WorldWideScience

Sample records for abrogates experimental metastasis

  1. Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

    Shepherd Trevor G

    2010-02-01

    reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system.

  2. Consumption of a high-fat diet abrogates inhibitory effects of methylseleninic acid on spontaneous metastasis of Lewis lung carcinoma in mice

    We investigated the effect of dietary supplementation with selenium (Se) on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice fed a high-fat diet. Mice were fed the AIN93G diet or that diet modified with 45% calories from fat supplemented with or without 2.5 mg Se/4029 kCal ...

  3. Non-motorized voluntary running does not affect experimental and spontaneous metastasis in mice

    The present study investigated the effects of non-motorized voluntary running on experimental metastasis of B16BL/6 melanoma and spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice. After 9 weeks of running, mice (n = 30 per group) received an intravenous injection of B16BL/6 c...

  4. Enhanced experimental tumor metastasis with age in senescence-accelerated mouse

    Tumor metastasis is affected by the host immune surveillance system. Since aging may attenuate the host immune potential, the experimental tumor metastasis may be enhanced with age. In the present study, we investigated this alteration of experimental tumor metastasis with age. We used senescence-accelerated mice prone 10 (SAMP10) as a model of aged animals. Natural killer cell (NK) activity, as an indicator of immune surveillance potential, in 8-month-old (aged) SAMP10 mice was observed to be much lower than that in 2-month-old (young) mice. When we examined the in vivo trafficking of lung-metastatic K1735M2 melanoma cells in SAMP10 with positron emission tomography (PET), K1735M2 cells labeled with [2-18F]2-deoxy-2-fluoro-D-glucose ([18F]FDG) were observed in both young and aged SAMP10 just after injection of the cells, whereas the clearance of 18F from the lungs was retarded in aged animals. The accumulation of 5-[125I]iodo-2'-deoxyuridine ([125I]IUdR)-labeled K1735M2 cells in the lungs of SAMP10 at 24 h after injection was significantly higher in aged mice. Corresponding to these results, the number of metastatic colonies in the lung was larger in the aged SAMP10 of the experimental tumor metastasis model. The present study demonstrated that the aging process produced a susceptible environment allowing the tumor cells to metastasize due to decrease in the host immune surveillance potential with age. (author)

  5. Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

    Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

  6. Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

    Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Rojas, Paola, E-mail: parojas2010@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Sequeira, Gonzalo, E-mail: chicon27_7@hotmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Cocca, Claudia, E-mail: cm_cocca@hotmail.com [Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Crocci, Máximo, E-mail: info@crescenti.com.ar [Instituto de Inmunooncología Crescenti, Buenos Aires (Argentina); Colombo, Lucas, E-mail: lucascol2003@yahoo.com.ar [Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires,Argentina (Argentina); Lanari, Claudia, E-mail: lanari.claudia@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); and others

    2013-05-01

    Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.

  7. Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

    Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models

  8. Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases.

    Watanabe, Kenta; Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Maruyama, Takayuki; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato; Inada, Masaki

    2016-09-01

    The metastasis of tumors to bone is known to be promoted by prostaglandin E2 (PGE2) produced by the tumor host stromal tissue. Although bone metastases frequently occur in prostate cancer patients, the significance of PGE2 in stromal responses to the tumor is not known. In this study, we report that PGE2 and its receptor EP4 play a pivotal role in bone destruction and metastasis in an experimental metastasis model of prostate cancer in nude mice. Using human prostate cancer PC-3 cells that are stably transfected with luciferase, we showed that the development of bone metastasis was accompanied by increased osteoclastic bone resorption in the bone metastasis microenvironment, and could be abrogated by an EP4 receptor antagonist. The growth of PC-3 cells in vitro was not influenced by PGE2 or by the EP4 receptor. However, cell-cell interactions between fixed PC-3 cells and host osteoblasts induced PGE2 production and RANKL expression in the osteoblasts. Addition of an EP4 antagonist suppressed both PGE2 and RANKL expression induced by the PC3-osteoblast interaction, which would have consequent effects on osteoclast activation and osteolysis. These results indicate that the blockage of PGE2-EP4 signaling prevents the bone destruction required for prostate cancer metastases, and that this is, in part due to the abrogation of bone cell responses. The study provides further evidence that an EP4 antagonist is a candidate for the treatment of prostate cancer in the blockade of bone metastasis. PMID:27450806

  9. Low dose radiation in combination with mytomycin C suppresses the metastasis of lewis lung carcinoma. An experimental study

    To find out a new and effective method to enhance the efficacy of cytotoxic agents against the metastasis of malignant tumor, the authors used C57BL/6 mice implanted with Lewis lung carcinoma cells in the right thighs, sacrificing them to count lung metastasis nodules 21 days after implantation as an experimental in situ metastasis animal model. The results indicated that treatment with 3.0 mg/kg mytomycin C(MMC) I.P. alone could not markedly reduce the number of metastasis nodules in lungs (control group: 41.7 +- 7.4, MMC treatment alone: 33.8 +- 11.5, P>0.05), when whole body irradiation (WBI) with 75 mGy X-rays was given 6 hours before MMC chemotherapy, the number of lung metastasis nodules was much fewer than that with MMC treatment alone (20.3 +- 4.7, P<0.01). The detection of immune parameters showed that MMC treatment significantly suppressed the functions of peritoneal macrophage and natural killer cells (P<0.05), while the immune function of 75 mGy + MMC group was much higher than that with MMC treatment alone (P<0.01). These results demonstrated that the protective effect of low dose radiation on the immune system against MMC might be one of the important factors due to this enhanced anti-metastasis efficacy of MMC chemotherapy

  10. Antioxidant oils and Salmonella enterica Typhimurium reduce tumor in an experimental model of hepatic metastasis

    Sorenson BS

    2011-05-01

    Full Text Available Brent S Sorenson, Kaysie L Banton, Lance B Augustin, Arnold S Leonard, Daniel A SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Fruit seeds high in antioxidants have been shown to have anticancer properties and enhance host protection against microbial infection. Recently we showed that a single oral dose of Salmonella enterica serovar Typhimurium expressing a truncated human interleukin-2 gene (SalpIL2 is avirulent, immunogenic, and reduces hepatic metastases through increased natural killer cell populations in mice. To determine whether antioxidant compounds enhance the antitumor effect seen in SalpIL2-treated animals, we assayed black cumin (BC, black raspberry (BR, and milk thistle (MT seed oils for the ability to reduce experimental hepatic metastases in mice. In animals without tumor, BC and BR oil diets altered the kinetics of the splenic lymphocyte response to SalpIL2. Consistent with previous reports, BR and BC seed oils demonstrated independent antitumor properties and moderate adjuvant potential with SalpIL2. MT oil, however, inhibited the efficacy of SalpIL2 in our model. Based on these data, we conclude that a diet high in antioxidant oils promoted a more robust immune response to SalpIL2, thus enhancing its antitumor efficacy.Keywords: antioxidants, colorectal cancer, tumor models, metastasis

  11. Effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits

    Objective: To investigate the effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits. Methods: VX2 carcinoma cells were surgically implanted into the left hepatic lobe in 48 New Zealand white rabbits, and the rabbit hepatic carcinoma models were thus established. The rabbits were randomly divided into 4 groups with 12 rabbits in each group. After hepatic arterial catheterization was completed physiological saline (control group), Lipiodol (Group A), Ad-p53 (Group B) and Lipiodol+Ad-p53 (Group C) were respectively infused into the rabbits of four groups via common hepatic artery. One week after the procedure the rabbits were sacrificed and the livers were removed for the determination of matrix metalloprotein-2 (MMP-2), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) of the tumor with immunohistochemistry technique. Results: The tumor growth in study groups (group A, B and C) was markedly suppressed, which was significantly different in comparison with that in control group (P 0.05). The positive rates of MMP-2, PCNA and VEGF in group B and C were significantly lower than those in control group (P < 0.05). The positive rates of MMP-2, PCNA and VEGF of the rabbits with metastasis were markedly higher than those without metastasis(P < 0.05). MMP-2 bore a certain relationship with VEGF and PCNA (P < 0.05). Conclusion: The increase of the positive rates of MMP-2, PCNA and VEGF indicates that the tumor possesses higher possibility for developing metastasis, proliferation and vascular formation. The interventional treatment with Adp53 or Lipiodol+Ad-p53 can inhibit the growth, metastasis and vascular formation of VX2 liver tumor in experimental rabbits. (J Intervent Radiol, 2010, 19 : 800-804) (authors)

  12. Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis

    Gkretsi, Vasiliki, E-mail: vasso.gkretsi@gmail.com [Department of Biomedical Research and Technology, Institute for Research and Technology-Thessaly, Centre for Research and Technology-Hellas (CE.R.T.H.), Larissa 41222 (Greece); Bogdanos, Dimitrios P. [Department of Biomedical Research and Technology, Institute for Research and Technology-Thessaly, Centre for Research and Technology-Hellas (CE.R.T.H.), Larissa 41222 (Greece); Department of Rheumatology, School of Medicine, University of Thessaly, University Hospital of Larissa, 41110 Larissa (Greece); Institute of Liver Studies, King' s College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)

    2015-06-10

    Migfilin is a novel cell–matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell–matrix and cell–cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin's role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin's expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal–regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis in vitro, providing the molecular mechanism involved and presenting Migfilin as potential therapeutic target against HCC metastasis. - Highlights: • Migfilin is a cell–matrix and cell–cell adhesion protein known to interact with VASP. • Nothing is known about Migfilin's role in hepatocellular carcinoma (HCC). • We eliminated Migfilin from 2 HCC cell lines and studied in vitro metastasis. • Its silencing inhibits cell invasion and promotes adhesion in HepG2 invasive cells. • We provide molecular mechanism by which Migfilin elimination halts HCC metastasis.

  13. Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis

    Migfilin is a novel cell–matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell–matrix and cell–cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin's role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin's expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal–regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis in vitro, providing the molecular mechanism involved and presenting Migfilin as potential therapeutic target against HCC metastasis. - Highlights: • Migfilin is a cell–matrix and cell–cell adhesion protein known to interact with VASP. • Nothing is known about Migfilin's role in hepatocellular carcinoma (HCC). • We eliminated Migfilin from 2 HCC cell lines and studied in vitro metastasis. • Its silencing inhibits cell invasion and promotes adhesion in HepG2 invasive cells. • We provide molecular mechanism by which Migfilin elimination halts HCC metastasis

  14. Inhibition of experimental lung metastasis by systemic lentiviral delivery of kallistatin

    Chao Julie

    2010-05-01

    Full Text Available Abstract Background Angiogenesis plays an important role in the development and progression of tumors. Kallistatin exerts anti-angiogenic and anti-inflammatory activities that may be effective in inhibiting tumor metastasis. We investigated the antitumor effect of lentivirus-mediated kallistatin gene transfer in a syngeneic murine tumor model. Methods Lentiviral vector encoding kallistatin (LV-Kallistatin was constructed. The expression of kallistatin was verified by enzyme-linked immunosorbent assay (ELISA, and the bioactivity of kallistatin was determined by using cell proliferation, migration, and invasion assays. In addition, antitumor effects of LV-Kallistatin were evaluated by the intravenous injection of virus into tumor-bearing mice. Results The conditioned medium from LV-Kallistatin-treated cells inhibited the migration and proliferation of endothelial cells. Meanwhile, it also reduced the migration and invasion of tumor cells. In the experimental lung metastatic model, tumor-bearing mice receiving LV-Kallistatin had lower tumor nodules and longer survival than those receiving control virus or saline. Moreover, the microvessel densities, the levels of vascular endothelial growth factor (VEGF, tumor necrosis factor (TNF-α, and nuclear factor κB (NF-κB transcriptional activity were reduced in the LV-Kallistatin-treated mice. Conclusion Results of this study showed that systemic administration of lentiviral vectors encoding kallistatin inhibited the growth of metastatic tumor and prolonged the survival of tumor-bearing mice. These results suggest that gene therapy using lentiviruses carrying the kallistatin gene, which exerts anti-angiogenic and anti-inflammatory activities, represents a promising strategy for the treatment of lung cancer.

  15. Inhibition of experimental lung metastasis by systemic lentiviral delivery of kallistatin

    Angiogenesis plays an important role in the development and progression of tumors. Kallistatin exerts anti-angiogenic and anti-inflammatory activities that may be effective in inhibiting tumor metastasis. We investigated the antitumor effect of lentivirus-mediated kallistatin gene transfer in a syngeneic murine tumor model. Lentiviral vector encoding kallistatin (LV-Kallistatin) was constructed. The expression of kallistatin was verified by enzyme-linked immunosorbent assay (ELISA), and the bioactivity of kallistatin was determined by using cell proliferation, migration, and invasion assays. In addition, antitumor effects of LV-Kallistatin were evaluated by the intravenous injection of virus into tumor-bearing mice. The conditioned medium from LV-Kallistatin-treated cells inhibited the migration and proliferation of endothelial cells. Meanwhile, it also reduced the migration and invasion of tumor cells. In the experimental lung metastatic model, tumor-bearing mice receiving LV-Kallistatin had lower tumor nodules and longer survival than those receiving control virus or saline. Moreover, the microvessel densities, the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, and nuclear factor κB (NF-κB) transcriptional activity were reduced in the LV-Kallistatin-treated mice. Results of this study showed that systemic administration of lentiviral vectors encoding kallistatin inhibited the growth of metastatic tumor and prolonged the survival of tumor-bearing mice. These results suggest that gene therapy using lentiviruses carrying the kallistatin gene, which exerts anti-angiogenic and anti-inflammatory activities, represents a promising strategy for the treatment of lung cancer

  16. INHIBITION OF HUMAN EXPERIMENTAL GASTRIC CARCINOMA METASTASIS IN VIVO BY P-SELECTIN MONOCLONAL ANTIBODY

    陈金联; 陈维雄; 朱金水; 陈尼维; 姚明; 周同

    2001-01-01

    Objeetive To study the role of cell adhesion molecule P-selectin monoclonal antibody ( MAb ) in tumor metastasis of an orthotopic metastatic model. Methods SCID mice were implanted orthotopically SGC-7901 human gastric cancer tissue. 3d later, animals received i. v. injections of PBS or P-selectin MAb ( 100μg /injection ) twice weekly for 3 weeks. 42d after operation, all animals were sacrificed. Tissues from all organs were obtained for histopathological evaluation. Results 10 of the animals ( n = 11 ) treated with PBS were found to develop metastatic tumors in the regional lymph nodes, liver, and lung. In contrast, 2 of the animals ( n = 9 ) treated with P-selectin MAb developed metastatic tumors in the organs examined. The expression of P-selectin mRNA in gastric cancer tissue of SCID mice with tumor metastasis was higher than that without such metastasis. Conclusion P-selectin expression is associated with tumor metastasis, and the metastasis may be inhibited by the MAb.

  17. Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats.

    Sangeetha, N; Nalini, N

    2015-01-01

    To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation. PMID:24740923

  18. Decoding Melanoma Metastasis

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis

  19. Decoding Melanoma Metastasis

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  20. Inhibition of experimental lung metastasis by systemic lentiviral delivery of kallistatin

    Chao Julie; Chang Chih-Jui; Chang Meng-Ya; Hsieh Jeng-Long; Wang Chrong-Reen; Chen Shin-Yao; Teo Min-Li; Shiau Ai-Li; Chao Lee; Wu Chao-Liang; Lee Che-Hsin

    2010-01-01

    Abstract Background Angiogenesis plays an important role in the development and progression of tumors. Kallistatin exerts anti-angiogenic and anti-inflammatory activities that may be effective in inhibiting tumor metastasis. We investigated the antitumor effect of lentivirus-mediated kallistatin gene transfer in a syngeneic murine tumor model. Methods Lentiviral vector encoding kallistatin (LV-Kallistatin) was constructed. The expression of kallistatin was verified by enzyme-linked immunosorb...

  1. Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes.

    Lin, W.C.; O'Connor, K. L.; Culp, L. A.

    1993-01-01

    Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co-localisation and co-growth in nu...

  2. Nutritional abrogation of photoimmunosuppression: in vivo investigations.

    Pilkington, Suzanne M; Gibbs, Neil K; Friedmann, Peter S; Rhodes, Lesley E

    2014-01-01

    Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide. PMID:24283330

  3. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg-/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  4. Experimental Study of the Prophylactic and Therapeutic Effects of Venin on Metastasis and Recurrence of Liver Cancer

    JingjingSun; ZhiyongWu; XindaZhou; YinkunLiu

    2004-01-01

    OBJECTIVE To study the inhibitory effect of venin on adhesion and invasive ability of SMMC-7721 cells and to examine the prophylactic and therapeutic effect of venin on liver cancer metastasis and recurrence after hepatectomy.METHODS The blocking effect of venin on the intercellular adhesive molecule (ICAM-1) of 7721 cells was analyzed by immunofluorescence flow cytometry. The influence of venin on the invasive ability of 7721 cells was observed by cell-migration experimentation and detachment of 7721 cells attached to fibronectin (FN), and the influence of venin on adhesion of 7721 cells to FN by the MTT method, 7721 cells to 7721 cells, 7721 cells to lymphocytes, and 7721 cells to endothelial cells by a cellular adhesion test. The preventive and therapeutic effect of venin onmetastasis and recurrence of a liver cancer model was observed in nudemice after hepatectomy. RESULTS The expression of ICAM-1 in the venin-treated group was significantly lower than that in the untreated group. Venin could not inhibit the invasive ability of 7721 cells, and could not exfoliate the 7721 cells adhered to FN. It could inhibit the adhesion between 7721 cells and 7721 cells, and between 7721 and endothelial cells, but could not inhibit the adhesion between 7721 and lymphocytes. The nude mice treated with venin had less intrahepatic or extrahepatic metastases and recurrences after hepatectomy. CONCLUSION Venin can inhibit the adhesive ability of SMMC-7721 cells and can also prevent and treat the metastasis and recurrence of liver cancer in nude mice after hepatectomy.

  5. Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis

    Hon S. Leong

    2014-09-01

    Full Text Available Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin, maturation (Tks5, or function (Tks4 resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.

  6. Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0 mouse melanoma cells.

    Sato, Ayuko; Yoshikawa, Noriko; Kubo, Erika; Kakuda, Mami; Nishiuchi, Arisa; Kimoto, Yoko; Takahashi, Yuta; Kagota, Satomi; Shinozuka, Kazumasa; Nakamura, Kazuki

    2013-01-01

    In a previous study performed by our group, we demonstrated that the water extract of Cordyceps sinensis (WECS) significantly prevented tumor metastasis from the spleen to the liver, using B16-F0 mouse melanoma cells as a model. In this study, we investigated the anti-metastatic activity of cordycepin (3'-deoxyadenosine), one of the components of WECS, using an identical model of mice injected with B16-F0 cells into the spleen. All mice inoculated with B16-F0 cells died due to liver metastases via the portal vein from the spleen. Control mice not administered cordycepin exhibited higher serum levels of alanine aminotransferase (ALT) due to damage to the liver by metastasized B16-F0 cells from the spleen, and survival times ranged from 17 to 22 days after tumor inoculation. Cordycepin was intraperitoneally administered to mice, and resulted in significantly lower serum ALT levels and longer survival times than those observed in control mice. Taken together, these results indicate that cordycepin may be the active ingredient in C. sinensis exerting an anti-metastatic effect, and may be a potential candidate anti-metastatic agent. PMID:24292575

  7. Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline.

    Gude, R P; Binda, M M; Presas, H L; Klein-Szanto, A J; Bonfil, R D

    1999-01-01

    Pentoxifylline (PTX), a methylxanthine derivative widely used as a hemorheological agent in the treatment of peripheral vascular disease, was studied to unveil the mechanisms responsible for its inhibitory action on B16-F10 experimental metastasis. In vitro pretreatment of B16-F10 cells with noncytotoxic concentrations of PTX significantly inhibited their adhesion to reconstituted basement membrane Matrigel(R) and type IV collagen as well as the relative activity of secreted 92 kD metalloproteinase. However, PTX pretreatment of B16-F10 cells did not affect their in vitro invasiveness. Heterotypic organ adhesion assays carried out with B16-F10 cells and suspended organ tissues demonstrated that pretreatment with noncytotoxic concentrations of PTX of both, tumor cells or lung tissue, brought about a dose-dependent inhibition of melanoma cell adhesion to lung. Immunohistochemical studies using antibodies against CD31 adhesion molecule (PECAM-1) revealed that B16-F10 cells adhere to lung endothelial cells. Our results suggest that PTX may exert its inhibitory effect on tumor lodgment, and as a consequence of that on experimental metastases, through an inhibitory action on cell adhesion molecules. PMID:10087444

  8. Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence.

    Zhang, Yin; Hong, Hao; Nayak, Tapas R; Valdovinos, Hector F; Myklejord, Duane V; Theuer, Charles P; Barnhart, Todd E; Cai, Weibo

    2013-07-01

    The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and (64)Cu to yield (64)Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of (64)Cu-NOTA-TRC105-800CW was 11.9 ± 1.2, 13.9 ± 3.9, and 13.4 ± 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with (64)Cu-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of (64)Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal. PMID:23471463

  9. "Abrogation of Rulings” Methodology: A Critique

    Gasser Auda

    2004-01-01

    Surveying the subject of abrogation (naskh) in the Qur’ān, ḥādīth and Islamic literature, it is clear that most abrogation cases were introduced after the Prophetic era in order to interpret certain Qur’ānic verses and Prophetic narrations (aḥādīth) that some scholars perceived as “conflicting.” Two striking examples are “The Verse of the Sword” (āyat al-saif) and “The Verse of the Barrier” (āyat al-ḥijāb). The Qur’ānic verses and aḥādīth,...

  10. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice

    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto, Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Ming ZHAO

    2014-01-01

    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  11. Folate-targeted paclitaxel-conjugated polymeric micelles inhibits pulmonary metastatic hepatoma in experimental murine H22 metastasis models

    Zhang Y

    2014-04-01

    Full Text Available Yan Zhang,1 Hui Zhang,2 Wenbin Wu,2 Fuhong Zhang,3,4 Shi Liu,3 Rui Wang,3 Yingchun Sun,1 Ti Tong,1 Xiabin Jing3 1Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China; 2Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, People's Republic of China; 3State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, People's Republic of China; 4Department of Otolaryngology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China Abstract: Hepatocellular carcinoma shows low response to most conventional chemotherapies; additionally, extrahepatic metastasis from hepatoma is considered refractory to conventional systemic chemotherapy. Target therapy is a promising strategy for advanced hepatoma; however, targeted accumulation and controlled release of therapeutic agents into the metastatic site is still a great challenge. Folic acid (FA and paclitaxel (PTX containing composite micelles (FA-M[PTX] were prepared by coassembling the FA polymer conjugate and PTX polymer conjugate. The main purpose of this study is to investigate the inhibitory efficacy of FA-M(PTX on the pulmonary metastasis of intravenously injected murine hepatoma 22 (H22 on BALB/c mice models. The lung metastatic burden of H22 were measured and tissues were analyzed by immunohistochemistry and histology (hematoxylin and eosin stain, followed by survival analysis. The results indicated that FA-M(PTX prevented pulmonary metastasis of H22, and the efficacy was stronger than pure PTX and simple PTX-conjugated micelles. In particular, the formation of lung metastasis colonies in mice was evidently inhibited, which was paralleled with the downregulated expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, the mice bearing pulmonary metastatic hepatoma in the FA

  12. Metastasis Suppressors and Their Roles in Breast Carcinoma

    Vaidya, Kedar. S.; Welch, Danny R.

    2007-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus di...

  13. Current Concepts of Metastasis Formation

    Peter Gassman

    2011-07-01

    Full Text Available The development of secondary distant organ and lymph node metastasis has an extraordinary impact on the prognosis of patients with solid cancer. In most cases the advent of metastatic growth represents the turning point from a local, potentially curable, disease to a systemic non-curable situation. As a highly regulated process, metastasis formation follows a distinct, non-random pattern characteristic for each tumor entity. Metastasis formation and strategies to prevent this lethal event in the progression of cancer is of fundamental interest for cancer science and patient care. In this special issue of Cancers, papers highlighting cellular mechanisms of metastasis formation, genetic and epigenetic aspects associated with organ and tumor specific metastasis formation, as well as papers outlining experimental and clinical therapeutic concepts for anti-metastatic treatment are included.

  14. Metastasis Suppressor Genes

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2013-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinica...

  15. Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model

    The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. (Author)

  16. Microenvironment Determinants of Brain Metastasis

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  17. Suppressive Effect of Juzen-Taiho-To on Lung Metastasis of B16 Melanoma Cells In Vivo

    Takako Matsuda

    2011-01-01

    Full Text Available Juzen-Taiho-To (JTT is well known to be one of Kampo (Japanese herbal medicine consisted of 10 component herbs and used for the supplemental therapy of cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of cancer metastasis using experimental mouse model. JTT was well mixed with rodent chow at concentrations of either 0.2 or 1.0%, and administered orally ad libitum, which was started 1 week before tumor cell injection and continue throughout the experiment. Oral administration of JTT at concentration 0.2 and 1.0% into C57BL/6 male mice significantly inhibited tumor metastasis in lungs, which was induced by the intravenous injection of 2 × 105 B16 melanoma cell. JTT at a concentration of 1.0% also significantly suppressed lung metastasis of B16 melanoma cell from hind footpad in C57BL/6 mice. In the second part of experiments, the influence of the depression of natural killer (NK cell, natural killer T (NKT cell and several types of cytokines on JTT-mediated inhibition of tumor cell metastasis. Intraperitoneal injection of anti asialo-GM1 antibody against NK cells and anti NK-1.1 monoclonal antibody (mAb to NKT cells abrogated the inhibitory action of JTT on lung metastasis of B16 melanoma cells. Although intraperitoneal administration of anti-IFN-γ mAb scarcely affected the inhibitory action of JTT on tumor cell metastasis, injection of amrinone, which used for IL-12 suppression, significantly decreased the ability of JTT to prevent tumor cell metastasis. These results strongly suggest that oral administration of JTT caused increase in the production of IL-12, which is responsible for the activation of both NK cell and NKT cell, in the lungs and results in inhibition of B16 melanoma cell metastasis in the lungs.

  18. Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-Ile-Gly-Ser-Arg (YIGSR).

    Iwamoto, Y; Nomizu, M; Yamada, Y.; Ito, Y.; K.Tanaka; Sugioka, Y.

    1996-01-01

    A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Co-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT 1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(AcY1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity in tumour cells in vivo. The effect of the peptides on angiogenesis and tu...

  19. Antibody-mediated neutralization of virus is abrogated by mycoplasma.

    Dickson, C; Elkington, J; Hales, A.; Weiss, R.

    1980-01-01

    The ability of a mouse mammary tumor cell line to abrogate antibody neutralization of vesicular stomatitis virus was shown to be due to the presence of mycoplasma. The mycoplasma was isolated from the cell line and typed as Mycoplasma orale. Colonies of this mycoplasma were used to deliberately infect cell cultures which then gained the capacity to reactivate antibody-neutralized virus. The extent of the reactivation depended on the source of neutralizing antiserum. Other species of mycoplasm...

  20. Cavitary pulmonar metastasis

    Seven cases of cavitary lung metastasis, four from head and neck neoplasma, two from uterine carcinoma and one from hepatoma are reported. The physiopathology and the most common sites of this kind of lesion are discussed. The rarity of the solitary excavated metastasis from hepatoma, not reported previously in the literature reviewed, is emphasized. (Author)

  1. Spinal subdural metastasis

    A case of metastasis to the thoracic spinal subdural space is reported. Metrizamide myelography showed narrowing of the upper thoracic subarachnoid space. A tumor in the spinal subdural space is unusual; only a few cases have been reported. The myelographic appearance is not specific; and epidural metastasis can produce the same myelographic picture. (orig.)

  2. Do we need to redefine a cancer metastasis and staging definitions?

    Welch, Danny R.

    2006-01-01

    Metastasis is the most lethal attribute of cancer cells and clinical decisions regarding treatment are based largely upon the likelihood of developing metastases. However, improvements in detection as well as recent experimental data have raised questions about the most appropriate definition of a metastasis, especially whether the mere presence of cells at secondary sites constitute a metastatic lesion. After reviewing the experimental basis of metastasis, a definition of metastasis is proff...

  3. Targeting Breast Cancer Metastasis

    Xin Jin; Ping Mu

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  4. ZD6474, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, inhibits growth of experimental lung metastasis and production of malignant pleural effusions in a non-small cell lung cancer model.

    Matsumori, Yuka; Yano, Seiji; Goto, Hisatsugu; Nakataki, Emiko; Wedge, Stephen R; Ryan, Anderson J; Sone, Saburo

    2006-01-01

    ZD6474 is a novel, orally active inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, with some additional activity against epidermal growth factor receptor (EGFR) tyrosine kinase. The purpose of this study was to determine the potential of ZD6474 in the control of established experimental lung metastasis and pleural effusions produced by human non-small cell lung cancer (NSCLC) cells. PC14PE6 (adenocarcinoma) and H226 (squamous cell carcinoma) cells express high levels of EGFR and only PC14PE6 cells overexpress VEGF. Neither ZD6474 nor the EGFR tyrosine kinase inhibitor gefitinib inhibit proliferation of PC14PE6 or H226 cells in vitro. Both PC14PE6 and H226 cells inoculated intravenously into nude mice induced multiple lung nodules after 5-7 weeks. In addition, PC14PE6 cells produced bloody pleural effusions. Daily oral treatment with ZD6474 did not reduce the number of lung nodules produced by PC14PE6 or H226 cells, but did reduce the lung weight and the size of lung nodules. ZD6474 also inhibited the production of pleural effusions by PC14PE6 cells. Histological analyses of lung lesions revealed that ZD6474 treatment inhibited activation of VEGFR-2 and reduced tumor vascularization and tumor cell proliferation. Therapeutic effects of ZD6474 were considered likely to be due to inhibition of VEGFR-2 tyrosine kinase because gefitinib was inactive in this model. These results indicate that ZD6474, an inhibitor of VEGFR-2, may be useful in controlling the growth of established lung metastasis and pleural effusions by NSCLC. PMID:16783964

  5. Management ovarian brain metastasis

    Ovarian cancer is the cause of the most frequent mortality and morbidity from gynaecologist malignant diseases. Nowadays, the standard treatment is the optimal debulkization with the following platinum chemotherapy at all the histological subtypes. Even despite the progress in the surgery and chemotherapy, in the last years 5-year-survival at the patients with initially progressive disease has remained relatively low. One of the least favourable situations is the presence of brain metastasis where the survival is limited only to a few weekends. The brain metastases are not very common at ovarian cancer even despite the fact that in the last years there has been in decrease. Brain metastases typically occur metachromically. Our patient had metachromic metastasis in the brain without the presence of extra cranial disease. Radiotherapy in the area of brain metastasis in a monotherapy was secure and well tolerated at the relatively good efficiency. (author)

  6. Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3

    Rolando Romina

    2008-02-01

    diglicydyl ether (BADGE did not affect RGZ activity. On the contrary, the specific antagonist GW9662 completely abrogated RGZ-induced decrease in cell viability. A decrease in NO levels was detected in the presence of either 1 or 100 μM RGZ. The natural ligand 15d-PGJ2 did not affect metabolic activity although it induced a significant decrease in NO production. Conclusion A significant decrease in the number of experimental LMM3 lung metastasis, but not on primary tumor growth, after oral RGZ administration was observed. In vitro, 100 μMRGZ also reduced cell viability and NO production, while no changes were observed in the presence of 15d-PGJ2. BADGE did not reverse RGZ effect while the antagonist GW9662 completely abrogated it, suggesting a PPARγ- dependent mechanism. Inhibition of lung metastatic nodules by RGZ administered in vivo, might be associated with the observed decrease in MMP-9 expression, in cell adhesion, migration and invasion. RGZ augmented its expression. PPARγ was detected in cell lysates by western blot and by immunohistochemistry in tumors from RGZ-treated mice. In summary we can suggest that RGZ or any other TZDs might be possible future approaches in the treatment of metastasis of PPARγ-expressing cells.

  7. Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3

    the contrary, the specific antagonist GW9662 completely abrogated RGZ-induced decrease in cell viability. A decrease in NO levels was detected in the presence of either 1 or 100 μM RGZ. The natural ligand 15d-PGJ2 did not affect metabolic activity although it induced a significant decrease in NO production. A significant decrease in the number of experimental LMM3 lung metastasis, but not on primary tumor growth, after oral RGZ administration was observed. In vitro, 100 μMRGZ also reduced cell viability and NO production, while no changes were observed in the presence of 15d-PGJ2. BADGE did not reverse RGZ effect while the antagonist GW9662 completely abrogated it, suggesting a PPARγ- dependent mechanism. Inhibition of lung metastatic nodules by RGZ administered in vivo, might be associated with the observed decrease in MMP-9 expression, in cell adhesion, migration and invasion. RGZ augmented its expression. PPARγ was detected in cell lysates by western blot and by immunohistochemistry in tumors from RGZ-treated mice. In summary we can suggest that RGZ or any other TZDs might be possible future approaches in the treatment of metastasis of PPARγ-expressing cells

  8. Lung Metastasis Mimicking Fingertip Infection

    Salih Soylemez; Murat Demiroglu; Mehmet Ali Yayla; Korhan Ozkan; Bugra Alpan; Harzem Ozger

    2015-01-01

    Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient’s pain during his terminal period, saves the functions of the limb, and increases life comfort.

  9. Genomics screens for metastasis genes

    Yan, Jinchun; Huang, Qihong

    2012-01-01

    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can syst...

  10. Application of Proteomics in the Study of Tumor Metastasis

    Zhen Cai; Jen-Fu Chiu; Qing-Yu He

    2004-01-01

    Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive.The identification of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clinical management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental approaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method ologies will continue to extend its application in studying cancer metastasis.

  11. Inflammation and Tumor Microenvironment in Lymph Node Metastasis

    In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis). Herein, principally reviewing experimental and clinical data related to malignant melanoma, we discuss diverse factors that are mechanistically involved in LN metastasis. We highlight recent data that link tumor microenvironment, including inflammation (at the cellular and cytokine levels) and tumor-induced lymphangiogenesis, with nodal metastasis. Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites. These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers

  12. Selectins mediate small cell lung cancer systemic metastasis.

    Franziska Heidemann

    Full Text Available Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181. However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

  13. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels. PMID:26571019

  14. Global secretome analysis identifies novel mediators of bone metastasis

    Mario Andres Blanco; Gary LeRoy; Zia Khan; Ma(s)a Ale(c)kovi(c); Barry M Zee; Benjamin A Garcia; Yibin Kang

    2012-01-01

    Bone is the one of the most common sites of distant metastasis of solid tumors.Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma.To comprehensively profile secreted proteins associated with bone metastasis,we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types.By comparing the secretomes of parental cells and their bone metastatic derivatives,we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines.We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis.Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1,CST2,and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1.Overall,our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

  15. Global secretome analysis identifies novel mediators of bone metastasis.

    Blanco, Mario Andres; LeRoy, Gary; Khan, Zia; Alečković, Maša; Zee, Barry M; Garcia, Benjamin A; Kang, Yibin

    2012-09-01

    Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets. PMID:22688892

  16. Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells.

    Olkhanud, Purevdorj B; Baatar, Dolgor; Bodogai, Monica; Hakim, Fran; Gress, Ronald; Anderson, Robin L; Deng, Jie; Xu, Mai; Briest, Susanne; Biragyn, Arya

    2009-07-15

    Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Moreover, the primary tumor growing in mammary pads activates remotely the expression of TARC/CCL17 and MDC/CCL22 in the lungs. These chemokines acting through CCR4 attract both tumor and immune cells. However, CCR4-mediated chemotaxis was not sufficient to produce metastasis, as tumor cells in the lung were efficiently eliminated by natural killer (NK) cells. Lung metastasis required CCR4(+) regulatory T cells (Treg), which directly killed NK cells using beta-galactoside-binding protein. Thus, strategies that abrogate any part of this process should improve the outcome through activation of effector cells and prevention of tumor cell migration. We confirm this prediction by killing CCR4(+) cells through delivery of TARC-fused toxins or depleting Tregs and preventing lung metastasis. PMID:19567680

  17. Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells.

    McLeskey, S W; Zhang, L.; Trock, B. J.; Kharbanda, S; Liu, Y; Gottardis, M. M.; Lippman, M E; Kern, F. G.

    1996-01-01

    Previously, we described FGF-1- or FGF-4-transfected MCF-7 breast carcinoma cells which are tumorigenic and metastatic in untreated or tamoxifen-treated ovariectomised nude mice. In this study, we have assessed the effects of AGM-1470, an antiangiogenic agent, and pentosan polysulphate (PPS), an agent that abrogates the effects of FGFs, on tumour growth and metastasis produced by these FGF-transfected MCF-7 cells. Untreated or tamoxifen-treated ovariectomised mice were injected with FGF-trans...

  18. Cathepsins mediate tumor metastasis

    Gong-Jun; Tan; Zheng-Ke; Peng; Jin-Ping; Lu; Fa-Qing; Tang

    2013-01-01

    Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.

  19. Evaluation of treatment response of cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET with 18F-FDG.

    Cheng, Caixa; Komljenovic, Dorde; Pan, Leyun; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig; Bäuerle, Tobias

    2011-01-01

    The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with (18)F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The (18)F-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutic impact on (18)F-FDG kinetics. PMID:21512659

  20. Skeletal metastasis: treatments, mouse models,and the Wnt signaling

    Kenneth C.Valkenburg; Matthew R.Steensma; Bart O.Williams; Zhendong Zhong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality.This is particularly true of cancers with a strong predilection for the bone,such as breast,prostate,and lung cancers.There is currently no reliable cure for skeletal metastasis,and palliative therapy options are limited.The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target.Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments.In this review,we discuss pathologic process of bone metastasis,the roles of the Wnt signaling,and the available experimental models and treatments.

  1. Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

    Xu, Mei; Chen, Gang; Fu, Wei; Liao, Mingjun; FRANK, JACQUELINE A.; Bower, Kimberly A.; Fang, Shengyun; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2012-01-01

    Both epidemiological and experimental studies indicate that ethanol exposure enhances tumor progression. Ethanol exposure promotes cancer cell invasion and is implicated in tumor metastasis. Metastasis consists of multiple processes involving intravasation and extravasation of cancer cells across the blood vessel walls. The integrity of the vascular endothelial barrier that lines the inner surface of blood vessels plays a critical role in cancer cell intravasation/extravasation. We examined t...

  2. Lung metastasis genes couple breast tumor size and metastatic spread

    Minn, Andy J.; Gupta, Gaorav P.; Padua, David; Bos, Paula; Nguyen, Don X.; Nuyten, Dimitry; Kreike, Bas; Zhang, Yi; Wang, Yixin; Ishwaran, Hemant; Foekens, John A; van de Vijver, Marc; Massagué, Joan

    2007-01-01

    The association between large tumor size and metastatic risk in a majority of clinical cancers has led to questions as to whether these observations are causally related or whether one is simply a marker for the other. This is partly due to an uncertainty about how metastasis-promoting gene expression changes can arise in primary tumors. We investigated this question through the analysis of a previously defined “lung metastasis gene-expression signature” (LMS) that mediates experimental breas...

  3. Inhibitory effects of fucoidan, a sulfated polysaccharides from Cucumaria frondosa on experimental metastasis in mice%海参岩藻聚糖硫酸酯抗肿瘤转移作用研究

    王静凤; 张珣; 李辉; 杨玉红; 薛长湖

    2012-01-01

    Objective In the present study, the experimental metastatic mouse model was established by intravenous injection of B16-F10 melanoma cells and the anti-metastatic effect of SC-FUC was investigated. Methods Forty mice were randomly selected and assigned into four groups (ten animals per group) t the normal control group, the model control group, low and high dosage groups (50 and 100 mg· kg-1 bw). Each mouse was treated daily by intraperitoneally injection of SC-FUC or normal saline before tumor inoculation for 5 days. On the 6th day, B16-F10 melanoma cells were transferred intravenously into the tail vein of each mouse except for the normal control group. The mice were sacrificed after 20 days of tumor induction, blood was collected for separating the serum and the lungs were dissected out to detect metastatic colonies. Levels of serum sialic acids, γ-glutamyl transpeptidase and hydroxypro-line, hexosamines, uronic acid in the lung tissues were measured respectively. Results SC-FUC inhibited the metastases formation by about 65. 25% as compared to model control animals. SC-FUC significantly reduced the concentrations of serum sialic acids content and γ-GT energy (P<0.01), which reflected occurrence, development, metastasis and curative effect of the lung cancer to certain extent. Biochemical parameters such as hydroxyproline, hexosamines and uronic acid levels were also reduced clearly (F<0.01) in the SC-FUC-treated animals. Conclusion SC-FUC can inhibit the experimental metastasis of B16-F10 melanoma cells in C57BL/6 mice.%目的 建立小鼠黑色素瘤B16细胞实验性肺转移模型,探讨海参岩藻聚糖硫酸酯(sea cucumber fucoidan,SC-FUC)的体内抑制肿瘤肺转移作用.方法 连续腹腔注射SC-FUC 26 d后,检测小鼠肺转移灶数量、血清中唾液酸的含量、γ-谷氨酰转肽酶活力和肺组织中羟脯氨酸、氨基己糖、糖醛酸的含量.结果 SC-FUC剂量组小鼠的肺转移灶数量显著减少(P<0.01),

  4. Transforming growth factor-β suppresses metastasis in a subset of human colon carcinoma cells

    TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling. To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. Abrogation of TGFβ signaling through introduction of a dominant negative TGFβ receptor II (TGFβRII) in non-metastatic FETα human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFβ signaling in FETα-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFβ signaling is a metastasis suppressor, we rescued TGFβ signaling in CBS metastatic colon cancer cells that had lost TGFβ receptor expression due to epigenetic repression. Restoration of TGFβ signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFβ signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. The observations presented here indicate a metastasis suppressor role for TGF

  5. Retinoblastoma presenting as metastasis

    Objective: The purpose of this study was to evaluate the frequency of metastatic retinoblastoma on initial presentation. Design: Prospective study. Place and duration of study: Supra Regional Centre for Retinoblastoma, Department of Ophthalmology, Khyber Teaching Hospital Peshawar Pakistan from July 1, 1999 to January 31, 2003. Methods: Data was collected from 80 registered Retinoblastoma patients admitted and examined under anaesthesia for tumours assessment. Diagnosis was supported with the help of CT scan and confirmed by histopathology of the enucleated specimen for evidence of optic nerve invasion by the tumour. Results: Twenty (25%) patients were presenting as Metastasis on initial presentation. Mean age was 3.5 years, range was 7 months to 12 years. Out of these 20 patients with metastasis, 10 were male and 10 were female. Eighteen (90%) of them were from lower socio-economic group. Conclusion: Failure in early diagnosis of retinoblastoma, advance age and unilateral disease are associated with extraocular spread; this tragic scenario can be prevented best be early detection and prompt treatment plan implementation. (author)

  6. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia

    2008-01-01

    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

  7. Extraneural Glioblastoma Multiforme Vertebral Metastasis

    Goodwin, C. Rory; Liang, Lydia; Abu-Bonsrah, Nancy; Hdeib, Alia; Elder, Benjamin D.; Kosztowski, Thomas; Bettegowda, Chetan; Laterra, John; Burger, Peter; Sciubba, Daniel M.

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common malignant central nervous system tumor; however, extraneural metastasis is uncommon. Of those that metastasize extraneurally, metastases to the vertebral bodies represent a significant proportion. We present a review of 28 cases from the published literature of GBM metastasis to the vertebra. The mean age at presentation was 38.4 years with an average overall survival of 26 months. Patients were either asymptomatic with metastasis discovered at autopsy or presented with varying degrees of pain, weakness of the extremities, or other neurologic deficits. Of the cases that included the time to spinal metastasis, the average time was 26.4 months with a reported survival of 10 months after diagnosis of vertebral metastasis. A significant number of patients had no treatments for their spinal metastasis, although the intracranial lesions were treated extensively with surgery and/or adjuvant therapy. With increasing incremental gains in the survival of patients with GBM, clinicians will encounter patients with extracranial metastasis. As such, this review presents timely information concerning the presentation and outcomes of patients with vertebral metastasis. PMID:26704201

  8. Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis.

    Kirstein, Jennifer M; Hague, M Nicole; McGowan, Patricia M; Tuck, Alan B; Chambers, Ann F

    2016-08-01

    Progression from a primary tumor to distant metastases requires extensive interactions between tumor cells and their microenvironment. The primary tumor is not only the source of metastatic cells but also can also modulate host responses to these cells, leading to an enhancement or inhibition of metastasis. Tumor-mediated stimulation of bone marrow can result in pre-metastatic niche formation and increased metastasis. However, a primary tumor can also inhibit metastasis through concomitant tumor resistance-inhibition of metastatic growth by existing tumor mass. Here, we report that the presence of a B16F10 primary tumor significantly restricted numbers and sizes of experimental lung metastases through reduction of circulating platelets and reduced formation of metastatic tumor cell-associated thrombi. Tumor-bearing mice displayed splenomegaly, correlated with primary tumor size and platelet count. Reduction in platelet numbers in tumor-bearing animals was responsible for metastatic inhibition, as restoration of platelet numbers using isolated platelets re-established both tumor cell-associated thrombus formation and experimental metastasis. Consumption of platelets due to a B16F10 primary tumor is a form of concomitant tumor resistance and demonstrates the systemic impact of a growing tumor. Understanding the interplay between primary tumors and metastases is essential, as clarification of concomitant tumor resistance mechanisms may allow inhibition of metastatic growth following tumor resection. Key messages Mice with a primary B16F10 tumor had reduced metastasis vs. mice without a primary tumor. Tumor-bearing mice had splenomegaly and fewer platelets and tumor-associated thrombi. Restoring platelets restored tumor-associated thrombi and increased metastasis. This work shows the impact that a primary tumor can have on systemic metastasis. Understanding these interactions may lead to improved ways to inhibit metastasis. PMID:27048169

  9. Experimental Research on Inhabitation Effect of Hedyotis Diffusa Willd on Lewis Lung Canser Spontaneous Metastasis in Mouse%白花蛇舌草抑制Lewis肺癌小鼠自发转移的实验研究

    李洁; 李玉基; 李博

    2012-01-01

    Objective: To observe the effect of Hedyotis diffusa on inhibiting Lewis lung spontaneous metastasis in mouse. Methods: To establish the spontaneous metastasis model with subcutaneous injection Lewis lung cancer tumor cell suspension into the C57BL mouse through right axillaries and observe the changes of mouse's weight, solid tumor growth, lung metastasis, and immune organ index. Results: For the mice in Hedyotis diffusa role groups, the quality of mice' life obviously improved; the index of immune organs and the tumor inhibition rate were increased significantly, pulmonary metastasis nodules was significantly reduced compared with the blank group. Conclusion: Hedyotis diffusa has an inhibitory effect on Lewis lung cancer spontaneous metastasis.%目的:观察白花蛇舌草对Lewis肺癌小鼠自发转移的影响.方法:在C57BL小鼠右侧腋下皮下注射接种肺癌Lewis瘤细胞悬液,复制自发转移模型,观察小鼠体重变化、实体瘤生长情况、肺转移瘤生长情况、免疫器官指数等指标变化.结果:白花蛇舌草作用组的小鼠,小鼠生活质量得到明显改善,免疫器官指数、抑瘤率明显增加,肺部转移结节数较空白组明显减少.结论:白花蛇舌草可抑制Lewis肺癌小鼠自发转移.

  10. Unusual splenic metastasis from oesophageal cancer.

    Murthy S; Prabhakaran P; Rao S; Kumar R

    1991-01-01

    The most common visceral metastasis from oesophageal carcinomas are lungs and liver. A case of splenic metastasis from a squamous carcinoma of oesophagus is reported. To our knowledge, splenic metastasis without any nodal disease has not been described previously. The pattern of reported metastasis is summarised.

  11. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway

  12. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  13. Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice.

    Felix, Klaus; Gerstmeier, Simone; Kyriakopoulos, Antonios; Howard, O M Zack; Dong, Hui-Fang; Eckhaus, Michael; Behne, Dietrich; Bornkamm, Georg W; Janz, Siegfried

    2004-04-15

    The role of the micronutrient, selenium, in human cancers associated with chronic inflammations and persistent infections is poorly understood. Peritoneal plasmacytomas (PCTs) in strain BALB/c (C), the premier experimental model of inflammation-dependent plasma cell transformation in mice, may afford an opportunity to gain additional insights into the significance of selenium in neoplastic development. Here, we report that selenium-depleted C mice (n = 32) maintained on a torula-based low-selenium diet (5-8 micro g of selenium/kg) were totally refractory to pristane induction of PCT. In contrast, 11 of 26 (42.3%) control mice maintained on a selenium adequate torula diet (300 micro g of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 micro g of selenium/kg) developed PCT by 275 days postpristane. Abrogation of PCT was caused in part by the striking inhibition of the formation of the inflammatory tissue in which PCT develop (pristane granuloma). This was associated with the reduced responsiveness of selenium-deficient inflammatory cells (monocytes and neutrophils) to chemoattractants, such as thioredoxin and chemokines. Selenium-deficient C mice exhibited little evidence of disturbed redox homeostasis and increased mutant frequency of a transgenic lacZ reporter gene in vivo. These findings implicate selenium, via the selenoproteins, in the promotion of inflammation-induced PCT and suggest that small drug inhibitors of selenoproteins might be useful for preventing human cancers linked with chronic inflammations and persistent infections. PMID:15087411

  14. Effects of incision and irradiation on regional lymph node metastasis in carcinoma of the hamster tongue

    The effects of incision and irradiation on regional lymph node metastasis in DMBA-induced squamous cell carcinomas of the hamster tongue are reported. Metastasis to the submandibular lymph nodes was confirmed histologically in 48.0% of the animals. The incidence of lymph node metastasis was significantly increased (65.9%) after repeated incisions of tongue carcinomas. Three gray whole-body irradiation also increased the rate of metastasis from 31.0% to 46.3%. Higher incidences of lymphatic vessel invasion after incision and concomitant lymph node metastasis in the lymphatic invasion-positive group indicated a stepwise relationship leading to an increase in lymph node metastasis after incision. Because of the high incidence of metastases and close resemblance to human carcinomas in the tumor cell deposition and establishment of metastatic foci, DMBA-induced tongue carcinoma with invasion may serve as an experimental model of human oral carcinomas

  15. The culture of referendum in Albania: Technical and theoritecal reflections on the abrogative referendum

    Valbona Pajo Bala

    2014-01-01

    The aim of this paper is to analyse the Albanian constitutional and legal framework on referenda, in general, focusing special attention to the abrogative referenda of a law or part thereof. Given the absence of any concrete case of an abrogative referenda held in Albania, which does not creates very much room for discussion in that regard, the paper, through a comparative approach on the referenda culture in other european states, aims at offering to the reader a more complete view on the me...

  16. Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function.

    Zeng, Shao-Lin; Wang, Li-Hui; Li, Ping; Wang, Wei; Yang, Jiong

    2015-08-01

    Mesenchymal stem cells (MSCs) have been investigated in the treatment of numerous autoimmune diseases. However, the immune properties of MSCs on the development of asthma have remained to be fully elucidated. Airway dendritic cells (DCs) have an important role in the pathogenesis of allergic asthma, and disrupting their function may be a novel therapeutic approach. The present study used a mouse model of asthma to demonstrate that transplantation of MSCs suppressed features of asthma by targeting the function of lung myeloid DCs. MSCs suppressed the maturation and migration of lung DCs to the mediastinal lymph nodes, and thereby reducing the allergen-specific T helper type 2 (Th2) response in the nodes. In addition, MSC-treated DCs were less potent in activating naive and effector Th2 cells and the capacity of producing chemokine (C-C motif) ligand 17 (CCL17) and CCL22, which are chemokines attracting Th2 cells, to the airways was reduced. These results supported that MSCs may be used as a potential treatment for asthma. PMID:25936350

  17. Cutaneous metastasis in anorectal adenocarcinoma

    Krishnendra Varma

    2015-01-01

    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  18. Endobronchial metastasis in breast cancer.

    Albertini, R E; Ekberg, N L

    1980-01-01

    Ten patients with endobronchial metastasis from primary breast cancer were found among 1200 fibreoptic bronchoscopies. Six of these patients had radiological signs suggesting bronchial obstruction. The diagnosis was verified in nine cases by means of bronchoscopic biopsy or cytology and in one by thoracotomy. Endobronchial metastasis should be considered when symptoms or chest films suggest endobronchial disease in a patient with a history of breast cancer.

  19. Choroidal and cutaneous metastasis from gastric adenocarcinoma

    2013-01-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pai...

  20. Vector transmission of leishmania abrogates vaccine-induced protective immunity.

    Nathan C Peters

    2009-06-01

    Full Text Available Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is "leishmanization," in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.

  1. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance.

    Fischer, Kari R; Durrans, Anna; Lee, Sharrell; Sheng, Jianting; Li, Fuhai; Wong, Stephen T C; Choi, Hyejin; El Rayes, Tina; Ryu, Seongho; Troeger, Juliane; Schwabe, Robert F; Vahdat, Linda T; Altorki, Nasser K; Mittal, Vivek; Gao, Dingcheng

    2015-11-26

    The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We show that within a predominantly epithelial primary tumour, a small proportion of tumour cells undergo EMT. Notably, lung metastases mainly consist of non-EMT tumour cells that maintain their epithelial phenotype. Inhibiting EMT by overexpressing the microRNA miR-200 does not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment owing to reduced proliferation, apoptotic tolerance and increased expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment. PMID:26560033

  2. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

  3. Metastasis genetics, epigenetics, and the tumor microenvironment

    KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...

  4. Penile metastasis from rectal carcinoma

    Murhekar K

    2007-01-01

    Full Text Available Penile metastases are infrequent and often originate from genitor-urinary organs including bladder and prostate. In the present communication, we report an unusual case of penile metastasis from rectal adenocarcinoma. Though uncommon, this presentation is not unknown. A review of literature of penile metastases in colorectal cancers is also summarized here.

  5. Pulmonary Metastasis from Pseudomyxoma Peritonei

    Toshiyuki Kitai

    2012-01-01

    Full Text Available Pseudomyxoma peritonei (PMP is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.

  6. Gingival Metastasis from Gallbladder Cancer

    Te-Sheng Chang

    2002-08-01

    Full Text Available Gallbladder cancer is generally diagnosed at an advanced stage. The liver is the mostcommonly invaded organ by direct extension and/or metastasis, followed by regional lymphnodes. Oral soft tissue metastasis is extremely unusual. This report describes the case of a62-year-old woman diagnosed with advanced metastatic gallbladder cancer, who initiallypresented with abdominal pain. Diagnosis of gallbladder cancer was made about 3 monthsafter her symptoms developed, when a laparoscopic cholecystectomy was performedbecause of the suspicion of gallstones. Liver metastasis was also discovered during surgery.A postoperative investigation revealed additional lung and bone metastases. A visible leftgingival tumor was found on physical examination and was confirmed as gallbladder cancermetastasis by compatible histopathology 1 month after surgery. The patient responded poorlyto chemotherapy and unfortunately died 5 months after the diagnosis. The clinical presentationof gallbladder cancer was relatively typical, apart from the unusual gingival metastasis.The medical literature contains quite a few examples of metastatic lesions locatedstrictly in the oral soft tissue, however no case of gallbladder cancer metastasizing to theoral soft tissue has been previously reported.

  7. TLR4 initiated and cAMP mediated abrogation of bacterial invasion of the bladder

    Song, Jeongmin; Bishop, Brian L.; Li, Guojie; Duncan, Matthew J.; Abraham, Soman N

    2007-01-01

    The remarkable resistance of the urinary tract to infection has been attributed to its physical properties and the innate immune responses triggered by pattern recognition receptors lining the tract. We report a distinct TLR4 mediated mechanism in bladder epithelial cells (BECs) that abrogates bacterial invasion, a necessary step for successful infection. Compared to controls, uropathogenic type 1 fimbriated Escherichia coli and Klebsiella pneumoniae invaded BECs of TLR4 mutant mice in 10-fol...

  8. The vascular basement membrane as "soil" in brain metastasis.

    W Shawn Carbonell

    Full Text Available Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's "seed and soil" concept. However, there is little direct evidence for this "neurotropic" growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the "soil" for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the beta1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies.

  9. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    -alpha (TNF-alpha) may contribute to the increased metastasis. Treatment with anti-IL17 + celecoxib, an anti-inflammatory drug completely abrogated the development of metastasis and significantly reduced the primary tumor burden. Conclusions The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options. PMID:19643025

  10. Pedunculated hepatocellular carcinoma and splenic metastasis

    Mao-Lin Yan; Yao-Dong Wang; Zhi-De Lai; Yi-Feng Tian; Hong-Biao Chen; Fu-Nan Qiu; Song-Qiang Zhou

    2009-01-01

    Only a few cases of pedunculated hepatocellular carcinoma (P-HCC) have been reported in the literature. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes,kidney, bone marrow and adrenals. Metastasis to spleen is mostly via hematogenous metastasis, direct metastasis to spleen was very rare. We report a case of P-HCC presenting as a left upper abdominal lesions which involved the spleen that was actually a P-HCC with splenic metastasis. This case is unique as P-HCC directly involved the spleen which is not via hematogenous metastasis.

  11. Matrix-Gla protein promotes osteosarcoma lung metastasis and associates with poor prognosis.

    Zandueta, Carolina; Ormazábal, Cristina; Perurena, Naiara; Martínez-Canarias, Susana; Zalacaín, Marta; Julián, Mikel San; Grigoriadis, Agamemnon E; Valencia, Karmele; Campos-Laborie, Francisco J; Rivas, Javier De Las; Vicent, Silvestre; Patiño-García, Ana; Lecanda, Fernando

    2016-08-01

    Osteosarcoma (OS) is the most prevalent osseous tumour in children and adolescents and, within this, lung metastases remain one of the factors associated with a dismal prognosis. At present, the genetic determinants driving pulmonary metastasis are poorly understood. We adopted a novel strategy using robust filtering analysis of transcriptomic profiling in tumour osteoblastic cell populations derived from human chemo-naive primary tumours displaying extreme phenotypes (indolent versus metastatic) to uncover predictors associated with metastasis and poor survival. We identified MGP, encoding matrix-Gla protein (MGP), a non-collagenous matrix protein previously associated with the inhibition of arterial calcification. Using different orthotopic models, we found that ectopic expression of Mgp in murine and human OS cells led to a marked increase in lung metastasis. This effect was independent of the carboxylation of glutamic acid residues required for its physiological role. Abrogation of Mgp prevented lung metastatic activity, an effect that was rescued by forced expression. Mgp levels dramatically altered endothelial adhesion, trans-endothelial migration in vitro and tumour cell extravasation ability in vivo. Furthermore, Mgp modulated metalloproteinase activities and TGFβ-induced Smad2/3 phosphorylation. In the clinical setting, OS patients who developed lung metastases had high serum levels of MGP at diagnosis. Thus, MGP represents a novel adverse prognostic factor and a potential therapeutic target in OS. Microarray datasets may be found at: http://bioinfow.dep.usal.es/osteosarcoma/ Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27172275

  12. OVARIAN METASTASIS IN PATIENT WITH ENDOMETRIAL CARCINOMA

    ZHOU Feng-zhi; CHEN Yi-nan; ZHANG Guo-nan

    2005-01-01

    Objective: To study the clinical pathological characteristics of ovarian metastasis of endometrial carcinoma and the factors affecting prognosis. Methods: Retrospective analysis was made to the clinical pathological outcome of endometrial carcinoma patients receiving surgical treatment in our hospital from January 1990 to December 2002. Results:Among the 191 cases of endometrial carcinoma patients, 17 cases (8.9%) had ovarian metastasis and young patients were more likely to have ovarian metastasis. The multiple factor analysis showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included the depth of myometrial invasion, lymph node metastasis and pathological types. Conclusion: Ovarian metastasis in patients with endometrial carcinoma is associated with poor prognosis, the depth of myometrial invasion, lymph node metastasis and histologic types are independent risk factors affecting the prognosis. For young patients at early stage of the disease, it should be prudent as to whether to retain the ovary.

  13. Pericytes limit tumor cell metastasis

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

    2006-01-01

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

  14. Tissue Dissociation for Metastasis Studies.

    Kabeer, Farhia; Podsypanina, Katrina

    2016-01-01

    The main requirement for most metastasis-related applications is the conversion of solid tissue into a single-cell suspension. In theory, this suspension represents the diversity of cells present in the tissue, whether malignant or benign. We have found that cell viability, as measured by trypan blue staining or fluorescence-activated cell sorting (FACS), is critical for evaluating the success of the tissue-dissociation procedure. The recommended goal is at least 70% cell viability. PMID:26832679

  15. Complications of vertebral metastasis surgery

    Pascal-Moussellard, H.; Broc, G.; Pointillart, V.; Siméon, F.; Vital, J. M.; Sénégas, J.

    1998-01-01

    The authors report their experience concerning complications of spinal metastasis surgery. The purpose of this study was to assess the frequency of such complications and analyse the factors influencing their occurrence. The records of 145 patients treated between 1982 and 1991 for metastatic disease of the spine were retrospectively reviewed for intra- and postoperative complications. Other factors such as radiation therapy, emergent nature of surgery, and neurologic deficits were analysed f...

  16. A review of penile metastasis

    Luigi Mearini; Renato Colella; Alessandro Zucchi; Elisabetta Nunzi; Carlo Porrozzi; Massimo Porena

    2012-01-01

    Penile cancer as primary disease is relatively rare in developed countries. The penis is a rare site of metastases in spite of its rich vascularization. Approximately 500 cases have been reported in the literature; almost 70% of primary lesions are of pelvic origin (from genitourinary or recto-sigmoid primary tumors). We describe a case of penile metastasis from lung cancer. The rarity of the event prompted us to also explore related reviews and discuss the incidence, physiopathology, diagnos...

  17. Raman spectroscopy of bone metastasis

    Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

    2012-02-01

    Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

  18. Microenvironment Determinants of Brain Metastasis

    Zhang Chenyu; Yu Dihua

    2011-01-01

    Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To mee...

  19. Imaging of ocular melanoma metastasis.

    Balasubramanya, Rashmi; Selvarajan, Santosh Kumar; Cox, Mougnyan; Joshi, Ganesh; Deshmukh, Sandeep; Mitchell, Donald G; O'Kane, Patrick

    2016-09-01

    Ocular melanoma is the most common adult primary intraocular tumour. Although helpful for detecting liver lesions. In particular, newer hepatobiliary contrast agents which offer an additional hepatobiliary phase of excretion help in the detection of even tiny liver metastases. Diffusion-weighted imaging is helpful when an i.v. contrast cannot be administered. Treated lesions are also better evaluated with MRI. CT is useful for evaluating lung nodules, large liver metastasis or in patients in whom MRI is medically contraindicated. The disadvantage lies in its inability to detect small liver metastasis and the radiation dose involved. The lesions treated with iodized oil as part of chemoembolization procedures can be followed on CT. Ultrasound can be used only for detecting hepatic metastases. However, it is heavily operator dependent, technically challenging and time consuming especially in patients who are large. Extrahepatic metastasis cannot be seen on ultrasound. Its utility is primarily for the biopsy of liver lesions. Positron emission tomography (PET)-CT can detect lung nodules and large liver lesions but is insensitive to small liver lesions. Moreover, the high radiation dose is a major disadvantage. PMID:27168029

  20. A role for collagen XXIII in cancer cell adhesion, anchorage-independence, and metastasis

    Spivey, Kristin A.; Chung, Ivy; Banyard, Jacqueline; Adini, Irit; Feldman, Henry A.; Bruce R Zetter

    2011-01-01

    Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer that has been used as a tissue and fluid biomarker for non-small cell lung cancer and prostate cancer. To determine whether collagen XXIII facilitates cancer cell metastasis in vivo and to establish a function for collagen XXIII in cancer progression, collagen XXIII knockdown cells were examined for alterations in in vivo metastasis as well as in vitro cell adhesion. In experimental and...

  1. Abrogation of the Transactivation Activity of p53 by BCCIP Down-regulation*

    Meng, Xiangbing; Yue, Jingyin; Liu, Zhihe; Shen, Zhiyuan

    2006-01-01

    The tumor suppression function of p53 is mostly conferred by its transactivation activity, which is inactivated by p53 mutations in ~50% of human cancers. In cancers harboring wild type p53, the p53 transactivation activity may be compromised by other mechanisms. Identifying the mechanisms by which wild type p53 transactivation activity can be abrogated may provide insights into the molecular etiology of cancers harboring wild type p53. In this report, we show that BCCIP, a BRCA2 and CDKN1A-i...

  2. Metastasis-Initiating Cells in Renal Cancer

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  3. Solitary pulmonary metastasis from prostate sarcomatoid cancer

    Oyamada Yoshitaka; Maeshima Arafumi; Goto Taichiro; Kato Ryoichi

    2010-01-01

    Abstract Background Pulmonary metastasis from prostate cancer is considered to be a late event, and patients can be treated with chemotherapy or hormonal manipulation. However, there has been only a few reports on surgical resection for pulmonary metastasis from prostate cancer. Case Presentation We present a surgical case of solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent pelvic evisceration for prostate cancer. Histopathological examination revealed a poorly ...

  4. CT diagnosis of peritoneal metastasis tumor

    Objective: To study the CT findings and diagnosis of peritoneal metastasis. Methods: The CT findings of 17 cases with surgical- pathologically proved peritoneal metastasis were analyzed retrospectively. Results The CT findings of peritoneal metastasis included: (1)ascites (12 cases ); (2)the aternation of parietal peritoneum including broad band thickening (7 cases), nodular sign (2 cases), and massive thickening (1 cases); (3) the involved omentum and mesenterium: 'smut' appearances (7 cases), nodular sign (2 cases), 'omental cake' (5 cases); (4) the invlovement of mesenteric vessels; (5) single-or multi-cystic lesions within peritoneum (1 case) . Conclusion: CT scan is the first choice for metastasis of peritoneum. (authors)

  5. Prostate cancer and metastasis initiating stem cells

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  6. Angiotensin II facilitates breast cancer cell migration and metastasis.

    Sylvie Rodrigues-Ferreira

    Full Text Available Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

  7. A review of penile metastasis

    Luigi Mearini

    2012-06-01

    Full Text Available Penile cancer as primary disease is relatively rare in developed countries. The penis is a rare site of metastases in spite of its rich vascularization. Approximately 500 cases have been reported in the literature; almost 70% of primary lesions are of pelvic origin (from genitourinary or recto-sigmoid primary tumors. We describe a case of penile metastasis from lung cancer. The rarity of the event prompted us to also explore related reviews and discuss the incidence, physiopathology, diagnosis and therapy of penile secondary cancer.

  8. Oral metastasis of chondroblastic osteosarcoma

    Rakesh Kumar Dumpala

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary malignant mesenchymal tumor, accounting for approximately 20% of sarcomas, with 5% incidence in the jaws. They present various clinical and histological aspects as well as variable disease prognosis and outcome. About 50% of all osteosarcomas are osteoblastic, 25% fibroblastic, 25% chondroblastic. Metastasis of osteosarcoma in the oral cavity is rare, and very few cases have been described so far in the literature. This article presents a metastatic case of chondroblastic osteosarcoma in the mandibular right-attached gingiva arising from 4 th rib. This case report further suggests that chondroblastic osteosarcoma has poor prognosis.

  9. Pulmonary metastasis in thyroid cancer

    Although thyroid cancer (TC) in its differentiated form is generally associated with a good prognosis and a near normal life expectancy, a subset of patients especially with distant metastatic disease may run an aggressive course leading to poor survival and early death. The clinical presentation and the manner in which the disease progresses differs with the site and type of the metastatic disease. The behaviour and course of skeletal metastasis has been described elsewhere. The biological behaviour and treatment of pulmonary metastatic disease is focussed on

  10. Toe metastasis: A rare pattern of cervical cancer spread ☆

    Ciccone, Marcia A.; Conturie, Charlotte L.; Lee, Cassie M.; Matsuo, Koji

    2014-01-01

    Highlights • Toe metastasis is a rare pattern of cervical cancer spread. • Enlarged erythematous toe is an important sign suggesting bone metastasis. • Toe metastasis represents a grave prognostic indicator of cervical cancer.

  11. Intradural extramedullary metastasis from papillary carcinoma of thyroid

    Akhavan, Ali; Mehrabaniyan, Mohammad Reza; Jarahi, Mohammadreza; Navabii, Hossein

    2012-01-01

    Although spinal metastasis is a common finding in malignancies, however intradural extramedullary metastasis is very rare. This paper presents a 71-year-old woman, known case of papillary carcinoma of thyroid with intradural extramedullary metastasis in thoracic spine.

  12. MicroRNA and Metastasis.

    Ma, L

    2016-01-01

    Noncoding RNAs are important regulatory molecules of cellular processes. MicroRNAs (miRNAs) are small noncoding RNAs that bind to complementary sequences in the 3' untranslated region of target mRNAs, leading to degradation of the target mRNAs and/or inhibition of their translation. Some miRNAs are essential for normal animal development; however, many other miRNAs are dispensable for development but play a critical role in pathological conditions, including tumorigenesis and metastasis. miRNA genes often reside at fragile chromosome sites and are deregulated in cancer. Some miRNAs function as oncogenes or tumor suppressors, collectively termed "oncomirs." Specific metastasis-regulating miRNAs, collectively termed "metastamirs," govern molecular processes and pathways in malignant progression in either a tumor cell-autonomous or a cell-nonautonomous manner. Recently, exosome-transferred miRNAs have emerged as mediators of the tumor-stroma cross talk. In this chapter, we focus on the functions, mechanisms of action, and therapeutic potential of miRNAs, particularly oncomirs and metastamirs. PMID:27613133

  13. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    Yo-Han Han

    2016-08-01

    Full Text Available Arctigenin (ARC has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC. In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2 and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  14. Supratentorial metastasis of medulloblastoma in adults.

    Kumar, Sushil; Handa, Amit; Jha, Deepak K; Choudhary, Ajay

    2016-01-01

    Two adults, 31 and 20 years of age, developed supratentorial metastasis 3½ years and 11 months, respectively, after gross total removal of their posterior fossa medulloblastoma. The first case developed spinal metastasis as well. Both had undergone craniospinal irradiation. Case 1 underwent laminectomy and case 2 underwent craniotomy because their presenting symptoms required so. PMID:27366282

  15. Influence of p53 abrogation on penclomedine and radiation-induced cell kill

    Purpose: Penclomedine [(3.5-dichloro-2,4-dimethoxy-6-trichloromethyl)pyridine], a synthetic pyridine derivative, has documented activity against human and murine tumor cells and is currently being investigated in Phase I clinical trials. Cells exposed to Penclomedine reveal abundant chromosomal aberrations suggesting that its mechanism of action may be through DNA alkylation. Since p53 is considered to be a DNA damage responsive element, we investigated the influence of p53 abrogation on Penclomedine sensitivity, on sensitivity to ionizing radiation and to both modalities combined. Material and Methods: Three malignant cell lines, derived from a human colorectal carcinoma, were used in this study: RKO cells which contain wild-type p53 alleles, RKO cells transfected with an over expressed mutant p53 transgene (p53.13) and RKO cells transfected with an over expressed HPV-16 E6 gene (RC 10.03) resulting in abrogation of normal p53 function. Cells were exposed to increasing concentrations of Penclomedine (0-120 μg/ml) for variable periods of time (4, 6, 8, 12, 24 hours) as well as to graded doses of ionizing radiation (0-8 Gy), either alone or following 24 hour exposure to Penclomedine. Cell viability was monitored by the colony-forming assay and Trypan blue exclusion. Cell numbers were counted using a hemocytometer and Coulter counter. Both asynchronous and synchronized cell populations were studied with synchrony attained by mitotic shake off. S phase cell determination was by anti-BrdU immuno labeling. Results: Each cell line exhibited a dose and time-dependent reduction in cell viability following Penclomedine treatment. However, RC 10.03 cells showed a dramatic enhancement in cell kill compared to the parental RKO cells (P<0.05). No significant difference in radiation sensitivity amongst the 3 cell lines was observed when cells were exposed either as an asynchronous population or in early G1. Conclusion: The results of this study suggest that radiation

  16. Palmar cutaneous metastasis from carcinoma cervix

    Elamurugan T

    2011-01-01

    Full Text Available Carcinoma of the uterine cervix is the most common gynecological malignancy in developing countries. However, its cutaneous metastasis is a rare entity. The reported incidence of cutaneous metastasis ranges from 0.1 to 2%. Frequent sites of cutaneous metastasis in decreasing order are: abdominal wall, vulva and anterior chest wall. To the best of our knowledge, only three cases of cutaneous metastasis to the upper extremity have been reported in the world. We report a case of a 74-year-old postmenopausal lady diagnosed to have carcinoma cervix (stage IIIB who presented with cutaneous metastasis to palm and thigh, 10 months after radical radiotherapy. At presentation, the primary disease had resolved completely. She had a small nodular growth in the left palm and left thigh. Fine needle aspirate cytology and core needle biopsy from both the nodular lesions were positive for squamous cell carcinoma.

  17. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  18. Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

    Bäuerle, Tobias; Komljenovic, Dorde; Martin R. Berger; Semmler, Wolfhard

    2012-01-01

    Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.

  19. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  20. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding

    Guo-Zhong Gong; Yong-Fang Jiang; Yan He; Li-Ying Lai; Ying-Hua Zhu; Xian-Shi Su

    2004-01-01

    AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21 promoter and explore its possible mechanism for influencing p53 function.METHODS: p53 function of transactivation on p21 promoter was studied with a luciferase reporter system in which the luciferase gene is driven by p21 promoter, and the p53-DNA binding ability was observed with the use of electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A expression vectors were used to transfect hepatoma cell lines to observe whether HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence and p53 transactivation on p21 promoter.Western blot experiment was used for detection of HCV NS5A and p53 proteins expression.RESULTS: Relative luciferase activity driven by p21 promoter increased significantly in the presence of endogenous p53 protein. Compared to the control group, exogenous p53 protein also stimulated p21 promoter driven luciferase gene expression in a dose-dependent way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53 transactivation on p21 promoter with increase of the dose of HCV NS5A expression plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA sequence and, when co-transfected with increased dose of HCV NS5A expression vector, the p53 binding affinity to its DNA gradually decreased and finally disappeared. Between the Huh 7 cells transfected with p53 expression vector alone or co-transfected with HCV NS5A expression vector, there was no difference in the p53 protein expression.CONCLUSION: HCV NS5A inhibits p53 transactivation on p21 promoter through abrogating p53 binding affinity to its specific DNA sequence. It does not affect p53 protein expression.

  1. MR imaging of leptomeningeal metastasis

    Seven patients with CNS neoplasia and leptomeningeal metastases on contrast-enhanced CT were evaluated with MR imaging. Diffuse sulcal and cisternal tumor seeding was not apparent on T1- or T2-weighted images. In two of three patients, MR imaging demonstrated fewer nodular or focal cisternal masses than did the CT study. Ependymal and subependymal metastases were indistinguishable from periventricular abnormalities associated with radiation therapy and/or hydrocephalus. The findings suggest that leptomeningeal metastasis may be very subtle or not apparent on MR imaging, and therefore contrast-enhanced CT and MR imaging should be considered complementary techniques in the initial diagnosis and follow-up of tumors which may metastasize to the leptomeninges

  2. Drug Development for Metastasis Prevention.

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors. PMID:27279241

  3. Brain metastasis treated with Cyberknife

    WANG Zhi-zhen; YUAN Zhi-yong; ZHANG Wen-cheng; YOU Jin-qiang; WANG Ping

    2009-01-01

    Background Cyberknife can greatly raise the fractional dose of stereotactic radiosurgery,thus improving its clinical efficacy.We retrospectively analyzed clinical outcomes of brain metastasis treated with Cyberknife.Methods We analyzed 40 cases of brain metastases treated with Cyberknife in the Tianjin Cancer Hospital from August 1,2006 to August 1,2007,for a total of 68 lesions with maximal diameter of 0.4-7.5 cm (average 1.88 cm).Total hypofractional radiated dosage was 18-36 Gy (5-25 Gy/F,1-5 F) by Cyberknife.We evaluated the remission rate of clinical symptoms,correlation factors to new loci,3-month local control rates,and 3-month and 1-year survival rates.All patients were followed up for more than 14 months.Results After 1 week,clinical remission was 90.0% (36/40).After 3 months,the local control rate and therapeutic effective rate were 77.9% (53/68) and 94.1% (64/68),respectively,as observed by cranium augmentation CT or MRI.The three-month,six-month and 1-year survival rates were 97.5% (39/40),82.5% (33/40) and 67.5% (27/40),respectively.Fourteen patients had neopathy outside the original lesion after 3 months.Neopathy was not correlated with age,whole-brain radiotherapy,number of original lesions,maximum diameter of the original lesion,therapeutic dose per fraction,therapeutic frequency or total therapeutic dose.Conclusions Cyberknife got perfect clinical outcomes by higher dosage per fraction.It is an appropriate and valid treatment shortcut for brain metastasis.

  4. PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis.

    Samanta, Debangshu; Park, Youngrok; Andrabi, Shaida A; Shelton, Laura M; Gilkes, Daniele M; Semenza, Gregg L

    2016-08-01

    Intratumoral hypoxia stimulates enrichment of breast cancer stem cells (BCSC), which are critical for metastasis and patient mortality. Here we report a metabolic adaptation that is required for hypoxia-induced BCSC enrichment and metastasis. Hypoxia-inducible factors coordinately regulate expression of genes encoding phosphoglycerate dehydrogenase (PHGDH) and five downstream enzymes in the serine synthesis pathway and mitochondrial one-carbon (folate) cycle. RNAi-mediated silencing of PHGDH expression in both estrogen receptor-positive and negative breast cancer cells led to decreased NADPH levels, disturbed mitochondrial redox homeostasis, and increased apoptosis, which abrogated BCSC enrichment under hypoxic conditions. PHGDH-deficient cells exhibited increased oxidant levels and apoptosis, as well as loss of BCSC enrichment, in response to treatment with carboplatin or doxorubicin. PHGDH-deficient cells were relatively weakly tumorigenic and tumors that did form were deficient in BCSCs, abolishing metastatic capacity. Our findings highlight a role for PHGDH in the formation of secondary (recurrent or metastatic) tumors, with potential implications for therapeutic targeting of advanced cancers. Cancer Res; 76(15); 4430-42. ©2016 AACR. PMID:27280394

  5. Lymph Node Metastasis of Gastric Cancer

    Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer

  6. Lymph Node Metastasis of Gastric Cancer

    Akagi, Tomonori, E-mail: tomakagi@med.oita-u.ac.jp [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Shiraishi, Norio [Surgical division, Center for community medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Kitano, Seigo [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan)

    2011-04-26

    Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer.

  7. Targeting hypoxic tumour cells to overcome metastasis

    The microenvironment within solid tumours can influence the metastatic dissemination of tumour cells, and recent evidence suggests that poorly oxygenated (hypoxic) cells in primary tumours can also affect the survival and proliferation of metastatic tumour cells in distant organs. Hypoxic tumour cells have been historically targeted during radiation therapy in attempts to improve loco-regional control rates of primary tumours since hypoxic cells are known to be resistant to ionizing radiation-induced DNA damage. There are, therefore, a number of therapeutic strategies to directly target hypoxic cells in primary (and metastatic) tumours, and several compounds are becoming available to functionally inhibit hypoxia-induced proteins that are known to promote metastasis. This mini-review summarizes several established and emerging experimental strategies to target hypoxic cells in primary tumours with potential clinical application to the treatment of patients with tumour metastases or patients at high risk of developing metastatic disease. Targeting hypoxic tumour cells to reduce metastatic disease represents an important advance in the way scientists and clinicians view the influence of tumour hypoxia on therapeutic outcome

  8. Imaging of bone metastasis: An update

    Gerard; J; O’Sullivan; Fiona; L; Carty; Carmel; G; Cronin

    2015-01-01

    Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques whichfuse morphological and functional data are the most sensitive and specific, and positron emission tomography(PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

  9. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

    Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

  10. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31+ vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models

  11. Complexity and Dynamic Heterogeneity of the Process of Cancer Metastasis

    Chambers, Ann

    2010-03-01

    Cancer metastasis -- the spread of cancer from a primary tumor to distant parts of the body -- is responsible for most cancer deaths. If cancer is detected early, before it has spread, it can often be treated with local therapies like surgery and radiation. If cancer is detected after it has already spread, it is much harder to treat successfully. Cancer cells may be distributed to many organs, may be present as tiny micrometastases that are hard to detect, and cancer cells can be in a dormant state that may be resistant to treatment that is directed against actively dividing cells. A better understanding of the process of metastasis thus is needed in order to improve survival from cancer. Cancer is not a static disease, but one that can undergo stepwise evolution and progression from early, treatable cancer to aggressive cancer that is harder to treat. Furthermore, cancers are made up of many cells, and there is considerable heterogeneity among the cells in a tumor. Thus, cancer is ``plastic,'' with heterogeneity among cancer cells and changes over time. Understanding this ``dynamic heterogeneity'' has proven to be difficult. Input from physical sciences disciplines may help to shed light on this complex aspect of cancer biology. Here the process of cancer metastasis will be discussed, and experimental models for imaging the process described. The concept of ``dynamic heterogeneity'' of the metastatic process will be discussed, and some of the questions that need to be addressed for better understanding of metastasis will be outlined. An evolving dialogue between cancer biologists and physical scientists may lead to new ways of studying and understanding this lethal aspect of cancer.

  12. Screening candidate metastasis-associated genes in three-dimensional HCC spheroids with different metastasis potential

    Chen, Rongxin; Dong, Yinying; Xie, Xiaoying; Chen, Jie; Gao, Dongmei; Liu, Yinkun; Ren, Zhenggang; Cui, Jiefeng

    2014-01-01

    Purpose: Previously, we have established a tissue-like HCC spheroid which better mirrors the biological features of tumorigenesis and metastasis. This study was to find out metastasis-associated genes between two 3D HCC spheroids with different metastasis potential using comparative PCR arrays. Materials and Methods: Two HCC spheroids derived from high-metastatic MHCC97H cells and low-metastatic Hep3B cells were formed respectively in a rotating wall vessel bioreactor after 3D culture for 15 ...

  13. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  14. Isolated malignant melanoma metastasis to the pancreas

    Larsen, Anne K; Krag, Christen; Geertsen, Poul;

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  15. Silencing FAT10 inhibits metastasis of osteosarcoma.

    Ma, Chengbin; Zhang, Zhiyu; Cui, Yan; Yuan, Hongmou; Wang, Feng

    2016-08-01

    Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients. PMID:27279480

  16. Stereotactic body radiotherapy for solitary spine metastasis

    Lee, Sun Young [Dept. of Radiation Oncology, Sun Medical Center, Daejeon (Korea, Republic of); Chun, Mison [Dept. of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Mi Jo [Dept. of Radiation Oncology, Eulji Universtiy School of Medicine, Daejeon (Korea, Republic of)

    2013-12-15

    A clear consensus has not been established regarding the best treatment for solitary bone metastasis. Here, we reviewed the medical records of patients with a controlled primary malignancy who had only solitary spine metastasis without metastasis to the extraspinal bone or viscera and underwent treatment between April 2007 and December 2012 with stereotactic body radiosurgery using CyberKnife, with a total dose of 24 Gy in three to four fractions. During that time, there were only four cases. This was effective in each case, and all the four patients had no local failure and remained alive at a median follow-up of 68 months (range, 64 to 80 months). Although our experience is limited, this study suggests that stereotactic body radiotherapy could be a feasible, safe, effective, and noninvasive alternative treatment for solitary spine metastasis in patients who are medically inoperable or unsuitable for surgery.

  17. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  18. Tetrandrine: A Potent Abrogator of G2 Checkpoint Function in Tumor Cells and Its Mechanism

    2007-01-01

    Objective To assess the ability of tetrandrine (Tet) to enhance the sensitivity to irradiation and its mechanism in cell lines of human breast cancer p53-mutant MCF-7/ADR, p53-wild-type MCF-7 and human colon carcinoma p53-mutant HT-29 as well as in C26 colorectal carcinoma-bearing BALB/c mice. Methods MCF-7/ADR, HT-29 and MCF-7 cells were exposed to irradiation in the absence or presence of tetrandrine. The effect of Tet on the cytotoxicity of X-irradiation in these three cells was determined and the effect of tetrandrine on cell cycle arrest induced by irradiation in its absence or presence was studied by flow cytometry, Moreover, mitotic index measurement determined mitosis of cells to enter mitosis. Western blotting was employed to detect cyclin B1 and Cdc2 proteins in extracts from irradiated or non-irradiated cells of MCF-7/ADR, HT-29 and MCF-7 treated with tetrandrine at various concentrations. Tumor growth delay assay was conducted to determine the radio-sensitization of tetrandrine in vivo. Results Clonogenic assay showed that tetrandrine markedly enhanced the lethal effect of X-rays on p53-mutant MCF-7/ADR and HT-29 cells and the sensitization enhancement ratio (SER) of tetrandrine was 1.51 and 1.63, but its SER was only 1.1 in p53-wt MCF-7 cells. Irradiated p53-mutant MCF-7/ADR and HT-29 cells were only arrested in G2/M phase while MCF-7 cells were arrested in G1 and G2/M phases. Radiation-induced G2 phase arrests were abrogated by tetrandrine in a concentration-dependent manner in MCF-7/ADR and HT-29 cells,whereas redistribution within MCF-7 cell cycle changed slightly. The proportion of cells in M phase increased from 1.3% to 14.7% in MCF-7/ADR cells, and from 1.5% to 13.2% in HT-29 cells, but 2.4% to 7.1% in MCF-7 cells. Furthermore, the levels of cyclin B 1 and Cdc2 expression decreased after X-irradiation in MCF-7/ADR and HT-29 cells, and the mitotic index was also lower. Tet could reverse the decrease and induce the irradiated cells to enter mitosis

  19. Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

    Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo; Andrea Monti Hughes; Silvia I. Thorp; Jorge E. Cardoso; Marcel A. Garabalino; Ana J. Molinari; Elisa M. Heber; Paula Curotto; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; David W. Nigg; Amanda E. Schwint

    2013-11-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

  20. Three-dimensional context regulation of metastasis

    Erler, Janine Terra; Weaver, Valerie M

    2009-01-01

    stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia...... is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix...

  1. Molecular mechanisms of metastasis in prostate cancer

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  2. Tracheal metastasis of small cell lung cancer

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  3. Leptomeningeal metastasis of spinal cord

    Ten patients with leptomeningeal metastases of spinal cord were studied with a 1.5-T MR imager. Six patients had primary central nervous system (CNS) tumors, and the other four had their primary tumor outside of the CNS. All patients had positive CSF cytologic findings, and cervical cords were generally examined. MR findings on T1-weighted images before and after gadolinium-DTPA administration were divided into three types. Type 1, the diffuse form (four cases), was characterized by (1) increased CSF intensity, (2) poor cord-CSF interface, and (3) perimedullary enhancement; type 2, the nodular form (one case) by discrete nodules adherent to the cord surface; and type 3, predominance of intramedullary metastases (three cases), by localized cord swelling with central enhancement. In two cases, no significant findings were found. In conclusion, T1-weighted images with Gd-DTPA enhancement were valuable in the MR imaging of spinal meningeal metastasis. The main route of intramedullary tumor spread is believed to be via arterial seeding, but the authors study suggests that intramedullary metastases resulting from direct extension from the CSF were not infrequent

  4. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  5. Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis.

    Chow, Bryna S Man; Kocan, Martina; Bosnyak, Sanja; Sarwar, Mohsin; Wigg, Belinda; Jones, Emma S; Widdop, Robert E; Summers, Roger J; Bathgate, Ross A D; Hewitson, Tim D; Samuel, Chrishan S

    2014-07-01

    Fibrosis is a hallmark of chronic kidney disease, for which there is currently no effective cure. The hormone relaxin is emerging as an effective antifibrotic therapy; however, its mechanism of action is poorly understood. Recent studies have shown that relaxin disrupts the profibrotic actions of transforming growth factor-β1 (TGF-β1) by its cognate receptor, relaxin family peptide receptor 1 (RXFP1), extracellular signal-regulated kinase phosphorylation, and a neuronal nitric oxide synthase-dependent pathway to abrogate Smad2 phosphorylation. Since angiotensin II also inhibits TGF-β1 activity through its AT2 receptor (AT2R), we investigated the extent to which relaxin interacts with the AT2R. The effects of the AT2R antagonist, PD123319, on relaxin activity were examined in primary rat kidney myofibroblasts, and in kidney tissue from relaxin-treated male wild-type and AT2R-knockout mice subjected to unilateral ureteric obstruction. Relaxin's antifibrotic actions were significantly blocked by PD123319 in vitro and in vivo, or when relaxin was administered to AT2R-knockout mice. While heterodimer complexes were formed between RXFP1 and AT2Rs independent of ligand binding, relaxin did not directly bind to AT2Rs but signaled through RXFP1-AT2R heterodimers to induce its antifibrotic actions. These findings highlight a hitherto unrecognized interaction that may be targeted to control fibrosis progression. PMID:24429402

  6. JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

    Malabika Sen

    2015-03-01

    Full Text Available Aberrant activation of the Janus kinase (JAK/signal transducer and activator of transcription (STAT 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC. AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50 values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3Tyr705 expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3Tyr705 expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

  7. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  8. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  9. Abrogation of Plasminogen Activator Inhibitor-1-Vitronectin Interaction Ameliorates Acute Kidney Injury in Murine Endotoxemia

    Gupta, Kamlesh K.; Donahue, Deborah L.; Sandoval-Cooper, Mayra J.; Castellino, Francis J.; Ploplis, Victoria A.

    2015-01-01

    Sepsis-induced acute kidney injury (AKI) contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1) and vitronectin (Vn) are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1−/−) or expressing a PAI-1-mutant (PAI-1R101A/Q123K) in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1−/− and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT) mice after LPS challenge. Also, PAI-1−/− mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC) in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity. PMID:25799354

  10. miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice.

    Cyrielle Clapé

    Full Text Available BACKGROUND: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo. RESULTS: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5 activity. We show here that ERK5 is a miR-143 target in prostate cancer. CONCLUSIONS: miR-143 is as a new target for prostate cancer treatment.

  11. Detection of cancer before distant metastasis

    To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the first metastasis has formed from a primary breast cancer tumor. The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TXNXM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1BNXM0 (25% of total patients with T1BNXM0). Validation of the model was done with data for all patients. From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1B patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TXNXM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood. To reduce the rate of distant metastasis in surgically treated TXNXM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be

  12. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease.

    Royce, Simon G; Shen, Matthew; Patel, Krupesh P; Huuskes, Brooke M; Ricardo, Sharon D; Samuel, Chrishan S

    2015-11-01

    This study determined if the anti-fibrotic drug, serelaxin (RLN), could augment human bone marrow-derived mesenchymal stem cell (MSC)-mediated reversal of airway remodeling and airway hyperresponsiveness (AHR) associated with chronic allergic airways disease (AAD/asthma). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD were either untreated or treated with MSCs alone, RLN alone or both combined from weeks 9-11. Changes in airway inflammation (AI), epithelial thickness, goblet cell metaplasia, transforming growth factor (TGF)-β1 expression, myofibroblast differentiation, subepithelial and total lung collagen deposition, matrix metalloproteinase (MMP) expression, and AHR were then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total collagen deposition, and increased MMP-9 levels above that induced by OVA alone (all p<0.05 vs OVA group). RLN alone more broadly reversed OVA-induced epithelial thickening, TGF-β1 expression, myofibroblast differentiation, airway fibrosis and AHR (all p<0.05 vs OVA group). Combination treatment further reversed OVA-induced AI and airway/lung fibrosis compared to either treatment alone (all p<0.05 vs either treatment alone), and further increased MMP-9 levels. RLN appeared to enhance the therapeutic effects of MSCs in a chronic disease setting; most likely a consequence of the ability of RLN to limit TGF-β1-induced matrix synthesis complemented by the MMP-promoting effects of MSCs. PMID:26426509

  13. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease

    Simon G. Royce

    2015-11-01

    Full Text Available This study determined if the anti-fibrotic drug, serelaxin (RLN, could augment human bone marrow-derived mesenchymal stem cell (MSC-mediated reversal of airway remodeling and airway hyperresponsiveness (AHR associated with chronic allergic airways disease (AAD/asthma. Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA-induced chronic AAD were either untreated or treated with MSCs alone, RLN alone or both combined from weeks 9–11. Changes in airway inflammation (AI, epithelial thickness, goblet cell metaplasia, transforming growth factor (TGF-β1 expression, myofibroblast differentiation, subepithelial and total lung collagen deposition, matrix metalloproteinase (MMP expression, and AHR were then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total collagen deposition, and increased MMP-9 levels above that induced by OVA alone (all p < 0.05 vs OVA group. RLN alone more broadly reversed OVA-induced epithelial thickening, TGF-β1 expression, myofibroblast differentiation, airway fibrosis and AHR (all p < 0.05 vs OVA group. Combination treatment further reversed OVA-induced AI and airway/lung fibrosis compared to either treatment alone (all p < 0.05 vs either treatment alone, and further increased MMP-9 levels. RLN appeared to enhance the therapeutic effects of MSCs in a chronic disease setting; most likely a consequence of the ability of RLN to limit TGF-β1-induced matrix synthesis complemented by the MMP-promoting effects of MSCs.

  14. Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells.

    McLeskey, S W; Zhang, L; Trock, B J; Kharbanda, S; Liu, Y; Gottardis, M M; Lippman, M E; Kern, F G

    1996-05-01

    Previously, we described FGF-1- or FGF-4-transfected MCF-7 breast carcinoma cells which are tumorigenic and metastatic in untreated or tamoxifen-treated ovariectomised nude mice. In this study, we have assessed the effects of AGM-1470, an antiangiogenic agent, and pentosan polysulphate (PPS), an agent that abrogates the effects of FGFs, on tumour growth and metastasis produced by these FGF-transfected MCF-7 cells. Untreated or tamoxifen-treated ovariectomised mice were injected with FGF-transfected cells, treated with AGM-1470 or PPS, and tumour growth and metastasis analysed. The sensitivity of FGF-transfected and parental MCF-7 cells to AGM-1470 or PPS was also determined in vitro. Both AGM-1470 and PPS inhibited tumour growth in otherwise untreated or tamoxifen-treated mice injected with either FGF- or FGF-4-transfected MCF-7 cells. This effect was more reliably seen in tamoxifen-treated animals. AGM-1470 was about 10(5) times less potent in inhibiting the anchorage-dependent growth of parental MCF-7 or FGF-transfected MCF-7 cells than in inhibiting the growth of human umbilical vein endothelial cells. PPS did not affect the in vitro growth of the transfectants or parental cells. Thus, the growth-inhibitory effect on tumours was in excess of the effect of either drug on the same cells in tissue culture, implying that stromal elements are important determinants of the effects of these drugs. There was a positive correlation between tumour size and the extent of proximal lymph node metastasis. However, neither drug had a significant effect on the extent of metastasis to proximal or distal lymph nodes or lungs. AGM-1470 or PPS may be helpful in cases of breast carcinoma in which angiogenesis is due to expression of FGFs by the tumour cells and may be more effective when combined with tamoxifen. PMID:8624263

  15. Platelet P2Y12 is involved in murine pulmonary metastasis.

    Yanhua Wang

    Full Text Available The involvement of platelets in tumor progression is well recognized. The depletion of circulating platelets or pharmacologic inhibitors of platelet activation decreases the metastatic potential of circulating tumor cells in metastasis mouse models. The platelet ADP receptor P2Y12 amplifies the initial hemostatic responses activated by a variety of platelet agonists and stabilizes platelet aggregation, playing a crucial role in granule secretion, integrin activation and thrombus formation. However, the relationship between P2Y12 and tumor progression is not clear. In our study, the Lewis Lung Carcinoma (LLC spontaneous metastatic mouse model was used to evaluate the role of P2Y12 in metastasis. The results demonstrated that P2Y12 deficiency significantly reduced pulmonary metastasis. Further studies indicated that P2Y12 deficiency diminished the ability of LLC cells to induce platelet shape change and release of active TGFβ1 by a non-contact dependent mechanism resulting in a diminished, platelet-induced EMT-like transformation of the LLC cells, and that transformation probably is a prerequisite of LLC cell metastasis. Immunohistochemical analyses indicated an obvious P2Y12 deficiency related attenuation of recruitment of VEGFR1+ bone marrow derived cell clusters, and extracellular matrix fibronectin deposition in lungs, which presumably are required for pre-metastatic niche formation. In contrast to the LLC cells, non-epithelial melanoma B16 cells induced platelet aggregation in a cell number and P2Y12-dependent manner. Also, a platelet induced EMT-like transformation of B16 cells is dependent on P2Y12. In agreement with the LLC cell model, platelet P2Y12 deficiency also results in significantly less lung metastasis in the B16 melanoma experimental metastasis model. These results demonstrate that P2Y12 is a safe drug target for anti-thrombotic therapy, and that P2Y12 may serve as a new target for inhibition of tumor metastasis.

  16. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  17. Are we ready to abrogate compulsory vaccinations for children?: The opinion of apulian family pediatricians; Italy, 2013

    Martinelli, Domenico; Tafuri, Silvio; Fortunato, Francesca; Cozza, Vanessa; Germinario, Cinzia A; Prato, Rosa

    2014-01-01

    In Italy, vaccination against diphtheria, tetanus, polio and hepatitis B is compulsory for infants countrywide, except in Veneto region where since 2007 Health Authorities have experimented the suspension of mandatory vaccination. In light of the recent discussion on the potential abrogation in other regions, we explored the opinion of family pediatricians who play a crucial role in promoting immunization programmes in Italy. In November 2009, we interviewed by phone the family pediatricians ...

  18. The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation.

    Renshaw, M W; McWhirter, J R; Wang, J Y

    1995-01-01

    Proliferation of normal cells in a multicellular organism requires not only growth factors but also the proper attachment to the extracellular matrix. A hallmark of neoplastic transformation is the loss of anchorage dependence which usually accompanies the loss of growth factor requirement. The Bcr-Abl tyrosine kinase of human leukemias is shown here to abrogate only the anchorage, not the growth factor, requirement. Bcr-Abl-transformed cells grow in soft agar but do not proliferate in serum-...

  19. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways

    Highlights: ► KNK437, a benzylidene lactam compound, is a novel radiosensitizer. ► KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1α under hypoxia. ► KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1α (HIF-1α). HIF-1α is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1α. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1α in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1α levels in KNK437-treated cells. This suggested that the absence of HIF-1α in hypoxic cells was not due to the enhanced protein degradation. HIF-1α is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1α mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1α levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  20. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1{alpha} survival pathways

    Oommen, Deepu, E-mail: oommen1978@gmail.com [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer KNK437, a benzylidene lactam compound, is a novel radiosensitizer. Black-Right-Pointing-Pointer KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1{alpha} under hypoxia. Black-Right-Pointing-Pointer KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1{alpha} (HIF-1{alpha}). HIF-1{alpha} is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1{alpha}. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1{alpha} in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1{alpha} levels in KNK437-treated cells. This suggested that the absence of HIF-1{alpha} in hypoxic cells was not due to the enhanced protein degradation. HIF-1{alpha} is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1{alpha} mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1{alpha} levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  1. The relationship between MHC antigen expression and metastasis.

    Gopas, J; Rager-Zisman, B; Bar-Eli, M; Hämmerling, G J; Segal, S

    1989-01-01

    From the studies summarized here a complex picture of the role played by MHC products in determining tumorigenicity and metastasis is emerging. In order to be able to understand this relationship better, it is necessary to consider several factors. 1. Each tumor system or neoplastic tissue is unique, and its behavior reflects the influence of cell-specific characteristics, as well as its ability to modulate other cells and tissues--including cells belonging to the immune system--and also to be modulated by other cells and soluble factors. 2. Since metastasis formation is a multistep process in which only small subpopulations of tumor cells with complex and defined phenotypes are able to colonize secondary tissues, elimination of even one single phenotypic component of this structured process can easily reverse the metastatic capacity of the cells. Acquisition of metastatic ability, on the other hand, would be a more difficult task, since any new characteristic expressed by the cells or induced experimentally, such as gene transfection or results of IFN treatment, must be expressed in a temporal manner and in concert with other cellular characteristics. Therefore, an experimental protocol measuring a specific element in determining metastasis can easily produce conflicting results, depending on the type of cells and genetic background of the host studied. 3. The level of specific MHC products on tumor cells is one among many other cell characteristics that may determine the metastatic potential of cells. Moreover, each of the class 1 MHC products, and the relationship among them, including other than the classical K, L, or D products (Brickell et al., 1983), should be regarded as independent entities, with possible different regulatory roles in cell-cell recognition, in a general sense, which may be involved in determining invasiveness and homing as well as recognition by the immune system. 4. Both specific T-cell and nonspecific natural mediated immunity (which is

  2. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K;

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody...

  3. RUNX2 promotes breast cancer bone metastasis by increasing integrin α5-mediated colonization.

    Li, Xiao-Qing; Lu, Jun-Tao; Tan, Cong-Cong; Wang, Qing-Shan; Feng, Yu-Mei

    2016-09-28

    Runt-related transcription factor 2 (RUNX2) is regarded as an important contributor to breast cancer bone metastasis. However, previous studies did not provide direct clinical evidence for a role of RUNX2 in bone-specific metastasis in breast cancer, and the mechanism of RUNX2 in cancer cell recruitment and adhesion to the bone remains unclear. In this study, we showed that RUNX2 expression is positively correlated with the risk of bone-specific metastasis in lymph node-negative breast cancer patients. Then, we identified ITGA5 as a transcriptional target of RUNX2 from multiple candidate genes encoding adhesion molecules or chemokine receptors. We further provided experimental and clinical evidence that RUNX2, in an integrin α5-dependent manner, promotes the attraction and adhesion of breast cancer cells to the bone and confers cancer cell survival and bone colonization advantages. Overall, our findings clarify an adhesion-dependent mechanism of RUNX2 for the osteotropism and bone colonization of breast cancer cells and implicate RUNX2 and integrin α5 as potential molecular markers for the prediction of bone metastasis and therapeutic targets for the treatment of breast cancer bone metastasis. PMID:27317874

  4. Breast metastasis from carcinoma of gall bladder

    Ajaz Ahmad Malik

    2013-01-01

    Full Text Available Carcinoma of gall bladder has early lymphatic and haematogenous spread. Most common extra abdominal site of metastasis is the lung. Metastasis to breast from carcinoma of breast is very rare. Our case describes an interesting case of carcinoma of gall bladder metastising to breast. A 50-year-old female presented to our outpatient department with a small nodule on upper outer quadrant of left breast. Patient had a history of cholecystectomy done for symptomatic gall stones 2 years back. Histopathological examination of the gall bladder specimen showed adenocarcinoma of the gall bladder with invasion to lamina propria. No additional treatment was offered to the patient. The breast nodule was excised and sent for histopathological examination. Histopathological examination revealed metastising adenocarcinoma. Patient was subjected to palliative chemotherapy (Gamcitabine and carboplatin. However, patient died of hepatic encephalopathy after 5 months. Our case reports an unusual site of metastasis from carcinoma of gall bladder which is very rare.

  5. Hematogenous Gastric Metastasis of Pancreatic Cancer

    Sasajima, Junpei; Okamoto, Kotaro; Taniguchi, Masato

    2016-01-01

    While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas.

  6. Radiotherapy for metastasis from breast and lung cancer. Bone and Brain metastasis

    Bone or brain metastasis is the common and serious condition restricting the quality of life (QOL) of the cancer patients and radiotherapy frequently plays an important role in relief of their symptoms. Because radiotherapy is given with palliative intent to the patients with limited, if variable, life expectancy, radiation schedules need to be identified which give maximum patient benefit with minimum associated morbidity and minimum disturbance of the patients' remaining life. We retrospectively analyzed 222 patients with the bone or the brain metastasis from lung or breast cancer to evaluate the effect of radiotherapy on their prognosis and QOL. The 3-year survival rates of the patients with breast and lung cancer were 21% and 3%, respectively (p<0.0001), and breast cancer patients seemed to have better prognosis than lung cancer patients for both bone metastasis (p<0.0001) and brain metastasis (p=0.09). Symptom relief by radiotherapy was obtained 84% for bone metastasis and 64% for brain metastasis and it was not affected by primary lesion (lung or breast). Sixty seven per cent of the bone and the brain metastasis was derived from adenocarcinoma and it had a tendency to give the better prognosis comparing with squamous cell carcinoma. Radiation schedules should be flexibly corresponded to the patients' tumor type (metastatic site, primary disease or histology), even if it is 'just' a palliative therapy, considering their prognosis and QOL. (author)

  7. Renal cell carcinoma presenting as mandibular metastasis

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  8. Cranial computed tomographic abnormalities in leptomeningeal metastasis

    Sixty-four (57.6%) of 111 cancer patients with cerebrospinal fluid cytology positive for malignant cells had cranial computed tomographic (CT) scans within 2 weeks before or after a lumbar puncture. Twenty-two (34.3%) of the 64 had abnormal CT findings indicative of leptomeningeal metastasis. Thirteen (59.6%) of these 22 patients had associated parenchymal metastases. Recognition of leptomeningeal disease may alter the management of patients with parenchymal metastases. Communicating hydrocephalus in cancer patients should be considered to be related to leptomeningeal metastasis until proven otherwise

  9. Extracellular galectin-3 in tumor progression and metastasis

    MauroSergioPavao

    2014-06-01

    Full Text Available Galectin-3, the only chimera galectin found in vertebrates, is one of the best-studied galectins. It is expressed in several cell types and is involved in a broad range of physiological and pathological processes, such as cell adhesion, cell activation and chemoattraction, cell cycle, apoptosis and cell growth and differentiation. However, this molecule raises special interest due to its role in regulating cancer cell activities. Galectin-3 has high affinity for beta-1,6-N-acetylglucosamine branched glycans, which are formed by the action of the beta-1,6-N-acetylglucosaminyltransferase V (Mgat5. Mgat5-related changes in protein/lipid glycosylation on cell surface lead to alterations in the clustering of membrane proteins through lattice formation, resulting in functional advantages for tumor cells. Galectin-3 presence enhances migration and/or invasion of many tumors. Galectin-3-dependent clustering of integrins promotes ligand-induced integrin activation, leading to cell motility. Galectin-3 binding to mucin-1 increases transendothelial invasion, decreasing metastasis-free survival in an experimental metastasis model. Galectin-3 also affects endothelial cell behavior by regulating capillary tube formation. This lectin is found in the tumor stroma, suggesting a role for microenvironmental galectin-3 in tumor progression. Galectin-3 also seems to be involved in the recruitment of tumor-associated macrophages, possibly contributing to angiogenesis and tumor growth. This lectin can be a relevant factor in turning bone marrow in a sanctuary for leukemia cells, favoring resistance to therapy. Finally, galectin-3 seems to play a relevant role in orchestrating distinct cell events in tumor microenvironment and for this reason, it can be considered a target in tumor therapies. In conclusion, this review aims to describe the processes of tumor progression and metastasis involving extracellular galectin-3 and its expression and regulation.

  10. Unusual presentation of oesophageal carcinoma with adrenal metastasis

    Adrenal gland is a common site of metastasis in many cancers but it is very rare in oesophageal carcinoma. We report one such case found to have adrenal metastasis on follow-up PET/computed tomography scan

  11. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    Yalın Dirik

    2014-01-01

    CONCLUSION: Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed.

  12. Para-recurrent lymph node metastasis was a significant predictor for cervical lymph nodes metastasis in thoracic esophageal carcinoma

    Objective: To evaluate correlation factors of cervical lymph nodes metastasis in thoracic esophageal carcinoma. Methods: Local-regional metastasis of lymph node for 126 cases with esophageal squamous cell cancer after surgery from 2004 to 2009 were reviewed. Risk factors of cervical lymph nodes metastasis were examined by multiple Logistic regression analysis. Results: In 126 cases, supraclavicular lymph node metastasis rate was 43.7% (55/126). By logistic regression, none of the primary site, T stage, N stage, histological grade, lymph node metastasis rate, lymph node metastasis degree and number of lymph nodes metastatic field was not the high risk of cervical lymph nodes metastasis. In addition, multivariate analysis found that lymph node metastasis in mediastinum region 1 was high risk factor for lymph node metastasis of region 1 (χ2 =12.14, 9.27, P =0.000, 0.002), lymph node metastasis in region III and region 2 were high risk factors for lymph node metastasis of region IIa (χ2 =14.56, 8.27, 8.02, 3.93, P =0.000, 0.004, 0.005, 0.047). Conclusion: Mediastinal para-recurrent nerve lymph node metastasis is a significant predictor for cervical lymph nodes metastasis. (authors)

  13. Invasive cancer cells and metastasis

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  14. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

    2012-01-01

    Background The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be “back to nature” and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane), a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. Methods T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. Results In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM) induced cell proliferation, addition of genistein (20 μM) 16 h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM) induced necrotic cells. Conclusions Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method

  15. Metastasis and bone loss: Advancing treatment and prevention

    Coleman, Robert E.; Lipton, Allan; Roodman, G. David; Guise, Theresa A.; Boyce, Brendon F.; Brufsky, Adam M.; Clézardin, Philippe; Peter I Croucher; Gralow, Julie R.; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R.; Smith, Matthew R.; Suva, Larry J.

    2010-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced...

  16. Leptomeningeal metastasis after surgical resection of brain metastases

    Ree, T.C.; Dippel, Diederik; Avezaat, Cees; Vecht, C J; Bent, Martin; Sillevis Smitt, Peter

    1999-01-01

    textabstractOBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metas...

  17. Diagnosis of bone metastasis from thyroid carcinoma

    Bechsgaard, Thor; Lelkaitis, Giedrius; Jensen, Karl E;

    2015-01-01

    (MRI), but histology revealed a metastasis from thyroid carcinoma, although the patient had no previous history of thyroid malignancy and resection of the thyroid gland was without malignancy. Ultrasound-guided biopsy was possible due to cortical destruction and the multidisciplinary approach with re...

  18. Altered tumor cell glycosylation promotes metastasis

    LuborBorsig

    2014-02-01

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

  19. A new protein Girdin in tumor metastasis

    WANG Jing; FU Li; GU Feng; MA Yong-jie

    2010-01-01

    @@ The phosphatidylinositol 3-kinase/Akt serine/threonine kinase system regulates multiple cellular processes through the phosphorylation of a great number of downstream substrates and has been recognized as an important pathway for signal transduction, and in cancer invasion and metastasis.

  20. Leptomeningeal metastasis: a CT and MRI study

    Oschmann, P. [Dept. of Neurology, Univ. of Giessen (Germany); Bauer, T. [Dept. of Radiology, Univ. of Giessen (Germany); Kaps, M. [Dept. of Neurology, Univ. of Giessen (Germany); Trittmacher, S. [Dept. of Radiology, Univ. of Giessen (Germany); Dorndorf, W. [Dept. of Neurology, Univ. of Giessen (Germany)

    1994-08-01

    We evaluated 35 patients with leptomeningeal metastasis (LM) that was proved by repeated positive cytology (33 patients) and/or autopsy (10 patients) with T1-weighted Gadolinium-DTPA-enhanced MRI and contrast-enhanced CT. The patients (20 women and 15 men) ranged in age from 5-77 years (mean 56 years). Tumour histology included 26 carcinomas, 1 sarcoma, 6 leucaemias, 1 medulloblastoma and 1 primary CNS lymphoma. Intracranial abnormalities were noted in 58% of cases by CT and 88% by MRI, and included hydrocephalus, meningeal or ependymal enhancement, subarachnoidal or intraparenchymal nodules. Leptomeningeal metastasis was detected by MRI in 13 of 17 examined patients, including the three cases with a positive CT. It was proved that MRI is equal or superior to CT in demonstrating meningeal or ependymal enhancement and quantifying enhanced subarachnoidal or parenchymal nodules. However, in the evaluation of leptomeningeal metastasis both modalities had a high incidence of false-negative studies, 89% (31 of 35) by CT and 24% (4 of 17) by MRI. In contrast, two patients with initially negative cytology had pathological MRI findings. Our data indicate that Gadolinium-enhanced MRI is the preferred imaging modality in leptomeningeal metastasis, and suggest that CT does not add significant additional information. However, LM is primarily a histological diagnosis by detecting tumour cells in the cerebrospinal fluid. (orig.)

  1. Nasopharyngeal carcinoma with bone marrow metastasis.

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  2. Leptomeningeal metastasis: a CT and MRI study

    We evaluated 35 patients with leptomeningeal metastasis (LM) that was proved by repeated positive cytology (33 patients) and/or autopsy (10 patients) with T1-weighted Gadolinium-DTPA-enhanced MRI and contrast-enhanced CT. The patients (20 women and 15 men) ranged in age from 5-77 years (mean 56 years). Tumour histology included 26 carcinomas, 1 sarcoma, 6 leucaemias, 1 medulloblastoma and 1 primary CNS lymphoma. Intracranial abnormalities were noted in 58% of cases by CT and 88% by MRI, and included hydrocephalus, meningeal or ependymal enhancement, subarachnoidal or intraparenchymal nodules. Leptomeningeal metastasis was detected by MRI in 13 of 17 examined patients, including the three cases with a positive CT. It was proved that MRI is equal or superior to CT in demonstrating meningeal or ependymal enhancement and quantifying enhanced subarachnoidal or parenchymal nodules. However, in the evaluation of leptomeningeal metastasis both modalities had a high incidence of false-negative studies, 89% (31 of 35) by CT and 24% (4 of 17) by MRI. In contrast, two patients with initially negative cytology had pathological MRI findings. Our data indicate that Gadolinium-enhanced MRI is the preferred imaging modality in leptomeningeal metastasis, and suggest that CT does not add significant additional information. However, LM is primarily a histological diagnosis by detecting tumour cells in the cerebrospinal fluid. (orig.)

  3. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Purvi ePatel

    2012-10-01

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

  4. A link between inflammation and metastasis

    Hansen, M. T.; Forst, B.; Cremers, N.;

    2015-01-01

    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional t...

  5. Inguinal lymph node metastasis of colon cancer

    Sloane McGraw

    2011-01-01

    Full Text Available We present a case of adenocarcinoma of colon with unusual metastasis to inguinal lymph nodes. Our patient is a young male with bilateral inguinal lymphadenopathy, bone pains, and jaundice who presented as carcinoma of unknown primary. He was diagnosed as widely metastatic adenocarcinoma of colon for which he received chemotherapy and has had a good response to the treatment.

  6. Cerebral metastasis from malignant pleural mesothelioma

    El Molla, Mohamed; Gragnaniello, Cristian; Al-Khawaja, Darweesh; Chiribao-Negri, Concepcion; Eftekhar, Behzad

    2013-01-01

    Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis.

  7. Evaluating human cancer cell metastasis in zebrafish

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  8. S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction

    Mathias Dahlmann; Dennis Kobelt; Wolfgang Walther; Giridhar Mudduluru; Ulrike Stein

    2016-01-01

    The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, w...

  9. Significant Overexpression of DVL1 in Taiwanese Colorectal Cancer Patients with Liver Metastasis

    Shiu-Ru Lin

    2013-10-01

    Full Text Available Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs. Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2 in the cancer patients. We used a weighted enzymatic chip array (WEnCA including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I–III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214 of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588–12.837; p < 0.0001 on univariate analysis; OR: 3.768; 95% CI: 1.469–9.665; p = 0.006 on multivariate analysis. IHC staining of the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of CRC cells. High expression of DVL1 was observed in 55% (33/60 of CRC tumor specimens and was associated significantly with tumor depth, perineural invasion and liver metastasis status (all p < 0.05. Our experimental results demonstrated that DVL1 is significantly overexpressed in CRC patients with liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients.

  10. 白花蛇舌草抑制肝癌H22小鼠淋巴管转移的实验研究%Experimental Study on Inhibitory Effect of Hedyotis Diffusa Willd on Lymphatic Metastasis of Mice with Hepatocarcinoma H22

    李洁; 李怀芝; 韩冰冰

    2014-01-01

    目的:观察白花蛇舌草对小鼠肝癌淋巴管转移的影响。方法:在小鼠右下肢爪垫内侧皮下注射接种腹水型肝癌H22瘤株,复制淋巴管转移模型。将模型小鼠随机分为5组,空白组每天灌生理盐水,大、中、小剂量组每天灌白花蛇舌草水煎液,对照组给予环磷酰胺腹腔注射。观察小鼠体质量、免疫器官、肺部转移率、爪垫移植瘤、淋巴结转移瘤等指标变化。结果:白花蛇舌草作用组的小鼠,体质量和免疫器官胸腺质量明显增长,肺部瘤结节数和肺部转移瘤生长指数均下降,且淋巴结转移数明显减少。结论:白花蛇舌草对H22肝癌淋巴管转移有一定抑制作用。%Objective:To observe effects of Hedyotis diffusa Willd in treating hepatocarcinoma lymphatic metastasis of mice. Methods:The H22 lymphatic metastasis models were established by subcutaneous injecting H22 cell line into the palmula of right lower limb. The model mice were randomly divided into 5 groups. The blank group was given normal saline daily,and large,medium,small-dose group were given Hedyotis diffusa Willd,and the control group were received cyclophosphamide by intraperitoneal injection daily. The changes of mouse’s body weight,the weight of immune organ,lung metastasis,paw pads transplantation tumor and lymph node metastasis were observed. Results:In Hedyotis diffusa Willd group,body weight and the weight of immune organs increased,lung nodules and lung metastasis tumor growth index were decreased,and the number of lymph node metastases was reduced. Conclusion:Hedyotis diffusa Willd has an inhibitory ef-fect on the metastasis of hepatocarcinoma lymphatic.

  11. Computed tomographic evaluation of intracranial metastasis

    Hong, Jin Kyo; Eun, Chung Kie; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1982-09-15

    Computed tomography was proved to be the most accurate diagnostic tool in the analysis of brain metastasis than any other classical methods. The authors studied CT findings of intracranial metastasis in 31 cases proven clinically and histologically. The results were as follows: 1. Age distribution of the cases was 15 males and 16 females with peak age of 6th decade in males and 4th decade in female. 2. Metastic lesions were multiple in 18 cases and single in 13 cases. 3. The most common degree of edema was grade III, 43% of total metastatic foci. Marked edematous low densities with relatively small nodular high densities in precontrast scan and variable contrast enhancement of the nodular densities were the most frequent CT findings. 4. No specific characteristics according to the primary cancer was noted. All four cases of choriocarcinoma showed hemorrhagic tendency.

  12. Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    Coelho, Bianca Feliciano; de Souza Albernaz, Marta; Iscaife, Alexandre; Moreira Leite, Katia Ramos; de Souza Junqueira, Mara; Bernardes, Emerson Soares; da Silva, Emerson Oliveira; Santos-Oliveira, Ralph

    2015-01-01

    Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans. PMID:25847010

  13. [Thyroid's metastasis of tonsillar squamous cell carcinoma].

    Scanelli, Giovanni; Aimoni, Claudia; Marchetti, Elisabetta; Geminiani, Matteo; Pastore, Antonio

    2005-09-01

    The authors describe the case of a 58 years old man, affected by squamous cell carcinoma of the tonsil, who underwent left tonsillectomy with bilateral neck dissection, followed by radiotherapy. After a 6 months period, the patient began to suffer from dysphonia, dysphagia and loss of weight: a painless neoformation was detected at the right lobe of the tyhroid, resulted a metastasis of the tonsillar neoplasm. The search for intranodular thyroglobulin was negative; the patient underwent thyroidectomy which showed a massive infiltration of the right cricothyroid space, cricoid and thyroid wing cartilage necrosis and intralaryngeal tumor infiltration. The authors describe the thyroid metastasis treatment, present an up-to-date review of the literature and suggest a thyroid careful clinical evaluation in every patient with a previous history of oropharyngeal cancer. PMID:16229323

  14. Breast carcinoma metastasis to the lacrimal gland

    Nickelsen, Marie N.; Von Holstein, Sarah; Hansen, Alastair B.;

    2015-01-01

    A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomog...... study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis....

  15. Isolated penile metastasis from bladder carcinoma

    Metastases of the penis are uncommon, with only approximately 300 cases reported since 1870. In up to 70 % of patients, the primary tumour is located in the urogenital tract. Furthermore, isolated metastases of the penis are exceptionally rare. We report a case of solitary squamous cell metastasis of the penis presenting with painful swelling initially thought to be inflammatory in origin. The CT and MR imaging findings are presented with a short review of the literature. (orig.)

  16. Wnt and Wnt inhibitors in bone metastasis

    Sottnik, Joseph L; Christopher L. Hall; Zhang, Jian; Evan T. Keller

    2012-01-01

    Bone metastasis is a clinically devastating development of progressive cancers including prostate carcinoma, breast carcinoma and multiple myeloma. Bone metastases are typically painful, lead to adverse skeletal-related events, such as fracture, and are highly resistant to therapy. A major contribution to the ability of cancers to successfully establish bone metastases is their ability to exploit mechanisms of normal bone remodeling. Wnts are a large family of morphogenic proteins that are cr...

  17. Carcinoma cervix presenting with clivus metastasis

    Arpitha S Rao

    2015-01-01

    Full Text Available We present an unusual case of a large metastatic lesion from carcinoma cervix located in the clivus. Patient presented with severe headache and vomiting, mimicking an intracranial pathology. Radiological imaging suggested metastatic origin of the lesion and later on investigations revealed primary in the uterine cervix. The anatomic importance of extradural neural axis component in the process of metastasis of carcinoma cervix to the clivus is highlighted in this case report.

  18. Stress Proteins and Pancreatic Cancer Metastasis

    Cano, Carla E.; Iovanna, Juan L.

    2010-01-01

    Tumor metastasis is challenged by its resistance to microenvironmental stress infringed during escape from the primary tumor and the colonization of a foreign secondary tissue. Because of its great metastatic potential and its strong resistance to anticancer drugs, pancreatic cancer is regarded as a paradigm of the adaptation of cancer cells to microenvironmental stress. Thus, to understand how pancreatic cancer cells adapt to the different endogenous and therapy-related stresses is crucial f...

  19. Intracranial metastasis of spinal intramedullary anaplastic astrocytoma

    Kataria, Rashim; Bhasme, Vishal; Chopra, Sanjeev; V D Sinha; Singhvi, Shashi

    2011-01-01

    Meningeal spread of spinal intramedullary astrocytoma into the cranium is rare. Only few case reports are available so far in the literature. We report a case of intramedullary high grade astrocytoma of the conus, developing intracranial metastasis after three months of partial excision of the spinal mass. The need for radical surgery, entire neuroaxis radiation, and adjuvant chemotherapy is suggested in the management of malignant spinal cord astrocytoma to prevent dissemination.

  20. Intramuscular metastasis from malignant melanoma: MR findings

    We present a rare case of intramuscular metastasis from malignant melanoma. The lesion showed intermediate to high signal intensity on T1-weighted magnetic resonance (MR) images and mixed signal intensities containing high and low signals on T2-weighted images. The signal intensity on T1-weighted images, which is due to the paramagnetic effect of melanin, is a characteristic MR finding of this entity. (orig.)

  1. Isolated penile metastasis from bladder carcinoma

    Demuren, O.A. [Department of Radiology and Imaging, Armed Forces Hospital, Riyadh (Saudi Arabia); Koriech, O. [Department of Oncology, Armed Forces Hospital, Riyadh (Saudi Arabia)

    1999-10-01

    Metastases of the penis are uncommon, with only approximately 300 cases reported since 1870. In up to 70 % of patients, the primary tumour is located in the urogenital tract. Furthermore, isolated metastases of the penis are exceptionally rare. We report a case of solitary squamous cell metastasis of the penis presenting with painful swelling initially thought to be inflammatory in origin. The CT and MR imaging findings are presented with a short review of the literature. (orig.) With 2 figs., 9 refs.

  2. Cancer stem cells, tumor dormancy, and metastasis

    EmilyChen

    2012-01-01

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

  3. Mandibular metastasis of cholangiocarcinoma: A case report

    You, Tae Min; Kim, Kee-Deog; Jeong, Ho-Gul; Park, Wonse

    2015-01-01

    Tumors metastasizing from distant regions to the oral and maxillofacial region are uncommon, comprising only 1%-2% of all malignancies. Cholangiocarcinoma is a malignancy that arises from cholangiocytes, which are epithelial cells that line the bile ducts. These cancers are difficult to diagnose and have a poor prognosis. In this paper, we report a rare case of mandibular metastasis of cholangiocarcinoma diagnosed at the primary site and discuss the radiographic findings observed in this case.

  4. Microenvironmental regulation of tumor progression and metastasis

    Quail, DF; Joyce, JA

    2013-01-01

    Cancers develop in complex tissue environments, which they depend upon for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable, and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequence...

  5. Cerebral metastasis from malignant pleural mesothelioma

    El Molla, Mohamed; Gragnaniello, Cristian; Al-Khawaja, Darweesh; Chiribao-Negri, Concepcion; Eftekhar, Behzad

    2013-01-01

    Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis. PMID:24963909

  6. Therapy for bone metastasis from different cancers

    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  7. Neuroradiological aspects of brain metastasis of choriocarcinomas

    Kida, Y.; Kobayashi, T.; Yoshida, J.; Shibuya, N.; Kageyama, N. (Nagoya Univ. (Japan). Faculty of Medicine)

    1981-04-01

    We have had experience with 24 cases of brain metastasis of choriocarcinoma between 1965 to 1979. Twenty-two cases died, while the other two cases survived. Their neuroradiological findings, especially that of CT scan and angiography, are discussed. The angiograms showed a prominent abnormal neovascularization, with a marked tumor stain in the peripheral zone. However, the central zone appeared avascular or hypovascular. A-V fistulas or early venous filling were seen in two among the 6 cases thus examined. CT scans were studied in 9 lesions of 4 patients. Half of them showed a definite high density, even in plain CT's. A central lucency was found in 7 lesions. In plain CT a highly dense area corresponding to tumors is rare; there have, though, been a few such reports in cases of the brain metastasis of malignant melanoma and colon cancer. This was considered to show hemorrhage associated with the tumor. A follow-up study by CT scan is very important for patients with choriocarcinoma, and also for patients with a hydatidiform mole, because of the rapid progress of the symptoms and signs in cases of brain metastasis.

  8. Bone Metastasis from Renal Cell Carcinoma

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  9. Rational Operation for Primary Gastric Carcinoma with Liver Metastasis

    Caigang Liu; Ping Lu; Jinsong Gu; Junqing Chen

    2007-01-01

    OBJECTIVE To investigate the prognosis of advanced gastric carcinoma patients with liver metastasis, and provide a foundation for rational operations.METHODS The operations and prognosis of 102 primary gastric carcinoma patients with liver metastasis were studied retrospectively. RESULTS In gastric carcinoma patients with H1 metastasis who under went a resection operation, the 6-month, 1- and 2-year post-operative survival rates were 61%, 42% and 7%. There was a statistically significant difference in survival between resected and non-resected patients (P=0.000) In gastric carcinoma cases with H2 metastasis, resection operations resulted in 54%,16% and 8% respective survival rates, with no significant difference compared to patients not receiving a resection (P=0.132). Gastric carcinoma patients with H3 metastasis who received a resection operation showed 25%, 13% and 0% respective survivals with no significantly better prognosis compared to the non-resected cases (P=0.135). There was no statistically significant difference in survival between the cases with or without peritoneal metastasis (P=0.152).CONCLUSION A resection operation provides a better prognosis for gastric carcinoma patients with H1 metastasis independent of peritoneal metastasis, but resection has no benefit for gastric carcinoma cases with H2 or H3 metastasis. Peritoneal metastases are not the significant influencing factor for the prognosis of gastric cancer with liver metastasis.

  10. The impact of surgical extent and sex on the hepatic metastasis of colon cancer

    Sorski, Liat; Levi, Ben; Shaashua, Lee; Neeman, Elad; Benish, Marganit; Matzner, Pini; Hoffman, Aviad; Ben-Eliyahu, Shamgar

    2013-01-01

    Purpose Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor-inoculation approaches in BALB/c mice. Methods Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were induced either by intra-portal inoculation or intrasplenic inoculation, employing different tumor loads. Following intrasplenic inoculation, the entire spleen or an injected hemispleen were removed. Additionally, the magnitude of the surgical trauma accompanying the injection procedure was manipulated. Results Increasing the surgical trauma by adding laparotomy or extending the length of the surgery and hypothermia did not significantly affect the number of liver metastases or liver weight for any of the injection methods and tumor loads. The development of metastasis was significantly greater in males than in females under all conditions studied – a difference not explained by the direct effects of sex hormones on in vitro CT26 proliferation or vitality. Conclusion Concurring with less controlled clinical observations, the surgical extensiveness did not significantly affect CT26 hepatic metastasis, potentially due to a ceiling effect of the surgical trauma on the metastatic process. The sexual dimorphism observed for the CT26 metastasis should be investigated in the context of surgical stress and considering anti-CT26 immunoreactivity. PMID:24190423

  11. Downregulation of Integrins in Cancer Cells and Anti-Platelet Properties Are Involved in Holothurian Glycosaminoglycan-Mediated Disruption of the Interaction of Cancer Cells and Platelets in Hematogenous Metastasis.

    Qian, Wenhui; Tao, Li; Wang, Yingyu; Zhang, Feng; Li, Mengqiu; Huang, Shile; Wang, Aiyun; Chen, Wenxing; Yue, Zhiqiang; Chen, Lei; Liu, Yuping; Huang, Chenhu; Zhang, Lei; Li, Yao; Lu, Yin

    2015-01-01

    Activated platelets have been recognized as an accessory character in the cascade of tumor hematogenous metastasis, and intervention of tumor cell attachment to the activated platelets or microemboli formation might be a leading strategy to prevent tumor cells surviving in the blood vessels and sequential metastasis. Recently, we have demonstrated that holothurian glycosaminoglycan (hGAG), a sulfated polysaccharide with potent anticoagulant activity extracted from the sea cucumber Holothuria leucospilota Brandt, was highly efficacious against tumor metastasis. In this study, we identified the potential effects of hGAG on the disruption of interactions of cancer cells and platelets and the underlying mechanisms, which were supported by the following evidence: hGAG (1) inhibited thrombin-induced platelet activation and aggregation, (2) reduced adhesion between platelet and breast cancer cells, and abrogated platelets/cancer cells adhering to fibrinogen, (3) attenuated platelet-cancer cell complex formation (the number and size of aggregates) and (4) suppressed both mRNA and protein levels of β1 and β3 integrins, matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of the MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 in MDA-MB-231 cells. These results suggested that both the antiplatelet properties and mitigation of the levels of cellular adhesion molecules contributed to the anticancer effects of hGAG, and might thus be exploited for clinical adjuvant therapy to attenuate tumor hematogenous metastasis. PMID:26488158

  12. Synergistic defense system by cooperative natural effectors against metastasis of B16 melanoma cells in H-2-associated control: different behavior of H-2+ and H-2- cells in metastatic processes

    H-2+ and H-2- cells of B16 melanoma were established by repeated fluorescence-activated cell sorting. The H-2- line formed no metastasis in untreated C57BL/6 mice, whereas the H-2+ cells showed evidence of metastatic development. This difference was ascribed mainly to the increased susceptibility of H-2- cells to attack by natural effector mechanisms, particularly asialo GM1+ NK cells. After treatment with both anti-asialo GM1 serum and whole body irradiation (400 rad), numerous colonies of H-2- cells formed in the lung, whereas the metastasis was only marginally enhanced by irradiation and moderately by treatment with anti-asialo GM1 serum. With the H-2+ cells, treatment with each modality significantly increased the number of metastatic colonies. Therefore collaboration of asialo GM1+ NK cells and radiosensitive natural effectors seems to be the main mechanism involved in the synergistic effects on defense against H-2- cell metastasis, and to a lesser extent against H-2+ cell metastasis. Irradiation (1000 rad) to the right lung to abrogate the organ-associated defense increased the colonies, particularly in the H-2+ cells. On the other hand, treatment with anti-asialo GM1 serum increased colonization in the early phase of metastasis with H-2- cells and may have abolished asialo GM1+ NK cells capable of recognizing the reduced expression of H-2 antigens and eliminating H-2- cells in the blood-born phase. Natural defense mechanisms probably exert suppressive effects on the metastasis of H-2+ cells, mainly in the organ-associated phase after extravasation

  13. MicroRNA regulation network in colorectal cancer metastasis

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  14. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  15. Cutaneous metastasis from squamous carcinoma of the base of tongue

    Tashnin Rahman

    2015-01-01

    Full Text Available Context: Cutaneous metastasis from head and neck cancer is uncommon and it is seen from laryngeal cancer. Cutaneous metastasis from the base of tongue is relatively rare. Case Report: A 55-year-old male, who was a treated case of squamous carcinoma of the base of tongue presented with metastatic nodule on the skin of face and thigh. But, there was complete resolution of the tumor at the primary site. In the present case, clinically obvious cutaneous nodules with metastasis appeared soon after the completion of treatment with concurrent chemo-radiotherapy. The metastasis to the skin of face clinically appeared like an inflammatory lesion. Fine needle aspiration cytology confirmed the diagnosis of metastasis to skin at both the sites. Conclusion: Our case has highlighted that there could be associated occult skin metastasis at the time of diagnosis in squamous carcinoma of the base of tongue.

  16. Unusual Presentation of Renal Cell Carcinoma: Gluteal Metastasis

    Yunus Emre Goger; Mehmet Mesut Piskin; Mehmet Balasar; Mehmet Kilinc

    2013-01-01

    Renal cell carcinoma (RCC) has widespread and unpredictable metastatic potential. The most common sites of metastatic RCC are the lungs, lymph nodes, bones, liver, and brain; however the soft tissue metastasis is rare (2,3). Here we report a 76-year-old male patient who had renal cell carcinoma presented with gluteal metastasis. To our knowledge this is the first renal cell cancer case with gluteal metastasis at the initial diagnosis.

  17. Intraneural metastasis of gastric carcinoma leads to sciatic nerve palsy

    Ichikawa Jiro; Matsumoto Seiichi; Shimoji Takashi; Tanizawa Taisuke; Gokita Tabu; Hayakawa Keiko; Aoki Kaoru; Ina Saori; Kanda Hiroaki

    2012-01-01

    Abstract Background Soft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature. Case presentation A case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she devel...

  18. Patrolling Monocytes Control Tumor Metastasis to the Lung

    Hanna, Richard N.; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Graham D. Thomas; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz

    2015-01-01

    The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical “patrolling” monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased ...

  19. Spinal Leptomeningeal Metastasis from Gastric Cancer: Case Report

    Çokmert, Suna; Doğanay, Latife; Paköz, Burak; Yüksel, Alper; Gezer, Emrah; Alakavuklar, Mehmet Niyazi

    2015-01-01

    Leptomeninges are a rare region for metastasis in solid tumors. The most common causes of leptomeningeal metastasis are breast cancer, lung cancer, melanoma and leukemia-lymphomas. Leptomeningeal metastasis associated with gastric cancer is an exceedingly rare condition but it is rapidly progressive and poor prognosis. The diagnosis is confirmed by examination of the cerebrospinal fluid and imaging methods. There are several treatment options for patients with LMC, including intrathecal chemo...

  20. Steps in Prostate Cancer Progression that lead to Bone Metastasis

    Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

    2011-01-01

    Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current...

  1. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    Lahdenranta, Johanna; Hagendoorn, Jeroen; Padera, Timothy P; Hoshida, Tohru; Nelson, Gregory; Kashiwagi, Satoshi; Jain, Rakesh K.; Fukumura, Dai

    2009-01-01

    Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and ly...

  2. Prostatic adenocarcinoma with and without metastasis to bone in dogs

    The signalment, clinical signs, and histologic tumor pattern were compared retrospectively in 12 dogs having primary prostatic adenocarcinoma with (5 cases) and without metastasis (7 cases) to bone. Weight loss and lumbar pain were observed more frequently in dogs having prostatic adenocarcinoma with metastasis to bone. A distinctive histologic pattern was not associated with prostatic adenocarcinoma that had metastasized to bone. The alveolar papillary pattern was the predominant histologic type observed in both groups. Metastasis to extra pelvic bony sites included the scapulas, ribs, and digits. The results of this study indicate that skeletal metastasis was not uncommon in dogs having prostatic adenocarcinoma

  3. Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase.

    Okada, Motoi; Kim, Ha Won; Matsu-ura, Kaoru; Wang, Yi-Gang; Xu, Meifeng; Ashraf, Muhammad

    2016-01-01

    Previously, we reported that a novel subpopulation of young mesenchymal stem cells (YMSCs) existed in old bone marrow, which possessed high antiaging properties as well as excellent efficacy for cardiac repair. MicroRNAs (miRNAs) have emerged as key regulators in post-transcriptional gene expression programs, and however, it is unknown whether miRNAs directly control stem cell senescence. Here we present the first evidence that miR-195 overexpressed in old MSCs (OMSCs) induces stem cell senescence deteriorating their regenerative ability by directly deactivating telomerase reverse transcriptase (Tert), and abrogation of miR-195 can reverse stem cell aging. MiRNAs profiling analysis in YMSCs and OMSCs by microarray showed that miR-140, miR-146a/b, and miR-195 were significantly upregulated in OMSCs, which led us to hypothesize that these are age-induced miRNAs involved in stem cell senescence. Of these miRNAs, we found miR-195 directly targeted 3'-untranslated region of Tert gene by computational target prediction analysis and luciferase assay, and knockdown of miR-195 significantly increased Tert expression in OMSCs. Strikingly, miR-195 inhibition significantly induced telomere relengthening in OMSCs along with reduced expression of senescence-associated β-galactosidase. Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1. Notably, abrogation of miR-195 markedly restored proliferative abilities in OMSCs. Transplantation of OMSCs with knocked out miR-195 reduced infarction size and improved LV function. In conclusion, rejuvenation of aged stem cells by miR-195 inhibition would be a promising autologous therapeutic strategy for cardiac repair in the elderly patients. PMID:26390028

  4. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice.

    Lea-Maxie Haag

    Full Text Available BACKGROUND: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. METHODOLOGY/PRINCIPAL FINDINGS: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. CONCLUSION/SIGNIFICANCE: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might

  5. Choriocarcinoma: a rare case of stomach metastasis

    Raju Agarwal

    2014-06-01

    Full Text Available Choriocarcinoma is a rare form of cancer which commonly occurs in women of reproductive age, rarely in post-menopausal women and in women under 20 years of age. We report a rare case of uterine choriocarcinoma with stomach metastasis in a 29 year-old woman who presented with upper gastrointestinal symptoms. The presented case report emphasizes the need for innovative treatment approach and appropriate diagnostic technology to enable early diagnosis and correct treatment. Furthermore the case highlights the need for healthcare workers to consider rare causes of gastrointestinal signs and symptoms. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 787-789

  6. Choroidal metastasis of a breast carcinoma

    The case of a 55-year-old woman with diagnosis of multinodular Grade II ductal infiltrating carcinoma in left breast was presented in this article. She presented with temporal visual field defect in her left eye. A choroidal metastatic tumor was diagnosed by indirect binocular ophthalmoscopy, confirmed by ocular echography. The primary tumor was removed by surgery and the choroidal lesion was treated with systemic chemotherapy, hormonal therapy and external beam radiation therapy. Six months after the treatment, the choroidal metastasis showed complete regression, and the best visual acuity of 20/20 was recovered, which was the initial value at the diagnosis of disease

  7. Monoclonal Antibody Testing for Cancer Metastasis

    1993-01-01

    Malignant cells are characterized by the ability to invade surrounding normal tissues. Tumor invasion is abetted by proteolytic enzymes that have been correlated with recurrent disease and metastasis. These enzymes are involved in a cascade of proteolytic interactions with other enzymes and inhibitors which allow cancer cells to dissolve surrounding extracellular matrix, thereby enabling the cells to rapidly invade adjacent tissues and migrate to metastatic sites distant from the primary tumor. Among these proteases are the plasminogen activators (PA), collagenase IV, faminase, and in some cases cathepsin D, which together mediate key steps in the invasion process of metastasis. Cells which have the selective advantage for invasion and metastasis are those capable of regulating their proteolytic activity and proliferation. Cells in the process of invasion would be probably down-regulated for proliferation, but subsequent to attachment and adhesion at a distant site, would then be in a proliferative mode, up-regulating DNA replication. Urokinase (uPA) can be present in the tissues in several molecular forms. The inactive proenzyme is a single chain protein (scuPA) that is cleaved at Lys. 158 to form the double chain, high molecular weight active form (HMW-uPA) of 54 kD. A low molecular weight form (LMW-uPA) can also be produced by cleavage of the HMW-U PA at Lys. 135 - Lys. 136 giving a 35 kD active enzyme. Recently, it has been shown that the HMW active form of urokinase, bound to the tumor cell membrane, is responsible for the local lysis of the extracellular matrix, hence the tissue invasion mechanism for metastasis (Andreasen et al, 19861. Receptor- (membrane) bound uPA is twice as efficient (catalytically) as free fluid-phase uPA. Tho unbound uPA and the LMW form is not responsible for most of the local dissolution of extracellular matrix in the immediate vicinity of the metastatic tumor cell. High levels of urokinase (greater than 3.49 ng/mg of total protein

  8. Contemporary approaches for imaging skeletal metastasis

    David Ulmert; Lilja Solnes; Daniel LJ Thorek

    2015-01-01

    The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges.

  9. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

    Yano, S; Shinohara, H; Herbst, R S; Kuniyasu, H; Bucana, C D; Ellis, L M; Davis, D W; McConkey, D J; Fidler, I J

    2000-09-01

    We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target. PMID:10987313

  10. CT findings of solitary intracranial metastasis

    Suh, Dae Chul; Lee, Kyung Soo; Chang, Kee Hyun [Collge of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1987-04-15

    The authors retrospectively reviewed and analyzed CT scans of fifty patients with solitary intracranial lesion selected from 118 patients who had been confirmed to have intracranial metastasis from 1979 to 1985. The results were as follows: 1. The most common primary tumors with solitary metastasis, in order of frequency, were lung cancer, breast cancer, choriocarcinoma, colon cancer, lymphoma and others. 2. Precontrast scans obtained in 35 cases showed cystic very low density in 20%, slightly low density in 9%, isodensity in 20%, high density in 51% when he densities of the lesions were compared with that of the normal brain tissue. 3. After contrast enhancement 43 out of 50 showed one of 4 patterns of enhancement. Homogeneous enhancement without necrosis were found in 26%, homogeneous enhancement with necrosis in 18%, ring-enhancement in 26% and irregular enhancement in 16%. No enhancement was found in 14%. 4. The locations of the metastatic lesions were intra axial in 45 and extra axial in 5. Among the intra axial lesions, the parietal lobe was the most common location. Extra axial metastases were epidural, calvarial and leptomeningeal. 5. Degrees of surrounding edema were mild in 32%, moderate in 19% and severe in 49%.

  11. Bioinformatics analysis of metastasis-related proteins in hepatocellular carcinoma

    Pei-Ming Song; Yang Zhang; Yu-Fei He; Hui-Min Bao; Jian-Hua Luo; Yin-Kun Liu; Peng-Yuan Yang; Xian Chen

    2008-01-01

    AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomark-er candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools.METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OHIH) and human protein reference database (HPRD).RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transcluction. OMIM analysis linked these proteins to 186 OMIM entries.CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation, migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global charac-teristic of metastasis-related proteins and many differen-tially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.

  12. A Case of Sphenoid Sinus Metastasis in Hepatocellular Carcinoma.

    Lee, Tae Hoon; Rangan, Vikram; Khallafi, Hicham

    2016-06-01

    Sphenoid sinus metastasis from hepatocellular carcinoma (HCC) has been reported only rarely. We present a case of solitary sphenoid sinus metastasis of a 2.7 × 2.3 cm single HCC lesion. (Hepatology 2016;63:2050-2053). PMID:26928869

  13. Solitary Metastasis of Gastric Cancer to Fibula: A Case Report

    Gastric cancer is one of the most common and most fatal neoplasms in human. Its skeletal metastasis is less frequent, particularly when solitary. The objective of this article is to represent a case of solitary fibular metastasis from this cancer not reported before based on Medline search

  14. Hypoxia-induced metastasis model in embryonic zebrafish

    Rouhi, Pegah; Jensen, Lasse D.; Cao, Ziquan;

    2010-01-01

    early events of tumor cell invasion and dissemination in living animals. We recently developed a zebrafish metastasis model to dissect the detailed events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent Di...

  15. Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells

    Rong-guang SHAO; Chun-Xia CAO; Yves POMMIER

    2004-01-01

    AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29 cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution,protein level, and kinase activity were determined by clonogenic assay, flow cytometry, DNA synthesis assay,immunoblotting, and kinase assays, respectively. RESULTS: UCN-01 abrogated an S/G2-phase checkpoint in HT29 cells treated with ara-C. When UCN-01 was added after treatment with ara-C, the rate of recovery of DNA synthesis was enhanced and colony-forming ability diminished. Thus, premature recovery of DNA synthesis was associated with increased cytotoxicity. Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chkl kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of Chkl kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was combined with ara-C suggested a rationale for the use of this drug combination for tumors that might be susceptible to cell cycle checkpoint abrogation.

  16. Angiosarcoma of the Thyroid and Regional Lymph Node Metastasis

    Lutfi Dogan

    2013-10-01

    Full Text Available Thyroid angiosarcomas are typically infiltrative and large tumors with very similar clinical findings of anaplastic carcinoma of thyroid. Early hematogenous metastasis is very frequent, but regional lymph node metastasis is quite rare. We present a case of angiosarcoma of the thyroid gland in a 68 years old man with regional lymph node metastasis. Total thyroidectomy with right modified radical neck dissection was applied. Four out of 19 lymph nodes dissected were seen to contain metastasis. Metastatic tumor was composed of sarcomatous areas containing large numbers of blood filled clefts. There after the surgery PET-CT was performed and multiple metastatic involvements were reported. Thyroid angiosarcomas are completely different tumors from angiomatoid anaplastic carcinomas. Longer survival with these tumors is only possible with agressive surgery and in case of regional LN metastasis, neck dissection should be done.

  17. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    Hiren Mandaliya

    2016-01-01

    Full Text Available Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated.

  18. Abrogating endocrine resistance by targeting ER alpha and PI3K in breast cancer

    ToddWMiller

    2012-10-01

    Full Text Available Antiestrogen therapies targeting estrogen receptor alpha (ER signaling are a mainstay for patients with ER+ breast cancer. While many cancers exhibit resistance to antiestrogen therapies, a large body of clinical and experimental evidence indicates that hyperactivation of the phosphatidylinositol 3-kinase (PI3K pathway promotes antiestrogen resistance. In addition, continued ligand-independent ER signaling in the setting of estrogen deprivation may contribute to resistance to endocrine therapy. PI3K activates several proteins which promote cell cycle progression and survival. In ER+ breast cancer cells, PI3K promotes ligand-dependent and -independent ER transcriptional activity. Models of antiestrogen-resistant breast cancer often remain sensitive to estrogen stimulation and PI3K inhibition, suggesting that clinical trials with combinations of drugs targeting both the PI3K and ER pathways are warranted. Herein, we review recent findings on the roles of PI3K and ER in antiestrogen resistance, and clinical trials testing drug combinations which target both pathways. We also discuss the need for clinical investigation of ER downregulators in combination with PI3K inhibitors.

  19. Mixed adenoneuroendocrine carcinoma with brain metastasis

    Xiao-ling YAN

    2015-05-01

    Full Text Available Objective To study clinicopathological features, diagnosis, differential diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC.  Methods One case of MANEC with brain metastasis was reported focusing on the following aspects: clinical manifestations, histopathological features and immunophenotypes, and the relevant literatures were reviewed.  Results A 35-year-old male presented headache and vomiting, and his head CT scan showed a lesion located in the right temporal lobe. The tumor was detected after separating the cerebral cortex during the surgery. The tumor diameter was 3 cm. The tumor was soft and rubbery with ill-defined margins, and rich in blood supply. Under optical microscopy, the tumor was consisted of small round cells of the same size, with focal tumor cells arranged around blood vessels in a pseudorosette manner or papillary manner with brisk mitotic activity. The boundary between tumor and brain tissue was ill-defined. By using immunohistochemical staining, the tumor cells were diffusely positive for synaptophysin (Syn and CD56, and negative for glial fibrillary acidic protein (GFAP, pan cytokeratin (PCK, CD3, CD20, vimentin (Vim, leukocyte common antigen (LCA, thyroid transcription factor-1 (TTF-1, S-100 protein (S-100, neurofilament (NF, nestin (Nes, CK5/6, CK8/18 and CD99. Ki-67 labeling index was about 62%. Sigmoidoscopy was performed later in another hospital and showed a mass in the patient's colon. The colon tumor was biphasic in appearance, and was consisted of two distinct components: isomorphic small round cells and low-middle differentiated adenocarcinoma cells. The small round tumor cells were diffusely positive for Syn and CD56, and negative for PCK. The adenocarcinoma cells showed opposite results.  Conclusions MANEC is a rare tumor, which is defined in 2010 by WHO Classification of Digestive, and to the best of our knowledge, MANEC of the colon with brain metastasis has never been described

  20. FEATURES OF BILATERAL BREAST CANCER NODAL METASTASIS

    Ye. A. Fesik

    2014-01-01

    Full Text Available This article focuses on issues related to the identification and investigation of the lymph node metastases with bilateral breast cancer. The presence of metastases in the lymph nodes determines the stage of the disease, and introducing a form of tumor progression, characterizes the course and prognosis for the future in a specific patient. Thus, the identification of possible morphological and immunohistochemical characteristics of the tumor tissue and their comparison with the frequency and severity of regional lymph nodes would help to solve the problem of the identification of prognostic factors and markers associated with the risk of nodal metastasis in bilateral breast cancer. This work is relevant due to the fact that the literature on this issue to date are treated ambiguously, and answers to many questions, unfortunately, no.The authors performed a morphological study of the tumor tissue from 600 patients suffering from unilateral and bilateral breast cancer. To avoid false results were studied only cases corresponding to the histological type of invasive carcinoma of non-specific type. The study found that a greater number and a greater percentage of the affected lymph node metastases were observed in patients with bilaterally synchronous tumors. The patients of this group of metastatic lymph nodes was detected more frequently in the presence of infiltrative component of three or more types of structures with the presence of these discrete groups of tumor cells, and the observed maximum degree of inflammatory infiltration of the tumor stroma. In the group of patients with unilateral breast cancer nodal metastasis often detects when triple negative molecular genetic type of the lesion, with large amounts of tumor site, in the presence of infiltrative component of three or more types of structures with the obligatory presence of these microalveolar structures and discretely spaced groups of tumor cells and the highest severity of

  1. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis.

    Besmer, Dahlia M; Curry, Jennifer M; Roy, Lopamudra D; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y; Gendler, Sandra J; Mukherjee, Pinku

    2011-07-01

    MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. PMID:21558393

  2. Axillary node metastasis from primary ovarian carcinoma

    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  3. Unexplained liver laceration after metastasis radiofrequency ablation

    Esther U(n)a; Javier Trueba; Jose Manuel Montes

    2009-01-01

    Many studies have established the role of radiofrequency (RF) ablation as a minimally invasive treatment for liver metastases. Although relatively safe, several complications have been reported with the increased use of RF ablation. We describe here a case of unexplained liver laceration after a RF procedure. A woman who presented a solitary metachronous liver metastasis underwent RF ablation treatment for this lesion. Six hours later the patient displayed fatigue and pallor.Emergency blood tests showed a haemoglobin level of < 7 g/dL and markedly elevated transaminase levels.A computed tomography examination revealed two areas of liver laceration with haematoma, one of them following the path of the needle and the other leading away from the first. Following a blood transfusion, the patient was haemodynamically stable and completely recovered 24 h later. The patient remained in bed for 1 wk. No surgical intervention was required, and she was discharged 1 wk later.

  4. Comparison study of metastasis hepatic coagulation

    In our contribution we are interested in tissue coagulation by Nd-YAG and Ar lasers in order to know which laser is necessary to use for the destruction of hepatic metastasis. For that we have developed a mathematical model, in which the liver tissue is considered homogeneous, and isotropic, the absorbed energies is optimized by the beam broadening model and the transfer of heat is modeled by the bioheat equation. The solution of this equation by the finite volumes method gives the space-time variation of the temperature, which makes it possible to determine the necrosis depth by using the Arrhenius integral. The results obtained show that the temperature of coagulation is reached for strong intensity in the case of the Nd-YAG laser compared with the Ar laser, and that the volume of the coagulated zone is considerable in the case of the Nd-YAG laser, from this fact it is selected in gastro-enterology. (author)

  5. Isolated Uterine Metastasis of Invasive Ductal Carcinoma

    Deniz Arslan

    2013-01-01

    Full Text Available Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.

  6. Oncoprotein metastasis and its suppression revisited

    Radulescu Razvan T

    2010-04-01

    Full Text Available Abstract The past two decades have witnessed an increasing appreciation of the role of the tumor microenvironment, of genetic and epigenetic alterations in normal cells adjacent to tumors and of the migration of normal cells with aberrant intrinsic properties in cancer pathophysiology. Aside from these insights, a novel concept termed "oncoprotein metastasis" (OPM has recently been advanced and proposed to reflect protein-based neoplastic phenomena that might occur even before any modifications relating to the morphology, location or (epigenetic outfit of cells during the malignant process. Here, evidence is presented that supports the OPM perception and thus should contribute not only to further rethink the definition of a normal cell, but also the treatment of cancer disease in the years to come.

  7. Ventricular metastasis resulting in disseminated intravascular coagulation

    Davis Ian D

    2005-05-01

    Full Text Available Abstract Background Disseminated Intravascular Coagulation (DIC complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC has rarely been associated with DIC. Case presentation A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient. Conclusion Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.

  8. Hand1 overexpression inhibits medulloblastoma metastasis.

    Asuthkar, Swapna; Guda, Maheedhara R; Martin, Sarah E; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J; Velpula, Kiran K

    2016-08-19

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. PMID:27297109

  9. PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin β1-ERK1/2 and-MMP2 signaling

    Wu Jian

    2009-11-01

    Full Text Available Abstract Background Phosphatase of regenerating liver-3 (PRL-3 plays a causative role in tumor metastasis, but the underlying mechanisms are not well understood. In our previous study, we observed that PRL-3 could decrease tyrosine phosphorylation of integrin β1 and enhance activation of ERK1/2 in HEK293 cells. Herein we aim to explore the association of PRL-3 with integrin β1 signaling and its functional implications in motility, invasion, and metastasis of colon cancer cell LoVo. Methods Transwell chamber assay and nude mouse model were used to study motility and invasion, and metastsis of LoVo colon cancer cells, respectively. Knockdown of integrin β1 by siRNA or lentivirus were detected with Western blot and RT-PCR. The effect of PRL-3 on integrin β1, ERK1/2, and MMPs that mediate motility, invasion, and metastasis were measured by Western blot, immunofluorencence, co-immunoprecipitation and zymographic assays. Results We demonstrated that PRL-3 associated with integrin β1 and its expression was positively correlated with ERK1/2 phosphorylation in colon cancer tissues. Depletion of integrin β1 with siRNA, not only abrogated the activation of ERK1/2 stimulated by PRL-3, but also abolished PRL-3-induced motility and invasion of LoVo cells in vitro. Similarly, inhibition of ERK1/2 phosphorylation with U0126 or MMP activity with GM6001 also impaired PRL-3-induced invasion. In addition, PRL-3 promoted gelatinolytic activity of MMP2, and this stimulation correlated with decreased TIMP2 expression. Moreover, PRL-3-stimulated lung metastasis of LoVo cells in a nude mouse model was inhibited when integrin β1 expression was interfered with shRNA. Conclusion Our results suggest that PRL-3's roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin β1-ERK1/2-MMP2 signaling.

  10. Evaluation of inoperable pancreatic carcinoma based on tumor metastasis

    Many pancreatic cancers are detected only after they are far advanced, and thus show a poor prognosis. We evaluated the survival of patients with inoperable pancreatic carcinoma, and strategy treatment. Subjects were 72 persons with advanced inoperable pancreatic carcinoma selected from among 144 examined at our department from May 1992 to March 2001. Patient factors (age, gender, and nutrition), tumor factors (hepatic metastasis, peritoneal dissemination, and distant metastasis), and treatment (radiotherapy, systemic chemotherapy, and hepatic arterial infusion therapy (HAI)) were studied and survival evaluated statistically. Overall mean survival was 175 days and the 1-year survival ratio was 13.5%. With multivariate analysis, prognostic factors were hepatic metastasis and radiotherapy. We therefore re-evaluated 56 patients treated with radiotherapy. In the group with no hepatic metastasis whose mean survival was 247 days, the prognostic factor was systemic chemotherapy. In the group with hepatic metastasis, mean survival was 140 days and the prognostic factor was the prognostic nutritional index (PNI) on admission. HAI was also a significant factor, which prolonged survival time with univariate analysis. Radiotherapy will be conducted for all inoperable pancreatic carcinomas. For the group with no hepatic metastasis, systemic chemotherapy is effective and for the group with hepatic metastasis. HAI will be selected. (author)