial fluid pressure.  

PubMed

The anti-tumor effect of ursolic acid (UA) and UA-induced changes in tumor physiology in tumor-bearing mice were examined. MTT colorimetric assay, clonogenic assay, and growth-delay assay for the determination of tumoricidal effects of UA were evaluated. UA-induced apoptosis was measured by fluorescent microscopy, stained by propidium iodide. Oxygen consumption (QO2) after treatment with UA was measured using a Clark-type electrode chamber. Systemic toxicity in mice was assayed by LD50(30). We also measured UA-induced changes in several tumor physiological parameters. Inhibitory effect of UA on various tumor cell lines was observed using MTT and clonogenic assays in vitro. UA-induced apoptosis significantly increased in a dose-dependent manner. Cellular QO2 values were significantly reduced by UA. In animal studies, UA significantly reduced tumor interstitial fluid pressure (TIFP) to approximately 40% of the control values at 2-3 days post-treatment (P<0.05). An i.p. administration of 100 mg/kg of UA significantly (P<0.01) inhibited tumor growth of FSaII. In conclusion, UA showed anti-tumor effect on various tumor cells in vitro as well as a moderate retardation of growth in two tumor models in vivo. We gained some insight regarding the pathophysiological benefits of UA (i.e., reduction in TIFP) as a cancer therapeutic agent. Consequently, these observations can be used for further study of UA or to facilitate clinical applications of UA for treating cancer patients. PMID:11724362

Lee, I; Lee, J; Lee, Y H; Leonard, J

2001-01-01

139

[Effect of fenugreek on the growth of different genesis tumors].  

PubMed

This paper deals with antitumor properties of a fenugreek (Trigonella Foenum Graecum L.) as to the different genesis tumors--the Ca755 mouse mammary carcinoma and the Guerin's carcinoma in rats. Fenugreek powder was shown to inhibit (25-40 %) growth of certain tumors, decrease (27-63%) level of malone dialdehyde in liver, heart and kidney. Consumption of fenugreek was accompanied with decreased polyamines (spermine, spermidine, putrescine) content in tumor tissue. Inclusion of fenugreek to allowance was shown to improve certain blood value. PMID:23534282

Zhilenko, V V; Zalietok, S P; Klenov, O O

2012-01-01

140

Inhibition of rat colon tumor isograft growth with dequalinium chloride.  

PubMed

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma. PMID:3778199

Bleday, R; Weiss, M J; Salem, R R; Wilson, R E; Chen, L B; Steele, G

1986-11-01

141

Question 2.7: Logistic growth of a tumor. Zobl et al. [1] have studied the growth functions of tumors by inducing novel sarcomas in the kidneys of rats with Polyoma virus. These tumors  

E-print Network

of tumors by inducing novel sarcomas in the kidneys of rats with Polyoma virus. These tumors initially growQuestion 2.7: Logistic growth of a tumor. Zobl et al. [1] have studied the growth functions description of the data. Apparently, the reduction in the growth rate of the tumor does not decline linearly

Utrecht, Universiteit

142

Inhibition of protein synthesis in ehrlich ascites tumor cells by irradiation (365 nm) in the presence of skin-photosensitizing furocoumarins  

Microsoft Academic Search

Riassunlo La sintesi proteica nelle cellule del tumore ascitico di Ehrlich viene inhibita dall'irradiazione a 365 nm in presenza di furocumarine fotosensibilizzatrici cutanee (psoralene, xantotossina e 8-metilpsoralene).

F. Bordin; F. Baccichetti; R. Bevilacqua; L. Musajo

1973-01-01

143

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

144

Bioassay and Attributes of a Growth Factor Associated with Crown Gall Tumors 1  

PubMed Central

An improved bioassay is described for a factor that promotes tumor growth which was first obtained from extracts of pinto bean leaves with crown gall tumors. Sixteen primary pinto bean leaves per sample are inoculated with sufficient Agrobacterium tumefaciens to initiate about 5 to 10 tumors per leaf and treated with tumor growth factor at day 3 after inoculation. The diameters of 30 to 48 round tumors (no more than 3 randomly selected per leaf) are measured per test sample at day 6. Mean tumor diameter increased linearly with the logarithm of the concentration of tumor growth factor applied. The tumor growth factor was separated by column chromatography from an ultraviolet light-absorbing compound previously reported to be associated with fractions having maximal tumor growth factor activity. Partly purified tumor growth factor showed no activity in a cytokinin bioassay or an auxin bioassay, and negligible activity in gibberellin bioassays. Representatives of these three classes of growth factors did not promote tumor growth. Extracts from crown gall tumors on primary pinto bean leaves, primary castor bean leaves, Bryophyllum leaves, carrot root slices, and tobacco stems showed tumor growth factor activity, whereas extracts from healthy control tissues did not. Extracts from actively growing parts of healthy pinto beans, Bryophyllum, and tobacco, however, showed tumor growth factor activity. Tumor growth factor is proposed to be a normal plant growth factor associated with rapidly growing tissues. Its synthesis may be activated in nongrowing tissues by infection with Agrobacterium sp. PMID:16657534

Lippincott, Barbara B.; Lippincott, James A.

1970-01-01

145

Robo4 vaccines induce antibodies that retard tumor growth.  

PubMed

Tumor endothelial specific expression of Robo4 in adults identifies this plasma membrane protein as an anti-cancer target for immunotherapeutic approaches, such as vaccination. In this report, we describe how vaccination against Robo4 inhibits angiogenesis and tumor growth. To break tolerance to the auto-antigen Robo4, mice were immunised with the extracellular domain of mouse Robo4, fused to the Fc domain of human immunoglobulin within an adjuvant. Vaccinated mice show a strong antibody response to Robo4, with no objectively detectable adverse effects on health. Robo4 vaccinated mice showed impaired fibrovascular invasion and angiogenesis in a rodent sponge implantation assay, as well as a reduced growth of implanted syngeneic Lewis lung carcinoma. The anti-tumor effect of Robo4 vaccination was present in CD8 deficient mice but absent in B cell or IgG1 knockout mice, suggesting antibody dependent cell mediated cytotoxicity as the anti-vascular/anti-tumor mechanism. Finally, we show that an adjuvant free soluble Robo4-carrier conjugate can retard tumor growth in carrier primed mice. These results point to appropriate Robo4 conjugates as potential anti-angiogenic vaccines for cancer patients. PMID:25348086

Zhuang, Xiaodong; Ahmed, Forhad; Zhang, Yang; Ferguson, Henry J; Steele, Jane C; Steven, Neil M; Nagy, Zsuzsanna; Heath, Victoria L; Toellner, Kai-Michael; Bicknell, Roy

2015-01-01

146

Systemic Par-4 inhibits non-autochthonous tumor growth  

PubMed Central

The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy. PMID:21613819

Brandon, Jason; Qiu, Shirley; Shelton, Brent J; Spear, Brett; Bondada, Subbarao; Bryson, Scott

2011-01-01

147

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress  

PubMed Central

Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF) is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and ?-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- ?-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-? action on proliferation confirming its impact on TGF?/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo. Conclusion This is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and ?-catenin expression. PMID:20875132

2010-01-01

148

Black Tea-Induced Decrease in IL10 and TGF-? of Tumor Cells Promotes Th1\\/Tc1 Response in Tumor Bearer  

Microsoft Academic Search

Several lines of evidence support that impairment of host immune function by tumor may be related to several strategies of tumor escape from immunosurveillance. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice, the tumor cells secrete immunosuppressive cytokines, transforming growth factor beta (TGF-?) and interleukin-10 (IL-10) that induce a general T helper cells type 2 (Th2) dominance dampening the

Debaprasad Mandal; Sankar Bhattacharyya; Lakshmishri Lahiry; Sreya Chattopadhyay; Gaurisankar Sa; Tanya Das

2007-01-01

149

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

150

Effects of dietary L-carnitine and coenzyme Q10 at different supplemental ages on growth performance and some immune response in ascites-susceptible broilers  

Microsoft Academic Search

Effects of dietary L-carnitine and coenzyme Q10 (CoQ10) at different supplemental ages on performance and some immune response were investigated in ascites-susceptible broilers. A 3 × 2 × 2 factorial design was used consisting of L-carnitine supplementation (0, 75, and 100 mg\\/kg), CoQ10 supplementation (0 and 40 mg\\/kg) and different supplemental ages (from day 1 on and from day 10 on). A total of 480 one-day-old

Ailian Geng; Baoming Li; Yuming Guo

2007-01-01

151

Hyper or hypothyroidism: its association with the development of ascites syndrome in fast-growing chickens  

Microsoft Academic Search

The ascites syndrome in broiler chickens is attributed to the progress in genetic selection for rapid growth, coupled with the metabolic burden imposed by exposure to a relatively low-ambient temperature (Ta). The syndrome is mainly characterized by hematocrit elevation, decline in blood oxygen saturation, accumulation of fluid in the abdominal cavity, and finally, death. Ascitic chickens have demonstrated hypothyroidism coupled

Dror Luger; Dmitri Shinder; Shlomo Yahav

2002-01-01

152

CD151-?3?1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling  

PubMed Central

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-?3?1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or ?3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-?3?1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of ?-catenin and Axin-2 as well as resistance to the inhibition in ?-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-?3?1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling. PMID:25356755

Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; van Nagell, John R.; Wang, Chi; Chen, Li; Plattner, Rina; Kaetzel, David M.; Luo, Jia; Lu, Michael; West, Dava; Liu, Chunming; Ueland, Fred R.; Drapkin, Ronny; Zhou, Binhua P.; Yang, Xiuwei H.

2014-01-01

153

MEDI3617, a human anti-angiopoietin 2 monoclonal antibody, inhibits angiogenesis and tumor growth in human tumor xenograft models.  

PubMed

Angiopoietin 2 (Ang2) is an important regulator of angiogenesis, blood vessel maturation and integrity of the vascular endothelium. The correlation between the dynamic expression of Ang2 in tumors with regions of high angiogenic activity and a poor prognosis in many tumor types makes Ang2 an ideal drug target. We have generated MEDI3617, a human anti-Ang2 monoclonal antibody that neutralizes Ang2 by preventing its binding to the Tie2 receptor in vitro, and inhibits angiogenesis and tumor growth in vivo. Treatment of mice with MEDI3617 resulted in inhibition of angiogenesis in several mouse models including: FGF2-induced angiogenesis in a basement extract plug model, tumor and retinal angiogenesis. In xenograft tumor models, treatment with MEDI3617 resulted in a reduction in tumor angiogenesis and an increase in tumor hypoxia. The administration of MEDI3617 as a single agent to mice bearing human tumor xenografts resulted in tumor growth inhibition against a broad spectrum of tumor types. Combining MEDI3617 with chemotherapy or bevacizumab resulted in a delay in tumor growth and no body weight loss was observed in the combination groups. These results, combined with pharmacodynamic studies, demonstrate that treatment of tumor-bearing mice with MEDI3617 significantly inhibited tumor growth as a single agent by blocking tumor angiogenesis. Together, these data show that MEDI3617 is a robust antiangiogenic agent and support the clinical evaluation and biomarker development of MEDI3617 in cancer patients. PMID:22327175

Leow, Ching Ching; Coffman, Karen; Inigo, Ivan; Breen, Shannon; Czapiga, Meggan; Soukharev, Serguei; Gingles, Neill; Peterson, Norman; Fazenbaker, Christine; Woods, Rob; Jallal, Bahija; Ricketts, Sally-Ann; Lavallee, Theresa; Coats, Steve; Chang, Yong

2012-05-01

154

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...

155

Antiproliferative and hepatoprotective activity of metabolites from Corynebacterium xerosis against Ehrlich Ascites Carcinoma cells  

PubMed Central

Objective To find out the effective anticancer drugs from bacterial products, petroleum ether extract of Corynebacterium xerosis. Methods Antiproliferative activity of the metabolite has been measured by monitoring the parameters like tumor weight measurement, tumor cell growth inhibition in mice and survival time of tumor bearing mice, etc. Hepatoprotective effect of the metabolites was determined by observing biochemical, hematological parameters. Results It has been found that the petroleum ether extract bacterial metabolite significantly decrease cell growth (78.58%; P<0.01), tumor weight (36.04 %; P<0.01) and increase the life span of tumor bearing mice (69.23%; P<0.01) at dose 100 mg/kg (i.p.) in comparison to those of untreated Ehrlich ascites carcinoma (EAC) bearing mice. The metabolite also alters the depleted hematological parameters like red blood cell, white blood cell, hemoglobin (Hb%), etc. towards normal in tumor bearing mice. Metabolite show no adverse effect on liver functions regarding blood glucose, serum alkaline phosphatases, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase activity and serum billirubin, etc. in normal mice. Histopathological observation of these mice organ does not show any toxic effect on cellular structure. But in the case of EAC bearing untreated mice these hematological and biochemical parameters deteriorate extremely with time whereas petroleum ether extract bacterial metabolite receiving EAC bearing mice nullified the toxicity induced by EAC cells. Conclusion Study results reveal that metabolite possesses significant antiproliferative and hepatoprotective effect against EAC cells. PMID:25183099

Islam, Farhadul; Ghosh, Soby; Khanam, Jahan Ara

2014-01-01

156

‘Doubling down’ on the autophagy pathway to suppress tumor growth  

PubMed Central

In this issue of Genes & Development, Wei and colleagues (pp. 1204–1216) use elegant genetic approaches to simultaneously delete the essential autophagy gene FIP200 (FAK family-interacting protein of 200 kDa) and the signaling adaptor p62/SQSTM1 within established murine tumors, which reveals an unexpected synergism between the autophagy pathway and p62 in driving tumor growth. Intriguingly, these observations suggest that the combined targeting of autophagy and p62 may serve as an effective approach to treat specific cancers. PMID:24888584

Leidal, Andrew M.; Debnath, Jayanta

2014-01-01

157

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

158

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. PMID:22670223

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

2012-01-01

159

Massive ascites of unknown origin  

PubMed Central

Massive ascites of unknown origin is an uncommon condition, which represent a diagnostic challenge. Patients with delayed diagnosis and treatment may have a poor prognosis. A 22-year-old female was referred to this hospital due to a 4-year progressive abdominal distension with massive ascites of unknown origin. By thorough investigations, she was eventually diagnosed as chronic calcified constrictive pericarditis. She received pericardiectomy and had an uneventful postoperative course. With a few day paracentesis, ascites did not progress any more. She was doing well at 5-month follow-up and has returned to work. Extracardiac manifestations, such as massive ascites and liver cirrhosis, were rare in patients with constrictive pericarditis. Pericardiectomy can be a radical solution for the treatment of chronic constrictive pericarditis. In order to avoid delayed diagnosis and treatment, physicians have to bear in mind this rare manifestation of chronic calcified constrictive pericarditis. PMID:24600502

Yuan, Shi-Min

2014-01-01

160

Formal asymptotic limit of a diffuse-interface tumor-growth  

E-print Network

Formal asymptotic limit of a diffuse-interface tumor-growth model Danielle Hilhorst , Johannes-interface tumor-growth model, which has the form of a phase-field system. We discuss the singular limit perturbation, interface mo- tion, matched asymptotic expansion, tumor-growth model. 1 Introduction Diffuse

Paris-Sud XI, Université de

161

The role of mechanical forces in tumor growth and therapy.  

PubMed

Tumors generate physical forces during growth and progression. These physical forces are able to compress blood and lymphatic vessels, reducing perfusion rates and creating hypoxia. When exerted directly on cancer cells, they can increase cells' invasive and metastatic potential. Tumor vessels-while nourishing the tumor-are usually leaky and tortuous, which further decreases perfusion. Hypoperfusion and hypoxia contribute to immune evasion, promote malignant progression and metastasis, and reduce the efficacy of a number of therapies, including radiation. In parallel, vessel leakiness together with vessel compression causes a uniformly elevated interstitial fluid pressure that hinders delivery of blood-borne therapeutic agents, lowering the efficacy of chemo- and nanotherapies. In addition, shear stresses exerted by flowing blood and interstitial fluid modulate the behavior of cancer and a variety of host cells. Taming these physical forces can improve therapeutic outcomes in many cancers. PMID:25014786

Jain, Rakesh K; Martin, John D; Stylianopoulos, Triantafyllos

2014-07-11

162

3D Multi-Cell Simulation of Tumor Growth and Angiogenesis  

PubMed Central

We present a 3D multi-cell simulation of a generic simplification of vascular tumor growth which can be easily extended and adapted to describe more specific vascular tumor types and host tissues. Initially, tumor cells proliferate as they take up the oxygen which the pre-existing vasculature supplies. The tumor grows exponentially. When the oxygen level drops below a threshold, the tumor cells become hypoxic and start secreting pro-angiogenic factors. At this stage, the tumor reaches a maximum diameter characteristic of an avascular tumor spheroid. The endothelial cells in the pre-existing vasculature respond to the pro-angiogenic factors both by chemotaxing towards higher concentrations of pro-angiogenic factors and by forming new blood vessels via angiogenesis. The tumor-induced vasculature increases the growth rate of the resulting vascularized solid tumor compared to an avascular tumor, allowing the tumor to grow beyond the spheroid in these linear-growth phases. First, in the linear-spherical phase of growth, the tumor remains spherical while its volume increases. Second, in the linear-cylindrical phase of growth the tumor elongates into a cylinder. Finally, in the linear-sheet phase of growth, tumor growth accelerates as the tumor changes from cylindrical to paddle-shaped. Substantial periods during which the tumor grows slowly or not at all separate the exponential from the linear-spherical and the linear-spherical from the linear-cylindrical growth phases. In contrast to other simulations in which avascular tumors remain spherical, our simulated avascular tumors form cylinders following the blood vessels, leading to a different distribution of hypoxic cells within the tumor. Our simulations cover time periods which are long enough to produce a range of biologically reasonable complex morphologies, allowing us to study how tumor-induced angiogenesis affects the growth rate, size and morphology of simulated tumors. PMID:19834621

Shirinifard, Abbas; Gens, J. Scott; Zaitlen, Benjamin L.; Pop?awski, Nikodem J.; Swat, Maciej; Glazier, James A.

2009-01-01

163

Tumor growth and its effect on Magnetic Resonance Imaging signal  

NASA Astrophysics Data System (ADS)

The goal of this project is twofold. On one hand, we have developed computer code based on simple probabilistic rules to model the growth (or shrinking) of cancerigenous tissue. We assume that initially there exists a differentiated cell, which has a time- dependent probability of reproducing. If it did reproduce, then we assume that it has a finite probability of dying before reproducing again. This simple model falls into the Eden-type kind, and presents appropriate bulk growth characteristics, as it follows Gompert observational law. We propose new methods of geometrical characterization of the tumor. Besides its total mass, we also consider higher multipolar order of mass distribution and surface fractal dimension. In addition, we study how the geometrical properties of the tumor affect the Magnetic Resonance Imaging (MRI) signal. To this end, we consider a human brain in the presence of radiofrequency fields. We calculate the MRI image of this object. Then, we introduce a tumor in the white-gray matter region and reobtain the MRI image. We associate the signal changes with the geometrical properties of the tumor.

Cersosimo, Homero; Colon, Jorge; Ramos, Elio; Zypman, Fredy

2000-03-01

164

Genetic parameters of ascites-related traits in broilers: correlations with feed efficiency and carcase traits.  

PubMed

(1) Pulmonary hypertension syndrome followed by ascites is a metabolic disorder in broilers that occurs more often in fast-growing birds and at cool temperatures. (2) Knowledge of the genetic relationships among ascites-related traits and performance traits like carcase traits or feed efficiency traits is required to design breeding programmes that aim to improve the degree of resistance to ascites syndrome as well as production traits. The objective of this study was to estimate these genetic correlations. (3) Three different experiments were set up to measure ascites-related traits (4202 birds), feed efficiency traits (2166 birds) and carcase traits (2036 birds). The birds in different experiments originated from the same group of parents, which enabled the estimation of genetic correlations among different traits. (4) The genetic correlation of body weight (BW) measured under normal conditions and in the carcase experiment with the ascites indicator trait of right ventricle to total ventricle ratio (RV:TV) measured under cold conditions was 0.30. The estimated genetic correlation indicated that single-trait selecting for BW leads to an increase in occurrence of the ascites syndrome but that there are realistic opportunities of multi-trait selection of birds for improved BW and resistance to ascites. (5) Weak but positive genetic relationships were found between feed efficiency and ascites-related traits suggesting that more efficient birds tend to be slightly more susceptible to ascites. (6) The relatively low genetic correlation between BW measured in the carcase or in the feed efficiency experiments and BW measured in the ascites experiment (0.49) showed considerable genotype by environment interaction. (7) These results indicate that birds with high genetic potential for growth rate under normal temperature conditions have lower growth rate under cold-stress conditions due to ascites. PMID:15835251

Pakdel, A; van Arendonk, J A M; Vereijken, A L J; Bovenhuis, H

2005-02-01

165

DIFFERENCES IN RADIOSENSITIVITY AND RECOVERY FROM THE EFFECTS OF RADIATION BETWEEN TWO TYPES OF ASCITES HEPATOMA IN THE RAT  

Microsoft Academic Search

Two new types of ascites hepatoma, AH 7974 and AH 130, were derived in ; the rat and transplanted successively throughout numbers of generations. The ; former is characterized by high resistance to nitrogen mustard compounds, while ; the latter is very sensitive to these chemical agents. These tumors were ; maintained in ascites and inoculated subcutaneously on the backs

Masayama

1959-01-01

166

[Seasonal patterns of breast tumor growth in Far North residents].  

PubMed

Earlier, we established a relationship between sex hormone receptor concentration in tumor and 5-year survival, on the one hand, and seasonality, on the other. The parameters showed a distinct 6-month cycle. That pointed to certain environmental factors which could synchronize hormone-dependent tumor process in the breast of women living in the North. The present study is concerned with a relationship of 6-month rhythm of tumor growth and latitude of residence. Said rhythm was reliably identified as a parameter of 5-year survival in the Far North (68 deg. northern latitude, p < 0.001). Maximum values of 5-year survival were registered in those diagnosed with cancer in winter or summer, while those diagnosed in spring or fall had unfavorable prognosis. Northern magnetic storms recur at 6-month intervals and most frequently in spring and fall. Electromagnetic radiation is known to suppress melatonin production and, that might have stimulated tumor process. Therefore, it is most likely that solar electromagnetic radiation might synchronize hormone-dependent tumor process in women resident in the North. PMID:17037040

Borisenkov, M F; Bazhenov, S M

2005-01-01

167

The Wilms' Tumor Gene WT1 ? 17AA/? KTS Splice Variant Increases Tumorigenic Activity Through Up-Regulation of Vascular Endothelial Growth Factor in an In Vivo Ovarian Cancer Model  

PubMed Central

The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a variety of cancer-related processes. In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. To this end, we established stable ovarian cancer cell lines transduced with lentiviral constructs containing each of the four WT1 splice variants (? 17AA/? KTS, + 17AA/? KTS, ? 17AA/+ KTS, and + 17AA/+ KTS). In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 ? 17AA/? KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice inoulated with WT1 ? 17AA/? KTS-expressing cells was significantly shorter than that in mice inoculated with control cells (P = .0115). Immunoblot analysis revealed that WT1 ? 17AA/? KTS significantly increased the expression of vascular endothelial growth factor (VEGF) compared with the control. Greater numbers of CD31-immunopositive vessels were observed in tumors from mice injected with cells expressing WT1 ? 17AA/? KTS than in tumors from control mice. Finally, WT1 ? 17AA/? KTS significantly increased tumor microvessel density compared with that in the control (P < .05). Treatment with anti-VEGF antibody (bevacizumab) inhibited tumor growth, dissemination, and ascites production in mice injected with cells expressing WT1 ? 17AA/? KTS. The overexpression of WT1 ? 17AA/? KTS induced a more aggressive phenotype in ovarian cancer cells through VEGF up-regulation in an in vivo ovarian cancer model. Our findings indicated that WT1 ? 17AA/? KTS enhanced tumorigenic activity and could decreased patient survival through up-regulation of VEGF expression in ovarian cancers. PMID:25389453

Yamanouchi, Keiko; Ohta, Tsuyoshi; Liu, Zhiyang; Oji, Yusuke; Sugiyama, Haruo; Shridhar, Viji; Matsumura, Sohei; Takahashi, Toshifumi; Takahashi, Kazuhiro; Kurachi, Hirohisa

2014-01-01

168

The Wilms' Tumor Gene WT1 - 17AA/- KTS Splice Variant Increases Tumorigenic Activity Through Up-Regulation of Vascular Endothelial Growth Factor in an In Vivo Ovarian Cancer Model.  

PubMed

The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a variety of cancer-related processes. In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. To this end, we established stable ovarian cancer cell lines transduced with lentiviral constructs containing each of the four WT1 splice variants (- 17AA/- KTS, + 17AA/- KTS, - 17AA/+ KTS, and + 17AA/+ KTS). In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 - 17AA/- KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice inoulated with WT1 - 17AA/- KTS-expressing cells was significantly shorter than that in mice inoculated with control cells (P = .0115). Immunoblot analysis revealed that WT1 - 17AA/- KTS significantly increased the expression of vascular endothelial growth factor (VEGF) compared with the control. Greater numbers of CD31-immunopositive vessels were observed in tumors from mice injected with cells expressing WT1 - 17AA/- KTS than in tumors from control mice. Finally, WT1 - 17AA/- KTS significantly increased tumor microvessel density compared with that in the control (P < .05). Treatment with anti-VEGF antibody (bevacizumab) inhibited tumor growth, dissemination, and ascites production in mice injected with cells expressing WT1 - 17AA/- KTS. The overexpression of WT1 - 17AA/- KTS induced a more aggressive phenotype in ovarian cancer cells through VEGF up-regulation in an in vivo ovarian cancer model. Our findings indicated that WT1 - 17AA/- KTS enhanced tumorigenic activity and could decreased patient survival through up-regulation of VEGF expression in ovarian cancers. PMID:25389453

Yamanouchi, Keiko; Ohta, Tsuyoshi; Liu, Zhiyang; Oji, Yusuke; Sugiyama, Haruo; Shridhar, Viji; Matsumura, Sohei; Takahashi, Toshifumi; Takahashi, Kazuhiro; Kurachi, Hirohisa

2014-10-01

169

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

2010-01-01

170

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. PMID:21188120

Sebastian, Martin

2010-01-01

171

Environmental enrichment does not impact on tumor growth in mice  

PubMed Central

The effect of environmental enrichment (EE) on a variety of physiologic and disease processes has been studied in laboratory mice. During EE, a large group of mice are housed in larger cages than the standard cage and are given toys and equipment, enabling more social contact, and providing a greater surface area per mouse, and a more stimulating environment. Studies have been performed into the effect of EE on neurogenesis, brain injury, cognitive capacity, memory, learning, neuronal pathways, diseases such as Alzheimer’s, anxiety, social defeat, emotionality, depression, drug addiction, alopecia, and stereotypies. In the cancer field, three papers have reported effects on mice injected with tumors and housed in enriched environments compared with those housed in standard conditions. One paper reported a significant decrease in tumor growth in mice in EE housing. We attempted to replicate this finding in our animal facility, because the implications of repeating this finding would have profound implications for how we house all our mice in our studies on cancer. We were unable to reproduce the results in the paper in which B16F10 subcutaneous tumors of mice housed in EE conditions were smaller than those of mice housed in standard conditions. The differences in results could have been due to the different growth rate of the B16F10 cultures from the different laboratories, the microbiota of the mice housed in the two animal facilities, variations in noise and handling between the two facilities, food composition, the chemical composition of the cages or the detergents used for cleaning, or a variety of other reasons. EE alone does not appear to consistently result in decreased tumor growth, but other factors would appear to be able to counteract or inhibit the effects of EE on cancer progression. PMID:24555065

Kershaw, Michael H

2013-01-01

172

Lifespan Based Pharmacokinetic-Pharmacodynamic Model of Tumor Growth Inhibition by Anticancer Therapeutics  

PubMed Central

Accurate prediction of tumor growth is critical in modeling the effects of anti-tumor agents. Popular models of tumor growth inhibition (TGI) generally offer empirical description of tumor growth. We propose a lifespan-based tumor growth inhibition (LS TGI) model that describes tumor growth in a xenograft mouse model, on the basis of cellular lifespan T. At the end of the lifespan, cells divide, and to account for tumor burden on growth, we introduce a cell division efficiency function that is negatively affected by tumor size. The LS TGI model capability to describe dynamic growth characteristics is similar to many empirical TGI models. Our model describes anti-cancer drug effect as a dose-dependent shift of proliferating tumor cells into a non-proliferating population that die after an altered lifespan TA. Sensitivity analysis indicated that all model parameters are identifiable. The model was validated through case studies of xenograft mouse tumor growth. Data from paclitaxel mediated tumor inhibition was well described by the LS TGI model, and model parameters were estimated with high precision. A study involving a protein casein kinase 2 inhibitor, AZ968, contained tumor growth data that only exhibited linear growth kinetics. The LS TGI model accurately described the linear growth data and estimated the potency of AZ968 that was very similar to the estimate from an established TGI model. In the case study of AZD1208, a pan-Pim inhibitor, the doubling time was not estimable from the control data. By fixing the parameter to the reported in vitro value of the tumor cell doubling time, the model was still able to fit the data well and estimated the remaining parameters with high precision. We have developed a mechanistic model that describes tumor growth based on cell division and has the flexibility to describe tumor data with diverse growth kinetics. PMID:25333487

Mo, Gary; Gibbons, Frank; Schroeder, Patricia; Krzyzanski, Wojciech

2014-01-01

173

Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis  

NASA Astrophysics Data System (ADS)

Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies.

Zheng, Wenjing; Yang, Licong; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Zhou, Yunshan; Liu, Jie

2014-06-01

174

The Ruthenium Complex cis -(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines  

Microsoft Academic Search

The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl2(NH3)4]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic\\u000a activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3),\\u000a and human T cell leukemia (Jurkat) cell lines

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

2010-01-01

175

The management of ascites in cirrhosis: Report on the consensus conference of the International Ascites Club  

Microsoft Academic Search

Ascites is a common complication of cirrhosis, and heralds a new phase of hepatic decompensation in the progression of the cirrhotic process. The development of ascites carries a significant worsening of the prognosis. It is important to diagnose noncirrhotic causes of ascites such as malignancy, tuberculosis, and pancreatic ascites since these occur with increased frequency in patients with liver disease.

Kevin P. Moore; Florence Wong; Pere Gines; Mauro Bernardi; Andreas Ochs; Francesco Salerno; Paolo Angeli; Michael Porayko; Richard Moreau; Guadelupe Garcia-Tsao; Wladimiro Jimenez; Ramon Planas; Vicente Arroyo

2003-01-01

176

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells  

PubMed Central

Exogenous ribonucleases are known to inhibit tumor growth via apoptosis induction in tumor cells, allowing to consider them as promising anticancer drugs for clinical application. In this work the antitumor potential of binase was evaluated in vivo and the mechanism of cytotoxic effect of binase on tumor cells was comprehensively studied in vitro. We investigated tumoricidal activity of binase using three murine tumor models of Lewis lung carcinoma (LLC), lymphosarcoma RLS40 and melanoma B-16. We show for the first time that intraperitoneal injection of binase at a dose range 0.1–5 mg/kg results in retardation of primary tumor growth up to 45% in LLC and RLS40 and inhibits metastasis up to 50% in LLC and RLS40 and up to 70% in B-16 melanoma. Binase does not exhibit overall toxic effect and displays a general systemic and immunomodulatory effects. Treatment of RLS40-bearing animals with binase together with polychemotherapy revealed that binase decreases the hepatotoxicity of polychemotherapy while maintaining its antitumor effect. It was demonstrated that the cytotoxic effect of binase is realized via the induction of the intrinsic and extrinsic apoptotic pathways. Activation of intrinsic apoptotic pathway is manifested by a drop of mitochondrial potential, increase in calcium concentration and inhibition of respiratory activity. Subsequent synthesis of TNF-? in the cells under the action of binase triggers extrinsic apoptotic pathway through the binding of TNF with cell-death receptors and activation of caspase 8. Thus binase is a potential anticancer therapeutics inducing apoptosis in cancer cells. PMID:23759588

Mironova, Nadezhda L.; Petrushanko, Irina Y.; Patutina, Olga A.; Sen’kova, Aexandra V.; Simonenko, Olga V.; Mitkevich, Vladimir A.; Markov, Oleg V.; Zenkova, Marina A.; Makarov, Alexander A.

2013-01-01

177

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells.  

PubMed

Exogenous ribonucleases are known to inhibit tumor growth via apoptosis induction in tumor cells, allowing to consider them as promising anticancer drugs for clinical application. In this work the antitumor potential of binase was evaluated in vivo and the mechanism of cytotoxic effect of binase on tumor cells was comprehensively studied in vitro. We investigated tumoricidal activity of binase using three murine tumor models of Lewis lung carcinoma (LLC), lymphosarcoma RLS 40 and melanoma B-16. We show for the first time that intraperitoneal injection of binase at a dose range 0.1-5 mg/kg results in retardation of primary tumor growth up to 45% in LLC and RLS 40 and inhibits metastasis up to 50% in LLC and RLS 40 and up to 70% in B-16 melanoma. Binase does not exhibit overall toxic effect and displays a general systemic and immunomodulatory effects. Treatment of RLS 40-bearing animals with binase together with polychemotherapy revealed that binase decreases the hepatotoxicity of polychemotherapy while maintaining its antitumor effect. It was demonstrated that the cytotoxic effect of binase is realized via the induction of the intrinsic and extrinsic apoptotic pathways. Activation of intrinsic apoptotic pathway is manifested by a drop of mitochondrial potential, increase in calcium concentration and inhibition of respiratory activity. Subsequent synthesis of TNF-? in the cells under the action of binase triggers extrinsic apoptotic pathway through the binding of TNF with cell-death receptors and activation of caspase 8. Thus binase is a potential anticancer therapeutics inducing apoptosis in cancer cells. PMID:23759588

Mironova, Nadezhda L; Petrushanko, Irina Y; Patutina, Olga A; Sen'kova, Aexandra V; Simonenko, Olga V; Mitkevich, Vladimir A; Markov, Oleg V; Zenkova, Marina A; Makarov, Alexander A

2013-07-01

178

Interferon-? and celecoxib inhibit lung-tumor growth through modulating M2/M1 macrophage ratio in the tumor microenvironment  

PubMed Central

Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFN? and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFN? alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFN? alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFN? and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFN? and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFN? and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFN? and celecoxib have potential to be further optimized into a new anticancer therapy. PMID:25284985

Ren, Fuqiang; Fan, Mingyu; Mei, Jiandong; Wu, Yongqiang; Liu, Chengwu; Pu, Qiang; You, Zongbing; Liu, Lunxu

2014-01-01

179

Antivascular Endothelial Growth Factor Receptor (Fetal Liver Kinase 1) Monoclonal Antibody Inhibits Tumor Angiogenesis and Growth of Several Mouse and Human Tumors  

Microsoft Academic Search

Tumor angiogenesis is mediated by tumor-secreted angiogenic growth factors that interact with their surface receptors expressed on endothelial cells. Vascular endothelial growth factor (VEGF) and its receptor (fetal liver kinase 1 (Flk-1)\\/kinase insert domain-containing receptor) play an important role in vascular permeability and tumor angiogenesis. Previ- ously, we reported on the development of anti-Flk-1 and antikinase insert domain-containing receptor monoclonal

Marie Prewett; James Huber; Yiwen Li; Angel Santiago; William O'Connor; Karen King; Jay Overholser; Andrea Hooper; Bronislaw Pytowski; Larry Witte; Peter Bohlen; Daniel J. Hicklin

1999-01-01

180

Phenomenological modeling of tumor diameter growth based on a mixed effects  

E-print Network

Phenomenological modeling of tumor diameter growth based on a mixed effects model T. Bastogne a,, A tumor volume-based models have been devel- oped for the phenomenological modeling of tumor growth-00390380,version1-2Jun2009 #12;1 Introduction In systems theory1,2 , phenomenological or black-box models

Boyer, Edmond

181

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

182

An infant with biliary ascites.  

PubMed

Biliary ascites in children due to perforation of bile duct is a rare entity. The exact pathogenesis is not known but there are proposed mechanisms including congenital weakness of ductal wall, pancreaticobiliary malunion, tuberculosis, necrotizing enterocolitis and rupture of choledochal cyst. Presentation may be acute or sub-acute. Progressive insidious course is the common presentation in children with jaundice, clay colored stool, abdominal distension with slightly elevated liver enzymes but well documented cholestasis. Clinical suspicion with ultrasound, CT, MRCP and ascitic tap provides clue to the diagnosis. Both conservative and surgical interventions are in practice for managing these children. We report a 7 months old infant with biliary ascites due to perforation of bile duct. PMID:25518792

Saeed, Anjum; Mouzan, Mohammed El; Assiri, Asaad; Alsarkhy, Ahmed; Majeed, Kashif

2014-11-01

183

Association between weight gain, blood parameters, and thyroid hormones and the development of ascites syndrome in broiler chickens.  

PubMed

The present study examined the association between thyroid hormones and the development of ascites on one hand and the ability to predict ascites from growth rate and hematocrit on the other hand. Ascites syndrome was induced in broiler chickens in two trials by exposing the chicks to low ambient temperature (Ta) and by supplying a pellet form of diet. Weight gain, hematocrit, hemoglobin, and plasma thyroxin (T4) and triiodothyronine (T3) concentrations were measured weekly for each bird, and comparisons were made between birds that eventually died from ascites and those that did not. Mortality from ascites amounted to 24.3 and 24.2% in Trials 1 and 2, respectively. Weight gain did not differ between ascitic and healthy chickens up to approximately 2 wk before death but was significantly lower in the ascitic broilers 1 to 2 wk before death. Hematocrit was significantly higher in broilers with ascites with the exception of ascitic broilers that died at the age of 7 wk (Trial 1). In ascitic broilers, T4 and T3 concentrations declined significantly during the week of death. The present findings raise the question of whether the association between low levels of thyroid hormones and the development of ascites is one of the physiological responses in the syndrome cascade, or whether the failure to maintain thyroid hormones concentration is one of the triggers of the syndrome initiation. This question requires further investigation. It can be concluded that a high rate of weight gain is not always a good predictor of ascites development. Hematocrit and thyroid hormones can provide a good indication but only during the last week of life, and not in all cases. None of these parameters, however, can predict the development of ascites at an early age. PMID:11469663

Luger, D; Shinder, D; Rzepakovsky, V; Rusal, M; Yahav, S

2001-07-01

184

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 PMID:2478587

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

185

Extracellular Matrix Metalloproteinase Inducer Stimulates Tumor Angiogenesis by Elevating Vascular Endothelial Cell Growth Factor and Matrix Metalloproteinases  

Microsoft Academic Search

Matrix metalloproteinases (MMPs) are endopeptidases that play pivotal roles in promoting tumor disease progression, including tumor angiogenesis. In many solid tumors, MMP expression could be attributed to tumor stromal cells and is partially regulated by tumor-stroma interactions via tumor cell-associated extracellular matrix metalloproteinase in- ducer (EMMPRIN). The role of EMMPRIN during tumor angiogenesis and growth was explored by modulating EMMPRIN

Yi Tang; Marian T. Nakada; Prabakaran Kesavan; Francis McCabe; Hillary Millar; Patricia Rafferty; Peter Bugelski

2005-01-01

186

Radiotherapy planning for glioblastoma based on a tumor growth model: Improving target volume delineation  

E-print Network

Glioblastoma are known to infiltrate the brain parenchyma instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In clinical practice, a uniform margin is applied to account for microscopic spread of disease. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth: Anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain...

Unkelbach, Jan; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A

2013-01-01

187

Nicotinic Acetylcholine Receptor Signaling in Tumor Growth and Metastasis  

PubMed Central

Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer. PMID:21541211

Singh, Sandeep; Pillai, Smitha; Chellappan, Srikumar

2011-01-01

188

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

189

Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth.  

PubMed

In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on "reprogramming" of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression. PMID:21900753

Zhu, Wei; Huang, Ling; Li, Yahong; Qian, Hui; Shan, Xiuhong; Yan, Yongmin; Mao, Fei; Wu, Xiaosheng; Xu, Wen-Rong

2011-09-15

190

Pharmacokinetics, micro-SPECT\\/CT imaging and therapeutic efficacy of 188Re-DXR-liposome in C26 colon carcinoma ascites mice model  

Microsoft Academic Search

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated 188Re-N,N-bis(2-mercaptoethyl)-N?,N?-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (188Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality 188Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h

Liang-Cheng Chen; Chih-Hsien Chang; Chia-Yu Yu; Ya-Jen Chang; Yu-Hsien Wu; Wan-Chi Lee; Chung-Hsin Yeh; Te-Wei Lee; Gann Ting

2008-01-01

191

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

192

Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor-superantigen conjugate  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We construct and purify a fusion protein VEGF-SEA. Black-Right-Pointing-Pointer VEGF-SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. Black-Right-Pointing-Pointer T cells driven by VEGF-SEA were accumulated around tumor cells bearing VEGFR by mice image model. Black-Right-Pointing-Pointer VEGF-SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. Black-Right-Pointing-Pointer The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF-SEA treated with 15 {mu}g, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4{sup +} and CD8{sup +} T cells driven by VEGF-SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF-SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers.

Sun, Qingwen [Shanghai Chest Hospital, Shanghai 200433 (China) [Shanghai Chest Hospital, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Jiang, Songmin [State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China)] [State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Han, Baohui [Shanghai Chest Hospital, Shanghai 200433 (China)] [Shanghai Chest Hospital, Shanghai 200433 (China); Sun, Tongwen [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China)] [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China); Li, Zhengnan; Zhao, Lina; Gao, Qiang [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)] [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Sun, Jialin, E-mail: jialin_sun@126.com [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China)] [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China)

2012-11-02

193

Ascites in poultry: recent investigations.  

PubMed

In recent years, ascites research has centred on gaining an increased understanding of pulmonary hypertension syndrome together with the potential role of primary cardiac pathologies. The impact at a cellular level of factors which trigger ascites and substances that protect against it has also been documented. Primary pulmonary hypertension has been induced when birds are exposed to hypoxia during incubation. The conditions experienced during this phase of development may impact on the ability of the bird to regulate its basal metabolic rate through endocrine signals controlled by thyroid activity. The extent of ventilation in the lung influences the ability of the bird to oxygenate haemoglobin. Ventilation/ perfusion mismatches may occur prior to or post-hatching. This factor has been studied extensively using the pulmonary artery/bronchus clamp model. At high altitude, a decreased ventilation/perfusion ratio may occur following the effective increase in physiological dead space due to the lowered oxygen tension at the level of the parabronchi. This explains the mechanism by which ascites is triggered by hypoxia in this particular situation. The effects of ascites are ameliorated by the use of beta agonists and dietary arginine, which act by increasing ventilation and blood flow in the lungs and thus correcting a ventilation/perfusion mismatch. Transient bacterial and viral infections may also influence the induction of pulmonary hypertension. The increases in blood viscosity associated with ascites are most probably a consequence of the condition rather than a cause. A bird may alleviate the effects of pulmonary hypertension by decreasing blood viscosity through inhibition of platelet function, increased erythrocyte deformability and the production of coronary relaxants. Evidence is accumulating that primary cardiac pathology may be associated with a number of ascites cases. Broilers that subsequently develop ascites, exhibit lower heart rates than their normal flock mates. Furthermore, during ascites, hypoxic broilers exhibit bradycardia as opposed to the expected tachycardia. In these cases, a tachycardia induced by feed restriction may protect the bird by raising its cardiac output. Right atrio-ventricular regurgitant flow velocities in chickens are relatively slow compared with similar regurgitant flows induced by pulmonary hypertension in other species. The conduction system in the avian heart is specialized and contains a recurrent bundle branch that innervates the right atrio-ventricular valve, thus initiating active valve closure before right ventricular systole. This predisposes the heart to right ventricular volume overload through a valvular incompetance following a failure of valvular innervation. The resultant elevated diastolic wall stress can trigger the production of angiotensin II and its converting enzyme, which mediate ventricular hypertrophy. Subclinical myocardial damage, irrespective of its cause, can be detected by the presence of troponin T in the blood. Reactive oxygen species may damage cell membranes compromising cellular function in a number of body systems. A positive correlation exists between oxidized glutathione concentrations and right ventricular weight ratio. This indicates a failure to cope with oxidative stress at the level of the respiratory membrane. It is not known if it is possible to modulate levels of antioxidants at this location and hence protect the bird. The final description of the ascites aetiology may lie in the concept of a circuit of events between the cardiac, pulmonary and vascular systems that satisfy the metabolic requirements of the bird. A deficit in one of these systems, at a level that prevents adequate compensation from other components, triggers the pathological cascade that results in the end point of clinical ascites. PMID:16147559

Currie, R J

1999-08-01

194

Acetyl11Keto -Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis  

Microsoft Academic Search

The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-B-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor

Xiufeng Pang; Zhengfang Yi; Xiaoli Zhang; Bokyung Sung; Weijing Qu; Xiaoyuan Lian; Bharat B. Aggarwal; M. Liu

2009-01-01

195

Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth  

PubMed Central

Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anti-cancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study we identified an interaction between Gli proteins and a transcription co-activator TAF9, and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and down-regulate Gli/TAF9 dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, a key control point of multiple oncogenic pathways, may be an effective anti-cancer strategy. PMID:23686308

Bosco-Clément, Genevičve; Zhang, Fang; Chen, Zhao; Zhou, Hai-Meng; Li, Hui; Mikami, Iwao; Hirata, Tomomi; Yagui-Beltran, Adam; Lui, Natalie; Do, Hanh T.; Cheng, Tiffany; Tseng, Hsin-Hui; Choi, Helen; Fang, Li-Tai; Kim, Il-Jin; Yue, Dongsheng; Wang, Changli; Zheng, Qingfeng; Fujii, Naoaki; Mann, Michael; Jablons, David M.; He, Biao

2014-01-01

196

Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth  

PubMed Central

One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion. PMID:24121491

Wegiel, Barbara; Gallo, David; Csizmadia, Eva; Harris, Clair; Belcher, John; Vercellotti, Gregory M.; Penacho, Nuno; Seth, Pankaj; Sukhatme, Vikas; Ahmed, Asif; Pandolfi, Pier Paolo; Helczynski, Leszek; Bjartell, Anders; Persson, Jenny Liao; Otterbein, Leo E

2013-01-01

197

Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma.  

PubMed

Caveolin-1 (Cav-1) can ambiguously behave as either tumor suppressor or oncogene depending on its phosphorylation state and the type of cancer. In this study we show that Cav-1 was phosphorylated on tyrosine 14 (pCav-1) by Src-kinase family members in various human cell lines and primary mouse cultures of rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma affecting childhood. Cav-1 overexpression in the human embryonal RD or alveolar RH30 cells yielded increased pCav-1 levels and reinforced the phosphorylation state of either ERK or AKT kinase, respectively, in turn enhancing in vitro cell proliferation, migration, invasiveness and chemoresistance. In contrast, reducing the pCav-1 levels by administration of a Src-kinase inhibitor or through targeted Cav-1 silencing counteracted the malignant in vitro phenotype of RMS cells. Consistent with these results, xenotransplantation of Cav-1 overexpressing RD cells into nude mice resulted in substantial tumor growth in comparison to control cells. Taken together, these data point to pCav-1 as an important and therapeutically valuable target for overcoming the progression and multidrug resistance of RMS. PMID:24427291

Faggi, Fiorella; Mitola, Stefania; Sorci, Guglielmo; Riuzzi, Francesca; Donato, Rosario; Codenotti, Silvia; Poliani, Pietro Luigi; Cominelli, Manuela; Vescovi, Raffaella; Rossi, Stefania; Calza, Stefano; Colombi, Marina; Penna, Fabio; Costelli, Paola; Perini, Ilaria; Sampaolesi, Maurilio; Monti, Eugenio; Fanzani, Alessandro

2014-01-01

198

Sanguinarine Suppresses Prostate Tumor Growth and Inhibits Survivin Expression  

PubMed Central

Prostate cancer is a frequently occurring disease and is the second leading cause of cancer-related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer, and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis, and short patient survival. In the present study, the authors performed a cell-based rapid screen of the Prestwick Chemical Library consisting of 1120 Food and Drug Administration–approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anticancer agents for prostate cancer. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over “normal” prostate epithelial cells. The authors found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits growth of human prostate cancer cells and in vivo tumor formation. Administration of sanguinarine, beginning 3 days after ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume. In addition, sanguinarine sensitized paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of prostate cancer overexpressing survivin. PMID:21318089

Sun, Meng; Lou, Wei; Chun, Jae Yeon; Cho, Daniel S.; Nadiminty, Nagalakshmi; Evans, Christopher P.; Chen, Jun; Yue, Jiao; Zhou, Qinghua; Gao, Allen C.

2010-01-01

199

Sanguinarine suppresses prostate tumor growth and inhibits survivin expression.  

PubMed

Prostate cancer is a frequently occurring disease and is the second leading cause of cancer-related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer, and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis, and short patient survival. In the present study, the authors performed a cell-based rapid screen of the Prestwick Chemical Library consisting of 1120 Food and Drug Administration-approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anticancer agents for prostate cancer. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over "normal" prostate epithelial cells. The authors found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits growth of human prostate cancer cells and in vivo tumor formation. Administration of sanguinarine, beginning 3 days after ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume. In addition, sanguinarine sensitized paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of prostate cancer overexpressing survivin. PMID:21318089

Sun, Meng; Lou, Wei; Chun, Jae Yeon; Cho, Daniel S; Nadiminty, Nagalakshmi; Evans, Christopher P; Chen, Jun; Yue, Jiao; Zhou, Qinghua; Gao, Allen C

2010-03-01

200

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

201

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

202

Vascular-promoting therapy reduced tumor growth and progression by improving chemotherapy efficacy.  

PubMed

In this issue of Cancer Cell, Wong and colleagues describe a novel approach of increasing the number of functional blood vessels in tumors using a low-dose therapy regimen of Cilengtide and Verapamil. This method enhanced Gemcitabine delivery, uptake, and metabolism within tumor cells to reduce tumor growth and progression. PMID:25584889

Bridges, Esther; Harris, Adrian L

2015-01-12

203

DNA Metabolism in Liver and Kidney Tumors of Different Growth Rates1  

Microsoft Academic Search

SUMMARY The incorporation of 14C-labeled thymidine into DNA was studied in liver and kidney tumors of different growth rates. Low incorporation was observed for the normal kidney cortex whereas greatly increased rates were found even in the very slowly growing 8997-K renal cortical tumor. The largest in corporation was observed in the most rapidly growing of the kidney tumors examined,

Michael A. Lea; Harold P. Morris; George Weber

204

The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics  

PubMed Central

Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1–RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression. PMID:23318458

Kang, R; Tang, D; Schapiro, NE; Loux, T; Livesey, KM; Billiar, TR; Wang, H; Van Houten, B; Lotze, MT; Zeh, HJ

2013-01-01

205

Differential feeding patterns induced by tumor growth and by TPN  

Microsoft Academic Search

The effects of anorexia induced by early tumor, and anorexia induced by total parenteral nutrition (TPN) on food intake and the indexes of food intake, were investigated in rats infused with saline after jugular catheter placement and concomitant inoculation with methylcholanthrene (MCA)-induced tumor cells on day 0, and in rats without catheters receiving tumor only. Tumor became palpable around day

Michael M Meguid; Zhong-Jin Yang; John R Gleason; Akio Kubota

1999-01-01

206

Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis  

PubMed Central

Prostaglandins derived from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis. COX-2 inhibitors, which block the formation of prostaglandins, suppress tumor growth, whereas sEH inhibitors, which increase endogenous EETs, stimulate primary tumor growth and metastasis. However, the functional interactions of these two pathways in cancer are unknown. Using pharmacological inhibitors as probes, we show here that dual inhibition of COX-2 and sEH synergistically inhibits primary tumor growth and metastasis by suppressing tumor angiogenesis. COX-2/sEH dual pharmacological inhibitors also potently suppress primary tumor growth and metastasis by inhibiting tumor angiogenesis via selective inhibition of endothelial cell proliferation. These results demonstrate a critical interaction of these two lipid metabolism pathways on tumorigenesis and suggest dual inhibition of COX-2 and sEH as a potential therapeutic strategy for cancer therapy. PMID:25024195

Zhang, Guodong; Panigrahy, Dipak; Hwang, Sung Hee; Yang, Jun; Mahakian, Lisa M.; Wettersten, Hiromi I.; Liu, Jun-Yan; Wang, Yanru; Ingham, Elizabeth S.; Tam, Sarah; Kieran, Mark W.; Weiss, Robert H.; Ferrara, Katherine W.; Hammock, Bruce D.

2014-01-01

207

Cirrhotic ascites review: Pathophysiology, diagnosis and management  

PubMed Central

Ascites is a pathologic accumulation of peritoneal fluidcommonly observed in decompensated cirrhotic states.Its causes are multi-factorial, but principally involve significant volume and hormonal dysregulation in the setting of portal hypertension. The diagnosis of ascites is considered in cirrhotic patients given a constellation of clinical and laboratory findings, and ultimately confirmed, with insight into etiology, by imaging and paracentesis procedures. Treatment for ascites is multi-modal including dietary sodium restriction, pharmacologic therapies, diagnostic and therapeutic paracentesis, and in certain cases transjugular intra-hepatic portosystemic shunt. Ascites is associated with numerous complications including spontaneous bacterial peritonitis, hepato-hydrothorax and hepatorenal syndrome. Given the complex nature of ascites and associatedcomplications, it is not surprising that it heralds increased morbidity and mortality in cirrhotic patients and increased cost-utilization upon the health-care system. This review will detail the pathophysiology of cirrhotic ascites, common complications derived from it, and pertinent treatment modalities. PMID:23717736

Moore, Christopher M; Van Thiel, David H

2013-01-01

208

The clinical effects of dendritic cell vaccines combined with cytokine-induced killer cells intraperitoneal injected on patients with malignant ascites  

PubMed Central

Malignant ascites (MA) is a pathological condition due to a variety of primary abdominal and extra-abdominal neoplasms. It is a primary cause of morbidity and presents many difficulties in evaluation and treatment. In this study we used dendritic cell vaccines combined with cytokine-induced killer (CIK) cells intraperitoneal injected in patients with MA, and evaluated the safety and efficacy of this treatment. The results showed that the percentage of CD3+ CD56+ CIK cells after treatment increased significantly while the percentage of CD4+ CD25+ Treg cells decreased (P < 0.05). The clinical response rate (RR) was 40.9% and disease control rate (DCR) was 77.3%. We then studied and identified the mechanisms of the anti-tumor effects of the vaccines by analyzing a series of cytokines that are commonly involved in tumor progression and ascitic development including granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-10 (IL-10), interferon-? (IFN-?), tumor necrosis factor-? (TGF-?), tumor necrosis factor-? (TGF-?), Vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). These data demonstrated that intraperitoneal injection with DC vaccines combined with CIK cells in patients with malignant peritoneal effusion is safe and feasible. This therapy modality can achieve a certain clinical benefit even in patients resistant to conventional treatments.

Ai, Yue-Qin; Cai, Kai; Hu, Jian-Hua; Jiang, Long-Wei; Gao, Yan-Rong; Zhao, Hua; Jia, Shao-Chang

2014-01-01

209

CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression  

PubMed Central

Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (?18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P<0.0002) and decreased survival probability (P=0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P<0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB. PMID:21252912

Liu, Z; Yang, X; Li, Z; McMahon, C; Sizer, C; Barenboim-Stapleton, L; Bliskovsky, V; Mock, B; Ried, T; London, W B; Maris, J; Khan, J; Thiele, C J

2011-01-01

210

In vitro and in vivo evaluation of anisomycin against Ehrlich ascites carcinoma.  

PubMed

Anisomycin eminently inhibits cell proliferation in vitro. The aim of this study was to explore the potential of anisomycin to treat tumors in vivo and its mechanism(s) of action. The results showed that peritumoral administration of anisomycin significantly suppressed Ehrlich ascites carcinoma (EAC) growth resulting in the survival of approximately 60% of the mice 90 days after EAC inoculation. Enhancement of infiltrating lymphocytes was noted in the tumor tissue, which was dramatically superior to adriamycin. The growth inhibitory rate of EAC cells was enhanced with increasing concentrations of anisomycin, following an enhanced apoptotic rate. The total apoptotic rate induced by 160 ng/ml of anisomycin was higher when compared to that induced by 500 ng/ml of adriamycin. DNA breakage and nanostructure changes were also noted in the EAC cells. The levels of caspase-3 mRNA, caspase-3 and cleaved-caspase-3 proteins in the anisomycin?treated EAC cells were augmented in a dose- and time-dependent manner, following the activation of caspase-8 and caspase-9, which finally triggered PARP cleavage. The cleaved-caspase-3, cleaved-caspase-8 and cleaved-caspase-9 proteins were mainly localized in the nuclei of the cells. These results indicate that anisomycin efficaciously represses in vitro and in vivo growth of EAC cells through caspase signaling, significantly superior to the effects of adriamycin. This suggests the potential of anisomycin for the treatment of breast cancer. PMID:23525555

You, Pengtao; Xing, Feiyue; Huo, Jie; Wang, Baoyu; Di, Jingfang; Zeng, Shan; Liu, Jing

2013-06-01

211

PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth  

SciTech Connect

Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-(1-11C)tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-(1-11C)tyrosine uptake data were compared to uptake data of L-(1-14C)tyrosine and with data on the incorporation of L-(1-14C)tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-(1-14C)tyrosine into tumor proteins tallied with the L-(1-11C)tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-(1-11C)tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth.

Daemen, B.J.; Elsinga, P.H.; Mooibroek, J.; Paans, A.M.; Wieringa, A.R.; Konings, A.W.; Vaalburg, W. (University Hospital, Groningen (Netherlands))

1991-08-01

212

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

2011-11-01

213

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.

214

Key Molecule Reprograms Microenvironment to Support Tumor Growth | Physical Sciences in Oncology  

Cancer.gov

A team of investigators from the Ohio State University Comprehensive Cancer Center has identified two key molecules that cause normal cells in the tissue surrounding a tumor, the stroma, to produce nutrients that fuel tumor growth. The results of this study, which were published in the journal Nature Cell Biology, demonstrate what happens when normal cells called fibroblasts in mouse mammary tumors lose an important tumor-suppressor gene called Pten.

215

Dysregulation of CXCL9 and reduced tumor growth in Egr-1 deficient mice  

PubMed Central

Background Early growth response-1 (Egr-1) is an immediate-early transcription factor inducible in the vasculature in response to injury, shear stress, and other stimuli. Mice lacking Egr-1 have a profound deficit in the ability to recover from femoral artery ligation, suggesting a role in neovascularization. Previous studies have shown that manipulating Egr-1 expression can have either positive or negative effects on tumor growth. We hypothesized that Egr-1 knockout mice might exhibit reduced tumor growth, possibly due to a reduced capacity to respond to angiogenic signals from a growing tumor. Results We injected 106 Lewis lung carcinoma (LLC1) cells subcutaneously in the flank of wild type and Egr-1 knockout mice. The average mass of tumors from wild type mice at 12 days after implantation was 413 +/- 128 mg, while those from Egr-1-/- mice was 219 +/- 81 mg (p = 0.001, mean +/- SD). However, sectioning the tumors and staining with anti-CD31 antibodies revealed no difference in the vascularity of the tumors and there was no difference in angiogenic growth factor expression. Expression of the chemokine Mig (CXCL9) was increased 2.8-fold in tumors from knockout mice, but no increase was found in serum levels of Mig. Natural killer cells have a 1.7-fold greater prevalence in the CD45+ cells found in tumors from Egr-1-/- mice compared to those from wild type mice. Immunohistochemical staining suggests that Mig expression in the tumors comes from invading macrophages. Conclusion Mice deficient in Egr-1 exhibit reduced growth of LLC1 tumors, and this phenomenon is associated with overexpression of Mig locally within the tumor. There are no obvious differences in tumor vascularity in the knockout mice. Natural killer cells accumulate in the tumors grown in Egr-1-/- mice, providing a potential mechanism for the reduction in growth. PMID:19200397

Caso, Giuseppe; Barry, Catherine; Patejunas, Gerald

2009-01-01

216

Genotype-by-Environment Interaction with Broiler Genotypes Differing in Growth Rate. 4. Association Between Responses to Heat Stress and to Cold-Induced Ascites  

Microsoft Academic Search

Males and females, selected from a com- mercial line to represent its phenotypic variation for BW, were mated with similarly ranked mates to produce sire families representing a wide genetic variation in potential growth rate (GR). Following 5 wk of rearing at normal ambient temperatures, birds representing all sire families were exposed to cold (Days 37 to 47, Trial 1)

N. Deeb; A. Shlosberg; A. Cahaner

217

p62/SQSTM1 synergizes with autophagy for tumor growth in vivo.  

PubMed

Autophagy is crucial for cellular homeostasis and plays important roles in tumorigenesis. FIP200 (FAK family-interacting protein of 200 kDa) is an essential autophagy gene required for autophagy induction, functioning in the ULK1-ATG13-FIP200 complex. Our previous studies showed that conditional knockout of FIP200 significantly suppressed mammary tumorigenesis, which was accompanied by accumulation of p62 in tumor cells. However, it is not clear whether FIP200 is also required for maintaining tumor growth and how the increased p62 level affects the growth in autophagy-deficient FIP200-null tumors in vivo. Here, we describe a new system to delete FIP200 in transformed mouse embryonic fibroblasts as well as mammary tumor cells following their transplantation and show that ablation of FIP200 significantly reduced growth of established tumors in vivo. Using similar strategies, we further showed that either p62 knockdown or p62 deficiency in established FIP200-null tumors dramatically impaired tumor growth. The stimulation of tumor growth by p62 accumulation in FIP200-null tumors is associated with the up-regulated activation of the NF-?B pathway by p62. Last, we showed that overexpression of the autophagy master regulator TFEB(S142A) increased the growth of established tumors, which correlated with the increased autophagy of the tumor cells. Together, our studies demonstrate that p62 and autophagy synergize to promote tumor growth, suggesting that inhibition of both pathways could be more effective than targeting either alone for cancer therapy. PMID:24888590

Wei, Huijun; Wang, Chenran; Croce, Carlo M; Guan, Jun-Lin

2014-06-01

218

p62/SQSTM1 synergizes with autophagy for tumor growth in vivo  

PubMed Central

Autophagy is crucial for cellular homeostasis and plays important roles in tumorigenesis. FIP200 (FAK family-interacting protein of 200 kDa) is an essential autophagy gene required for autophagy induction, functioning in the ULK1–ATG13–FIP200 complex. Our previous studies showed that conditional knockout of FIP200 significantly suppressed mammary tumorigenesis, which was accompanied by accumulation of p62 in tumor cells. However, it is not clear whether FIP200 is also required for maintaining tumor growth and how the increased p62 level affects the growth in autophagy-deficient FIP200-null tumors in vivo. Here, we describe a new system to delete FIP200 in transformed mouse embryonic fibroblasts as well as mammary tumor cells following their transplantation and show that ablation of FIP200 significantly reduced growth of established tumors in vivo. Using similar strategies, we further showed that either p62 knockdown or p62 deficiency in established FIP200-null tumors dramatically impaired tumor growth. The stimulation of tumor growth by p62 accumulation in FIP200-null tumors is associated with the up-regulated activation of the NF-?B pathway by p62. Last, we showed that overexpression of the autophagy master regulator TFEBS142A increased the growth of established tumors, which correlated with the increased autophagy of the tumor cells. Together, our studies demonstrate that p62 and autophagy synergize to promote tumor growth, suggesting that inhibition of both pathways could be more effective than targeting either alone for cancer therapy. PMID:24888590

Wei, Huijun; Wang, Chenran; Croce, Carlo M.; Guan, Jun-Lin

2014-01-01

219

Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer  

PubMed Central

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. Materials and methods The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE2 and celecoxib levels were determined. Results CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 ?g/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 ?g/ml were needed to affect tumor cell viability. Conclusion These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth. PMID:18247029

de Heer, Pieter; Sandel, Maro H.; Guertens, Gunther; de Boeck, Gert; Koudijs, Margaretha M.; Nagelkerke, J. Fred; Junggeburt, Jan M. C.; de Bruijn, Ernst A.; van de Velde, Cornelis J. H.

2008-01-01

220

Role of IL13 in regulation of anti-tumor immunity and tumor growth  

Microsoft Academic Search

Major mediators of anti-tumor immunity are CD4 + T h1 cells and CD8 + cytotoxic T lymphocytes (CTLs). In tumor-bearing animals, the T h1- and CTL-mediated anti-tumor immunity is down-regulated in multiple ways. Better understanding of negative regulatory pathways of tumor immunity is crucial for the development of anti-tumor vaccines and immunotherapies. Since immune deviation toward T h2 suppresses T

Masaki Terabe; Jay A. Berzofsky

2004-01-01

221

Clinically relevant doses of candesartan inhibit growth of prostate tumor xenografts in vivo through modulation of tumor angiogenesis.  

PubMed

Angiotensin II receptor type 1 blockers (ARBs), widely used antihypertensive drugs, have also been investigated for their anticancer effects. The effect of ARBs on prostate cancer in experimental models compared with meta-analysis data from clinical trials is conflicting. Whereas this discrepancy might be due to the use of supratherapeutic doses of ARBs in cellular and animal models as compared with the clinical doses used in human trials, further investigation of the effects of clinical doses of ARBs on prostate cancer in experimental models is warranted. In the current study, we sought to determine the effects of candesartan on prostate cancer cellular function in vitro and tumor growth in vivo, and characterize the underlying mechanisms. Our analysis indicated that clinically relevant doses of candesartan significantly inhibited growth of PC3 cell tumor xenografts in mice. Interestingly, the same concentrations of candesartan actually promoted prostate cancer cellular function in vitro, through a modest but significant inhibition in apoptosis. Inhibition of tumor growth by candesartan was associated with a decrease in vascular endothelial growth factor (VEGF) expression in tumors and inhibition of tumor angiogenesis, but normalization of tumor vasculature. Although candesartan did not impair PC3 cell viability, it inhibited endothelial-barrier disruption by tumor-derived factors. Furthermore, candesartan significantly inhibited expression of VEGF in PC3 and DU145 cell lines independent of angiotensin II type 2 receptor, but potentially via angiotensin II type 1 receptor inhibition. Our findings clearly demonstrate the therapeutic potential of candesartan for prostate cancer and establish a link between ARBs, VEGF expression, and prostate tumor angiogenesis. PMID:24990940

Alhusban, Ahmed; Al-Azayzih, Ahmad; Goc, Anna; Gao, Fei; Fagan, Susan C; Somanath, Payaningal R

2014-09-01

222

Sca1-positive murine pituitary adenoma cells show tumor growth advantage  

PubMed Central

The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. We investigated whether cells within pituitary adenomas that spontaneously develop in Rb+/? mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with EGF and bFGF. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1+ cell population that showed increased sphere formation potential, lower hormone mRNA expression, higher expression of stem cell markers (Notch1, Sox2, Nestin), and increased proliferation rates. When transplanted into NOD scid gamma mice brains, Sca1+ pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 [100%] vs. 7/12 [54%] of mice transplanted with Sca1+ and Sca1? cells, respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that those derived from Sca1+ pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1+ cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells. PMID:24481638

Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar; Svendsen, Clive; Melmed, Shlomo

2014-01-01

223

Tumor Growth Modeling from the Perspective of Multiphase Porous Media Mechanics  

PubMed Central

Multiphase porous media mechanics is used for modeling tumor growth, using governing equations obtained via the Thermodynamically Constrained Averaging Theory (TCAT). This approach incorporates the interaction of more phases than legacy tumor growth models. The tumor is treated as a multiphase system composed of an extracellular matrix, tumor cells which may become necrotic depending on the nutrient level and the pressure, healthy cells and an interstitial fluid which transports nutrients. The governing equations are numerically solved within a Finite Element framework for predicting the growth rate of the tumor mass, and of its individual components, as a function of the initial tumor-to-healthy cell density ratio, nutrient concentration, and mechanical strain. Preliminary results are shown. PMID:23285734

Sciumč, G.; Shelton, S.E.; Gray, W.G.; Miller, C.T.; Hussain, F.; Ferrari, M.; Decuzzi, P.; Schrefler, B.A.

2013-01-01

224

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

2013-11-01

225

Echocardiographic characteristics of chickens with ascites syndrome.  

PubMed

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

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

2006-12-01

226

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

227

p53 status in stromal fibroblasts modulates tumor growth in an SDF1-dependent manner  

PubMed Central

The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell non-autonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell non-autonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor-stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development. PMID:20952507

Addadi, Yoseph; Moskovits, Neta; Granot, Dorit; Lozano, Guillermina; Carmi, Yaron; Apte, Ron N.; Neeman, Michal; Oren, Moshe

2010-01-01

228

Neutrophils but not eosinophils are involved in growth suppression of IL-4-secreting tumors.  

PubMed

Local expression of IL-4 by gene-modified tumor cells increases their immunogenicity by inducing an inflammatory response that is dominated by eosinophils. Eosinophils have been implicated as antitumor effector cells because the application of a granulocyte-depleting Ab inhibited rejection of IL-4 transfected tumors. This Ab did not discriminate between eosinophils and neutrophils and, therefore, this experiment could not exclude neutrophils as primary effector cells, whereas eosinophils were innocent bystander cells in IL-4 transfected tumors. We analyzed tumor growth suppression and granulocyte infiltration in IL-5-deficient (IL-5(-/-)) mice that had a deficiency of eosinophils, using two tumor lines (B16-F10 and MCA205) transfected to secrete IL-4. IL-4-expressing tumors were at least as efficiently rejected in IL-5(-/-) mice as in wild-type mice, despite an almost complete absence of tumor-infiltrating eosinophils. However, neutrophils were present in undiminished amounts and their depletion partially restored tumor growth. Furthermore, the growth of IL-5-secreting tumors was not impaired in either wild-type or IL-5(-/-) mice, even though it induced eosinophilia in both mouse strains. These findings demonstrate that eosinophils can be induced in IL-5(-/-) mice by exogenous IL-5 and argue against a compensatory effect of neutrophils in the absence of eosinophils. We conclude that 1) infiltration of IL-4 transfected tumors by eosinophils is completely IL-5 dependent, 2) eosinophils have no tumoricidal activity, and 3) neutrophils are responsible, at least in part, for tumor suppression. PMID:9551990

Noffz, G; Qin, Z; Kopf, M; Blankenstein, T

1998-01-01

229

Sca1? murine pituitary adenoma cells show tumor-growth advantage.  

PubMed

The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. In this study, we investigated whether the cells within pituitary adenomas that spontaneously develop in Rb+/- mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, and CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1(+) cell population that showed increased sphere formation potential, lower mRNA hormone expression, higher expression of stem cell markers (Notch1, Sox2, and Nestin), and increased proliferation rates. When transplanted into non-obese diabetic-severe combined immunodeficiency gamma mice brains, Sca1(+) pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 (100%) vs 7/12 (54%) of mice transplanted with Sca1(+) and Sca1(-) cells respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that tumors derived from Sca1(+) pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1(+) cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor-proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells. PMID:24481638

Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar; Svendsen, Clive; Melmed, Shlomo

2014-04-01

230

Echocardiographic characteristics of chickens with ascites syndrome  

Microsoft Academic Search

1. B- and M-mode echocardiography was used to compare cardiac function in broilers with spontaneous ascites syndrome with that of normal chickens.2. Thirty ascitic chickens and 15 normal chickens aged three, 4, 5 and 6 weeks from the same flock (180 birds in total) were examined. They were restrained gently in a natural standing position, and echocardiographs were obtained with

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

2006-01-01

231

The Echocardiographic Characteristics of Ascites Syndrome Chickens  

Microsoft Academic Search

B-mode and M-mode echocardiography was used to compare the cardiac functioning of broilers with spontaneous ascites syndrome with that of normal chickens. 2. Thirty ascitic chickens and fifteen normal chickens at the ages of three, four, five and six weeks from the same flock were used. They were restrained gently in a natural standing position, and echocardiographs were obtained with

Ganzhen Deng; Yi Zhang; Dingzong Guo; Xiuli Peng; Chengye Li

232

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

233

Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity.  

PubMed

Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity. PMID:22421704

Novosyadlyy, Ruslan; Leroith, Derek

2012-06-01

234

Control exponential growth of tumor cells with slow spread of oncolytic virus.  

PubMed

Great attention has been paid to cancer therapy by means of oncolytic viruses, but the fast virus-spread, which eliminates all tumor cells, cannot be applied to solid tumors. As slow virus-spread is applied, solid tumors are expected to be controlled but complicated dynamical behaviors appear. In this paper we investigate bifurcations of equilibria in the oncolytic virus dynamics model with exponential growth of tumor cells and slow virus-spread. We find conditions of parameters for saddle-node bifurcation, Hopf bifurcation and Bogdanov-Takens bifurcation. Those conditions give thresholds for slow virus-spread to control the population of tumor cells within an appropriate range. PMID:25435412

Si, Wen; Zhang, Weinian

2015-02-21

235

Mice Lacking NCF1 Exhibit Reduced Growth of Implanted Melanoma and Carcinoma Tumors  

PubMed Central

The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1m1J mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1m1J mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1m1J mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors. PMID:24358335

Kelkka, Tiina; Pizzolla, Angela; Laurila, Juha Petteri; Friman, Tomas; Gustafsson, Renata; Källberg, Eva; Olsson, Olof; Leanderson, Tomas; Rubin, Kristofer; Salmi, Marko; Jalkanen, Sirpa; Holmdahl, Rikard

2013-01-01

236

Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma tumors.  

PubMed

The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1 (m1J) mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1 (m1J) mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1 (m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors. PMID:24358335

Kelkka, Tiina; Pizzolla, Angela; Laurila, Juha Petteri; Friman, Tomas; Gustafsson, Renata; Källberg, Eva; Olsson, Olof; Leanderson, Tomas; Rubin, Kristofer; Salmi, Marko; Jalkanen, Sirpa; Holmdahl, Rikard

2013-01-01

237

The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens  

PubMed Central

Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM) approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA) regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3) beginning at postimplantation day 3 (PID 3). Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7), starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA's potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation. PMID:24228059

Smeester, Branden A.; O'Brien, Elaine E.; Ericson, Marna E.; Triemstra, Jennifer L.; Beitz, Alvin J.

2013-01-01

238

Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors  

PubMed Central

Purpose Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers. Experimental Design To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared to subcutaneous adipose derived mesenchymal stromal cells (SC-ASC), bone marrow derived mesenchymal stromal cells (BM-MSC) and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts. Results O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Co-culture with O-ASC increased endometrial cancer cell proliferation in-vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC-injected mice, tumors in O-ASC-injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC-exhibited enhanced motility as compared to SC-ASC in response to Hec1a secreted factors. Conclusions Visceral adipose contains a population of multipotent MSC that promote endometrial tumor growth more potently than MSC from subcutaneous adipose tissue. We propose that O-ASC recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells. PMID:22167410

Klopp, Ann H.; Zhang, Yan; Solley, Travis; Amaya-Manzanares, Felipe; Marini, Frank; Andreeff, Michael; Debeb, Bisrat; Woodward, Wendy; Schmandt, Rosemarie; Broaddus, Russell; Lu, Karen; Kolonin, Mikhail G.

2011-01-01

239

Effect of Dietary Modifications Designed to Reduce Early Growth Rate on Live Performance and on Incidence and Severity of Ascites in Two Commercial Broiler Strains When Maintained Under Low Ventilation or Low Temperature Models1  

Microsoft Academic Search

Two studies were conducted in environmental chambers to evaluate different dietary modifications on the incidence or severity of ascites, leg disorders, and sudden death syndrome in males of tw o commercial broiler strains and their reciprocal crosses. A high energy-high nutrient density diet (HE) series served as the positive control. Two other diet series consisted of a high fiber (HF)

S. E. Madrigal; S. E. Watkins; N. B. Anthony; C. E. Wall; C. A. Fritts; P. W. Waldroup

240

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. PMID:22815767

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

2012-01-01

241

Sucrose octasulfate regulates fibroblast growth factor-2 binding, transport, and activity: potential for regulation of tumor growth.  

PubMed

The antithrombotic activity of heparin has largely been credited with the success found in some cancer treatment by heparin. There are, however, many potent growth factors involved in tumor and blood vessel growth that bind to heparin with high affinity and their regulation by heparin may play a role in heparin's efficacy. We therefore chose to study the activity of a heparin analog, sucrose octasulfate (SOS), which has been similarly shown to interact with heparin-binding growth factors. Using mouse melanoma and lung carcinoma models, we demonstrate in vivo inhibition of tumor growth by SOS. SOS, however, showed little effect in coagulation assays indicating that this activity was not a primary mechanism of action for this molecule. Studies were then performed to assess the effect of SOS on basic fibroblast growth factor (FGF-2) activity, a growth factor which promotes tumor and blood vessel growth and is produced by B16 melanoma cells. SOS potently inhibited FGF-2 binding to endothelial cells and stripped pre-bound FGF-2 from cells. SOS also regulated FGF-2 stimulated proliferation. Further, SOS facilitated FGF-2 diffusion through Descemet's membrane, a heparan sulfate-rich basement membrane from the cornea, suggesting a possible role in FGF-2 clearance. Our results suggest that molecules such as SOS have the potential to remove growth factors from tumor microenvironments and the approach offers an attractive area for further study. PMID:18163458

Fannon, Michael; Forsten-Williams, Kimberly; Nugent, Matthew A; Gregory, Kalvin J; Chu, Chia Lin; Goerges-Wildt, Adrienne L; Panigrahy, Dipak; Kaipainen, Arja; Barnes, Carmen; Lapp, Cathy; Shing, Yuen

2008-05-01

242

Sucrose Octasulfate Regulates Fibroblast Growth Factor-2 Binding, Transport, and Activity: Potential for Regulation of Tumor Growth  

PubMed Central

The antithrombotic activity of heparin has largely been credited with the success found in some cancer treatment by heparin. There are, however, many potent growth factors involved in tumor and blood vessel growth that bind to heparin with high affinity and their regulation by heparin may play a role in heparin’s efficacy. We therefore chose to study the activity of a heparin analog, sucrose octasulfate (SOS), which has been similarly shown to interact with heparin-binding growth factors. Using mouse melanoma and lung carcinoma models, we demonstrate in vivo inhibition of tumor growth by SOS. SOS, however, showed little effect in coagulation assays indicating that this activity was not a primary mechanism of action for this molecule. Studies were then performed to assess the effect of SOS on basic fibroblast growth factor (FGF-2) activity, a growth factor which promotes tumor and blood vessel growth and is produced by B16 melanoma cells. SOS potently inhibited FGF-2 binding to endothelial cells and stripped pre-bound FGF-2 from cells. SOS also regulated FGF-2 stimulated proliferation. Further, SOS facilitated FGF-2 diffusion through Descemet’s membrane, a heparan sulfate-rich basement membrane from the cornea, suggesting a possible role in FGF-2 clearance. Our results suggest that molecules such as SOS have the potential to remove growth factors from tumor microenvironments and the approach offers an attractive area for further study. PMID:18163458

FANNON, MICHAEL; FORSTEN-WILLIAMS, KIMBERLY; NUGENT, MATTHEW A.; GREGORY, KALVIN J.; CHU, CHIA LIN; GOERGES-WILDT, ADRIENNE L; PANIGRAHY, DIPAK; KAIPAINEN, ARJA; BARNES, CARMEN; LAPP, CATHY; SHING, YUEN

2008-01-01

243

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

PubMed

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

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

2010-06-01

244

Host-derived tumor endothelial marker 8 promotes the growth of melanoma.  

PubMed

Tumor endothelial marker 8 (TEM8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. To assess the functional role of TEM8, we disrupted the TEM8 gene in mice by targeted homologous recombination. TEM8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis. However, histopathologic analysis revealed an excess of extracellular matrix in several tissues, including the ovaries, uterus, skin, and periodontal ligament of the incisors, the latter resulting in dental dysplasia. When challenged with B16 melanoma, tumor growth was delayed in TEM8(-/-) mice, whereas the growth of other tumors, such as Lewis lung carcinoma, was unaltered. These studies show that host-derived TEM8 promotes the growth of certain tumors and suggest that TEM8 antagonists may have utility in the development of new anticancer therapies. PMID:19622764

Cullen, Mike; Seaman, Steven; Chaudhary, Amit; Yang, Mi Young; Hilton, Mary Beth; Logsdon, Daniel; Haines, Diana C; Tessarollo, Lino; St Croix, Brad

2009-08-01

245

On a Nonlinear Model for Tumor Growth: Global in Time Weak Solutions  

NASA Astrophysics Data System (ADS)

We investigate the dynamics of a class of tumor growth models known as mixed models. The key characteristic of these type of tumor growth models is that the different populations of cells are continuously present everywhere in the tumor at all times. In this work we focus on the evolution of tumor growth in the presence of proliferating, quiescent and dead cells as well as a nutrient. The system is given by a multi-phase flow model and the tumor is described as a growing continuum ? with boundary ?? both of which evolve in time. Global-in-time weak solutions are obtained using an approach based on penalization of the boundary behavior, diffusion and viscosity in the weak formulation.

Donatelli, Donatella; Trivisa, Konstantina

2014-07-01

246

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

247

PACAP Induces Signaling and Stimulation of 5Hydroxytryptamine Release and Growth in Neuroendocrine Tumor Cells  

Microsoft Academic Search

Neuroendocrine tumors, although rare, are currently diagnosed with increasing frequency, owing to improved imaging techniques\\u000a and a greater clinical awareness of this condition. To date, BON is a very well established and characterized human pancreatic\\u000a neuroendocrine tumor cell line used to study the signal transduction and genetic regulation of neuroendocrine tumors secretion\\u000a and growth. The secretory activity of BON cells

Patrizia M. Germano; Sandy N. Lieu; Janjing Xue; Helen J. Cooke; Fievos L. Christofi; Yuxin Lu; Joseph R. Pisegna

2009-01-01

248

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

249

WT1-Mediated Growth Suppression of Wilms Tumor Cells Expressing a WT1 Splicing Variant  

Microsoft Academic Search

A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these

Daniel A. Haber; Seon Park; Shyamala Maheswaran; Christoph Englert; Gian G. Re; Debra J. Hazen-Martin; Donald A. Sens; A. Julian Garvin

1993-01-01

250

CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma  

Microsoft Academic Search

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non-tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF)

Fang Xie; Qin Shi; Qin Wang; Yan Ge; Yongjing Chen; Jianling Zuo; Yongping Gu; Haizhen Deng; Hui Mao; Zhenhua Hu; Yinghui Zhou; Xueguang Zhang

2010-01-01

251

Growth characteristics of human Wilms' tumor in nude mice.  

PubMed

Ten Wilms' tumors (WT) were heterotransplated into athymic (nude) mice. Eight of the tumors (80%) grew and were serially passaged as many as 20 times. The histology of the primary heterotransplants resembled that of the surgically excised tumors (seven classical and one anaplastic). Histological examination of serial passages of the classical WT demonstrated the tendency of the stromal and tubular components to disappear. The anaplastic tumor, however, maintained histological features identical to the primary tumor through all passages examined. One WT cell line that exhibited a prominent skeletal muscle component failed to grow beyond the third passage. Spontaneous glomerular differentiation was noted in several heterotransplants. The site of transplantation (subcutaneous, peritoneal, or renal capsule) had no effect on the differentiation of the tumors, and attempts to produce intravenous metastases were unsuccessful. Unilateral nephrectomy of WT-bearing mice gave a transient increase in pulse labeling of the tumors with bromodeoxyuridine, a thymidine analogue, compared with sham-operated controls or mice bearing Ewings' sarcoma heterotransplants. The increased labeling of tumor nuclei reached a maximum at 48 h. Similar increased labeling was observed in the remaining kidney following unilateral nephrectomy. These data show that although WT is a malignant neoplasm, its cells retain the capacity to respond to physiological signals resulting from nephrectomy and that differentiation cannot be modulated by the site of heterotransplantation or serial passage in athymic mice. PMID:2854254

Garvin, A J; Congleton, L; Inabnett, T; Gansler, T; Sens, D A

1988-01-01

252

Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors  

E-print Network

The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress ...

Martin, John D.

253

Molecularly Targeted Drug Slows Tumor Growth in Patients with Metastatic Kidney Cancer  

Cancer.gov

Researchers from the National Cancer Institute (NCI) reported today that the molecularly targeted drug bevacizumab slowed tumor growth in patients with metastatic renal cell carcinoma, the most common form of kidney cancer in adults.

254

Mass General study identifies growth factor essential to the most common malignant pediatric brain tumor  

Cancer.gov

A multi-institutional team led by Massachusetts General Hospital researchers has identified a molecular pathway that appears to be essential for the growth and spread of medulloblastoma, the most common malignant brain tumor in children.

255

Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors  

PubMed Central

Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo is critical but challenging. Intravital microscopy (IVM) of subcutaneous tumors provides dynamic, continuous, long-term imaging at high resolution. Although popular, subcutaneous tumor models are often criticized for being ectopic and lacking orthotopic tissue microenvironments critical for proper development. Similar IVM of orthotopic and especially spontaneous tumors is seldom possible. Here, we generate and characterize tumor models in mice for breast, lung, prostate and ovarian cancer by co-engrafting tumor spheroids with orthotopic tissue in dorsal skin window chambers for IVM. We use tumor cells and tissue, both genetically engineered to express distinct fluorescent proteins, in order to distinguish neoplastic cells from engrafted tissue. IVM of this new, two-colored model reveals classic tumor morphology with red tumor cell nests surrounded by green stromal elements. The co-implanted tissue forms the supportive stroma and vasculature of these tumors. Tumor growth and angiogenesis are more robust when tumor cells are co-implanted with orthotopic tissue versus other tissues, or in the skin alone. The orthotopic tissue promotes tumor cell mitosis over apoptosis. With time, tumor cells can adapt to new environments and ultimately even grow better in the non-orthotopic tissue over the original orthotopic tissue. These models offer a significant advance by recreating an orthotopic microenvironment in an ectopic location that is still easy to image by IVM. These “ectopic-orthotopic” models provide an exceptional way to study tumor and stroma cells in cancer, and directly show the critical importance of microenvironment in the development of multiple tumors. PMID:24715954

Schnitzer, Jan E

2013-01-01

256

Vascular endothelial growth factor c promotes ovarian carcinoma progression through paracrine and autocrine mechanisms.  

PubMed

Vascular endothelial growth factor C (VEGFC) has been reported to promote tumor progression in several tumor types, mainly through the stimulation of lymphangiogenesis and lymphatic metastasis. However, the expression and biological significance of the VEGFC/VEGF receptor (VEGFR)-3 pathway in ovarian cancer growth and dissemination are unclear, and have been investigated in this study. Soluble VEGFC was detected in the plasma and ascites of patients with ovarian carcinoma, and VEGFR3 expression was found in their tumor tissues. In human ovarian carcinoma xenograft models, high levels of soluble VEGFC in ascites and serum were detected, in association with disease progression, tumor burden, and volume of ascites. Peak VEGFC expression preceded para-aortic lymph node infiltration by HOC8 neoplastic cells. Histological detection of tumor cells in blood and lymphatic vessels indicated both hematogenous and lymphatic dissemination. Overexpression of VEGFC in the VEGFR3-positive and luciferase-expressing IGROV1 cells promoted carcinoma dissemination after orthotopic transplantation in the ovary of immunodeficient mice. In vitro, VEGFC released by the tumor cells stimulated tumor cell migration in an autocrine manner. Cediranib, an inhibitor of VEGFR1-3 and c-kit, inhibited in vivo metastasis of VEGFC-overexpressing IGROV1 and in vitro autocrine effects. These findings suggest that the VEGFC/VEGFR3 pathway acts as an enhancer of ovarian cancer progression through autocrine and paracrine mechanisms, hence offering a potential target for therapy. PMID:24508126

Decio, Alessandra; Taraboletti, Giulia; Patton, Veronica; Alzani, Rachele; Perego, Patrizia; Fruscio, Robert; Jürgensmeier, Juliane M; Giavazzi, Raffaella; Belotti, Dorina

2014-04-01

257

Management of adult patients with ascites caused by cirrhosis  

Microsoft Academic Search

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of

Bruce A. Runyon

1998-01-01

258

Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis  

Microsoft Academic Search

Neoplastic cells require an appropriate pericellular environment and new formation of stroma and blood vessels in order to constitute a soilid tumor. Tumor progression also involves degradation of various extracellular matrix (ECM) constituents. In this review we have focused on the possible involvement of ECM-resident growth factors and enzymes in neovascularization and cell invasion. We demonstrate that the pluripotent angiogenic

Israel Vlodavsky; Gil Korner; Rivka Ishai-Michaeli; Pnina Bashkin; Rachel Bar-Shavit; Zvi Fuks

1990-01-01

259

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.

260

Acetyl-11-Keto-?-Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis  

PubMed Central

The role of angiogenesis in tumor growth and metastasis is well established. Identification of small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we demonstrated that acetyl-11-keto-?-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg of AKBA) after solid tumors reached about 100 mm3 (n=5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively and suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 kinase (KDR/Flk-1) with IC50 of 1.68 ?mol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mTOR, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways. PMID:19567671

Pang, Xiufeng; Yi, Zhengfang; Zhang, Xiaoli; Sung, Bokyung; Qu, Weijing; Lian, Xiaoyuan; Aggarwal, Bharat B.; Liu, Mingyao

2009-01-01

261

Olmesartan Potentiates the Anti-Angiogenic Effect of Sorafenib in Mice Bearing Ehrlich's Ascites Carcinoma: Role of Angiotensin (1–7)  

PubMed Central

Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1–7) agonist or an angiotensin (1–7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1–7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1–7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer. PMID:24465768

Abd-Alhaseeb, Mohammad M.; Zaitone, Sawsan A.; Abou-El-Ela, Soad H.; Moustafa, Yasser M.

2014-01-01

262

Olmesartan potentiates the anti-angiogenic effect of sorafenib in mice bearing Ehrlich's ascites carcinoma: role of angiotensin (1-7).  

PubMed

Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1-7) agonist or an angiotensin (1-7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1-7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1-7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer. PMID:24465768

Abd-Alhaseeb, Mohammad M; Zaitone, Sawsan A; Abou-El-Ela, Soad H; Moustafa, Yasser M

2014-01-01

263

Infertility and chylous ascites? A case report  

PubMed Central

Introduction Chylous ascites is defined by an accumulation of chylous fluid in the peritoneal cavity and it clinically appears as a milky fluid in which laboratory examination reveals triglycerides, cholesterol, and sometimes chylomicrons and lymphocytes. Presentation of case We report the first case of primary chylous ascites observed during laparoscopy for unexplained secondary infertility. Discussion Chylous ascites has never been linked to fertility but bathes all internal reproductive organs surfaces and is considered a communication mean between ovaries. Conclusion Despite a lack of evidence, the question of peritoneal fluid role remains in infertility. PMID:22096750

Frey, C.; Poncelet, C.

2011-01-01

264

Tumor Microenvironments Correspond to Unique Metabolic Signatures that Affect Tumor Growth | Physical Sciences in Oncology  

Cancer.gov

Using a genetic construct that produces a green glow as a tumor responds to microenvironmental stresses, a team of investigators at Stanford University have shown that the way in which a tumor responds to stress can predict how it will grow in the body. This work, led by Albert Koong, M.D., was published in the journal Cancer Research.

265

Growth Hormone-Releasing Factor from a Human Pancreatic Tumor that Caused Acromegaly  

Microsoft Academic Search

A 44 amino acid peptide with growth hormone-releasing activity has been isolated from a human tumor of the pancreas that had caused acromegaly. The primary structure of the tumor-derived peptide is H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn- Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2. The synthetic replicate has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone. The tumor-derived peptide is identical

Roger Guillemin; Paul Brazeau; Peter Bohlen; Frederick Esch; Nicholas Ling; William B. Wehrenberg

1982-01-01

266

Regulation of Tumor Growth and Metastasis: The Role of Tumor Microenvironment  

PubMed Central

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body’s immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor’s surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols. PMID:24926201

Goubran, Hadi A; Kotb, Rami R; Stakiw, Julie; Emara, Mohamed E; Burnouf, Thierry

2014-01-01

267

Stochastic fluctuation induced the competition between extinction and recurrence in a model of tumor growth  

NASA Astrophysics Data System (ADS)

We investigate the phenomenon that stochastic fluctuation induced the competition between tumor extinction and recurrence in the model of tumor growth derived from the catalytic Michaelis-Menten reaction. We analyze the probability transitions between the extinction state and the state of the stable tumor by the Mean First Extinction Time (MFET) and Mean First Return Time (MFRT). It is found that the positional fluctuations hinder the transition, but the environmental fluctuations, to a certain level, facilitate the tumor extinction. The observed behavior could be used as prior information for the treatment of cancer.

Li, Dongxi; Xu, Wei; Sun, Chunyan; Wang, Liang

2012-04-01

268

Malignant ascites: A review of prognostic factors, pathophysiology and therapeutic measures  

PubMed Central

Malignant ascites indicates the presence of malignant cells in the peritoneal cavity and is a grave prognostic sign. While survival in this patient population is poor, averaging about 20 wk from time of diagnosis, quality of life can be improved through palliative procedures. Selecting the appropriate treatment modality remains a careful process, which should take into account potential risks and benefits and the life expectancy of the patient. Traditional therapies, including paracentesis, peritoneovenous shunt placement and diuretics, are successful and effective in varying degrees. After careful review of the patient’s primary tumor origin, tumor biology, tumor stage, patient performance status and comorbidities, surgical debulking and intraperitoneal chemotherapy should be considered if the benefit of therapy outweighs the risk of operation because survival curves can be extended and palliation of symptomatic malignant ascites can be achieved in select patients. In patients with peritoneal carcinomatosis who do not qualify for surgical cytoreduction but suffer from the effects of malignant ascites, intraperitoneal chemotherapy can be safely and effectively administered via laparoscopic techniques. Short operative times, short hospital stays, low complication rates and ultimately symptomatic relief are the advantages of laparoscopically administering heated intraperitoneal chemotherapy, making it not only a valuable treatment modality but also the most successful treatment modality for achieving palliative cure of malignant ascites. PMID:22590662

Sangisetty, Suma L; Miner, Thomas J

2012-01-01

269

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. PMID:18199835

Panigrahy, Dipak; Kaipainen, Arja; Huang, Sui; Butterfield, Catherine E.; Barnés, Carmen M.; Fannon, Michael; Laforme, Andrea M.; Chaponis, Deviney M.; Folkman, Judah; Kieran, Mark W.

2008-01-01

270

PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition.  

PubMed

Angiogenesis and inflammation are central processes through which the tumor microenvironment influences tumor growth. We have demonstrated recently that peroxisome proliferator-activated receptor (PPAR)alpha 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 PPARalpha would promote tumor growth. Surprisingly, the PPARalpha 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 PPARalpha-deficient tumors were still susceptible to fenofibrate, absence of PPARalpha 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 PPARalpha as well as its activation by ligands cause tumor suppression via overlapping antiangiogenic pathways. These findings reveal the potential utility of the well tolerated PPARalpha agonists beyond their use as lipid-lowering drugs in anticancer therapy. Our results provide a mechanistic rationale for evaluating the clinical benefits of PPARalpha agonists in cancer treatment, alone and in combination with other therapies. PMID:18199835

Panigrahy, Dipak; Kaipainen, Arja; Huang, Sui; Butterfield, Catherine E; Barnés, Carmen M; Fannon, Michael; Laforme, Andrea M; Chaponis, Deviney M; Folkman, Judah; Kieran, Mark W

2008-01-22

271

Evidence for the isolation, growth, and characterization of malignant cells in primary cultures of human tumors.  

PubMed

Isolation and growth of malignant cells from solid tumors have often met with disappointing results. Consequently, we have developed a cell culture methodology based on ex vivo explantation of tumor tissue, with subsequent monolayer cell outgrowth. In an attempt to assess methods for detection of malignant cells in these cultures, we analyzed and compared the results of cytopathology, growth in soft agar, and detection of telomerase activity with those of standard immunohistochemistry (IHC) techniques for the detection of cytokeratins, tumor marker p53, and proliferation marker Ki-67. The sensitivity of detection of malignant cells was 85% (22/26) for cytopathological examination, 30% (3/10) for soft agar growth, and 100% (12/12) for detection of telomerase activity. From these data, we concluded that both cytopathological examination and assessment of telomerase activity contribute to the detection of malignant cells in primary cultures of human solid tumors, whereas growth in soft agar was not a good indicator of malignant cells. Although not specific for malignant cells per se, IHC detection for epithelial cell cytokeratins showed a high degree of sensitivity (100%, 23/23), whereas the sensitivity for detection of tumor marker p53 and proliferation marker Ki-67 was 30% (7/23) and 70% (16/23), respectively. These data also provide proof that malignant tumor cells, derived from a diverse number of human solid tumors, can be isolated and grown in primary cell culture. PMID:12892529

Ochs, Robert L; Fensterer, Jeffrey; Ohori, N Paul; Wells, Alan; Gabrin, Michael; George, Lisa D; Kornblith, Paul

2003-01-01

272

Hybrid-primed lymphocytes and hybrid vaccination prevent tumor growth of lewis lung carcinoma in mice.  

PubMed

Dendritic cell (DC)-tumor cell hybrids are currently being evaluated as a novel antitumor vaccination strategy. We have explored in an animal model whether administration of DCs fused with poorly immunogenic carcinoma cells could elicit an antitumor response. Fusion of C57/BL6 mice bone marrow-derived DCs with Lewis lung carcinoma (LLC1) cells resulted in approximately 50% fusion efficiency. Hybrid cells (HCs) were used to explore 3 potential tumor therapy strategies: protective immunization, vaccination, and adoptive cellular therapy. Immunization with HCs induced activation of proliferating cytotoxic T cells, upregulation of distinct cytokines genes, and a significant retardation of tumor growth. Similar results were observed by vaccination with HCs in the tumor-bearing host. Finally, when T cells from HC-vaccinated mice were transferred into naive tumor-bearing mice, tumor growth was strongly retarded and an efficient proliferative and cytotoxic T-cell response was observed. Tumor growth was reduced by more than 50%, and tumor development was significantly delayed. Taken together, we demonstrate that HCs offer effective immunotherapy of poorly immunogenic carcinomas. This is independent of whether the HCs are taken for adoptive transfer or as a vaccine. PMID:16531818

Savai, Rajkumar; Schermuly, Ralph Theo; Schneider, Michael; Pullamsetti, Soni Savai; Grimminger, Friedrich; Seeger, Werner; Banat, Gamal-Andre

2006-01-01

273

Computational Modeling of 3D Tumor Growth and Angiogenesis for Chemotherapy Evaluation  

PubMed Central

Solid tumors develop abnormally at spatial and temporal scales, giving rise to biophysical barriers that impact anti-tumor chemotherapy. This may increase the expenditure and time for conventional drug pharmacokinetic and pharmacodynamic studies. In order to facilitate drug discovery, we propose a mathematical model that couples three-dimensional tumor growth and angiogenesis to simulate tumor progression for chemotherapy evaluation. This application-oriented model incorporates complex dynamical processes including cell- and vascular-mediated interstitial pressure, mass transport, angiogenesis, cell proliferation, and vessel maturation to model tumor progression through multiple stages including tumor initiation, avascular growth, and transition from avascular to vascular growth. Compared to pure mechanistic models, the proposed empirical methods are not only easy to conduct but can provide realistic predictions and calculations. A series of computational simulations were conducted to demonstrate the advantages of the proposed comprehensive model. The computational simulation results suggest that solid tumor geometry is related to the interstitial pressure, such that tumors with high interstitial pressure are more likely to develop dendritic structures than those with low interstitial pressure. PMID:24404145

Tang, Lei; van de Ven, Anne L.; Guo, Dongmin; Andasari, Vivi; Cristini, Vittorio; Li, King C.; Zhou, Xiaobo

2014-01-01

274

Tumor fibroblast–derived epiregulin promotes growth of colitis-associated neoplasms through ERK  

PubMed Central

Molecular mechanisms specific to colitis-associated cancers have been poorly characterized. Using comparative whole-genome expression profiling, we observed differential expression of epiregulin (EREG) in mouse models of colitis-associated, but not sporadic, colorectal cancer. Similarly, EREG expression was significantly upregulated in cohorts of patients with colitis-associated cancer. Furthermore, tumor-associated fibroblasts were identified as a major source of EREG in colitis-associated neoplasms. Functional studies showed that Ereg-deficient mice, although more prone to colitis, were strongly protected from colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted tumor growth rather than initiation. Additionally, we demonstrated that fibroblast-derived EREG requires ERK activation to induce proliferation of intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate the functional relevance of EREG-producing tumor-associated fibroblasts, we developed a novel system for adoptive transfer of these cells via mini-endoscopic local injection. It was found that transfer of EREG-producing, but not Ereg-deficient, fibroblasts from tumors significantly augmented growth of colitis-associated neoplasms in vivo. In conclusion, our data indicate that EREG and tumor-associated fibroblasts play a crucial role in controlling tumor growth in colitis-associated neoplasms. PMID:23549083

Neufert, Clemens; Becker, Christoph; Türeci, Özlem; Waldner, Maximilian J.; Backert, Ingo; Floh, Katharina; Atreya, Imke; Leppkes, Moritz; Jefremow, Andre; Vieth, Michael; Schneider-Stock, Regine; Klinger, Patricia; Greten, Florian R.; Threadgill, David W.; Sahin, Ugur; Neurath, Markus F.

2013-01-01

275

Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.  

PubMed

Molecular mechanisms specific to colitis-associated cancers have been poorly characterized. Using comparative whole-genome expression profiling, we observed differential expression of epiregulin (EREG) in mouse models of colitis-associated, but not sporadic, colorectal cancer. Similarly, EREG expression was significantly upregulated in cohorts of patients with colitis-associated cancer. Furthermore, tumor-associated fibroblasts were identified as a major source of EREG in colitis-associated neoplasms. Functional studies showed that Ereg-deficient mice, although more prone to colitis, were strongly protected from colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted tumor growth rather than initiation. Additionally, we demonstrated that fibroblast-derived EREG requires ERK activation to induce proliferation of intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate the functional relevance of EREG-producing tumor-associated fibroblasts, we developed a novel system for adoptive transfer of these cells via mini-endoscopic local injection. It was found that transfer of EREG-producing, but not Ereg-deficient, fibroblasts from tumors significantly augmented growth of colitis-associated neoplasms in vivo. In conclusion, our data indicate that EREG and tumor-associated fibroblasts play a crucial role in controlling tumor growth in colitis-associated neoplasms. PMID:23549083

Neufert, Clemens; Becker, Christoph; Türeci, Özlem; Waldner, Maximilian J; Backert, Ingo; Floh, Katharina; Atreya, Imke; Leppkes, Moritz; Jefremow, Andre; Vieth, Michael; Schneider-Stock, Regine; Klinger, Patricia; Greten, Florian R; Threadgill, David W; Sahin, Ugur; Neurath, Markus F

2013-04-01

276

Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo.  

PubMed

Thalidomide was recently suggested to be angiogenesis-inhibitor following the demonstration of its activity in a rabbit cornea micropocket model. The purpose of the present study was to test its efficacy in solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells were injected subcutaneously, intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg thalidomide starting either two or 10 days following tumor cell injection. The tumors were measured and compared with controls. There was no growth retardation in CT-26 bearing mice nor in mice with pulmonary or peritoneal metastases of B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth retardation was demonstrated, however the difference was not statistically significant. All tumors eventually reached maximal size, similar to controls. Morphological evaluation of the blood vessels oriented towards the tumor revealed that in both thalidomide and control groups, all mice had developed an intact network of new blood vessels. In our model for the oral administration of thalidomide inhibition of tumor growth and angiogenesis did not occur. We hypothesize that the lack of sustained antiangiogenic response was either due to immune modulation or to tumor heterogeneity and adaptation. PMID:9042240

Gutman, M; Szold, A; Ravid, A; Lazauskas, T; Merimsky, O; Klausner, J M

1996-01-01

277

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

278

A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors  

PubMed Central

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. PMID:14595012

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.

2003-01-01

279

Co-expression of hepatocyte growth factor and c-met in epithelial odontogenic tumors.  

PubMed

Hepatocyte growth factor (HGF) and its receptor, c-met, have been shown to regulate cell proliferation, motility and morphology in a variety of cell types. A significant role of the HGF/c-met pathway has been demonstrated in various tumors, however, little is known about the role of HGF/c-met pathway in odontogenic tumors. The aim of this study was to characterize the expression of HGF and c-met in 30 ameloblastomas, 7 unicystic ameloblastomas (luminal type), 10 calcifying cystic odontogenic tumors, 10 adenomatoid odontogenic tumors (AOTs), 30 keratocytic odontogenic tumors (KCOTs) and 6 ameloblastic carcinomas using an immunohistochemical method. HGF and c-met were generally immunolocalized in the cytoplasm of all epithelial tumor cells, except for keratinizing cells in acanthomatous ameloblastoma, in all the examined odontogenic tumors. These results, together with the expression of these two proteins in the epithelium of tooth germs, suggest that the HGF/c-met pathway is involved in the differentiation of odontogenic tumors. This pathway may also promote tumor proliferation in odontogenic tumors due to its potent mitogenic effect. The consistent and strong immunolocalization of HGF and c-met in squamous cells present in acanthomatous ameloblastomas, AOTs and ameloblastic carcinomas, and in the linings of KCOTs suggests that the HGF/c-met interaction may have an influence on squamous differentiation in these odontogenic tumors. PMID:21855117

Poomsawat, Sopee; Punyasingh, Jirapa; Vejchapipat, Paisarn; Larbcharoensub, Noppadol

2012-07-01

280

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. PMID:23431489

Loué, Védi André Serges; Gbary, Eléonore; Koui, Sylvanus; Akpa, Bédi; Kouassi, Adélaide

2013-01-01

281

Effect of Melatonin on Tumor Growth and Angiogenesis in Xenograft Model of Breast Cancer  

PubMed Central

As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. PMID:24416386

Jardim-Perassi, Bruna Victorasso; Arbab, Ali S.; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Varma, Nadimpalli R. S.; Iskander, A. S. M.; Shankar, Adarsh; Ali, Meser M.; de Campos Zuccari, Debora Aparecida Pires

2014-01-01

282

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

283

Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo.  

PubMed Central

Perlecan, a ubiquitous heparan sulfate proteoglycan, possesses angiogenic and growth-promoting attributes primarily by acting as a coreceptor for basic fibroblast growth factor (FGF-2). In this report we blocked perlecan expression by using either constitutive CMV-driven or doxycycline- inducible antisense constructs. Growth of colon carcinoma cells was markedly attenuated upon obliteration of perlecan gene expression and these effects correlated with reduced responsiveness to and affinity for mitogenic keratinocyte growth factor (FGF-7). Exogenous perlecan effectively reconstituted the activity of FGF-7 in the perlecan-deficient cells. Moreover, soluble FGF-7 specifically bound immobilized perlecan in a heparan sulfate-independent manner. In both tumor xenografts induced by human colon carcinoma cells and tumor allografts induced by highly invasive mouse melanoma cells, perlecan suppression caused substantial inhibition of tumor growth and neovascularization. Thus, perlecan is a potent inducer of tumor growth and angiogenesis in vivo and therapeutic interventions targeting this key modulator of tumor progression may improve cancer treatment. PMID:9788974

Sharma, B; Handler, M; Eichstetter, I; Whitelock, J M; Nugent, M A; Iozzo, R V

1998-01-01

284

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

285

Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies  

PubMed Central

Compelling evidence for naturally occurring immunosurveillance against malignancies informs and justifies some current approaches toward cancer immunotherapy. However, some types of immune reactions have also been shown to facilitate tumor progression. For example, our previous studies showed that although experimental tumor growth is enhanced by low levels of circulating antibodies directed against the nonhuman sialic acid N-glycolyl-neuraminic acid (Neu5Gc), which accumulates in human tumors, growth could be inhibited by anti-Neu5Gc antibodies from a different source, in a different model. However, it remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Here, we address this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as Neu5Gc, can alter tumor progression. We found that although growth was stimulated at low antibody doses, it was inhibited by high doses, over a linear and remarkably narrow range, defining an immune response curve (IRC; i.e., inverse hormesis). Moreover, modulation of immune responses against the tumor by altering antibody avidity or by enhancing innate immunity shifted the IRC in the appropriate direction. Thus, the dualistic role of immunosurveillance vs. inflammation in modulating tumor progression can be quantitatively distinguished in multiple model systems, and can occur over a remarkably narrow range. Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer. PMID:24711415

Pearce, Oliver M. T.; Läubli, Heinz; Verhagen, Andrea; Secrest, Patrick; Zhang, Jiquan; Varki, Nissi M.; Crocker, Paul R.; Bui, Jack D.; Varki, Ajit

2014-01-01

286

Heparin Affinity: Purification of a Tumor-Derived Capillary Endothelial Cell Growth Factor  

Microsoft Academic Search

A tumor-derived growth factor that stimulates the proliferation of capillary endothelial cells has a very strong affinity for heparin. This heparin affinity makes it possible to purify the growth factor to a single-band preparation in a rapid two-step procedure. The purified growth factor is a cationic polypeptide, has a molecular weight of about 18,000, and stimulates capillary endothelial cell proliferation

Y. Shing; J. Folkman; R. Sullivan; C. Butterfield; M. Klagsbrun

1984-01-01

287

Surface-Modified HK:siRNA Nanoplexes with Enhanced Pharmacokinetics and Tumor Growth Inhibition  

PubMed Central

We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK):siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting ?v?3 and ?v?5 integrins. With noninvasive imaging, systemically administered surface-modified HK:siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK:siRNA nanoplexes. We then determined whether the surface-modified HK:siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1. Repeated systemic administration of the selected surface modified HK:siRNA nanoplexes targeting Raf-1 showed 35% greater inhibition of tumor growth than unmodified HK:siRNA nanoplexes and 60% greater inhibition of tumor growth than untreated mice. The improved blood pharmacokinetic results and tumor localization observed with the integrin-targeting surface modification of HK:siRNA nanoplexes correlated with greater tumor growth inhibition. This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases. PMID:23360232

2013-01-01

288

A Chemokine Receptor Antagonist Inhibits Experimental Breast Tumor Growth  

Microsoft Academic Search

The leukocyte infiltrate of human and murine epithelial cancers is regulated by chemokine production in the tumor microenvironment. In this article, we tested the hypothesis that chemokine receptor antagonists may have anticancer activity by inhibiting this infiltrate. We first char- acterized CC chemokines, chemokine receptors, and the leukocyte infil- trate in the 410.4 murine model of breast cancer. We found

Stephen C. Robinson; Kate A. Scott; Julia L. Wilson; Richard G. Thompson; Amanda E. I. Proudfoot; Frances R. Balkwill

2003-01-01

289

A multinomial model of tumor growth treated by radiotherapy  

E-print Network

of cancer cell radio-sensitivity according to their states. This work gives also a new formulation in Radiobiology and assumes that a cancer cell contains m targets which must be all deactivated to produce cell of the radioactive treatments on cancer and healthy cells are characterized by two probabilities: (i) the tumor

Paris-Sud XI, Université de

290

Erythropoiesis regulation during the development of ascites syndrome in broiler chickens: a possible role of corticosterone.  

PubMed

The ascites syndrome in broiler chickens is attributed to metabolic burdening, which results from intensive genetic selection for rapid growth coupled with exposure to extreme environmental conditions, such as low ambient temperature. These conditions impose on the broilers difficulties in fulfilling tissue demands for oxygen, and the birds exhibit a decrease in blood oxygen saturation and high hematocrit values. It is unknown whether the increase in hematocrit results from alteration in erythropoiesis or from fluid exudation out of the blood system to the abdominal cavity. The present study was conducted to examine the association between abnormal stress response and erythropoiesis process in ascitic broilers. Ascitic chickens revealed a uniquely continuous stress response: expressing an increase (P < or = 0.05) in plasma corticosterone concentration 2 to 3 wk before death. At 5 wk of age, ascitic broilers exhibited an increase (P < 0.05) in hematocrit, blood cell count, and packed cells and blood volumes, with no significant change in plasma volume. These results confirm an accelerated erythropoiesis process in ascitic birds. Increased blood cell production in ascitic birds was matched by an increase (P < 0.05) in the proportion of immature red blood cells (23%) in comparison with broilers that remained healthy (7%), and by decreased (P < 0.05) hemoglobin content relative to red blood cells. We conclude that continually increased corticosterone concentrations, as an inducer of erythropoiesis proliferation and differentiation arrest, in ascitic chickens, resulted in increased production of red blood cells (partially immature) with decreased hemoglobin content; this decrease in hemoglobin might have contributed to enhanced development of hypoxemia and to aggravation of the syndrome. PMID:12661659

Luger, D; Shinder, D; Wolfenson, D; Yahav, S

2003-03-01

291

Genetic parameters of ascites-related traits in broilers: effect of cold and normal temperature conditions.  

PubMed

(1) Ascites syndrome is a growth-related disorder of broilers that occurs more often in fast-growing birds and at low temperatures. The objective of this study was to estimate genetic and phenotypic correlations among ascites-related traits measured either under cold or under normal temperature conditions, and to estimate genetic correlations between ascites-related traits measured under cold and normal conditions. (2) Several traits related to ascites were measured on more than 4000 chickens under cold conditions and on more than 700 chickens under normal conditions. (3) The heritability estimates for body weight (BW) measured under cold and normal conditions were 0.42 and 0.50, respectively, for haematocrit value 0.46 and 0.17, respectively, and for ratio of right to total ventricular weight 0.45 and 0.12, respectively. (4) The genetic correlation between BW and haematocrit value under cold conditions was -0.23 and between BW and ratio of right to total ventricular weight -0.27. Under normal conditions, however, these genetic correlations were 0.55 and 0.50, respectively. (5) These results demonstrate that the heritability estimates of ascites-related traits as well as genetic correlations between ascites-related traits and BW depend on the temperature conditions under which animals are kept. (6) Strong positive genetic correlations (around 0.8) were observed between total mortality, fluid in the abdomen and ratio of right to total ventricular weight under cold conditions. The genetic correlation between ratio of right to total ventricular weight under cold and normal conditions was 0.91. (7) These results suggest that the ratio of right to total ventricular weight measured under normal temperature conditions might serve as a good indicator trait for ascites. PMID:15835250

Pakdel, A; van Arendonk, J A M; Vereijken, A L J; Bovenhuis, H

2005-02-01

292

Depletion of Tumor-Associated Macrophages Slows the Growth of Chemically Induced Mouse Lung Adenocarcinomas  

PubMed Central

Chronic inflammation is a risk factor for lung cancer, and low-dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programing changes within 2?weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ?50% of control levels after 4–6?weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of insulin-like growth factor-I, CXCL1, IL-6, and CCL2 diminished with clodronate liposome treatment. Tumor-associated macrophages expressed markers of both M1 and M2 programing in vehicle and clodronate liposome-treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2) had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression. PMID:25505466

Fritz, Jason M.; Tennis, Meredith A.; Orlicky, David J.; Lin, Hao; Ju, Cynthia; Redente, Elizabeth F.; Choo, Kevin S.; Staab, Taylor A.; Bouchard, Ronald J.; Merrick, Daniel T.; Malkinson, Alvin M.; Dwyer-Nield, Lori D.

2014-01-01

293

Novel xenograft model expressing human hepatocyte growth factor shows ligand-dependent growth of c-Met-expressing tumors.  

PubMed

c-Met, a receptor tyrosine kinase responsible for cellular migration, invasion, and proliferation, is overexpressed in human cancers. Although ligand-independent c-Met activation has been described, the majority of tumors are ligand dependent and rely on binding of hepatocyte growth factor (HGF) for receptor activation. Both receptor and ligand are attractive therapeutic targets; however, preclinical models are limited because murine HGF does not activate human c-Met. The goal of this study was to develop a xenograft model in which human HGF (hHGF) is produced in a controllable fashion in the mouse. Severe combined immunodeficient mice were treated with adenovirus encoding the hHGF transgene (Ad-hHGF) via tail vein injection, and transgene expression was determined by the presence of hHGF mRNA in mouse tissue and hHGF in serum. Ad-hHGF administration to severe combined immunodeficient mice resulted in hHGF production that was (a) dependent on quantity of virus delivered; (b) biologically active, resulting in liver hypertrophy; and (c) sustainable over 40 days. In this model, the ligand-dependent human tumor cell line SW1417 showed enhanced tumor growth, whereas the ligand-independent cell lines SW480 and GTL-16 showed no augmented tumor growth. This novel xenograft model is ideal for investigating c-Met/HGF-dependent human tumor progression and for evaluating c-Met targeted therapy. PMID:17431125

Francone, Todd D; Landmann, Ron G; Chen, Chin-Tung; Sun, Mark Y; Kuntz, Eleanor J; Zeng, Zhaoshi; Dematteo, Ronald P; Paty, Philip B; Weiser, Martin R

2007-04-01

294

CD200-expressing human basal cell carcinoma cells initiate tumor growth.  

PubMed

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. PMID:23292936

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

295

Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4.  

PubMed

Hepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a role in the progression to invasive and metastatic cancers. A variety of cancer cells secrete molecules that enhance HGF expression in stromal fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. In addition to the ligand-dependent activation, Met receptor activation is negatively regulated by cell-cell contact and Ser985 phosphorylation in the juxtamembrane of Met. The loss of intercellular junctions may facilitate an escape from the cell-cell contact-dependent suppression of Met-signaling. Significance of juxtamembrane mutations found in human cancers is assumed to be a loss-of-function in the negative regulation of Met. In attempts to block the malignant behavior of cancers, NK4 was isolated as a competitive antagonist against HGF-Met signaling. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF. In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis. NK4 inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be "static" in both tumor growth and spreading. PMID:18646008

Matsumoto, Kunio; Nakamura, Takahiro; Sakai, Katsuya; Nakamura, Toshikazu

2008-08-01

296

Evaluation of minimally invasive indices for predicting ascites susceptibility in three successive hatches of broilers exposed to cool temperatures.  

PubMed

Broilers from three consecutive hatches were exposed to cool temperatures to amplify the incidence of pulmonary hypertension syndrome (PHS, ascites). The largest apparently healthy individuals on Day 42 were evaluated using minimally invasive diagnostic indices [percentage saturation of hemoglobin with oxygen, hematocrit (HCT), heart rate, electrocardiogram (ECG) Lead II, body weight), then they were subjected to the ongoing pressures of fast growth and cool temperatures to determine which of these indices are predictive of the subsequent onset of PHS. Approximately 20% of the males and females evaluated on Day 42 subsequently developed PHS by Day 51. When data for all hatches were pooled and broilers that subsequently developed ascites were compared with those that did not (nonascitic), body weights, heart rates, and percentage saturation of hemoglobin with oxygen were lower on Day 42 for ascitic than for nonascitic males, and HCT was higher in ascitic males and females than in nonascitic males and females, respectively. Comparisons of the ECG Lead II wave amplitudes for all hatches pooled indicated that RS-wave amplitude was larger in ascitic than in nonascitic males, and that S-wave amplitude was more negative in ascitic males and females than in nonascitic males and females. Necropsies conducted on Day 51 revealed higher right:total ventricular weight ratios in ascitic than in nonascitic broilers, whereas normalizing the left ventricle plus septum weight for differences in body weight generated similar values for ascitic and nonascitic males and females, respectively. These results support a primary role for pulmonary hypertension but not cardiomyopathy in the pathogenesis of ascites triggered by cool temperatures. Values obtained for minimally invasive diagnostic indices on Day 42 also establish predictive thresholds that can be used to evaluate the PHS susceptibility of large and apparently healthy male and female broilers. PMID:9776067

Wideman, R F; Wing, T; Kirby, Y K; Forman, M F; Marson, N; Tackett, C D; Ruiz-Feria, C A

1998-10-01

297

Antitumor activity of galactoxyloglucan-gold nanoparticles against murine ascites and solid carcinoma.  

PubMed

Galactoxyloglucan polysaccharide (PST001), isolated from the seed kernels of Tamarindus indica (Ti), was used both as reducing and capping agent for the preparation of gold nanoparticles (PST-Gold) of 20 nm size. The present study evaluated the anticancer effects of the PST-Gold nanoparticles both in vitro and in vivo. The cytotoxicity was evaluated in the murine cancer cell lines, Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC). Galactoxyloglucan-gold nanoparticles (PST-Gold) not only retained the anticancer effects of PST001, but also showed enhanced cytotoxicity via induction of apoptosis even at lower doses and lesser incubation times. In vivo antitumor activity was tested in DLA and EAC murine ascites and EAC solid-tumor syngeneic mouse models. PST-Gold nanoparticles reduced tumor burden and increased median survival and life span significantly in both tumor models compared to the controls. The PST-Gold nanoparticles were very effective as a chemopreventive agent, showing the best overall response when administered prior to tumor induction. In the case of solid tumors, intratumoral administration of the PST-Gold nanoparticles yielded significant results with regard to survival and increment in lifespan as compared to intraperitoneal mode of drug administration. Further studies in higher animal models and in patients at high-risk for recurrence are warranted to fully explore and develop the potential of PST-Gold nanoconjugates as a chemopreventive and therapeutic anti-cancer agent. PMID:24486833

Joseph, Manu M; Aravind, S R; George, Suraj K; Pillai, K Raveendran; Mini, S; Sreelekha, T T

2014-04-01

298

A tumor cell growth inhibitor from polygonum hypoleucum Ohwi  

Microsoft Academic Search

Polygonum hypoleucum Ohwi (P. hypoleucum Ohwi) has been used as a Chinese medicine for a long time. In the present study, four anthraquinones, emodin, emodin 1-O-?-D-glucoside (49A), physcion (62A), and physcion 1-O-?-D-glucoside (50A) were identified from P. hypoleucum Ohwi and their inhibitory effects on various tumor cells proliferation were investigated. On a percentage basis, emodin had the highest suppressing activity

Yuh-Chi Kuo; Chang-Ming Sun; Jun-Chih Ou; Wei-Jern Tsai

1997-01-01

299

News Note: Gene Therapy Method Slows Tumor Growth in Mice  

Cancer.gov

NCI researchers have developed a novel method in mice of delivering genes to cancer cells, that when expressed, promote cell death. These genes, known as suicide genes, cause a cell to kill itself through a process known as apoptosis. The new technique uses the survivin gene promoter to express the suicide gene and induce apoptosis in cancer cells. This method of gene delivery effectively targeted tumor cells with a minimum effect on normal cells.

300

Silencing Met receptor tyrosine kinase signaling decreased oral tumor growth and increased survival of nude mice  

PubMed Central

SUMMARY Objectives The hepatocyte growth factor receptor (Met) is frequently overexpressed in Head and Neck Squamous Cell Carcinoma (HNSCC), correlating positively with high-grade tumors and shortened patient survival. As such, Met may represent an important therapeutic target. The purpose of this study was to explore the role of Met signaling for HNSCC growth and locoregional dissemination. Materials and methods Using a lentiviral system for RNA interference, we knocked down Met in established HNSCC cell lines that express high levels of the endogenous receptor. The effect of Met silencing on in vitro proliferation, cell survival and migration was examined using western analysis, immunohisto-chemistry and live cell imaging. In vivo tumor growth, dissemination and mouse survival was assessed using an orthotopic tongue mouse model for HNSCC. Results We show that Met knockdown (1) impaired activation of downstream MAPK signaling; (2) reduced cell viability and anchorage independent growth; (3) abrogated HGF-induced cell motility on laminin; (4) reduced In vivo tumor growth by increased cell apoptosis; (5) caused reduced incidence of tumor dissemination to regional lymph nodes and (6) increased the survival of nude mice with orthotopic xenografts. Conclusion Met signaling is important for HNSCC growth and locoregional dissemination In vivo and that targeting Met may be an important strategy for therapy. PMID:24268630

Tao, X.; Hill, K.S.; Gaziova, I.; Sastry, S.K.; Qui, S.; Szaniszlo, P.; Fennewald, S.; Resto, V.A.; Elferink, L.A.

2013-01-01

301

Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth.  

PubMed

SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors, and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome. Mouse models validated Smarcb1 as a bona fide tumor suppressor, as Smarcb1 inactivation in mice results in 100% of the animals rapidly developing cancer. SMARCB1 was the first subunit of the SWI/SNF complex found mutated in cancer. More recently, at least seven other genes encoding SWI/SNF subunits have been identified as recurrently mutated in cancer. Collectively, 20% of all human cancers contain a SWI/SNF mutation. Consequently, investigation of the mechanisms by which SMARCB1 mutation causes cancer has relevance not only for rhabdoid tumors, but also potentially for the wide variety of SWI/SNF mutant cancers. Here we discuss normal functions of SMARCB1 and the SWI/SNF complex as well as mechanistic and potentially therapeutic insights that have emerged. PMID:24853101

Kim, Kimberly H; Roberts, Charles W M

2014-09-01

302

Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.  

PubMed

Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3? activation, while p38? phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors. PMID:24789042

Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

2014-07-01

303

Dual-Action Combination Therapy Enhances Angiogenesis while Reducing Tumor Growth and Spread.  

PubMed

Increasing chemotherapy delivery to tumors, while enhancing drug uptake and reducing side effects, is a primary goal of cancer research. In mouse and human cancer models in vivo, we show that coadministration of low-dose Cilengitide and Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine delivery. This approach reduces tumor growth, metastasis, and minimizes side effects while extending survival. At a molecular level, this strategy alters Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy efficacy. Overall, our data demonstrate that vascular promotion therapy is a means to improve cancer treatment. PMID:25584895

Wong, Ping-Pui; Demircioglu, Fevzi; Ghazaly, Essam; Alrawashdeh, Wasfi; Stratford, Michael R L; Scudamore, Cheryl L; Cereser, Biancastella; Crnogorac-Jurcevic, Tatjana; McDonald, Stuart; Elia, George; Hagemann, Thorsten; Kocher, Hemant M; Hodivala-Dilke, Kairbaan M

2015-01-12

304

Fufang Kushen injection inhibits sarcoma growth and tumor-induced hyperalgesia via TRPV1 signaling pathways.  

PubMed

Cancer pain is a deleterious consequence of tumor growth and related inflammation. Opioids and anti-inflammatory drugs provide first line treatment for cancer pain, but both are limited by side effects. Fufang Kushen injection (FKI) is GMP produced, traditional Chinese medicine used alone or with chemotherapy to reduce cancer-associated pain. FKI limited mouse sarcoma growth both in vivo and in vitro, in part, by reducing the phosphorylation of ERK and AKT kinases and BAD. FKI inhibited TRPV1 mediated capsaicin-induced ERK phosphorylation and reduced tumor-induced proinflammatory cytokine production. Thus, FKI limited cancer pain both directly by blocking TRPV1 signaling and indirectly by reducing tumor growth. PMID:25242356

Zhao, Zhizheng; Fan, Huiting; Higgins, Tim; Qi, Jia; Haines, Diana; Trivett, Anna; Oppenheim, Joost J; Wei, Hou; Li, Jie; Lin, Hongsheng; Howard, O M Zack

2014-12-28

305

A validated mathematical model of tumor growth including tumor-host interaction, cell-mediated immune  

E-print Network

between the stromal and the neoplastic tissue may ultimately prove to be as important as the cancer cell of the present work is to develop a validated ODE model of tumor progression with three interacting cell data (Diefenbach et al., 2001), verifying that the lysis of cancer cells by the effector constituents

Rey Juan Carlos, Universidad

306

Novel EphB4 Monoclonal Antibodies Modulate Angiogenesis and Inhibit Tumor Growth  

PubMed Central

EphB4 receptor tyrosine kinase and its cognate ligand EphrinB2 regulate induction and maturation of newly forming vessels. Inhibition of their interaction arrests angiogenesis, vessel maturation, and pericyte recruitment. In addition, EphB4 is expressed in the vast majority of epithelial cancers and provides a survival advantage to most. Here, we describe two anti-EphB4 monoclonal antibodies that inhibit tumor angiogenesis and tumor growth by two distinct pathways. MAb131 binds to fibronectin-like domain 1 and induces degradation of human EphB4, but not murine EphB4. MAb131 inhibits human endothelial tube formation in vitro and growth of human tumors expressing EphB4 in vivo. In contrast, MAb47 targets fibronectin-like domain 2 of both human and murine EphB4 and does not alter EphB4 receptor levels, but inhibits angiogenesis and growth of both EphB4-positive and EphB4-negative tumors in a mouse s.c. xenograft model. Combination of MAb47 and bevacizumab enhances the antitumor activity and induces tumor regression. Indeed, humanized antibodies hAb47 and hAb131 showed similar affinity for EphB4 and retained efficacy in the inhibition of primary tumor development and experimental metastasis. PMID:20133814

Krasnoperov, Valery; Kumar, S. Ram; Ley, Eric; Li, Xiuqing; Scehnet, Jeffrey; Liu, Ren; Zozulya, Sergey; Gill, Parkash S.

2010-01-01

307

Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth.  

PubMed

Ovarian cancer mortality ranks highest among all gynecologic cancers with growth factor pathways playing an integral role in tumorigenesis, metastatic dissemination, and therapeutic resistance. The HER and VEGF receptor (VEGFR) are both overexpressed and/or aberrantly activated in subsets of ovarian tumors. While agents targeting either the HER or VEGF pathways alone have been investigated, the impact of these agents have not led to overall survival benefit in ovarian cancer. We tested the hypothesis that cotargeting HER and VEGFR would maximize antitumor efficacy at tolerable doses. To this end, ovarian cancer xenografts grown intraperitoneally in athymic nude mice were tested in response to AC480 (pan-HER inhibitor, "HERi"), cediranib (pan-VEGFR inhibitor "VEGFRi"), or BMS-690514 (combined HER/VEGFR inhibitor "EVRi"). EVRi was superior to both HERi and VEGFRi in terms of tumor growth, final tumor weight, and progression-free survival. Correlative tumor studies employing phosphoproteomic antibody arrays revealed distinct agent-specific alterations, with EVRi inducing the greatest overall effect on growth factor signaling. These data suggest that simultaneous inhibition of HER and VEGFR may benefit select subsets of ovarian cancer tumors. To this end, we derived a novel HER/VEGF signature that correlated with poor overall survival in high-grade, late stage, serous ovarian cancer patient tumors. PMID:24130056

Becker, Marc A; Farzan, Thahir; Harrington, Sean C; Krempski, James W; Weroha, S John; Hou, Xiaonan; Kalli, Kimberly R; Wong, Tai W; Haluska, Paul

2013-12-01

308

Vascular CD39/ENTPD1 Directly Promotes Tumor Cell Growth by Scavenging Extracellular Adenosine Triphosphate12  

PubMed Central

Extracellular adenosine triphosphate (ATP) is known to boost immune responses in the tumor microenvironment but might also contribute directly to cancer cell death. CD39/ENTPD1 is the dominant ectonucleotidase expressed by endothelial cells and regulatory T cells and catalyzes the sequential hydrolysis of ATP to AMP that is further degraded to adenosine by CD73/ecto-5?-nucleotidase. We have previously shown that deletion of Cd39 results in decreased growth of transplanted tumors in mice, as a result of both defective angiogenesis and heightened innate immune responses (secondary to loss of adenosinergic immune suppression). Whether alterations in local extracellular ATP and adenosine levels as a result of CD39 bioactivity directly affect tumor growth and cytotoxicity has not been investigated to date. We show here that extracellular ATP exerts antitumor activity by directly inhibiting cell proliferation and promoting cancer cell death. ATP-induced antiproliferative effects and cell death are, in large part, mediated through P2X7 receptor signaling. Tumors in Cd39 null mice exhibit increased necrosis in association with P2X7 expression. We further demonstrate that exogenous soluble NTPDase, or CD39 expression by cocultured liver sinusoidal endothelial cells, stimulates tumor cell proliferation and limits cell death triggered by extracellular ATP. Collectively, our findings indicate that local expression of CD39 directly promotes tumor cell growth by scavenging extracellular ATP. Pharmacological or targeted inhibition of CD39 enzymatic activity may find utility as an adjunct therapy in cancer management. PMID:21390184

Feng, Lili; Sun, Xiaofeng; Csizmadia, Eva; Han, Lihui; Bian, Shu; Murakami, Takashi; Wang, Xin; Robson, Simon C; Wu, Yan

2011-01-01

309

Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide  

PubMed Central

Caveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using the human glioblastoma-derived cell line U-87MG, further support the role of Cav-1 as a negative regulator of tumor growth. Using a lentiviral transduction approach, we were able to stably overexpress Cav-1 in U-87MG cells. Gene expression microarray analyses demonstrated significant enrichment in gene signatures corresponding to downregulation of MAPK, PI3K/AKT and mTOR signaling, as well as activation of apoptotic pathways in Cav-1-overexpressing U-87MG cells. These same gene signatures were later confirmed at the protein level in vitro. To explore the ability of Cav-1 to regulate tumor growth in vivo, we further show that Cav-1-overexpressing U-87MG cells display reduced tumorigenicity in an ectopic xenograft mouse model, with marked hypoactivation of MAPK and PI3K/mTOR pathways. Finally, we demonstrate that Cav-1 overexpression confers sensitivity to the most commonly used chemotherapy for glioblastoma, temozolomide. In conclusion, Cav-1 negatively regulates key cell growth and survival pathways and may be an effective biomarker for predicting response to chemotherapy in glioblastoma. PMID:23598719

Quann, Kevin; Gonzales, Donna M.; Mercier, Isabelle; Wang, Chenguang; Sotgia, Federica; Pestell, Richard G.; Lisanti, Michael P.; Jasmin, Jean-François

2013-01-01

310

Intra-vital ultrasonographic monitoring of intra-cerebral tumor growth in a rat glioma model: technical note.  

PubMed

The assessment of therapeutic effects in rodent glioma models by comparison of post mortem tumor sizes has to deal with differing individual growth kinetics and the possibility of spontaneous tumor regression. This technical note describes the intravital ultrasonographical monitoring of cerebral tumor growth in individual animals. In the experiments C6 lacZ glioma cells were injected intracerebrally into female Wistar rats. Extended craniectomy allowed for transcutaneous sonographic examination of the tumor growth. Four animals were followed ultrasonographically, the volumes of the tumors were calculated and plotted graphically, and on day 21 histological evaluation was performed. Our results show that ultrasonography is an easy and reliable imaging modality for frequent assessment of tumor growth kinetics in the intra-cerebral rat glioma model. It allows for the intravital monitoring of treatment with new therapeutic strategies and increases the reliability of the model by visualization of the tumor size before initiation of treatment. PMID:15494118

Nestler, Ulf; Luecke, Marcus; Joedicke, Andreas; Winking, Michael

2004-10-01

311

MicroRNA-17 inhibits tumor growth by stimulating T-cell mediated host immune response  

PubMed Central

Background Melanoma is one of the fastest-rising types of cancer in North American. Accumulating evidence suggests that anti-tumor immune tolerance plays a critical role in tumor development. Methods B16 melanoma cells were injected into wild type and miR-17 overexpressing transgenic mice. Tumor growth was monitored and tumor bearing mice were sacrificed by the end of the forth week. Peripheral blood and spleen cells were subject to flow cytometry analysis and tumor samples were subject to immunohistochemistry staining. Meanwhile, Jurkat cells transfected with mock-control or miR-17 overexpressing plasmid were co-cultured with B16 cells. The influence of miR-17 on cell cycle, proliferation and survival was evaluated. Results The melanoma tumors formed in mice overexpressing miR-17 were less than that in wild type mice. In addition, the miR-17 tumors were less invasive and less angiogenic. The percentage of CD8+ T cells was suppressed in miR-17 transgenic mice before melanoma cell injection. Its level was significantly increased upon tumor grafting. More tumor infiltrating CD8+ cytotoxic T lymphocyte could be found in transgenic mice with tumor formation. Luciferase assay and protein analysis indicated that STAT3 was the target of miR-17. Decreased levels of STAT3 were associated with miR-17 over-expression. Down-regulation of STAT3 in Jurkat cells promoted cell proliferation and mitosis. Conclusions MiR-17 inhibits melanoma growth by stimulating CD8+ T cells mediated host immune response, which is due to its regulation of STAT3. PMID:25594054

Li, Haoran; Gupta, Shaan; Du, William W.; Yang, Burton B.

2014-01-01

312

p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions.  

PubMed

Although most pituitary tumors are well differentiated, histologically benign neoplasms, their clinical behavior is known to vary greatly. These lesions are relentlessly aggressive in some instances yet biologically indolent in others, but these prognostically relevant differences in behavior are not reflected in their histopathological appearance. As a means of identifying intrinsically aggressive pituitary tumors, we evaluated 70 pituitary adenomas and 7 primary pituitary carcinomas for their expression of the p53 gene product, a nuclear phosphoprotein whose immunohistochemical accumulation has served as an unfavorable prognostic factor for a wide range of human neoplasms. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross operatively or radiologically apparent infiltration of dura or bone. Conclusive nuclear immunopositivity for p53 was identified in a total of 12 tumors, all being either invasive adenomas or primary pituitary carcinomas. A clear and highly significant association was evident between p53 expression and tumor behavior, as the proportion of p53-positive cases among noninvasive adenomas, invasive adenomas, and pituitary carcinomas was 0, 15.2, and 100%, respectively (chi 2 = 44.72; degrees of freedom, 2; P < 0.001). A comparison of previously reported growth fraction data with p53 expression indicated that the mean Ki-67-derived growth fraction of p53-positive tumors was significantly higher than that of p53-negative tumors (10.41 +/- 2.20 versus 2.51 +/- 0.28%) (+/- standard error of the mean, two-sample t test for independent samples, P = 0.004). There was no apparent relationship between the functional status of the tumor and p53 expression; positivity was observed among somatotroph, lactotroph, corticotroph, and clinically nonfunctioning pituitary tumors. These data indicate that p53 expression, when conclusively present in pituitary tumors, may be of some diagnostic usefulness as a marker of biologically aggressive behavior. PMID:8692397

Thapar, K; Scheithauer, B W; Kovacs, K; Pernicone, P J; Laws, E R

1996-04-01

313

Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature  

PubMed Central

We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20–26 °C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30–31 °C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8+ T lymphocytes and CD8+ T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of cold-stress. Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response. PMID:24248371

Kokolus, Kathleen M.; Capitano, Maegan L.; Lee, Chen-Ting; Eng, Jason W.-L.; Waight, Jeremy D.; Hylander, Bonnie L.; Sexton, Sandra; Hong, Chi-Chen; Gordon, Christopher J.; Abrams, Scott I.; Repasky, Elizabeth A.

2013-01-01

314

ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis.  

PubMed

Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including anaplastic large-cell lymphoma (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared with other types of T-cell lymphoma or EGFR- and K-RAS-mutated NSCLC, respectively. Consistently, in both ALCL and NSCLC, we found that under hypoxic conditions, ALK directly regulated the abundance of hypoxia-inducible factors (HIF), which are key players of the hypoxia response in normal tissues and cancers. In ALCL, the upregulation of HIF1? and HIF2? in hypoxic conditions required ALK activity and its downstream signaling proteins STAT3 and C/EBP?. In vivo, ALK regulated VEGFA production and tumor angiogenesis in ALCL and NSCLC, and the treatment with the anti-VEGFA antibody bevacizumab strongly impaired ALCL growth in mouse xenografts. Finally, HIF2?, but not HIF1?, was required for ALCL growth in vivo whereas the growth and metastasis potential of ALK-rearranged NSCLC required both HIF1? and HIF2?. In conclusion, we uncovered an ALK-specific regulation of the hypoxia response across different ALK(+) tumor types and propose HIFs as a powerful specific therapeutic target in ALK-rearranged ALCL and NSCLC. PMID:25193384

Martinengo, Cinzia; Poggio, Teresa; Menotti, Matteo; Scalzo, Maria Stella; Mastini, Cristina; Ambrogio, Chiara; Pellegrino, Elisa; Riera, Ludovica; Piva, Roberto; Ribatti, Domenico; Pastorino, Fabio; Perri, Patrizia; Ponzoni, Mirco; Wang, Qi; Voena, Claudia; Chiarle, Roberto

2014-11-01

315

Zyflamend, a combination of herbal extracts, attenuates tumor growth in murine xenograft models of prostate cancer.  

PubMed

Prostate cancer (PrC) is the second deadliest cancer of males in the United States Hormone deprivation therapy (HDT), a common therapy for advanced forms of the disease, results in tumor regression; unfortunately, tumors inevitably become castrate-resistant. Diet is not an appropriate primary therapy for refractory forms of the disease; however, diet may be effective as an adjuvant to HDT, potentially extending the latency period and delaying relapse and/or inhibiting refractory growth. Zyflamend® is a combination of extracts from multiple herbs, each with reported anticancer properties. Zyflamend can inhibit growth of various PrC cell lines, but no studies have investigated its potential use in vivo using a model of castrate-resistant PrC. In this study, oral doses of Zyflamend at human equivalent doses inhibited androgen-dependent and castrate-resistant tumor growth in a mouse model that mimics advanced stages of the disease, and reduced the expression of a number of biomarkers linked to PrC progression including pAKT, prostate specific antigen, histone deacetylases, and androgen receptor. In summary, this is the first article to report that Zyflamend, when provided at human equivalent doses, can potentiate the effects of hormone deprivation on tumor regression and growth inhibition of androgen-dependent and castrate-resistant PrC tumors in vivo. PMID:22663543

Huang, E-Chu; McEntee, Michael F; Whelan, Jay

2012-01-01

316

The Tumor Microenvironment Contribution to Development, Growth, Invasion and Metastasis of Head and Neck Squamous Cell Carcinomas  

PubMed Central

Head and neck squamous cell carcinoma (HNSCC) is a complex tissue that contains tumor cells and the surrounding stroma, which is populated by different types of mesenchymal cells and the extracellular matrix (ECM). Collectively, they are referred to as the tumor microenvironment (TME). Recent studies have shown that TME has a more profound influence on the growth and metastasis of HNSCC than was previously appreciated. Because carcinoma-associated fibroblasts (CAFs) are frequently observed in the stroma of the tumor, this review focuses on the potential role of tumor-CAFs interactions in progression of HNSCC. Tumor-CAFs crosstalk enhances the production of growth factors, cytokines, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, which eventually facilitates tumor growth. In fact, factors and cells that do not support tumor growth are usually down regulated or mitigated in TME. Therefore TME may determine the fate of the tumors at the site of invasion and metastasis. For tumor cells that survive at these sites, stromal activation may serve to establish a supportive tumor stroma, fostering the outgrowth of the metastatic cells. The concept of tumor-stromal interactions and microenvironmental niche has profound consequences in tumor growth and metastasis and therefore, it's understanding will open up new strategies for the diagnosis, prognosis and therapy of HNSCC. PMID:23386906

Koontongkaew, Sittichai

2013-01-01

317

The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas.  

PubMed

Head and neck squamous cell carcinoma (HNSCC) is a complex tissue that contains tumor cells and the surrounding stroma, which is populated by different types of mesenchymal cells and the extracellular matrix (ECM). Collectively, they are referred to as the tumor microenvironment (TME). Recent studies have shown that TME has a more profound influence on the growth and metastasis of HNSCC than was previously appreciated. Because carcinoma-associated fibroblasts (CAFs) are frequently observed in the stroma of the tumor, this review focuses on the potential role of tumor-CAFs interactions in progression of HNSCC. Tumor-CAFs crosstalk enhances the production of growth factors, cytokines, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, which eventually facilitates tumor growth. In fact, factors and cells that do not support tumor growth are usually down regulated or mitigated in TME. Therefore TME may determine the fate of the tumors at the site of invasion and metastasis. For tumor cells that survive at these sites, stromal activation may serve to establish a supportive tumor stroma, fostering the outgrowth of the metastatic cells. The concept of tumor-stromal interactions and microenvironmental niche has profound consequences in tumor growth and metastasis and therefore, it's understanding will open up new strategies for the diagnosis, prognosis and therapy of HNSCC. PMID:23386906

Koontongkaew, Sittichai

2013-01-01

318

Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice.  

PubMed

Tumor cells secrete factors that stimulate the migration of peripheral blood leukocytes and enhance tumor progression by affecting angiogenesis. In these studies, we investigated the effect of morphine, a known immunosuppressant, on leukocyte migration and recruitment to conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells. Our results indicate that morphine treatment reduced the migration and recruitment of tumor-infiltrating leukocytes into Matrigel plugs and polyvinyl alcohol sponges containing conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells when compared with placebo. A reciprocal increase in peripheral blood leukocytes was observed at the time of plug or sponge removal in morphine-treated mice. Decreased angiogenesis was observed in conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells Matrigel plugs taken from morphine-treated wild-type mice when compared with placebo but was abolished in morphine-treated ?-opioid receptor knockout mice. In addition, in vitro studies using trans-well and electric cell substrate impedance sensing system studies reveal for the first time morphine's inhibitory effects on leukocyte migration and their ability to transmigrate across an activated endothelial monolayer. Taken together, these studies indicate that morphine treatment can potentially decrease leukocyte transendothelial migration and reduce angiogenesis associated with tumor growth. The use of morphine for cancer pain management may be beneficial through its effects on angiogenesis. PMID:24495739

Koodie, Lisa; Yuan, Hongyan; Pumper, Jeffery A; Yu, Haidong; Charboneau, Richard; Ramkrishnan, Sundaram; Roy, Sabita

2014-04-01

319

Novel monoclonal antibody inhibits tumor growth in breast cancer and angiosarcoma  

Cancer.gov

A monoclonal antibody targeting a protein known as SFPR2 has been shown by researchers at the University of North Carolina and its Lineberger Comprehensive Cancer Center to inhibit tumor growth in pre-clinical models of breast cancer and angiosarcoma. In a paper published in the April 19 issue of Molecular Cancer Therapeutics, a team used a monoclonal antibody to target SFRP2 expressed in cells from triple-negative breast cancer and the aggressive blood-vessel malignancy angiosarcoma, reducing the rate of tumor growth.

320

Hmgb1-IL-23-IL-17-IL-6-Stat3 axis promotes tumor growth in murine models of melanoma.  

PubMed

In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, IL-17 deficiency results in reduced melanoma tumor size, diminished numbers of proliferating cells and blood vessels, and decreased percentage of CD11b(+)Gr-1(+) MDSCs in tumor tissues. IL-17 promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066 in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth. Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17(-/-) mice results in markedly increased tumor size and p-Stat3 expression, whereas additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits melanoma tumor growth and reduces production of IL-23 and IL-17. All these data suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor development in murine models of melanoma, and blocking any portion of this axis will attenuate melanoma tumor growth. PMID:24453427

Tang, Qiu; Li, Jian; Zhu, Hongfei; Li, Pan; Zou, Zhenwei; Xiao, Yin

2013-01-01

321

Distribution of ceftazidime in ascitic fluid.  

PubMed Central

The pharmacokinetics of ceftazidime were investigated in eight normal subjects and eight patients with ascites after intravenous administration of 1 g of the drug. Samples of blood and ascitic fluid were collected for 6 h after dosage, and urine samples were collected for 24 h. Pharmacokinetic data were calculated by using a one-compartment model. The apparent volume of distribution and half-life of elimination (t1/2 beta) in patients with ascites were approximately three times those in normal subjects. In contrast, renal clearance was greater in the normal subjects. With respect to ascites, the mean area under the concentration-time curve was 95.3 +/- 38.3 micrograms X h/ml. The mean ratio of the area under the concentration-time curve for ascitic fluid to that for plasma was 69.9% (+/- 38.2). These data show that ceftazidime rapidly diffuses into the peritoneal space, in which concentrations greater than 10 micrograms/ml were present for at least 6 h. PMID:6378086

Benoni, G; Arosio, E; Raimondi, M G; Apolloni, E; Passarella, E; Lechi, A; Velo, G P

1984-01-01

322

Vav1 promotes lung cancer growth by instigating tumor-microenvironment cross-talk via growth factor secretion.  

PubMed

Vav1 is a signal transducer that functions as a scaffold protein and a regulator of cytoskeleton organization in the hematopoietic system, where it is exclusively expressed. Recently, Vav1 was shown to be involved in diverse human cancers, including lung cancer. We demonstrate that lung cancer cells that abnormally express Vav1 secrete growth factors in a Vav1-dependent manner. Transcriptome analysis demonstrated that Vav1 depletion results in a marked reduction in the expression of colony-stimulating-factor-1 (CSF1), a hematopoietic growth factor. The association between Vav1 expression and CSF1 was further supported by signal transduction experiments, supporting involvement of Vav1 in regulating lung cancer secretome. Blocking of ERK phosphorylation, led to a decrease in CSF1 transcription, thus suggesting a role for ERK, a downstream effector of Vav1, in CSF1 expression. CSF1-silenced cells exhibited reduced focus formation, proliferation abilities, and growth in NOD/SCID mice. CSF1-silenced H358 cells resulted in significantly smaller tumors, showing increased fibrosis and a decrease in tumor infiltrating macrophages. Finally, immunohistochemical analysis of primary human lung tumors revealed a positive correlation between Vav1 and CSF1 expression, which was associated with tumor grade. Additional results presented herein suggest a potential cross-talk between cancer cells and the microenvironment controlled by CSF1/Vav1 signaling pathways. PMID:25313137

Sebban, Shulamit; Farago, Marganit; Rabinovich, Shiran; Lazer, Galit; Idelchuck, Yulia; Ilan, Lena; Pikarsky, Eli; Katzav, Shulamit

2014-10-15

323

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.  

PubMed

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1? mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1? in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth. PMID:25102452

Norden, Diana M; Bicer, Sabahattin; Clark, Yvonne; Jing, Runfeng; Henry, Christopher J; Wold, Loren E; Reiser, Peter J; Godbout, Jonathan P; McCarthy, Donna O

2015-01-01

324

Effect of soy isoflavones on the growth of human breast tumors: findings from preclinical studies.  

PubMed

Breast cancer is the most common cancer among women worldwide, and many women with breast cancer live more than 5 years after their diagnosis. Breast cancer patients and survivors have a greater interest in taking soy foods and isoflavone supplements. However, the effect of isoflavones on breast cancer remains controversial. Thus, it is critical to determine if and when isoflavones are beneficial or detrimental to breast cancer patients. According to the available preclinical data, high concentrations of isoflavones inhibit the proliferation of breast cancer cells, regardless of their estrogen receptor (ER) status. In comparison, genistein, a major isoflavone, has stimulated tumor growth at low concentrations and mitigated tamoxifen efficacy in ER-positive breast cancer. Studies have indicated that the relative levels of genistein and estrogen at the target site are important to determine the genistein effect on the ER-positive tumor growth. However, studies using ovariectomized mice and subcutaneous xenograft models might not truly reflect estrogen concentrations in human breast tumors. Moreover, it may be an oversimplification that isoflavones stimulate hormone-dependent tumor growth due to their potential estrogenic effect since studies also suggest nonestrogenic anticancer effects of isoflavones and ER-independent anticancer activity of tamoxifen. Therefore, the concentrations of isoflavones and estrogen in human breast tumors should be considered better in future preclinical studies and the parameters that can estimate those levels in breast tumors are required in human clinical/epidemiological investigation. In addition, it will be important to identify the molecular mechanisms that either inhibit or promote the growth of breast cancer cells by soy isoflavones, and use those molecules to evaluate the relevance of the preclinical findings to the human disease and to predict the health effects of isoflavones in human breast tumors. PMID:25493176

Kwon, Youngjoo

2014-11-01

325

Effects of restraint stress on inoculated tumor growth and immune response in rats.  

PubMed

Rats were given injections s.c. of mammary adenocarcinoma cells which developed into undifferentiated carcinomas within a few days. The animals were either left alone or were stressed by restraint for 3 h a day for 11 days and then left for 12 days undisturbed to recover. During this schedule, some animals were sacrificed immediately after the 11-day stress period, whereas others were allowed the 12-day recovery period; unstressed animals were sacrificed as controls on these 2 days. Tumor burden was significantly increased during stress and markedly decreased after the recovery period as compared to unstressed rats. Higher mitotic activity was seen in the tumors of rats which recovered from stress. The immune system responded differently to stress in healthy and tumor-bearing animals. In the tumor-bearing animals, leukocytes were decreased by stress and increased after the recovery period. Lymphocytes were increased, and neutrophiles and large granular lymphocytes were decreased after the recovery period. Total T-cells and suppressor T-cells were decreased during stress and increased during recovery. The percentage of T-cell populations was unaffected by stress, but the percentage of suppressor T-cells increased during recovery. Natural killer cell activity was unaffected by stress but increased after the recovery period. These results indicate that (a) stress and recovery from stress differentially affect tumor development and growth, (b) stress and recovery from stress cause different effects on the immune system in healthy or tumor-bearing animals, (c) stress and recovery from stress stimulate or inhibit different parts of the immune system, and (d) a decreased lymphocyte count and total and suppressor T-cell numbers correlated best with enhanced tumor growth, whereas increased numbers of neutrophils, large granular lymphocytes, total and suppressor T-cells, natural killer cell activity, and a decreased percentage of T-suppressor cells correlated best with depressed tumor growth. PMID:3928147

Steplewski, Z; Vogel, W H; Ehya, H; Poropatich, C; Smith, J M

1985-10-01

326

Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway  

PubMed Central

Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway. PMID:21203463

Yasuniwa, Yoshihiro; Izumi, Hiroto; Wang, Ke-Yong; Shimajiri, Shohei; Sasaguri, Yasuyuki; Kawai, Kazuaki; Kasai, Hiroshi; Shimada, Takashi; Miyake, Koichi; Kashiwagi, Eiji; Hirano, Gen; Kidani, Akihiko; Akiyama, Masaki; Han, Bin; Wu, Ying; Ieiri, Ichiro; Higuchi, Shun; Kohno, Kimitoshi

2010-01-01

327

Effect of selumetinib on the growth of anastrozole-resistant tumors.  

PubMed

Despite significant improvement in the treatment outcome of hormone responsive postmenopausal breast cancer, some patients eventually acquire resistance to aromatase inhibitors (AIs). Using our MCF-7Ca xenograft model, we observed that although AIs such as anastrozole initially inhibit tumor growth effectively, tumors eventually began to grow. Our previous data show that anastrozole-resistant tumors upregulate growth factor receptor pathways as they adapt to grow in the low estrogen environment. Therefore, in the current study, we investigated the effect of inhibiting the growth factor receptor pathways with a MEK-1/2 inhibitor selumetinib (AZD6244, ARRY-142866). We treated the mice with anastrozole-resistant tumors with selumetinib alone or in combination with anastrozole. MCF-7Ca cells were inoculated sc into ovariectomized athymic nude mice supplemented throughout the experiment with androstenedione (100 ?g/day), the substrate for aromatase conversion to estrogen. Once the tumors reached a measurable size (~300 mm(3)), the mice were treated with anastrozole (200 ?g/day), supplemented with androstenedione (?(4)A). The tumors in the anastrozole group doubled in volume after 6 weeks, at which time the animals were regrouped to receive the following treatments: (i) anastrozole, (ii) anastrozole withdrawal (?(4)A alone), (iii) selumetinib (25 mg/kg/d, bid, po), and (iv) selumetinib + anastrozole, (n = 10 mice/group). The treatments were given for 6 weeks (till week 12) and then the mice were euthanized, the tumors were collected and analyzed. The tumors of mice treated with selumetinib + anastrozole had significantly lower growth rates than those treated with single agents (p = 0.008). Western blot analysis of the tumors showed that treatment with anastrozole resulted in upregulation of proteins in the growth factor receptor cascade such as p-mTOR, pAkt, pMEK, and pMAPK. This was accompanied by downregulation of ER? protein, consistent with previous findings. The treatment of mice with selumetinib resulted in downregulation of activated MAPK, along with p-mTOR, which likely resulted in upregulation of ER?. Our results suggest that inhibition of the growth factor receptor pathway with selumetinib can reverse anastrozole resistance. PMID:23508762

Sabnis, Gauri J; Kazi, Armina; Golubeva, Olga; Shah, Preeti; Brodie, Angela

2013-04-01

328

A huge renal cyst mimicking ascites: a case report  

PubMed Central

Background Renal cysts are common in old patients, and usually remain untreated. Giant renal cyst measuring more than 15 cm in diameter and containing more than 1500 mls of serous fluid are rarely seen. We report a case of a 75-year-old man with a giant right renal cyst. Case presentation A 75-year-old man presented with a five years history of suprapubic pain, abdominal distension. He had no urological symptoms. Physical examination revealed a distended abdomen with shifting dullness. Routine hematology, biochemistry, and serum tumor markers were within normal limits. Erroneously diagnosed as ascites on ultrasonographic examination. Abdominal paracentesis of supposed ascites was performed. The diagnosis of giant renal cyst was finally made by Computed tomography (CT) and patient underwent continuous percutaneous catheter drainage with negative pressure, whereby 8 liters of fluid were removed with negative cytology. Subsequent Computed tomography after 6 months revealed disparition of the cysts, and the patient remained asymptomatic. Conclusion Giant renal cysts are uncommon; we conclude that the CT remains the best exam in patients evaluated for giant renal cyst. This to the best of our knowledge is the largest renal cyst in the medical literature. Studies are needed with particular attention to the factors associated with renal cyst enlargement. PMID:24428865

2014-01-01

329

Some Cancer Mutations Slow Tumor Growth | Physical Sciences in Oncology  

Cancer.gov

A typical cancer cell has thousands of mutations scattered throughout its genome and hundreds of mutated genes. However, only a handful of those genes, known as drivers, are responsible for cancerous traits such as uncontrolled growth. Cancer biologists have largely ignored these so-called passenger mutations, believing they had little or no impact on cancer progression.

330

Cellular and Tumor Radiosensitivity is Correlated to Epidermal Growth Factor Receptor Protein Expression Level in Tumors Without EGFR Amplification;Epidermal growth factor receptor; Radiotherapy; Squamous cell carcinoma; Biomarker; Local tumor control  

SciTech Connect

Purpose: There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts. Methods and Materials: The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blot and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC. Results: EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation. Conclusions: Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.

Kasten-Pisula, Ulla; Saker, Jarob [Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany); Eicheler, Wolfgang; Krause, Mechthild; Yaromina, Ala [Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technical University, Dresden (Germany); OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technical University, Dresden (Germany); Meyer-Staeckling, Soenke [Institute for Tumor Biology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany); Scherkl, Benjamin; Kriegs, Malte [Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany); Brandt, Burkhard [Institute for Tumor Biology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany); Grenman, Reidar [Department of Otorhinolaryngology-Head and Neck Surgery and Department of Medical Biochemistry and Genetics, Turku University and University Hospital of Turku, Turku (Finland); Petersen, Cordula [Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany); Baumann, Michael [Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technical University, Dresden (Germany); OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technical University, Dresden (Germany); Dikomey, Ekkehard, E-mail: dikomey@uke.uni-hamburg.de [Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg (Germany)

2011-07-15

331

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors  

SciTech Connect

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)] [Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)] [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)] [Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)

2012-11-15

332

Dynamic quantitative intravital imaging of glioblastoma progression reveals a lack of correlation between tumor growth and blood vessel density.  

PubMed

The spatiotemporal and longitudinal monitoring of cellular processes occurring in tumors is critical for oncological research. We focused on glioblastoma multiforme (GBM), an untreatable highly vascularized brain tumor whose progression is thought to critically depend on the oxygen and metabolites supplied by blood vessels. We optimized protocols for orthotopic GBM grafting in mice that were able to recapitulate the biophysical constraints normally governing tumor progression and were suitable for intravital multiphoton microscopy. We repeatedly imaged tumor cells and blood vessels during GBM development. We established methods for quantitative correlative analyses of dynamic imaging data over wide fields in order to cover the entire tumor. We searched whether correlations existed between blood vessel density, tumor cell density and proliferation in control tumors. Extensive vascular remodeling and the formation of new vessels accompanied U87 tumor cell growth, but no strong correlation was found between local cell density and the extent of local blood vessel density irrespective of the tumor area or time points. The technique moreover proves useful for comparative analysis of mice subjected either to Bevacizumab anti-angiogenic treatment that targets VEGF or to AMD3100, an antagonist of CXCR4 receptor. Bevacizumab treatment massively reduced tumoral vessel densities but only transiently reduced U87 tumor growth rate. Again, there was no correlation between local blood vessel density and local cell density. Moreover, Bev applied only prior to tumor implantation inhibited tumor growth to the same extent as post-grafting treatment. AMD3100 achieved a potent inhibition of tumor growth without significant reduction in blood vessel density. These results indicate that in the brain, in this model, tumor growth can be sustained without an increase in blood vessel density and suggest that GBM growth is rather governed by stromal properties. PMID:24069154

Ricard, Clément; Stanchi, Fabio; Rodriguez, Thieric; Amoureux, Marie-Claude; Rougon, Genevičve; Debarbieux, Franck

2013-01-01

333

Extensive Loculated Ascites in Hepatic Amyloidosis  

PubMed Central

Context: Amyloidosis is a disease of extracellular deposition of misfolded proteinaceous subunits, which could be systemic or localized disease. Though hepatic amyloidosis was not uncommon in autopsy series, most cases of hepatic amyloidosis were asymptomatic. Ascites, jaundice, portal hypertension, and gastrointestinal bleeding from esophageal varices were reported in literature. Case report: A 42-year-old man with end-stage renal disease on hemodialysis and recent small bowel obstruction presented with chronic abdominal pain. Computed tomography of abdomen and pelvis showed extensive loculated ascites and multiple small bowel loops tethered to adhesions and hepatomegaly. Finally, hepatic venography and liver biopsy confirmed hepatic amyloidosis with portal hypertension. The patient was waiting for liver transplant for definite treatment. Conclusion: We report a rare case of hepatic amyloidosis with prior small bowel obstruction presented with extensive loculated ascites and multiple small bowel loops tethered to adhesions. PMID:25077085

Buppajarntham, Saranya; Kue-A-Pai, Pongsathorn

2014-01-01

334

Overexpression of hypoxia-inducible factor-1? and vascular endothelial growth factor in sacral giant cell tumors and the correlation with tumor microvessel density  

PubMed Central

Although classified as benign, giant cell tumors of the bone (GCTB) may be aggressive, recur and even metastasize to the lungs. In addition, the pathogenesis and histogenesis remain unclear; thus, the driving factors behind the strong tumor growth capacity of GCTB require investigation. In the present study, the expression levels of hypoxia-inducible factor (HIF)-1? and vascular endothelial growth factor (VEGF), which are promoted by hypoxic conditions, were determined in 22 sacral GCTB samples using immunohistochemistry and western blot analysis. Furthermore, CD34 expression was analyzed using these methods. The correlation between HIF-1? or VEGF expression and the tumor microvessel density (MVD) was then determined. The results demonstrated that HIF-1?, VEGF and CD34 were overexpressed in the 22 sacral GCTB specimens, and overexpression of HIF-1? and VEGF correlated with the tumor MVD. Thus, the present study has provided novel indicators for the tumor growth capacity of GCTBs. PMID:25289039

FU, SHAOFENG; BAI, RUI; ZHAO, ZHENQUN; ZHANG, ZHIFENG; ZHANG, GANG; WANG, YUXIN; WANG, YONG; JIANG, DIANMING; ZHU, DEZHI

2014-01-01

335

Targeting of the Receptor Protein Tyrosine Phosphatase B with a Monoclonal Antibody Delays Tumor Growth in a Glioblastoma Model  

Microsoft Academic Search

The receptor protein tyrosine phosphatase B (RPTPB )i s a functional biomarker for several solid tumor types. RPTPB expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPB is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPB is

Erik D. Foehr; Gustavo Lorente; Jane Kuo; Rosie Ram; Karoly Nikolich; Roman Urfer

336

Insulin-like Growth Factor-I Is an Autocrine Regulator of Chromogranin A Secretion and Growth in Human Neuroendocrine Tumor Cells1  

Microsoft Academic Search

Carcinoid tumors are predominantly found in the gastrointestinal tract and are characterized by hypersecretion of various substances, including bioamines and neuropeptides, leading to functional tumor disease. Here, we demonstrate that human BON carcinoid tumor cells express function- ally active insulin-like growth factor-I (IGF-I) receptors and secrete IGF-I, suggesting an autocrine action of this growth factor. The IGF-I receptor was functionally

Gotz von Wichert; Peter M. Jehle; Andreas Hoeflich; Stefan Koschnick; Henning Dralle; Eckhard Wolf; Bertram Wiedenmann; Bernhard O. Boehm; Guido Adler; Thomas Seufferlein

2000-01-01

337

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

338

Honokiol thwarts gastric tumor growth and peritoneal dissemination by inhibiting Tpl2 in an orthotopic model.  

PubMed

Honokiol is known to suppress the growth of cancer cells; however, to date, its antiperitoneal dissemination effects have not been studied in an orthotopic mouse model. In the present study, we evaluated the antiperitoneal dissemination potential of Honokiol in an orthotopic mouse model and assessed associations with tumor growth factor-?1 (TGF?1) and cells stimulated by a carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Our results demonstrate that tumor growth, peritoneal dissemination and peritoneum or organ metastasis of orthotopically implanted MKN45 cells were significantly decreased in Honokiol-treated mice and that endoplasmic reticulum (ER) stress was induced. Honokiol-treated tumors showed increased epithelial signatures such as E-cadherin, cytokeratin-18 and ER stress marker. In contrast, decreased expression of vimentin, Snail and tumor progression locus 2 (Tpl2) was also noted. TGF?1 and MNNG-induced downregulation of E-cadherin and upregulation of Tpl2 were abrogated by Honokiol treatment. The effect of Tpl2 inhibition in cancer cells or endothelial cells was associated with inactivation of CCAAT/enhancer binding protein B, nuclear factor kappa-light-chain-enhancer of activated B cell and activator protein-1 and suppression of vascular endothelial growth factor. Inhibition of Tpl2 in gastric cancer cells by small interfering RNA or pharmacological inhibitor was found to effectively reduce growth ability and vessel density in vivo. Honokiol-induced reversal of epithelial-to-mesenchymal transition (EMT) and ER stress-induced apoptosis via Tp12 may involve the paralleling processes. Taken together, our results suggest that the therapeutic inhibition of Tpl2 by Honokiol thwarts both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT. PMID:23828905

Pan, Hung-Chuan; Lai, De-Wei; Lan, Keng-Hsin; Shen, Chin-Chang; Wu, Sheng-Mao; Chiu, Chien-Shan; Wang, Keh-Bin; Sheu, Meei-Ling

2013-11-01

339

A cellular automata model for avascular solid tumor growth under the effect of therapy  

NASA Astrophysics Data System (ADS)

Tumor growth has long been a target of investigation within the context of mathematical and computer modeling. The objective of this study is to propose and analyze a two-dimensional stochastic cellular automata model to describe avascular solid tumor growth, taking into account both the competition between cancer cells and normal cells for nutrients and/or space and a time-dependent proliferation of cancer cells. Gompertzian growth, characteristic of some tumors, is described and some of the features of the time-spatial pattern of solid tumors, such as compact morphology with irregular borders, are captured. The parameter space is studied in order to analyze the occurrence of necrosis and the response to therapy. Our findings suggest that transitions exist between necrotic and non-necrotic phases (no-therapy cases), and between the states of cure and non-cure (therapy cases). To analyze cure, the control and order parameters are, respectively, the highest probability of cancer cell proliferation and the probability of the therapeutic effect on cancer cells. With respect to patterns, it is possible to observe the inner necrotic core and the effect of the therapy destroying the tumor from its outer borders inwards.

Reis, E. A.; Santos, L. B. L.; Pinho, S. T. R.

2009-04-01

340

Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress  

PubMed Central

Tumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPK?. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors. PMID:21576264

Zaugg, Kathrin; Yao, Yi; Reilly, Patrick T.; Kannan, Karuppiah; Kiarash, Reza; Mason, Jacqueline; Huang, Ping; Sawyer, Suzanne K.; Fuerth, Benjamin; Faubert, Brandon; Kalliomäki, Tuula; Elia, Andrew; Luo, Xunyi; Nadeem, Vincent; Bungard, David; Yalavarthi, Sireesha; Growney, Joseph D.; Wakeham, Andrew; Moolani, Yasmin; Silvester, Jennifer; Ten, Annick You; Bakker, Walbert; Tsuchihara, Katsuya; Berger, Shelley L.; Hill, Richard P.; Jones, Russell G.; Tsao, Ming; Robinson, Murray O.; Thompson, Craig B.; Pan, Guohua; Mak, Tak W.

2011-01-01

341

Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo  

PubMed Central

Platelet-derived growth factor (PDGF) and its receptors (PDGFR), including PDGFR? and PDGFR?, play important roles in tumorigenesis, tumor progression, and the regulation of stromal cell function. Constitutive activation of PDGFR signaling, gene rearrangement, and activating mutations of PDGFR have been identified in various types of human tumors and malignancies. PDGFR? and PDGFR? belong to the family of type III receptor tyrosine kinases and, upon stimulation, activate downstream signaling cascades. Crenolanib is a specific tyrosine kinase inhibitor that targets and inhibits the kinase activity of PDGFR and the FMS-related tyrosine kinase 3. Its clinical efficacy in several human tumors is currently under investigation in Phase II clinical trials. In this study, we examined the potential role of crenolanib in the treatment of non-small-cell lung cancer (NSCLC). Using A549 cells as a model system, we have shown that crenolanib is capable of suppressing proliferation and inducing apoptosis in a dose-dependent manner. Crenolanib-treated cells have reduced migratory activity in response to inducers of chemotaxis. Furthermore, the in vivo antitumor activity of crenolanib was confirmed in an NSCLC xenograft tumor model. Injection of crenolanib significantly inhibited the growth of tumor mass by inducing apoptosis in tumor cells. Our results provide strong evidence supporting the use of crenolanib as a potential therapeutic agent in treating NSCLC. This work sets a foundation for further development of targeted and personalized therapeutics for lung cancer. PMID:25328409

Wang, Ping; Song, Liqiang; Ge, Hui; Jin, Pule; Jiang, Yifang; Hu, Wenxia; Geng, Nan

2014-01-01

342

Luteolin and its inhibitory effect on tumor growth in systemic malignancies  

SciTech Connect

Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ER? expression and causes inhibition of IGF-1 mediated PI3K–Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducing factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent. - Highlights: ? Luteolin and tumor growth in breast carcinomas. ? Luteolin and pulmonary cancer. ? Luteolin and colon cancer.

Kapoor, Shailendra, E-mail: shailendrakapoor@yahoo.com [74 crossing place, Mechanicsville, VA (United States)

2013-04-01

343

A Generative Approach for Image-Based Modeling of Tumor Growth  

E-print Network

Machine Learning and Perception Group, Microsoft Research, Cambridge, UK 7 Department of Diagnostic approaches for com- prehensive integration of information from different image sources and different time in patients with glioma. The tumor growth model is based on a reaction-diffusion framework. Model

Paris-Sud XI, Université de

344

ture in vivo. So far, there is no evidence that tumors can stimulate the growth of  

E-print Network

ture in vivo. So far, there is no evidence that tumors can stimulate the growth of new lymphatic metastasis via the lymphatic vasculature as well as in various other disorders involving the lym- phatic system and their treatment. REFERENCES AND NOTES ___________________________ 1. N. Ferrara and T. Davis

Prentiss, Mara

345

Suppressing Activity of Common Intestinal Bacteria Reduces Tumor Growth | Physical Sciences in Oncology  

Cancer.gov

Over the past few years, cancer researchers have come to suspect that the bacteria living in our gastrointestinal system may play a role in the development of some types of cancer. Now, a team of investigators from the University of California, San Diego (UCSD) School of Medicine has discovered that common intestinal bacteria do promote tumor growth in genetically susceptible mice.

346

Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model  

SciTech Connect

Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ?1 ?M at 24 h after treatment and ?0.5 ?M at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.

Yin, Shu-Cheng [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China) [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)] [Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Tao, Ze-Zhang, E-mail: zezhangtao@gmail.com [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China)] [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China)

2013-09-13

347

Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy  

Microsoft Academic Search

Tumor–endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their “crosstalk” with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluated the in vitro and in vivo synergistic and\\/or additive effects of a combination of conditional oncolytic adenovirus plus

Fengshuo Jin; Zhihui Xie; Calvin J Kuo; Leland W K Chung; Chia-Ling Hsieh

2005-01-01

348

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

349

Extinction Effects of Multiplicative Non-Gaussian Lévy Noise in a Tumor Growth System with Immunization  

NASA Astrophysics Data System (ADS)

The extinction phenomenon induced by multiplicative non-Gaussian Lévy noise in a tumor growth model with immune response is discussed. Under the influence of the stochastic immune rate, the model is analyzed in terms of a stochastic differential equation with multiplicative noise. By means of the theory of the infinitesimal generator of Hunt processes, the escape probability, which is used to measure the noise-induced extinction probability of tumor cells, is explicitly expressed as a function of initial tumor cell density, stability index and noise intensity. Based on the numerical calculations, it is found that for different initial densities of tumor cells, noise parameters play opposite roles on the escape probability. The optimally selected values of the multiplicative noise intensity and the stability index are found to maximize the escape probability.

Hao, Meng-Li; Xu, Wei; Li, Dong-Xi; Liu, Di

2014-05-01

350

TESTIN suppresses tumor growth and invasion via manipulating cell cycle progression in endometrial carcinoma  

PubMed Central

Background The TESTIN gene was demonstrated to be a tumor suppressor in prostate and breast cancer through inhibiting tumor growth and invasion. Herein, we aimed to investigate the detailed functions of TESTIN in the highly sexual hormone (estrogen)-dependent malignancy, endometrial carcinoma. Material/Methods TESTIN mRNA and protein expression were measured by qRT-PCR, Western blot and immunohistochemistry. Upregulation of TESTIN was achieved by transfecting the pcDNA3.1-TESTIN plasmids into AN3CA cells. Knockdown of TESTIN was achieved by transfecting the shRNA-TESTIN into Ishikawa cells. MTT assay, colony formation assay, and Transwell assay were used to investigate the effects of TESTIN on cellular proliferation and invasion. The apoptotic status and cell cycle were analyzed using flow cytometry. MMP2 secretion was determined by ELISA assay. The xenograft assay was used to investigate the functions of TESTIN in nude mice. Results Compared to the non-malignant adjacent endometrium, 54% of tumor samples presented downregulation of TESTIN (P<0.001). Loss of TESTIN protein was correlated with advanced tumor stage (P=0.047), high grade (P=0.034), and lymphatic vascular space invasion (P=0.036). In vitro, overexpression of TESTIN suppressed cell proliferation, induced dramatic G1 arrest, and inhibited tumor invasion through blocking the secretion of MMP2. Loss of TESTIN accelerated cellular proliferation, promoted cell cycle progression, and enhanced tumor invasion by increasing the secretion of MMP2. Consistently, TESTIN could significantly delay the growth of xenografts in nude mice. Conclusions TESTIN was commonly downregulated in human endometrial carcinoma and was associated with poor prognostic markers. Moreover, TESTIN significantly inhibited tumor growth and invasion via arresting cell cycle in in vitro and in vivo experiments. Therefore, we propose that TESTIN might be a prognostic marker and therapeutic target for endometrial carcinoma. PMID:24929083

Gu, Zhenpeng; Ding, Guofeng; Liang, Kuixiang; Zhang, Hongtao; Guo, Guanghong; Zhang, Lili; Cui, Jinxiu

2014-01-01

351

microRNA-137 modulates pancreatic cancer cells tumor growth, invasion and sensitivity to chemotherapy  

PubMed Central

Background: We intended to investigate the role of microRNA 137 (miR-137) in regulating pancreatic cancer cells’ growth in vitro and tumor development in vivo. Methods: QTR-PCR was used to examine the expression of miR-137 in pancreatic cancer cell lines and tumor cells from human patients. Lentivirual vector containing miR-137 mimic was used to overexpress miR-137 in PANC-1 and MIA PaCa-2 cells. The effects of overexpressing miR-137 on pancreatic cancer cell invasion and chemo-sensitivity to 5-fluorouracil (5-FU) were examined by cell migration and survival essays in vitro. The molecular target of miR-137, pleiotropic growth factor (PTN), was down-regulated by siRNA to examine its effects on cancer cell invasion. MIA PaCa-2 cells with endogenously overexpressed miR-137 were transplanted into null mice to examine tumor growth in vivo. Results: We found miR-137 was markedly underexpressed in both pancreatic cancer cell lines and tumor cells from patients. In cancer cells, transfection of lentivirus containing miR-137 mimic was able to markedly upregulate endogenous expression of miR-137, inhibited cancer cell invasion and increased sensitivities to chemotherapy reagent 5-FU. PTN was significantly down-regulated by overexpressing miR-137 in pancreatic cancer cells, and knocking down PTN was effective to rescue the reduced cancer cell invasion ability caused by miR-137 overexpression. More importantly, overexpressing miR-137 led to significant inhibition on tumor formation, including reductions in tumor weight and tumor size in vivo. Conclusion: Our study demonstrated that miR-137 played an important role in pancreatic cancer development. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer. PMID:25550779

Xiao, Jie; Peng, Feng; Yu, Chao; Wang, Min; Li, Xu; Li, Zhipeng; Jiang, Jianxin; Sun, Chengyi

2014-01-01

352

KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth.  

PubMed

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play a central role in angiogenesis, which is necessary for solid tumors to expand and metastasize. Specific inhibitors of VEGFR-2 tyrosine kinase are therefore thought to be useful for treating cancer. We showed that the quinazoline urea derivative KRN633 inhibited tyrosine phosphorylation of VEGFR-2 (IC50 = 1.16 nmol/L) in human umbilical vein endothelial cells. Selectivity profiling with recombinant tyrosine kinases showed that KRN633 was highly selective for VEGFR-1, -2, and -3. KRN633 also blocked the activation of mitogen-activated protein kinases by VEGF, along with human umbilical vein endothelial cell proliferation and tube formation. The propagation of various cancer cell lines in vitro was not inhibited by KRN633. However, p.o. administration of KRN633 inhibited tumor growth in several in vivo tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. KRN633 also caused the regression of some well-established tumors and those that had regrown after the cessation of treatment. In these models, the trough serum concentration of KRN633 had a more significant effect than the maximum serum concentration on antitumor activity. KRN633 was well tolerated and had no significant effects on body weight or the general health of the animals. Histologic analysis of tumor xenografts treated with KRN633 revealed a reduction in the number of endothelial cells in non-necrotic areas and a decrease in vascular permeability. These data suggest that KRN633 might be useful in the treatment of solid tumors and other diseases that depend on pathologic angiogenesis. PMID:15634658

Nakamura, Kazuhide; Yamamoto, Atsushi; Kamishohara, Masaru; Takahashi, Kazumi; Taguchi, Eri; Miura, Toru; Kubo, Kazuo; Shibuya, Masabumi; Isoe, Toshiyuki

2004-12-01

353

Close Interactions between Mesenchymal Stem Cells and Neuroblastoma Cell Lines Lead to Tumor Growth Inhibition  

PubMed Central

Mesenchymal stem cells (MSCs) have attracted much interest in oncology since they exhibit marked tropism for the tumor microenvironment and support or suppress malignant cell growth depending on the tumor model tested. The aim of this study was to investigate the role of MSCs in the control of the growth of neuroblastoma (NB), which is the second most common solid tumor in children. In vivo experiments showed that systemically administered MSCs, under our experimental conditions, did not home to tumor sites and did not affect tumor growth or survival. However, MSCs injected intratumorally in an established subcutaneous NB model reduced tumor growth through inhibition of proliferation and induction of apoptosis of NB cells and prolonged the survival of hMSC-treated mice. The need for contact between MSCs and NB cells was further supported by in vitro experiments. In particular, MSCs were found to be attracted by NB cells, and to affect NB cell proliferation with different results depending on the cell line tested. Moreover, NB cells, after pre-incubation with hMSCs, acquired a more invasive behavior towards CXCL12 and the bone marrow, i.e., the primary site of NB metastases. In conclusion, this study demonstrates that functional cross-talk between MSCs and NB cell lines used in our experiments can occur only within short range interaction. Thus, this report does not support the clinical use of MSCs as vehicles for selective delivery of antitumor drugs at the NB site unless chemotherapy and/or radiotherapy create suitable local conditions for MSCs recruitment. PMID:23119082

Bianchi, Giovanna; Morandi, Fabio; Cilli, Michele; Daga, Antonio; Bocelli-Tyndall, Chiara; Gambini, Claudio

2012-01-01

354

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways.  

PubMed

Insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be a tumor suppressor in a variety of cancers. We previously have shown that IGFBP7 expression is inversely correlated with disease progression and poor outcome in breast cancer. Overexpression of IGFBP7 in MDA-MB-468, a triple-negative breast cancer (TNBC) cell line, resulted in inhibition of growth and migration. Xenografted tumors bearing ectopic IGFBP7 expression were significantly growth-impaired compared to IGFBP7-negative controls, which suggested that IGFBP7 treatment could inhibit breast cancer cell growth. To confirm this notion, 14 human patient primary breast tumors were analyzed by qRTPCR for IGFBP7 expression. The TNBC tumors expressed the lowest levels of IGFBP7 expression, which also correlated with higher tumorigenicity in mice. Furthermore, when breast cancer cell lines were treated with IGFBP7, only the TNBC cell lines were growth inhibited. Treatment of NOD/SCID mice harboring xenografts of TNBC cells with IGFBP7 systemically every 3-4 days inhibited tumorigenesis, with associated anti-angiogenic effects, together with increased apoptosis. Upon examining the mechanism of IGFBP7-mediated growth inhibition in TNBC cells, we found that cells not only were arrested in G1 phase of the cell cycle but also underwent senescence as a result of treatment with IGFBP7. Interestingly, IGFBP7 treatment was also associated with strong activation of the stress-associated p38 MAPK pathway, together with upregulation of p53 and the cyclin-dependent protein kinase (CDK) inhibitor, p21(cip1). Prolonged treatment of cells with IGFBP7 resulted in increased cell death, marked by an increase in apoptotic cells and associated cleaved PARP. This is the first study showing that exogenous IGFBP7 inhibits TNBC cell growth both in vitro and in vivo. Taken together, these results suggest IGFBP7 treatment might have therapeutic potential for TNBC. PMID:21997538

Benatar, Tania; Yang, Wenyi; Amemiya, Yutaka; Evdokimova, Valentina; Kahn, Harriette; Holloway, Claire; Seth, Arun

2012-06-01

355

Patrinia scabiosaefolia inhibits colorectal cancer growth through suppression of tumor angiogenesis.  

PubMed

Angiogenesis is an essential process for tumor development and metastasis, therefore inhibition of tumor angiogenesis has become a promising strategy for anticancer treatments. Patrinia scabiosaefolia, a well-known Oriental folk medicine, has been shown to be effective in the clinical treatment of gastrointestinal cancers. However, the precise mechanism of its tumoricidal activity remains largely unknown. Using a colorectal cancer (CRC) mouse xenograft model, the human colon carcinoma cell line HT-29 and human umbilical vein endothelial cells (HUVECs), in the present study we evaluated the effects of an ethanol extract of Patrinia scabiosaefolia (EEPS) on tumor angiogenesis in vivo and in vitro, and investigated the underlying molecular mechanisms. We found that EEPS treatment significantly reduced the tumor volume in CRC mice and decreased the intratumoral microvessel density in tumor tissues. In addition, EEPS inhibited several key processes of angiogenesis, including the proliferation, migration and tube formation of HUVECs. Moreover, EEPS treatment suppressed the expression of VEGF-A in CRC tumors and HT-29 cells. Collectively, our data suggest that Patrinia scabiosaefolia inhibits CRC growth likely via suppression of tumor angiogenesis. PMID:23820929

Chen, Liwu; Liu, Liya; Ye, Ling; Shen, Aling; Chen, Youqin; Sferra, Thomas J; Peng, Jun

2013-09-01

356

Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway.  

PubMed

JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in vitro release behavior and had a stronger inhibitory effect on proliferation, migration and invasion of HUVECs than free JK184. Furthermore, JK184 micelles had stronger tumor growth inhibiting effects in subcutaneous Panc-1 and BxPC-3 tumor models. Histological analysis showed that JK184 micelles improved anti-tumor activity by inducing more apoptosis, decreasing microvessel density and reducing expression of CD31, Ki67, and VEGF in tumor tissues. JK184 micelles showed a stronger inhibition of Gli expression in Hh signaling, which played an important role in pancreatic carcinoma. Furthermore, circulation time of JK184 in blood was prolonged after entrapment in polymeric micelles. Our results suggested that JK184 micelles are a promising drug candidate for treating pancreatic tumors with a highly inhibitory effect on Hh activity. PMID:25581613

Zhang, Nannan; Liu, Shichang; Wang, Ning; Deng, Senyi; Song, Linjiang; Wu, Qinjie; Liu, Lei; Su, Weijun; Wei, Yuquan; Xie, Yongmei; Gong, Changyang

2015-01-28

357

Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo  

PubMed Central

ABSTRACT Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. Results: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options. PMID:24937925

Hrgovic, Igor; Glavic, Zeljko; Kovacic, Zeljko; Mulic, Smaila; Zunic, Lejla; Hrgovic, Zlatko

2014-01-01

358

Enhancement of cancer vaccine therapy by systemic delivery of a tumor-targeting Salmonella-based STAT3 shRNA suppresses the growth of established melanoma tumors.  

PubMed

Cancer vaccine therapies have only achieved limited success when focusing on effector immunity with the goal of eliciting robust tumor-specific T-cell responses. More recently, there is an emerging understanding that effective immunity can only be achieved by coordinate disruption of tumor-derived immunosuppression. Toward that goal, we have developed a potent Salmonella-based vaccine expressing codon-optimized survivin (CO-SVN), referred to as 3342Max. When used alone as a therapeutic vaccine, 3342Max can attenuate growth of aggressive murine melanomas overexpressing SVN. However, under more immunosuppressive conditions, such as those associated with larger tumor volumes, we found that the vaccine was ineffective. Vaccine efficacy could be rescued if tumor-bearing mice were treated initially with Salmonella encoding a short hairpin RNA (shRNA) targeting the tolerogenic molecule STAT3 (YS1646-shSTAT3). In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4(+) and CD8(+) T cells. The combined strategy also increased apoptosis in tumors of treated mice, enhancing tumor-specific killing of tumor targets. Interestingly, mice treated with YS1646-shSTAT3 or 3342Max alone were similarly unsuccessful in rejecting established tumors, whereas the combined regimen was highly potent. Our findings establish that a combined strategy of silencing immunosuppressive molecules followed by vaccination can act synergistically to attenuate tumor growth, and they offer a novel translational direction to improve tumor immunotherapy. PMID:21527558

Manuel, Edwin R; Blache, Céline A; Paquette, Rebecca; Kaltcheva, Teodora I; Ishizaki, Hidenobu; Ellenhorn, Joshua D I; Hensel, Michael; Metelitsa, Leonid; Diamond, Don J

2011-06-15

359

Efficacy of local delivery of ardipusilloside I using biodegradable implants against cerebral tumor growth  

PubMed Central

Ardipusilloside I (ADS-I) is a natural compound that can be isolated from the Chinese medicinal herb Ardisiapusilla A.DC, and has been reported to inhibit the growth of glioblastoma cells in cultures. This study was designed to test its efficacy by the delivery using biodegradable implants against glioblastoma in vivo. ADS-I was incorporated into polymer microspheres, which were prepared by a mixture of poly (D, L-lactic acid) and poly (D, L-lactic-co-glycolic acid) polymers and then fabricated into wafers. The anti-glioma activities of ADS-I-loaded wafers were examined by methylthiazol tetrazolium (MTT) assay in cultured rat C6 glioma cells, and by magnetic resonance imaging (MRI) and survival monitoring in C6 glioma-bearing rats. Here, we showed that ADS-I-loaded wafers sustained ADS-I release in vitro for 36 days in Higuchi model of kinetics, and had the same cytotoxic activity as ADS-I in the solution against the growth of C6 glioma cells in cultures. In C6 glioma-bearing rats, ADS-I wafer implants inhibited tumor growth in a dose-dependent matter, and were more effective than the same dosage of ADS-I in the solution. The tumor suppression efficacies of ADS-I wafer implants were positively correlated with an increase in tumor cell apoptosis and prolonged animal survival, and were associated with a decrease in vascular endothelial growth factor, C-reactive protein, tumor necrosis factor-? and interleukin-6, and an increase in interleukin-2 expression. In conclusion, this study demonstrates significant efficacy of local delivery of ADS-I using polymer implants against glioma tumor growth in vivo, suggesting the potential of ADS-I-loaded wafers for glioma treatment.

Dang, Huan; Wang, Ji; Cheng, Jiang-Xue; Wang, Peng-Yuan; Wang, Ying; Cheng, Li-Fei; Du, Caigan; Wang, Xiao-Juan

2015-01-01

360

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

PubMed

Previously, we have shown that insulin-like growth factor binding protein-7 (IGFBP-7) expression is inversely correlated with disease progression in breast cancer and is associated with poor outcome. To further investigate the role of IGFBP-7 in the growth and metastatic behavior of breast cancer, primary breast tumors and metastatic tumors derived from the same patients were analyzed for IGFBP-7 expression. Immunohistochemical analysis revealed that IGFBP-7 is downregulated in half of the human metastatic breast tumors tested. IGFBP-7 has been linked to suppression of oncogenic pathways and can directly restore cellular senescence in melanomas, leading to their regression. It is possible that breast tumors with metastatic potential have escaped from IGFBP-7-induced suppression by its down-regulation. Twenty-two human primary breast tumor specimens were transplanted into human-bone NOD/SCID mice. One of the two triple negative primary breast tumors was serially xenotransplanted more than five times. Each serial transplant resulted in increased tumor take and rate of growth. Expression of IGFBP-7 was downregulated upon each serial implantation. To investigate the role of IGFBP-7 in breast tumor suppression, IGFBP-7 was overexpressed in the triple negative MDA-MB-468 human breast cancer line by stable transfection of a pSec-tag2-IGFBP-7 vector. The parental MDA-MB-468 breast cancer cells expressed extremely low levels of endogenous IGFBP-7. The production of IGFBP-7 protein by the MDA-MB-468 cells stably transfected with IGFBP-7 was confirmed by immunoblotting with anti-IGFBP-7 antibody. Ectopic overexpression of IGFBP-7 significantly reduced the growth of the IGFBP-7 transfected MDA-MB-468 cells compared to the parental MDA-MB-468 cells. We also assessed the role of IGFBP-7 on cell migration, a key determinant of malignant progression and metastasis. When parental MDA-MB-468 cells were treated with various amounts of conditioned medium derived from the IGFBP-7 overexpressing cell line, a significant difference in cell migration rate was observed between untreated and treated cells. IGFBP-7 strongly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPK) ERK-1/2, suggesting that IGFBP-7 mediates its anti-proliferative effects through negative feedback signaling. Levels of phospho-ERK-1/2 were higher in the parental MDA-MB-468 than in IGFBP-7-expressing cells derived from it. When injected subcutaneously into NOD/SCID mice, the increased expression of IGFBP-7 in the MDA-MB-468 transfected cells reduced the rate of tumor growth in comparison to the parental MDA-MB-468 controls. These results suggest that the growth of breast cancer could be prevented by the forced expression of IGFBP-7 protein. PMID:20464481

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

2011-04-01

361

Quantitative modeling of the physiology of ascites in portal hypertension  

PubMed Central

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy. PMID:22453061

2012-01-01

362

Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells.  

PubMed

Autophagy, measured as the sequestration of an endogenous cytosolic enzyme (LDH), showed a progressive rate reduction during diethylnitrosamine-induced rat liver carcinogenesis. In primary hepatocellular carcinomas the autophagic activity was only one-fourth of that seen in normal hepatocytes. Reduced autophagy was also observed in peritumorous hepatocytes and in cells from preneoplastic liver, and a complete suppression of autophagic protein degradation was seen in normal hepatocytes treated with ascitic fluid from an ascites hepatoma, suggesting that tumour cells and their precursors may produce autophagy-suppressive factors with an autocrine and paracrine action. In cells from the transplantable rat ascites hepatoma, Yoshida AH-130, autophagic activity was negligible during active (logarithmic) growth, but increased to approximately 0.4%/h at high cell density, i.e. in stationary phase. In contrast to normal hepatocytes, autophagy in the AH-130 cells was not inhibited by ascitic fluid. The hepatoma cells would thus appear to have lost some aspects of autophagy regulation while retaining others. However, even the highest rate of hepatoma cell autophagy was only one-tenth of the maximal activity seen in normal hepatocytes, confirming the hypothesis that reduced autophagy may be an important aspect of growth deregulation in liver cancer. PMID:8269618

Kisen, G O; Tessitore, L; Costelli, P; Gordon, P B; Schwarze, P E; Baccino, F M; Seglen, P O

1993-12-01

363

Transfection of the mullerian inhibiting substance gene inhibits local and metastatic tumor-growth.  

PubMed

Mullerian Inhibiting Substance (MIS), a gonadal growth factor important in sexual differentiation, has antiproliferative activity against several human carcinoma cell lines. In this study, we examine the effect of MIS-transfection on the growth characteristics of Chinese hamster ovary (CHO) and human ocular melanoma (OM431) cells, compared to wild-type lines and a CHO line transfected with a noncleavable, inactive MIS mutant. MIS-transfection inhibited proliferation of CHO cells in double-layer agarose, tumor spheroid, and murine subrenal capsule assays, as well as growth of CHO and OM431 cells in pulmonary metastasis studies. These results anticipate further study of targeted gene therapy of certain human tumors with MIS gene constructs. PMID:21573527

Boveri, J; Parry, R; Ruffin, W; Gustafson, M; Lee, K; He, W; Donahoe, P

1993-02-01

364

Development of ascites-resistant and ascites-susceptible broiler lines.  

PubMed

The rapid growth of modern broilers is associated with enhanced appetite and high metabolic rate and, consequently, high O(2) demand. Ascites syndrome (AS) develops in individuals that fail to fully supply the increasing demand for O(2) in their bodies under ascites-inducing conditions (AIC) such as high altitude or low temperatures. The tendency of broilers to develop AS is heritable, but efficacious selection against AS susceptibility (without affecting the normal expression of other important traits) requires identification of indirect selection criteria. In the present study, divergent AS-susceptible (AS-S) and AS-resistant (AS-R) lines were developed to confirm the heritability of AS and to facilitate future detection of criteria for indirect selection against AS susceptibility. The base population consisted of 85 sire families with a mean of 73 progeny per sire, reared in a commercial broiler house under low-challenge AIC (cold environment and pelleted feed). Chicks dying with AS manifestations were designated AS-susceptible, whereas the surviving birds were designated AS-resistant. By the end of the trial (d 48), AS mortality had accumulated to 17.2%, but AS incidence per family (%ASF) ranged from 0 to 49%, with a high heritability (0.57). Parents of 7 families with very high %ASF produced the first generation (S(1)) of the AS-S line, and parents of 7 families with very low %ASF produced the S(1) of the AS-R line. The S(1) males and females reproduced generation S(2) of the selected lines, whereas additional S(1) males were tested under high-challenge AIC (individual cages, cool wind, and pelleted feed). Progeny testing under this high-challenge AIC, followed by sib selection, was repeated in generations S(2) and S(3), resulting in a divergence of 86.6% in the incidence of AS between the AS-S (91.3%) and AS-R (4.7%) lines. The rapid genetic divergence, and family analysis of %ASF suggested that a single or few major genes are responsible for the difference between the 2 selected lines. These lines may facilitate more sensitive and effective genomic research aimed at detecting these genes or identifying the primary physiological cause of AS. PMID:17435013

Druyan, S; Ben-David, A; Cahaner, A

2007-05-01

365

Naďve rat umbilical cord matrix stem cells significantly attenuate mammary tumor growth through modulation of endogenous immune responses  

PubMed Central

Background aims Un-engineered human and rat umbilical cord matrix stem cells (UCMSCs) attenuate growth of several types of tumors in mice and rats. However, the mechanism by which UCMSCs attenuate tumor growth has not been studied rigorously. Methods The possible mechanisms of tumor growth attenuation by rat UCMSCs were studied using orthotopic Mat B III rat mammary tumor grafts in female F344 rats. Tumor-infiltrating leukocytes were identified and quantified by immunohistochemistry analysis. Potential cytokines involved in lymphocyte infiltration in the tumors were determined by microarray and Western blot analysis. The Boyden chamber migration assay was performed for the functional analysis of identified cytokines. Results Rat UCMSCs markedly attenuated tumor growth; this attenuation was accompanied by considerable lymphocyte infiltration. Immunohistochemistry analysis revealed that most infiltrating lymphocytes in the rat UCMSC-treated tumors were CD3+ T cells. In addition, treatment with rat UCMSCs significantly increased infiltration of CD8+ and CD4+ T cells and natural killer (NK) cells throughout tumor tissue. CD68+ monocytes/macrophages and Foxp3+ regulatory T cells were scarcely observed, only in the tumors of the phosphate-buffered saline control group. Microarray analysis of rat UCMSCs demonstrated that monocyte chemotactic protein-1 is involved in rat UCMSC-induced lymphocyte infiltration in the tumor tissues. Conclusions These results suggest that naďve rat UCMSCs attenuated mammary tumor growth at least in part by enhancing host anti-tumor immune responses. Naďve UCMSCs can be used as powerful therapeutic cells for breast cancer treatment, and monocyte chemotactic protein-1 may be a key molecule to enhance the effect of UCMSCs at the tumor site. PMID:23474329

Kawabata, Atsushi; Ohta, Naomi; Seiler, Garret; Pyle, Marla M.; Ishiguro, Susumu; Zhang, Yong Qing; Becker, Kevin G.; Troyer, Deryl; Tamura, Masaaki

2013-01-01

366

Deciphering the ovarian cancer ascites fluid peptidome  

PubMed Central

Background Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis). Results Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin. Conclusions Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer. PMID:24694173

2014-01-01

367

Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor.  

PubMed

Foregut neuroendocrine tumors [NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor (EGFR) by growth factors, gastrointestinal (GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGF? and various GI hormones to stimulate growth of the human foregut carcinoid,BON, the somatostatinoma QGP-1 and the rat islet tumor,Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGF? and the other growth-stimulating GI hormones increased Tyr(1068) EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs. PMID:23220008

Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Delle Fave, Gianfranco; Jensen, Robert T

2013-03-01

368

Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor  

PubMed Central

Foregut Neuroendocrine Tumors[NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor(EGFR) by growth factors, gastrointestinal(GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGF? and various GI hormones to stimulate growth of the human foregut carcinoid, BON, the somatostatinoma QGP-1 and the rat islet tumor, Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGF? and the other growth-stimulating GI hormones increased Tyr1068 EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs. PMID:23220008

Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Fave, Gianfranco Delle; Jensen, Robert T.

2012-01-01

369

The effects of selenium on tumor growth in epithelial ovarian carcinoma  

PubMed Central

Objective Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Methods Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. Results The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice was started 1 week after injection of the SKOV3ip1 cells. Treatment with selenium (1.5 mg/kg, 3 times/week) and paclitaxel injection showed no addictive effect of the inhibition of tumor growth. However, combination of selenium and paclitaxel showed the slightly increased food intake compared with paclitaxel alone. Conclusion Although selenium has growth-inhibiting effect in ovarian carcinoma cells in vitro, there is no additive effect on tumor growth in mice treated with combination of paclitaxel and selenium. However, food intake is slightly higher in selenium-treated mice during chemotherapy. PMID:22808362

Park, Jin Sun; Ryu, Ji Yoon; Jeon, Hye-Kyung; Cho, Young Jae; Park, Young Ae; Choi, Jung-Joo; Kim, Byoung-Gie; Bae, Duk-Soo

2012-01-01

370

Natural alkylglycerols restrain growth and metastasis of grafted tumors in mice.  

PubMed

Alkylglycerols are natural etherlipids abundant in shark liver oil (SLO) in a diacylated form. SLO is known to have antitumor properties and was recently described as an inhibitor of tumor neovascularization. However, most studies did not discriminate between the respective activities of alkylglycerols and of fatty acids, which both have potent biological properties. In this work, a mouse model was used to investigate the antitumor effects of SLO and of alkylglycerols purified from the same source, both administered orally. We demonstrated that either pure alkylglycerols or SLO reduced the tumor growth in a similar manner, suggesting that alkylglycerols were involved in this effect. In alkylglycerol-treated mice, metastasis dissemination was reduced by 64 +/- 8%, whereas SLO effect was 30 +/- 9% below control. Purified alkylglycerols also decreased significantly plasmalogen content in tumors, whereas SLO had no such effect. Finally, we demonstrated that a 5-day treatment with alkylglycerols curtailed the presence in tumors of von Willebrand factor, a marker of endothelial cells. This result suggested an anti-angiogenic effect of alkylglycerols. In summary, alkylglycerols were shown to decrease the growth, vascularization, and dissemination of Lewis lung carcinoma tumors in mice. These findings suggest that the antitumor activity of SLO is likely mediated by the presence of alkylglycerols. PMID:15203379

Pedrono, Frederique; Martin, Bénédicte; Leduc, Christine; Le Lan, Jacky; Saďag, Bernard; Legrand, Philippe; Moulinoux, Jacques-Philippe; Legrand, Alain B

2004-01-01

371

Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells.  

PubMed Central

The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN-alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3'-Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy. Images PMID:1901915

Puddu, P; Locardi, C; Sestili, P; Varano, F; Petrini, C; Modesti, A; Masuelli, L; Gresser, I; Belardelli, F

1991-01-01

372

Matrix Metalloprotease 1a-Deficiency Suppresses Tumor Growth and Angiogenesis  

PubMed Central

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 a Mmp1a knock-out 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. Co-implantation 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 a Mmp1a target. Mmp1a secretion is controlled by the ability of its prodomain to suppress auto-cleavage, whereas human MMP1 is efficiently secreted due to stable pro- and catalytic domain interactions. 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. PMID:23708660

Foley, Caitlin J.; Fanjul-Fernández, Miriam; Bohm, Andrew; Nguyen, Nga; Agarwal, Anika; Austin, Karyn; Koukos, Georgios; Covic, Lidija; López-Otín, Carlos; Kuliopulos, Athan

2013-01-01

373

3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis  

PubMed Central

Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

XIAN, SHU-LIN; CAO, WEI; ZHANG, XIAO-DONG; LU, YUN-FEI

2015-01-01

374

Osteopontin regulates human glioma cell invasiveness and tumor growth in mice  

PubMed Central

Human malignant glioma cells are characterized by local invasion. In the present study, we investigated the role of osteopontin (OPN) in the invasiveness of human glioma cells isolated from grade IV tumors. We found that the expression levels of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2) expression and cell invasiveness potential. When U87MG glioma cells (with a high-OPN expression level) were stably transformed with specific small hairpin RNA to knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth in implanted brains were dramatically reduced. Conversely, forced expression of OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2 secretion, enhanced cell invasiveness, and increased tumor growth in a rodent xenograft model. Expression of OPN was associated with increased expression of vimentin and decreased expression of glial fibrillary acidic protein. Treatment of glioma cells with 5-aza-2?-deoxycytidine (5-aza-dC) suppressed OPN expression in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC was associated with reductions in MMP-2 secretion, vimentin expression, cell invasion, intravasation, and tumor growth. These data suggest that OPN may play important roles in regulating cell invasion in glioma cells and that 5-aza-dC may serve as a therapeutic agent for human gliomas. PMID:20150368

Jan, Hsun-Jin; Lee, Chin-Cheng; Shih, Yung-Luen; Hueng, Dueng-Yuan; Ma, Hsin-I; Lai, Jing-Huei; Wei, Hen-Wei; Lee, Horng-Mo

2010-01-01

375

Use of tumor diameter to estimate the growth kinetics of cancer and sensitivity of screening tests.  

PubMed Central

A statistical method has been developed that is useful for studying the relationship between the growth kinetics of malignant tumors and the detection probability either through symptoms or by screening. Mathematical models that describe the distribution of pathological variables in malignant tumors, detected after various histories of screening, are derived and parameters for detection probabilities and the growth kinetics are then estimated by the maximum likelihood procedure. By this method the probabilities of detection through symptoms as well as by screening can be estimated as functions of pathological variable(s) such as tumor size. The growth rate of tumor can also be estimated from the distribution of pathological variables. The present method was applied to gastric cancer in Japan, where an annual screening program for the disease exists. The detection probability for the indirect X-ray used as the screening test was estimated to be 0.323 x (diameter)2/[1 + 0.323 x (diameter)2]. The doubling time of gastric cancer was estimated to be 2.90 months. PMID:2269242

Yamaguchi, N; Yanagawa, T; Yoshimura, T; Kohrogi, N; Tanaka, K; Nakamura, Y; Okubo, T

1990-01-01

376

Regulation of Macrophage Arginase Expression and Tumor Growth by the Ron Receptor Tyrosine Kinase1  

PubMed Central

M1 activation of macrophages promotes inflammation and immunity to intracellular pathogens, while M2 macrophage activation promotes resolution of inflammation, wound healing, and tumor growth. These divergent phenotypes are characterized, in part, by the expression of iNOS and arginase I (Arg1) in M1 vs. M2 activated macrophages, respectively. Here we demonstrate that the Ron receptor tyrosine kinase tips the balance of macrophage activation by attenuating the M1 phenotype while promoting expression of Arg1, through a Stat6-independent mechanism. Induction of the Arg1 promoter by Ron is mediated by an AP-1 site located 433 bp upstream of the transcription start site. Treatment of primary macrophages with MSP, the ligand for Ron, induces potent MAP kinase activation, upregulates Fos, and enhances binding of Fos to the AP-1 site in the Arg1 promoter. In vivo, Arg1 expression in tumor-associated macrophages (TAMs) from Ron?/? mice was significantly reduced compared with TAMs from control animals. Furthermore, we show that Ron is expressed specifically by Tie2-expressing macrophages (TEMs), a TAM subset that exhibits a markedly skewed M2 and pro-tumoral phenotype. Decreased Arg1 in TAMs from Ron?/? mice was associated with reduced syngeneic tumor growth in these animals. These findings indicate that Ron induces Arg1 expression in macrophages through a previously uncharacterized AP-1 site in the Arg1 promoter, and that Ron could be therapeutically targeted in the tumor microenvironment to inhibit tumor growth by targeting expression of Arg1 PMID:21810604

Sharda, Daniel R.; Yu, Shan; Ray, Manujendra; Squadrito, Mario Leonardo; De Palma, Michele; Wynn, Thomas A.; Morris, Sidney M.; Hankey, Pamela A.

2011-01-01

377

Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth  

PubMed Central

Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to det