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Sample records for tumors evade vascular

  1. Model of vascular desmoplastic multispecies tumor growth.

    Science.gov (United States)

    Ng, Chin F; Frieboes, Hermann B

    2017-10-07

    We present a three-dimensional nonlinear tumor growth model composed of heterogeneous cell types in a multicomponent-multispecies system, including viable, dead, healthy host, and extra-cellular matrix (ECM) tissue species. The model includes the capability for abnormal ECM dynamics noted in tumor development, as exemplified by pancreatic ductal adenocarcinoma, including dense desmoplasia typically characterized by a significant increase of interstitial connective tissue. An elastic energy is implemented to provide elasticity to the connective tissue. Cancer-associated fibroblasts (myofibroblasts) are modeled as key contributors to this ECM remodeling. The tumor growth is driven by growth factors released by these stromal cells as well as by oxygen and glucose provided by blood vasculature which along with lymphatics are stimulated to proliferate in and around the tumor based on pro-angiogenic factors released by hypoxic tissue regions. Cellular metabolic processes are simulated, including respiration and glycolysis with lactate fermentation. The bicarbonate buffering system is included for cellular pH regulation. This model system may be of use to simulate the complex interactions between tumor and stromal cells as well as the associated ECM and vascular remodeling that typically characterize malignant cancers notorious for poor therapeutic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Uncommon vascular tumor of the ovary. Primary ovarian epithelioid hemangioendothelioma or vascular sarcomatous transformation in ovarian germ cell tumor?

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    Illueca, Carmen; Machado, Isidro; García, Ana; Covisa, Amparo; Morales, Javier; Cruz, Julia; Traves, Victor; Almenar, Sergio

    2011-12-01

    Epithelioid hemangioendothelioma (EHE) is an unusual vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and bone. We submit a case of EHE, a tumor never before reported in the ovary. A 20-year-old woman was admitted with a medical history of unilateral ovarian tumor. The right ovary was totally removed and histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and prominent intracytoplasmic vacuoles associated with myxohyaline matrix. No morphologic evidence of germ cell tumor was observed. Immunohistochemically, the tumor cells were positive for CD31 and CD34. However, all germ cell tumor markers were negative. The final diagnosis was EHE of the ovarian gland and sarcomatous transformation in ovarian germ cell tumor was excluded after extensive histopathological and immunohistochemical study. EHE is an uncommon vascular tumor, which is rarely seen in female genital tract and this is the first report of EHE in ovarian gland. Final diagnosis depends on histopathological and immunohistochemical features.

  3. Synergism of Selective Tumor Vascular Thrombosis and Protease Activated Prodrug

    National Research Council Canada - National Science Library

    Liu, Cheng

    2008-01-01

    ... by administration of protease-activated prodrug. The activation of coagulation cascade and tumor vascular thrombosis as well as the following activation of the thrombolytic pathways led to explosive amplification of serine protease cascades...

  4. Cryospectrophotometric determination of tumor intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth.

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    Fenton, B M; Rofstad, E K; Degner, F L; Sutherland, R M

    1988-12-21

    To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 saturations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines

  5. A noninvasive multimodal technique to monitor brain tumor vascularization

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    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

    2007-09-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

  6. A noninvasive multimodal technique to monitor brain tumor vascularization

    International Nuclear Information System (INIS)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E

    2007-01-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present

  7. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography.

    Directory of Open Access Journals (Sweden)

    Sang Kyum Kim

    Full Text Available Human hepatocellular carcinoma (HCC has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability.In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography.H-ras12V transgenic mice (a HCC and hepatic adenoma model developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion, indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion.Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous closely simulated typical characteristics of human HCC vascular imaging.

  8. Molecular characterization of human breast tumor vascular cells.

    Science.gov (United States)

    Bhati, Rajendra; Patterson, Cam; Livasy, Chad A; Fan, Cheng; Ketelsen, David; Hu, Zhiyuan; Reynolds, Evangeline; Tanner, Catherine; Moore, Dominic T; Gabrielli, Franco; Perou, Charles M; Klauber-DeMore, Nancy

    2008-05-01

    A detailed understanding of the assortment of genes that are expressed in breast tumor vessels is needed to facilitate the development of novel, molecularly targeted anti-angiogenic agents for breast cancer therapies. Rapid immunohistochemistry using factor VIII-related antibodies was performed on sections of frozen human luminal-A breast tumors (n = 5) and normal breast (n = 5), followed by laser capture microdissection of vascular cells. RNA was extracted and amplified, and fluorescently labeled cDNA was synthesized and hybridized to 44,000-element long-oligonucleotide DNA microarrays. Statistical analysis of microarray was used to compare differences in gene expression between tumor and normal vascular cells, and Expression Analysis Systematic Explorer was used to determine enrichment of gene ontology categories. Protein expression of select genes was confirmed using immunohistochemistry. Of the 1176 genes that were differentially expressed between tumor and normal vascular cells, 55 had a greater than fourfold increase in expression level. The extracellular matrix gene ontology category was increased while the ribosome gene ontology category was decreased. Fibroblast activation protein, secreted frizzled-related protein 2, Janus kinase 3, and neutral sphingomyelinase 2 proteins localized to breast tumor endothelium as assessed by immunohistochemistry, showing significantly greater staining compared with normal tissue. These tumor endothelial marker proteins also exhibited increased expression in breast tumor vessels compared with that in normal tissues. Therefore, these genetic markers may serve as potential targets for the development of angiogenesis inhibitors.

  9. Molecular Characterization of Human Breast Tumor Vascular Cells

    OpenAIRE

    Bhati, Rajendra; Patterson, Cam; Livasy, Chad A.; Fan, Cheng; Ketelsen, David; Hu, Zhiyuan; Reynolds, Evangeline; Tanner, Catherine; Moore, Dominic T.; Gabrielli, Franco; Perou, Charles M.; Klauber-DeMore, Nancy

    2008-01-01

    A detailed understanding of the assortment of genes that are expressed in breast tumor vessels is needed to facilitate the development of novel, molecularly targeted anti-angiogenic agents for breast cancer therapies. Rapid immunohistochemistry using factor VIII-related antibodies was performed on sections of frozen human luminal-A breast tumors (n = 5) and normal breast (n = 5), followed by laser capture microdissection of vascular cells. RNA was extracted and amplified, and fluorescently la...

  10. Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

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    Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

    2007-01-01

    Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

  11. [Atypical vascular tumors of the gastrointestinal tract: four uncommon cases].

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    Burgos, L; Gutiérrez, J C López; Barrena, S; De la Torre, C; Suárez, O; Luis, A L

    2009-07-01

    A small but significant percentage of vascular tumors may develop at extracutaneous location. They are difficult to detect on the physical exam and usually they require immediate intervention. Pediatric surgeons must have acknowledge of its prognostic and therapeutic implications. We report 4 of these patients. Patient 1 was a healthy newborn who presented in the second week of life, recurrent severe gastrointestinal bleeding, thrombocytopenia and anemia. Diagnosis of multifocal linfangioendoteliomatosis with thrombocytopenia was established. Patient 2 had prenatal diagnosis of ascites and presented at birth sepsis, anemia, thrombocytopenia and hypoproteinemia. Upon laparotomy hemorrhagic ascites and thickening of rectum-sigmoid wall and mesentery were found. Pathologic diagnosis was Kaposiform hemangioendothelioma and the clinical course was consistent with Kassabach-Merrit phenomenon. Patient 3 had at birth, multifocal hepatic GLUT1- hemangiomatosis with severe cardiac insufficiency and coagulopathy. She died while waiting for a liver transplantation. Patient 4 is a girl who presented in the newborn period with vomiting and hematochezia. She required several transfusions and endoscopic biopsies showed a vascular tumor that infiltrated duodenum, jejunum and mesentery. Imaging studies and histologic findings on biopsy led to the diagnostic of juvenile hemangioma GLUT-1+. Vascular tumors of the digestive tract may be difficult to diagnosis and their classification is still incomplete. Pediatric surgeons must be acquainted with these varieties of tumors because they are always involved in diagnosis and therapeutic decision making.

  12. Malignant melanoma clinically masquerading vascular tumor: A diagnostic dilemma

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    Samiksha Pradhan

    2015-01-01

    Full Text Available Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent.

  13. Mathematical Modeling of Branching Morphogenesis and Vascular Tumor Growth

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    Yan, Huaming

    Feedback regulation of cell lineages is known to play an important role in tissue size control, but the effect in tissue morphogenesis has yet to be explored. We first use a non-spatial model to show that a combination of positive and negative feedback on stem and/or progenitor cell self-renewal leads to bistable or bi-modal growth behaviors and ultrasensitivity to external growth cues. Next, a spatiotemporal model is used to demonstrate spatial patterns such as local budding and branching arise in this setting, and are not consequences of Turing-type instabilities. We next extend the model to a three-dimensional hybrid discrete-continuum model of tumor growth to study the effects of angiogenesis, tumor progression and cancer therapies. We account for the crosstalk between the vasculature and cancer stem cells (CSCs), and CSC transdifferentiation into vascular endothelial cells (gECs), as observed experimentally. The vasculature stabilizes tumor invasiveness but considerably enhances growth. A gEC network structure forms spontaneously within the hypoxic core, consistent with experimental findings. The model is then used to study cancer therapeutics. We demonstrate that traditional anti-angiogenic therapies decelerate tumor growth, but make the tumor highly invasive. Chemotherapies help to reduce tumor sizes, but cannot control the invasion. Anti-CSC therapies that promote differentiation or disturb the stem cell niche effectively reduce tumor invasiveness. However, gECs inherit mutations present in CSCs and are resistant to traditional therapies. We show that anti-gEC treatments block the support on CSCs by gECs, and reduce both tumor size and invasiveness. Our study suggests that therapies targeting the vasculature, CSCs and gECs, when combined, are highly synergistic and are capable of controlling both tumor size and shape.

  14. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors.

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    Miettinen, Markku; Rikala, Maarit-Sarlomo; Rys, Janusz; Lasota, Jerzy; Wang, Zeng-Feng

    2012-04-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant

  15. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    National Research Council Canada - National Science Library

    Chen, Bin; He, Chong

    2007-01-01

    .... We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery...

  16. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    National Research Council Canada - National Science Library

    Chen, Bin; He, Chong

    2006-01-01

    .... We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery...

  17. MR Vascular Fingerprinting in Stroke and Brain Tumors Models.

    Science.gov (United States)

    Lemasson, B; Pannetier, N; Coquery, N; Boisserand, Ligia S B; Collomb, Nora; Schuff, N; Moseley, M; Zaharchuk, G; Barbier, E L; Christen, T

    2016-11-24

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  18. Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression.

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    Michael Welter

    Full Text Available We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total

  19. Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor-bearing mice is involved in the immune response.

    Science.gov (United States)

    Xu, Qingyu; Gu, Junfei; Lv, You; Yuan, Jiarui; Yang, Nan; Chen, Juan; Wang, Chunfei; Hou, Xuefeng; Jia, Xiaobin; Feng, Liang; Yin, Guowen

    2018-03-01

    Tumor vascular normalization involved in immune response is beneficial to the chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC). However, its vascular normalization in HCC and the role of the immune response in angiogenesis were unclear. In the present study, effects of Endostar on tumor vascular normalization were evaluated in hepatoma 22 (H22) tumor-bearing mice. Endostar was able to inhibit the proliferation and infiltration of tumor cells and improve α-fetoprotein, tumor necrosis factor-α and cyclic adenosine 5'-phosphate levels in the serum of H22-bearing mice, as well as the protein expression levels of the immune factors interferon-γ and cluster of differentiation (CD)86 in liver tissue. Endostar also exhibited more marked downregulation of the levels of vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, MMP-9 and interleukin-17 during day 3-9 treatment, resulting in short-term normalization of tumor blood vessels. The period of vascular normalization was 3-9 days. The results of the present study demonstrated that Endostar was able to induce the period of vascular normalization, contributing to a more efficacious means of HCC treatment combined with other chemotherapy, and this effect was associated with the immune response. It may be concluded that Endostar inhibited immunity-associated angiogenesis behaviors of vascular endothelial cells in response to HCC. The results of the present study provided more reasonable possibility for the combination therapy of Endostar for the treatment of HCC.

  20. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

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    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  1. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    National Research Council Canada - National Science Library

    Xia, Mengna; Liu, Hanli

    2007-01-01

    Objective/Hypothesis: By monitoring global and local vascular oxygenation and tissue oxygen tension in breast tumors under HBO exposure with several different gas interventions, we wish to prove the following two hypotheses: that 1...

  2. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    Science.gov (United States)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  3. Contrast-enhanced color Doppler US in breast cancer: Tumoral vascularity correlated with angiogenesis

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    Kim, Eun A; Yoon, Kwon Ha; Yun, Ki Jung; Lee, Kwang Man; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [Wonkwang University School of Medicine, Seoul (Korea, Republic of)

    2000-12-15

    To evaluate the effects of contrast-enhanced color Doppler ultrasonography (CDUS) on the depiction of vascularity and flow pattern in breast cancer and to determine the relationship between tumoral vascularity and angiogenesis. Twenty-one patients with breast cancer were prospectively evaluated with CDUS before and after injection of the contrast agent (SH U 508A, 2.5g, 300 mg/ml ). The tumoral vascularity was expressed as percentage of color Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The flow pattern (four-patterns; spotty, linear, branching, marginal) of the vascularity was analyzed. After surgery, tumor angiogenesis was assessed by microvessel density. The relationship between the vascularity on CDUS and microvessel density was statistically analyzed. At unenhanced CDUS, tumoral flow signals were detected in 12 lesions (48%); at contrast-enhanced CDUS, 18 lesions (86%). All These 18 lesions showed increased signals, compared with those at unenhanced CDUS. The percentage color Doppler area was 1.86 {+-} 0.48% at unenhanced CDUS and 5.23 {+-} 1.18% at contrast-enhanced CDUS. The flow patterns before contrast injection were spotty pattern in 11 tumors and linear pattern in one; after contrast injection, spotty in 8, linear in 4, branching in 5, and marginal in one. The tumoral vascularity at contrast-enhanced CDUS showed no significant correlation with microvessel density. Contrast-enhanced CDUS seems to be a valuable tool in the depiction of vascularity and characterization of flow pattern in breast cancer. However, tumoral vascularity on CDUS may not reflect tumoral angiogenesis.

  4. Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.

    Science.gov (United States)

    Trindade, Alexandre; Djokovic, Dusan; Gigante, Joana; Mendonça, Liliana; Duarte, António

    2017-03-14

    The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.

  5. Effect of inhibition of vascular endothelial growth factor signaling on distribution of extravasated antibodies in tumors.

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    Nakahara, Tsutomu; Norberg, Scott M; Shalinsky, David R; Hu-Lowe, Dana D; McDonald, Donald M

    2006-02-01

    Antibodies and other macromolecular therapeutics can gain access to tumor cells via leaky tumor vessels. Inhibition of vascular endothelial growth factor (VEGF) signaling can reduce the vascularity of tumors and leakiness of surviving vessels, but little is known about how these changes affect the distribution of antibodies within tumors. We addressed this issue by examining the distribution of extravasated antibodies in islet cell tumors of RIP-Tag2 transgenic mice and implanted Lewis lung carcinomas using fluorescence and confocal microscopic imaging. Extravasated nonspecific immunoglobulin G (IgG) and antibodies to fibrin or E-cadherin accumulated in irregular patchy regions of stroma. Fibrin also accumulated in these regions. Anti-E-cadherin antibody, which targets epitopes on tumor cells of RIP-Tag2 adenomas, was the only antibody to achieve detectable levels within tumor cell clusters at 6 hours after i.v. injection. Treatment for 7 days with AG-013736, a potent inhibitor of VEGF signaling, reduced the tumor vascularity by 86%. The overall area density of extravasated IgG/antibodies decreased after treatment but the change was less than the reduction in vascularity and actually increased when expressed per surviving tumor vessel. Accumulation of anti-E-cadherin antibody in tumor cell clusters was similarly affected. The patchy pattern of antibodies in stroma after treatment qualitatively resembled untreated tumors and surprisingly coincided with sleeves of basement membrane left behind after pruning of tumor vessels. Together, the findings suggest that antibody transport increases from surviving tumor vessels after normalization by inhibition of VEGF signaling. Basement membrane sleeves may facilitate this transport. Antibodies preferentially distribute to tumor stroma but also accumulate on tumor cells if binding sites are accessible.

  6. Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    El Kaffas, Ahmed; Sadeghi-Naini, Ali; Falou, Omar; Tran, William Tyler; Czarnota, Gregory J., E-mail: gregory.czarnota@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Departments of Medical Biophysics and Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1L7 (Canada); Zhou, Stephanie; Fernandes, Jason; Giles, Anoja [Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Hashim, Amr [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada)

    2015-08-15

    Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. Methods: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit to the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R{sup 2} of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS

  7. Presence of vascular anomalies with congenital hemihypertrophy and Wilms tumor: an evidence-based evaluation.

    Science.gov (United States)

    Kundu, Roopal V; Frieden, Ilona J

    2003-01-01

    Congenital hemihypertrophy is an uncommon condition of unknown etiology characterized by unilateral overgrowth of part or all of one side of the body. Hemihypertrophy is known to be associated with certain childhood tumors, most notably Wilms tumor (or nephroblastoma), and for this reason infants with hemihypertrophy are often followed with serial abdominal ultrasounds. Klippel-Trénaunay syndrome (KTS) is the triad of port-wine stain, venous varicosities, and soft tissue and/or bony hypertrophy. Children with KTS typically have localized rather than generalized hemihypertrophy, but occasionally the hypertrophy is more extensive than the vascular anomaly itself. Information is lacking about whether hemihypertrophy in this setting can also be a risk factor for Wilms tumor. We systematically reviewed the medical literature to determine whether well-documented cases of Wilms tumor in the setting of both hemihypertrophy and vascular anomalies have been described, and if found, whether the association was sufficiently frequent that routine screening for Wilms tumor in this setting should be recommended. A review of case reports and case series in the pediatric population was undertaken using specific inclusion and exclusion criteria. We found 4 of 58 subjects with hemihypertrophy and Wilms tumor had a reported vascular anomaly, but in only one case was a clear-cut diagnosis of KTS confirmed. The relationship of the other three vascular anomalies reported was of uncertain significance. In conclusion, our review suggests that the risk of Wilms tumor in the setting of localized soft-tissue hypertrophy in conjunction with a vascular malformation is quite low. More extensive hemihypertrophy extending to body sites remote from the vascular malformation itself could have a higher risk of Wilms tumor, although the magnitude of this risk is uncertain. Our findings suggest that routine serial abdominal ultrasounds in patients with vascular malformations in association with

  8. Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies.

    Science.gov (United States)

    Akerman, Simon; Fisher, Matthew; Daniel, Rachel A; Lefley, Diane; Reyes-Aldasoro, Constantino C; Lunt, Sarah Jane; Harris, Sheila; Bjorndahl, Meit; Williams, Leigh J; Evans, Helen; Barber, Paul R; Prise, Vivien E; Vojnovic, Borivoj; Kanthou, Chryso; Tozer, Gillian M

    2013-12-01

    Antiangiogenic therapy based on blocking the actions of vascular endothelial growth factor-A (VEGF) can lead to "normalization" of blood vessels in both animal and human tumors. Differential expression of VEGF isoforms affects tumor vascular maturity, which could influence the normalization process and response to subsequent treatment. Fibrosarcoma cells expressing only VEGF120 or VEGF188 isoforms were implanted either subcutaneously (s.c.) or in dorsal skin-fold "window" chambers in SCID mice. VEGF120 was associated with vascular fragility and hemorrhage. Tumor-bearing mice were treated with repeat doses of SU5416, an indolinone receptor tyrosine kinase inhibitor with activity against VEGFR-2 and proven preclinical ability to induce tumor vascular normalization. SU5416 reduced vascularization in s.c. implants of both VEGF120 and VEGF188 tumors. However, in the window chamber, SU5416 treatment increased red cell velocity in VEGF120 (representing vascular normalization) but not VEGF188 tumors. SU5416 treatment had no effect on growth or necrosis levels in either tumor type but tended to counteract the increase in interstitial fluid pressure seen with growth of VEGF120 tumors. SU5416 pretreatment resulted in the normally fragile blood vessels in VEGF120-expressing tumors becoming resistant to the vascular damaging effects of the tubulin-binding vascular disrupting agent (VDA), combretastatin A4 3-O-phosphate (CA4P). Thus, vascular normalization induced by antiangiogenic treatment can reduce the efficacy of subsequent VDA treatment. Expression of VEGF120 made tumors particularly susceptible to vascular normalization by SU5416, which in turn made them resistant to CA4P. Therefore, VEGF isoform expression may be useful for predicting response to both antiangiogenic and vascular-disrupting therapy. Copyright © 2013 UICC.

  9. A quantitative theory of solid tumor growth, metabolic rate and vascularization.

    Directory of Open Access Journals (Sweden)

    Alexander B Herman

    Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

  10. Intraoral epithelioid hemangioendothelioma: An intermediate vascular tumor- A case report

    Directory of Open Access Journals (Sweden)

    Bhari Sharanesha Manjunatha

    2009-01-01

    Full Text Available Vascular neoplasms, other than benign are characterized as intermediate or malignant. They are often enshrouded in controversy, because the same neoplasm could show variability in biologic behavior that may not be correlated with microscopic features. The intermediate grade vascular neoplasm is named as epithelioid hemangioendothelioma (EHE. Epithelioid hemangioendothelioma of the oral cavity has been infrequently reported. To the best of our knowledge, the review of the English litera-ture revealed a total of 30 cases of intraoral EHE reported till today. We report such a rare case in a 20 year old male, presented with a growth in lower anterior lingual gingiva since five months before the diagnosis with a history of similar swelling, twice in the same area. The differential diagnosis and brief review of literature is also discussed in the current article.

  11. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R

    2002-01-01

    The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice...... that the mechanism of action of CA4DP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and NIRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume....

  12. Interstitial hydraulic conductivity and interstitial fluid pressure for avascular or poorly vascularized tumors.

    Science.gov (United States)

    Liu, L J; Schlesinger, M

    2015-09-07

    A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Hemorrhagic epithelioid and spindle cell hemangioma: a newly recognized, unique vascular tumor of bone.

    Science.gov (United States)

    Keel, S B; Rosenberg, A E

    1999-05-01

    Epithelioid vascular tumors of bone are uncommon and include epithelioid hemangioma, epithelioid hemangioendothelioma, and epithelioid angiosarcoma. It is important to distinguish among them because they have significantly different biologic potential and require different forms of therapy. In the current study the authors describe six cases of a distinct benign epithelioid and spindle cell vascular tumor of bone that, because of their unusual morphology, were confused with aggressive vascular neoplasms. Cases were retrieved from the surgical pathology files of the Department of Pathology or from the consultation files of one of the authors. Hematoxylin and eosin stained slides were examined. Immunohistochemistry was performed on two cases and electron microscopy was performed on one case. The tumors arose in the small bones of the hands and feet and the tibia. Three patients had multifocal bone disease at the time of presentation. Histologically, all lesions were comprised of lobules of spindle cells that grew focally in a fascicular pattern and were associated with abundant hemorrhage. Plump epithelioid cells were intermixed and were present focally in the interlobular areas as well, in which they lined larger, more well developed vascular spaces, often protruding into the vascular lumen in a "tombstone" fashion. Immunohistochemically and ultrastructurally the neoplastic cells had features of endothelium. One case was treated by amputation, one by resection, three by curettage, and one by curettage plus radiation therapy. None of the lesions was locally aggressive nor did any metastasize. The authors believe that hemorrhagic epithelioid and spindle cell hemangioma of bone is a histologically benign bone tumor. It should be distinguished from malignant epithelioid vascular tumors of bone, which have metastatic potential and need to be treated more aggressively.

  14. Tumor vascular endothelium : Barrier or target in tumor directed drug delivery and immunotherapy

    NARCIS (Netherlands)

    Molema, Ingrid; de Leij, Lou; Meijer, D.K F

    The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immunomodulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and

  15. Effect of transarterial pulsed perfusion with heated saline on tumor vascular permeability in a rabbit VX2 liver tumor model

    International Nuclear Information System (INIS)

    Cao Wei; Li Jinghua; Feng Dayun; Wan Yi; Liu Yufeng; Yang Qingfeng; Cheng Jianwei; Zhao Siyuan; Zhang Hongxin

    2012-01-01

    Purpose: To evaluate the effect of transarterial pulsed perfusion with 60 °C saline on vascular permeability of tumor tissue, as well as its hepatic and renal toxicity, in a rabbit VX2 liver model. Materials and methods: VX2 carcinomas were grown in rabbit livers, forty male New Zealand white tumor-bearing rabbits were randomly divided into four groups, followed by transarterial perfusion with 37 °C saline 60 ml (n = 10) (control 1 group), transarterial pulsed perfusion with 37 °C saline 60 ml (n = 10) (control 2 group), transarterial continuous perfusion with 60 °C saline 60 ml (n = 10) (TCP group), transarterial pulsed perfusion with 60 °C saline 60 ml (n = 10) (TPP group), the duration of time for tumor tissues in the range 43–45 °C of the treated groups was measured with needle thermometer during perfusion. Vascular permeability was assessed using the extravasation of Evans blue (EB) dye in the tumor or normal liver tissues of the four groups separately, the tumor or normal liver tissues of the four groups were estimated by histopathologic examination, and hepatic and renal toxicity was evaluated by means of blood biochemical analysis. The vascular endothelial cells in the tumor were observed by transmission electron microscopy (TEM). Results: The duration of time for tumor tissues in the range 43–45 °C of TPP group showed significantly longer than that of TCP group (12.3 ± 3.3 min vs. 5.7 ± 2.5 min) (P 0.05), and there was no significant difference in the serum BUN, Cr levels among the four groups at 1, 2, 4, 8, 24 h after perfusion. Observed by hematoxylin and eosin staining, there were no obvious signs of tissue destruction in liver tissue and tumor tissue. TEM indicating the endothelial cell gap was broadened and the endothelial cells’ microvillus was decreased after heated perfusion. Conclusions: The vascular permeability of the rabbit VX2 tumor was significantly increased after transarterial pulsed perfusion with 60 °C saline without

  16. Microvascular corrosion casting in the study of tumor vascularity: a review.

    Science.gov (United States)

    Konerding, M A; Miodonski, A J; Lametschwandtner, A

    1995-01-01

    Tumor blood flow is dependent on the structure and three-dimensional (3-D) architecture of the vascular network. The latter can be best studied by scanning electron microscopy of microvascular corrosion casts. However, literature reviews show that nearly all studies using this technique render comparisons of different tumors more difficult since they are mainly based on descriptive terms that might lead to misunderstandings. Qualitative comparisons of 13 experimental and 3 human primary tumors of different origin show a high degree of similarity in the vasculature. Quantitative analysis of these casts reveals similar ranges of parameters such as diameters, intervascular and interbranching distances. Diameters of vessels with capillary wall structure range from 6 micron m to 55 micron m in the human primary tumors (renal clear cell carcinoma, basalioma), and from 5 micron m to 80 micron m in xenografted tumors (sarcomas, colon carcinoma). Intervascular distances in the human primary tumors range from 2 micron m to 52 micron m, and from 11 micron m to 105 micron m in the xenografts. Interbranching distances range from 34 micron m to 258 micron m in the former, and from 11 micron m to 160 micron m in the latter. Both qualitative and quantitative analyses of tumor microvascular corrosion casts enable pathophysiological conclusions to be drawn and contribute to a better understanding of tumor vascularity.

  17. Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh Jaggi

    2007-03-01

    Full Text Available Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature.Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy.The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

  18. Tumor MMP-1 Activates Endothelial PAR1 to Facilitate Vascular Intravasation and Metastatic Dissemination

    DEFF Research Database (Denmark)

    Juncker-Jensen, Anna; Deryugina, Elena I; Rimann, Ivo

    2013-01-01

    non-tumor-cell/non-matrix target, activation of which by carcinoma-produced MMP-1 regulates endothelial permeability and transendothelial migration. The inhibitory effects of specific PAR1 antagonists in live animals have also indicated that the mechanisms of MMP-1-dependent vascular permeability...

  19. Evader Interdiction and Collateral Damage

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory

    2011-01-01

    In network interdiction problems, evaders (hostile agents or data packets) are moving through a network towards their targets and we wish to choose sensor placement locations in order to intercept them before they reach their destinations. Sensor locations should be chosen economically, balancing security gains with cost, including the inconvenience sensors inflict upon innocent travelers. We give optimal sensor allocation algorithms for several classes of special graphs and hardness and optimal approximation results for general graphs, including for deterministic or Markov chain-based and oblivious or reactive evaders. In a similar-sounding but much different problem setting posed by [10] where the innocent travelers can also be reactive, we again give optimal algorithms for special cases and hardness and (essentially) optimal approximation results on general graphs.

  20. Model of interconnection of temperature and vascular parameters of experimental S-45 tumor on growth and radiation action

    International Nuclear Information System (INIS)

    Venkhvadze, R.Ya.; Gedenavishvili, Eh.G.; Karpov, V.V.

    1988-01-01

    The aim of this investigation was to search for analytical description of changes in vascularization, which could serve as the basis for a mathematical model to control without invasion the state of tumoral neoplasms in therapy 264 mongrel rats with tumor C-45 vaccinated subcutaneously and intramuscularly in the region of a right femur were examined; they were irradiated locally and once using X-ray unit with 15 and 30 Gy doses. Tumor and vascular tissue temperatures, area being under vessels are studied. Models, which can be used to estimate vascularization of tumoral tissue and to describe interaction of a vacular factor and temperature under radiation effect, are suggested. 4 refs

  1. Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography

    International Nuclear Information System (INIS)

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J.

    2007-01-01

    Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center

  2. Photoacoustic imaging of breast tumor vascularization: a comparison with MRI and histopathology

    Science.gov (United States)

    Heijblom, Michelle; Piras, Daniele; van den Engh, Frank M.; Klaase, Joost M.; Brinkhuis, Mariël.; Steenbergen, Wiendelt; Manohar, Srirang

    2013-06-01

    Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.

  3. Enhancing Nanoparticle Accumulation and Retention in Desmoplastic Tumors via Vascular Disruption for Internal Radiation Therapy.

    Science.gov (United States)

    Satterlee, Andrew B; Rojas, Juan D; Dayton, Paul A; Huang, Leaf

    2017-01-01

    Aggressive, desmoplastic tumors are notoriously difficult to treat because of their extensive stroma, high interstitial pressure, and resistant tumor microenvironment. We have developed a combination therapy that can significantly slow the growth of large, stroma-rich tumors by causing massive apoptosis in the tumor center while simultaneously increasing nanoparticle uptake through a treatment-induced increase in the accumulation and retention of nanoparticles in the tumor. The vascular disrupting agent Combretastatin A-4 Phosphate (CA4P) is able to increase the accumulation of radiation-containing nanoparticles for internal radiation therapy, and the retention of these delivered radioisotopes is maintained over several days. We use ultrasound to measure the effect of CA4P in live tumor-bearing mice, and we encapsulate the radio-theranostic isotope 177 Lutetium as a therapeutic agent as well as a means to measure nanoparticle accumulation and retention in the tumor. This combination therapy induces prolonged apoptosis in the tumor, decreasing both the fibroblast and total cell density and allowing further tumor growth inhibition using a cisplatin-containing nanoparticle.

  4. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  5. [Angiographic study of the vascularization of primary malignant tumors of the liver: histological correlation].

    Science.gov (United States)

    Pinchuk, L; Zeilicoff, R; Falcon, O; Kesner, L; Buquet, J; Figueroa, M; Cimino, C

    1977-06-01

    During the last seven years 118 patients with histologic diagnosis of malign tumor in the liver were examinated by selective angiography, amongst other diagnostic recourses: 14 patients had primitive tumors: 12 hepatoma, 1 cholangiocarcinoma and 1 hepatocholangiocarcinoma. In 12 patients resection was contraindicated preoperative by the angiographic demonstration of the extension of the tumor to both lobes. In 1 patient with cholangiocarcinoma, the tumor was resected with an outlive of 4 years. In 1 patient with hepatoma very vascular a hard league of the right hepatic artery was done. Two months later angiography demonstrated a rich revascularisation of the tumor with development of the colateral circulation. In our experience the hiper or hipovascularization is related with the degree of fibrosis which accompanies the tumor and no so much with the histologic type, the degrees of differentiation or the existence of intratumoral necrosis. Emphasis is been done to show the diagnostical difficulties of hipovascularized tumors and the importance of angiography in the preoperative evaluation of hepatic tumors.

  6. Recurrent multifocal cutaneous Kaposiform hemangioendothelioma: A rare vascular tumor of infancy and childhood

    Directory of Open Access Journals (Sweden)

    Bhagyalakshmi Atla

    2016-01-01

    Full Text Available Kaposiform hemangioendothelioma (KHE is a locally aggressive vascular tumor of childhood although cases occurring in adulthood are also described. The features overlap with juvenile capillary hemangioma and Kaposi sarcoma. We report a rare case of recurrent, multifocal (nose and chin cutaneous KHE initially occurring in a 3-year-old female child, uncomplicated by Kasabach–Merritt syndrome. Recurrences occurred over the next 6 years and resulted in complete distortion of the nose, requiring plastic repair.

  7. Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

    Directory of Open Access Journals (Sweden)

    Moritz Palmowski

    2009-09-01

    Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

  8. Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I, E-mail: mmakrigiorgos@lroc.harvard.ed [Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115 (United States)

    2010-11-07

    Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g{sup -1}, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to

  9. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Directory of Open Access Journals (Sweden)

    Antoni Vilaseca

    Full Text Available We investigate the effects of intermittent hypoxia (IH, a characteristic feature of obstructive sleep apnea (OSA, on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50 of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001 and circulating VEGF (p<0.001 in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  10. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Science.gov (United States)

    Vilaseca, Antoni; Campillo, Noelia; Torres, Marta; Musquera, Mireia; Gozal, David; Montserrat, Josep M; Alcaraz, Antonio; Touijer, Karim A; Farré, Ramon; Almendros, Isaac

    2017-01-01

    We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  11. Vascular Profile Characterization of Liver Tumors by Magnetic Resonance Imaging Using Hemodynamic Response Imaging in Mice

    Directory of Open Access Journals (Sweden)

    Yifat Edrei

    2011-03-01

    Full Text Available Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI, a functional magnetic resonance imaging (MRI method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1–2 mm detection compared with CE-MRI (82% versus 38%, respectively. In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels, which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.

  12. Comparison between model-predicted tumor oxygenation dynamics and vascular-/flow-related Doppler indices.

    Science.gov (United States)

    Belfatto, Antonella; Vidal Urbinati, Ailyn M; Ciardo, Delia; Franchi, Dorella; Cattani, Federica; Lazzari, Roberta; Jereczek-Fossa, Barbara A; Orecchia, Roberto; Baroni, Guido; Cerveri, Pietro

    2017-05-01

    Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images. We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View ® (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices. The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining

  13. Investigating the effect of tumor vascularization on magnetic targeting in vivo using retrospective design of experiment.

    Science.gov (United States)

    Mei, Kuo-Ching; Bai, Jie; Lorrio, Silvia; Wang, Julie Tzu-Wen; Al-Jamal, Khuloud T

    2016-11-01

    Nanocarriers take advantages of the enhanced permeability and retention (EPR) to accumulate passively in solid tumors. Magnetic targeting has shown to further enhance tumor accumulation in response to a magnetic field gradient. It is widely known that passive accumulation of nanocarriers varies hugely in tumor tissues of different tumor vascularization. It is hypothesized that magnetic targeting is likely to be influenced by such factors. In this work, magnetic targeting is assessed in a range of subcutaneously implanted murine tumors, namely, colon (CT26), breast (4T1), lung (Lewis lung carcinoma) cancer and melanoma (B16F10). Passively- and magnetically-driven tumor accumulation of the radiolabeled polymeric magnetic nanocapsules are assessed with gamma counting. The influence of tumor vasculature, namely, the tumor microvessel density, permeability and diameter on passive and magnetic tumor targeting is assessed with the aid of the retrospective design of experiment (DoE) approach. It is clear that the three tumor vascular parameters contribute greatly to both passive and magnetically targeted tumor accumulation but play different roles when nanocarriers are targeted to the tumor with different strategies. It is concluded that tumor permeability is a rate-limiting factor in both targeting modes. Diameter and microvessel density influence passive and magnetic tumor targeting, respectively. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. The irradiation effects on the cytoskeletons of C3H/He mouse mammary tumor cells and vascular basement membrane in relation to vascular invasion

    International Nuclear Information System (INIS)

    Kobayashi, Michiya

    1988-01-01

    We investigated the short-term effects of a single high-dose radiation upon transplanted MM46 tumor cells in mice by means of immunohistochemistry and electron microscopy. The irradiation induced: 1) giant cell formation from the 3rd day, 2) arrest of tumor cell mitosis in prophase and metaphase due to the disorganization of the mitotic spindles, 3) changes in immunoreactivity of laminin and cytoskeletons, and 4) multilayering of the vascular basal lamina and perivascular fibrosis. The above findings suggest a decrease in tumor cell compliance, growth and invasiveness and the potentiation of defensive host responses against vascular invasion after irradiation. The analysis of the temporal sequences of the events indicates that the time lapse between the optimal host response, tumor growth and invasion constitutes a critical period. (author)

  15. In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

    International Nuclear Information System (INIS)

    Garvin, Stina; Dabrosin, Charlotta

    2008-01-01

    Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

  16. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

    Directory of Open Access Journals (Sweden)

    Yves M. Dupertuis

    2015-10-01

    Full Text Available In the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM, which may contribute to implement the 3R principle (Reduce, Refine, Replace. Advantages and limitations of the CAM as an experimental model in cancer research are discussed. Improving the CAM model by using tumor spheroid grafting and positron emission and computed tomography imaging would help to overcome the drawbacks of poor tumor grafting efficiency and restrained 2-D tumor growth measurement to the CAM surface. Such a simple, reliable, reproducible and quantitative method for obtaining dose–response analysis and estimating treatment schedule (i.e. type, route, dose and timing would provide an alternative to the time-consuming and expensive evaluation step in animals before initiating clinical trials.

  17. Intrinsic subtypes and tumor grades in breast cancer are associated with distinct 3-D power Doppler sonographic vascular features

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yeun-Chung [Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Huang, Yao-Sian [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Huang, Chiun-Sheng [Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Chen, Jeon-Hor [Center for Functional Onco-Imaging and Department of Radiological Science, University of California Irvine, California, CA 92868 (United States); Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung 82445, Taiwan, ROC (China); Chang, Ruey-Feng, E-mail: rfchang@csie.ntu.edu.tw [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China)

    2014-08-15

    Purpose: This study aimed to investigate the three-dimensional (3-D) power Doppler ultrasonographic (PDUS) vascular features of breast carcinoma according to intrinsic subtypes, nodal stage, and tumor grade. Materials and methods: Total 115 receiving mastectomy breast carcinomas (mean size, 2.5 cm; range, 0.7–6.5 cm), including 102 invasive ductal carcinomas (IDC), 10 ductal carcinomas in situ (DCIS), and 3 invasive lobular carcinomas (ILC) diagnosed after mastectomy, were used in this retrospective study. Sixty IDC had nodal status and histopathologic tumor grades available for analysis. Vascular features, including number of vascular trees (NV), longest path length (LPL), total vessel length (TVL), number of bifurcations (NB), distance metric (DM), inflection count metric (ICM), vessel diameter (VD), and vessel-to-volume ratio (VVR) were extracted using 3-D thinning method. The Mann–Whitney U test, Student's t-test, one-way ANOVA, and Kruskal–Wallis test were performed as appropriate. Results: There was no significant difference of vascular features among IDC, DCIS and ILC. Except VD, vascular features in luminal type were significantly lower compared to HER2-enriched or triple negative types (p < 0.05). Compared to ER+ (estrogen receptor positive) tumors, all features in ER− (estrogen receptor negative) tumors were significantly higher (p < 0.01). Despite some significantly higher vascular features in high grade IDC compared to low and intermediate grade, there was no significant correlation between vascular features and nodal stages. Conclusion: Differences in 3-D PDUS vascular features among intrinsic types of IDC are attributed to their ER status. Vascular features extracted by 3-D PDUS correlate with tumor grades but not nodal stage in IDC.

  18. In Vivo FRET Imaging of Tumor Endothelial Cells Highlights a Role of Low PKA Activity in Vascular Hyperpermeability.

    Science.gov (United States)

    Yamauchi, Fumio; Kamioka, Yuji; Yano, Tetsuya; Matsuda, Michiyuki

    2016-09-15

    Vascular hyperpermeability is a pathological hallmark of cancer. Previous in vitro studies have elucidated roles of various signaling molecules in vascular hyperpermeability; however, the activities of such signaling molecules have not been examined in live tumor tissues for technical reasons. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we examined the activity of protein kinase A (PKA), which maintains endothelial barrier function. The level of PKA activity was significantly lower in the intratumoral endothelial cells than the subcutaneous endothelial cells. PKA activation with a cAMP analogue alleviated the tumor vascular hyperpermeability, suggesting that the low PKA activity in the endothelial cells may be responsible for the tumor-tissue hyperpermeability. Because the vascular endothelial growth factor (VEGF) receptor is a canonical inducer of vascular hyperpermeability and a molecular target of anticancer drugs, we examined the causality between VEGF receptor activity and the PKA activity. Motesanib, a kinase inhibitor for VEGF receptor, activated tumor endothelial PKA and reduced the vascular permeability in the tumor. Conversely, subcutaneous injection of VEGF decreased endothelial PKA activity and induced hyperpermeability of subcutaneous blood vessels. Notably, in cultured human umbilical vascular endothelial cells, VEGF activated PKA rather than decreasing its activity, highlighting the remarkable difference between its actions in vitro and in vivo These data suggested that the VEGF receptor signaling pathway increases vascular permeability, at least in part, by reducing endothelial PKA activity in the live tumor tissue. Cancer Res; 76(18); 5266-76. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. High-Resolution Multispectral Optoacoustic Tomography of the Vascularization and Constitutive Hypoxemia of Cancerous Tumors

    Directory of Open Access Journals (Sweden)

    Andrei Chekkoury

    2016-08-01

    Full Text Available Diversity of the design and alignment of illumination and ultrasonic transducers empower the fine scalability and versatility of optoacoustic imaging. In this study, we implement an innovative high-resolution optoacoustic mesoscopy for imaging the vasculature and tissue oxygenation within subcutaneous and orthotopic cancerous implants of mice in vivo through acquisition of tomographic projections over 180° at a central frequency of 24 MHz. High-resolution volumetric imaging was combined with multispectral functional measurements to resolve the exquisite inner structure and vascularization of the entire tumor mass using endogenous and exogenous optoacoustic contrast. Evidence is presented for constitutive hypoxemia within the carcinogenic tissue through analysis of the hemoglobin absorption spectra and distribution. Morphometric readouts obtained with optoacoustic mesoscopy have been verified with high-resolution ultramicroscopic studies. The findings described herein greatly extend the applications of optoacoustic mesoscopy toward structural and multispectral functional measurements of the vascularization and hemodynamics within solid tumors in vivo and are of major relevance to basic and preclinical oncological studies in small animal models.

  20. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

    International Nuclear Information System (INIS)

    Arias-Pulido, Hugo; Chaher, Nabila; Gong, Yun; Qualls, Clifford; Vargas, Jake; Royce, Melanie

    2012-01-01

    Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to

  1. Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct from osteoid osteoma and osteoblastoma, radiologically simulating a vascular tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kyriakos, Michael [Washington University School of Medicine, Division of Surgical Pathology, Campus Box 8118, St. Louis, MO (United States); El-Khoury, Georges Y. [University of Iowa, Department of Radiology, Roy J. and Lucille A. Carver School of Medicine, Iowa City, IA (United States); McDonald, Douglas J. [Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO (United States); Buckwalter, Joseph A. [University of Iowa, Department of Orthopaedics, Roy J. and Lucille A. Carver School of Medicine, Iowa City, IA (United States); Sundaram, Murali [Cleveland Clinic Foundation, Department of Radiology, Cleveland, OH (United States); DeYoung, Barry [University of Iowa, Department of Pathology, School of Medicine, Iowa City, IA (United States); O' Brien, Michael P. [University of Wisconsin Hospital, Department of Radiology, Madison, WI (United States)

    2007-03-15

    Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors. (orig.)

  2. Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct from osteoid osteoma and osteoblastoma, radiologically simulating a vascular tumor

    International Nuclear Information System (INIS)

    Kyriakos, Michael; El-Khoury, Georges Y.; McDonald, Douglas J.; Buckwalter, Joseph A.; Sundaram, Murali; DeYoung, Barry; O'Brien, Michael P.

    2007-01-01

    Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors. (orig.)

  3. Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Michael Kragh

    2002-01-01

    Full Text Available The potential of noninvasive laser Doppler flowmetry (LDF and near infrared spectroscopy (NIRS to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3 in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg, 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg, combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg, hydralazine (HDZ, 5 mg/kg, or nicotinamide (NTA, 500 mg/kg. Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  4. Arsenite enhances tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1

    International Nuclear Information System (INIS)

    Tsou, T.-C.; Yeh, Szu Ching; Tsai, E.-M.; Tsai, F.-Y.; Chao, H.-R.; Chang, Louis W.

    2005-01-01

    Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-α (TNF-α), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-α-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-κB (NF-κB). To elucidate the role of GSH in regulation of AP-1, NF-κB, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific γ-glutamylcysteine synthetase (γ-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-α-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-κB activations by TNF-α. Moreover, we found that depletion of GSH would also attenuate the TNF-α-induced VCAM-1 expression with a down-regulation of the TNF-α-induced NF-κB activation and without significant effect on AP-1. On the other hand, the TNF-α-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-κB activity, suggesting that activation of both AP-1 and NF-κB was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-α-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-κB activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines

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

    International Nuclear Information System (INIS)

    Sun, Qingwen; Jiang, Songmin; Han, Baohui; Sun, Tongwen; Li, Zhengnan; Zhao, Lina; Gao, Qiang; Sun, Jialin

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-02

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

  7. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

  8. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

    Directory of Open Access Journals (Sweden)

    Sarah Garrido-Urbani

    Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

  9. Plastic surgery for large wound defects using vascularized flops in treatment of skin and soft-tissue tumors

    International Nuclear Information System (INIS)

    Korotkevich, E.A.; Zalutskij, I.V.; Ismail-Zade, R.S.; Frolov, G.N.

    1992-01-01

    The results were presented on plastic and reconstructive -anaplastic surgery in resection of locally spread and relapse tumors of the skin and soft tissues after multiple courses of radiation and combined treatment. 38 patients with skin melanoma and softtissue sarcomas received radio- and/or chemotherapy in preoperative period under conditions of local hyperthermia of the tumor. Two types of plasty of large wound defects using vascularized flaps were considered

  10. Distal radius reconstruction with vascularized proximal fibular autograft after en-bloc resection of recurrent giant cell tumor

    OpenAIRE

    Yang, Yun-fa; Wang, Jian-wei; Huang, Pin; Xu, Zhong-he

    2016-01-01

    Background Giant cell tumors (GCTs) located in the distal radius are likely to recur, and the treatment of such recurrent tumors is very difficult. Here, we report our clinical experience in distal radius reconstruction with vascularized proximal fibular autografts after en-bloc excision of the entire distal radius in 17 patients with recurrent GCT (RGCT) of the distal radius. Methods All 17 patients with RGCT in distal radius underwent plain radiography and/or magnetic resonance imaging (MRI...

  11. Intra-operative Ultrasound as a Tool to Assess Free Borders of Primary Vascular Aortic Tumors During Resection

    Directory of Open Access Journals (Sweden)

    R.M. Andersen

    Full Text Available : Introduction: Primary vascular tumors are rare and, in general, have a poor prognosis. Complete resection is associated with a better prognosis. Radical resection depends on safe discrimination of tumor borders. Technical summary: A 54 year old woman presented with abdominal pain. Imaging revealed a mass in the thoracic aorta, highly suspicious of angiosarcoma which was confirmed post-operatively by histological analysis. Open surgery was performed. Prior to clamping of the aorta, intra-operative ultrasound established clear delineation of the tumor borders. Conclusion: Intra-operative ultrasound was, in this case, a safe and easy method to determine the tumor borders, providing a simple guide to in toto tumor removal. Keywords: Angiosarcoma, Intra-operative ultrasound, In toto tumor removal, Fludeoxyglucose positron emission tomography/computed tomography, Magnetic resonance imaging

  12. Determination of vascular endothelial- and fibroblast- growth factor receptors in a mouse fibrosarcoma tumor model following photodynamic therapy

    International Nuclear Information System (INIS)

    Ziolkowski, P.; Osieka, B.J.; Symonwicz, K.; Chmielwski, P.; Latos-Grazynski, L.; Bronowicz, A.

    2004-01-01

    The role of angiogenic molecules, like vascular endothelial growth factor and fibroblast growth factor in tumor angio genesis was well confirmed. Photodynamic therapy action is, to very high degree, based on tumor vasculature damage. Therefore, it seemed to be important to evaluate growth factor receptors after photodynamic therapy. The extent of receptor expression was studied by immuno-histochemical method. In this study, vascular endothelial growth factor receptor and fibroblast growth factor receptor have been evaluated at different time points after photodynamic therapy of tumor- bearing BALB/c mice. Two sensitizer: hematoporphyrin derivative and 21, 23-dithia porphyrin were given intraperitoneally in doses: 1.25, 2.5 and 5.0 mg/kg followed by light irradiation at total doses: 50 and 100 J/sq.cm 24 hours later. The number of vascular endothelial growth factor and receptor and fibroblast growth factor in control samples did not exceed 40 per one vessel, whereas after photodynamic therapy, a significant decrease in the number of both receptors was observed. No differences between hematoporphyrin derivative and dithia porphyrin- photodynamic therapy in anti- receptor activities were observed (p<0.001 for vascular endothelial growth factor and p<0.002 for receptor and fibroblast growth factor ). The observed decrease in vascular endothelial growth factor and receptor and fibroblast growth factor amount confirms that after photodynamic therapy, some proteins are inactivated and such a decrease may influence photodynamic therapy effectiveness

  13. Up-to-date Doppler techniques for breast tumor vascularity: superb microvascular imaging and contrast-enhanced ultrasound.

    Science.gov (United States)

    Park, Ah Young; Seo, Bo Kyoung

    2018-04-01

    Ultrasonographic Doppler techniques have improved greatly over the years, allowing more sophisticated evaluation of breast tumor vascularity. Superb microvascular imaging (SMI) and contrast-enhanced ultrasound (CEUS) with second-generation contrast agents are two representative up-to-date techniques. SMI is a sensitive Doppler technique that adopts an intelligent filter system to separate low-flow signals from artifacts. With the development of second-generation contrast agents, CEUS has also emerged as a useful Doppler technique for evaluating tumor microcirculation. Both techniques can improve the diagnostic performance of gray-scale ultrasonography by providing vascular information useful not only for the morphologic assessment of microvessels, but also for the quantitative analysis of perfusion. In this review, we explain the imaging principles and previous research underlying these two vascular techniques, and describe our clinical experiences.

  14. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (ptumors...

  15. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    compared to both colorectal liver metastases (p=0.10) and normal liver tissue (p=0.06). In neuroendocrine tumors, gene-expression was highly variable of VEGF (530-fold), integrin alphaV (23-fold) and integrin beta3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (pbeta3 there was also a borderline significant lower level of mRNA in neuroendocrine tumors...

  16. PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children.

    Science.gov (United States)

    Zamperlini-Netto, G; Zanette, A; Wehbi, E; Williams, S; Grant, R M; Brandao, L R

    2016-04-01

    Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was

  17. Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment

    International Nuclear Information System (INIS)

    Metaizeau, J.P.; Olive, D.; Bey, P.; Bordigoni, P.; Plenat, F.; Prevot, J.

    1984-01-01

    In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used a free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors

  18. Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

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    Mara P. Steinkamp

    2013-05-01

    Full Text Available Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse.

  19. Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Maruyama, Hitoshi; Takahashi, Masanori; Ishibashi, Hiroyuki; Okabe, Shinichiro; Yoshikawa, Masaharu; Yokosuka, Osamu

    2010-01-01

    Purpose: To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC). Materials and methods: This prospective study enrolled 10 patients with histologically proven HCC (14.4-39.0 mm, 26.1 ± 7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22-0.25) during the vascular phase (agent injection to 1 min) and late phase (15 min) following the injection of Sonazoid TM (0.0075 ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced. Results: Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules. Conclusion: Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid.

  20. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Koto, Masashi; Imai, Reiko; Saegusa, Kimiko; Michikawa, Yuichi; Imai, Takashi

    2003-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IF127, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  1. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Baba, Masayuki; Sugawara, Toshiyuki; Furuno, Aki; Saegusa, Kimiko; Michikawa, Y.; Imai, Takashi

    2004-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IFI27, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  2. Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP with Tookad.

    Directory of Open Access Journals (Sweden)

    Noa Madar-Balakirski

    Full Text Available BACKGROUND: Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA and draining veins (DV, leading to tumor necrosis and eradication within 24-48 h. METHODOLOGY/PRINCIPAL FINDINGS: A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70% with a transient increase (60% in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec+/-1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP. CONCLUSION/SIGNIFICANCE: Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.

  3. Identification of longitudinal tissue pO2 gradients as one cause for vascular hypoxia in window chamber tumors

    International Nuclear Information System (INIS)

    Dewhirst, Mark W.; Ong, Edgardo T.; Braun, Rod D.; Evans, Sydney M.; Wilson, David

    1997-01-01

    Purpose: We have previously found that vascular hypoxia exists in tumors, even in vessels with active blood flow. We have also reported that the arteriolar input seems to be constrained to entry into the tumor in one surface of the tissue and that the pO2 of tumor arterioles is lower than in comparable arterioles of normal tissues. Both of these features contribute to lowered intravascular pO2 and tissue hypoxia. In this report, we investigated the hypothesis that the anatomical constraint of arteriolar supply from one side of the tumor will lead to longitudinal tissue gradients in pO2 (i.e. the farther removed one is from the arteriolar source, the more hypoxic the vasculature will be). Materials and Methods: Fischer-344 rats had dorsal flap window chambers implanted in the skin fold with simultaneous transplantation of the R3230AC tumor. Tumors were studied at 9-10 days post transplantation, at a diameter of 3-4mm; the tissue thickness was 200μm. For magnetic resonance microscopic imaging, 1.0ml of GdDTPA-BSA complex was injected i.v. into rats bearing window chamber tumors; the upper glass window was removed, and a suffusion medium of balanced salt solution added in its place, prior to injection of the contrast agent. After 15s the skin flap was immersed in 10% formalin and then removed from the animal. The sample was imaged at 9.4T, using spin warp encoding (TR=200ms, TE=6ms) and fourier transformation of the scanning data. The resultant images had a voxel size of 40μm 3 . Phosphorescence quench imaging (PQI) was used to measure vascular pO2 following i.v. administration of 3.5mg Pd-mesotetra-(4-carboxyphenyl) porphyrin. Blue and green light excitations of the upper and lower surfaces of window chambers were made (penetration depth of light ∼ 50 vs >200μm, respectively). Results: In prior studies we demonstrated that arteriolar input into window chamber tumors appeared to be constrained to the fascial surface upon which the tumor grows. 3-D magnetic

  4. Distal radius reconstruction with vascularized proximal fibular autograft after en-bloc resection of recurrent giant cell tumor.

    Science.gov (United States)

    Yang, Yun-Fa; Wang, Jian-Wei; Huang, Pin; Xu, Zhong-He

    2016-08-17

    Giant cell tumors (GCTs) located in the distal radius are likely to recur, and the treatment of such recurrent tumors is very difficult. Here, we report our clinical experience in distal radius reconstruction with vascularized proximal fibular autografts after en-bloc excision of the entire distal radius in 17 patients with recurrent GCT (RGCT) of the distal radius. All 17 patients with RGCT in distal radius underwent plain radiography and/or magnetic resonance imaging (MRI) of the distal radius as the initial evaluation after hospitalization. Then the distal radius were replaced by vascularized proximal fibular autografts after en-bloc RGCT resection. We assessed all patients by using clinical examinations, plain radiography of the wrist and chest, and Mayo wrist scores in the follow-ups. After an average follow-up of 4.3 years (range: 1.5-10.0 years), no lung metastasis or local recurrence was detected in any of the 17 patients. In total, 14 patients had excellent or good functional wrist scores, 16 were pain free or had occasional pain, and 15 patients returned to work. The mean range of motion of the wrist was 101° (flexion-extension), and the mean grip strength was 77.2 % of the contralateral normal hand. En-bloc excision of the entire distal radius and distal radius reconstruction with a vascularized proximal fibular autograft can effectively achieve local tumor control and preserve wrist function in patients with RGCT of the distal radius.

  5. Correlation between CT perfusion parameters and microvessel density and vascular endothelial growth factor in adrenal tumors.

    Directory of Open Access Journals (Sweden)

    Hai-yan Qin

    Full Text Available We evaluated the correlation between computed tomography (CT perfusion parameters and markers of angiogenesis in adrenal adenomas and non-adenomas to determine if perfusion CT can be used to distinguish between them. Thirty-four patients with pathologically-confirmed adrenal tumors (17 adenomas, 17 non-adenomas received CT perfusion imaging before surgery. CT perfusion parameters (blood flow [BF], blood volume [BV], mean transit time [MTT], and permeability surface area product [PS] were calculated. Tumor tissue sections were examined with immunohistochemical methods for vascular endothelial growth factor (VEGF expression and microvessel density (MVD. The mean age of the 34 patients was 43 years. The median BV was significantly higher in adenomas than in non-adenomas [12.3 ml/100 g, inter-quartile range (IQR: 10.4 to 16.5 ml/100 g vs. 8.8 ml/100 g, IQR: 3.3 to 9.4 ml/100 g, p=0.001]. Differences in BF, MTT, and PS parameter values between adenomas and non-adenomas were not significant (p>0.05. The mean MVD was significantly higher in adenomas compared to non-adenomas (98.5 ± 28.5 vs. 53.5 ± 27.0, p<0.0001. Adenomas also expressed significantly higher median VEGF than non-adenomas (65%, IQR: 50 to 79% vs. 45%, IQR: 35 to 67%, p=0.02. A moderately strong correlation between BF and VEGF (r=0.53, p=0.03 and between BV and MVD among adenomas (r=0.57, p=0.02 exist. Morphology, MVD, and VEGF expression in adenomas differ significantly from non-adenomas. Of the CT perfusion parameters examined, both BF and BV correlate with MVD, but only BF correlates with VEGF, and only in adenomas. The significant difference in BV suggests that BV may be used to differentiate adenomas from non-adenomas. However, the small difference in BV shows that it may only be possible to use BV to identify adenomas vs. non-adenomas at extreme BV values.

  6. Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging.

    Science.gov (United States)

    Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio

    2017-07-01

    Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

  7. Dual regulation of myocardin expression by tumor necrosis factor-α in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Pavneet Singh

    Full Text Available De-differentiation of vascular smooth muscle cells (VSMCs plays a critical role in the development of atherosclerosis, a chronic inflammatory disease involving various cytokines such as tumor necrosis factor-α (TNFα. Myocardin is a co-factor of serum response factor (SRF and is considered to be the master regulator of VSMC differentiation. It binds to SRF and regulates the expression of contractile proteins in VSMCs. Myocardin is also known to inhibit VSMC proliferation by inhibiting the NF-κB pathway, whereas TNFα is known to activate the NF-κB pathway in VSMCs. NF-κB activation has also been shown to inhibit myocardin expression and smooth muscle contractile marker genes. However, it is not definitively known whether TNFα regulates the expression and activity of myocardin in VSMCs. The current study aimed to investigate the role of TNFα in regulating myocardin and VSMC function. Our studies showed that TNFα down-regulated myocardin expression and activity in cultured VSMCs by activating the NF-κB pathway, resulting in decreased VSMC contractility and increased VSMC proliferation. Surprisingly, we also found that TNFα prevented myocardin mRNA degradation, and resulted in a further significant increase in myocardin expression and activity in differentiated VSMCs. Both the NF-κB and p44/42 MAPK pathways were involved in TNFα regulation of myocardin, which further increased the contractility of VSMCs. These differential effects of TNFα on myocardin seemingly depended on whether VSMCs were in a differentiated or de-differentiated state. Taken together, our results demonstrate that TNFα differentially regulates myocardin expression and activity, which may play a key role in regulating VSMC functions.

  8. Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2017-01-01

    INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

  9. Assessment of arterial tumor vascularity in small hepatocellular carcinoma. Comparison between color Doppler ultrasonography and radiographic imagings with contrast medium: dynamic CT, angiography, and CT hepatic arteriography

    International Nuclear Information System (INIS)

    Furuse, Junji; Maru, Yasushi; Yoshino, Masahiro; Mera, Kiyomi; Sumi, Hajime; Sekiguchi, Ryuzo; Satake, Mitsuo; Hasebe, Takahiro; Ochiai, Atsushi

    2000-01-01

    Hepatocellular carcinoma (HCC) is characterized by tumor vascularization from the hepatic artery. The objective of our work was to compare color Doppler ultrasonography (CDU), including power Doppler ultrasonography (PDU) with radiographic imagings with contrast medium in regard to the detection of the arterial tumor vascularity of small hepatocellular carcinomas (HCC). We examined 42 small HCC lesions 2 cm or less in diameter in 37 patients for arterial tumor vascularity by conventional CDU, PDU, dynamic computed tomography (dCT), digital subtraction angiography (DSA), and CT hepatic arteriography (CTA). Color images were detected in 25 (59.5%) and 28 (66.7%) of the 42 lesions with conventional CDU and PDU, respectively, and tumor vascularity was detected in 26 (61.9%) by dCT, 23 (54.8%) by DSA, and 29 (69.0%) by CTA. Tumor vascularity could be detected in 51.9% by PDU and CTA, more than by conventional CDU, dCT, and DSA (44.4, 44.4, and 33.3%, respectively) in well-differentiated HCC, whereas the detection rates by these techniques were almost equal (86.7% by CDU, 93.3% by PDU, dCT, and DSA, 100% by CTA, respectively) in moderately and poorly differentiated HCC. PDU is superior to CDU, dCT and DSA and equal to CTA for the detection of tumor vascularity in small HCC, particularly in well-differentiated HCC

  10. Distribution of PLGA-modified nanoparticles in 3D cell culture models of hypo-vascularized tumor tissue.

    Science.gov (United States)

    Sims, Lee B; Huss, Maya K; Frieboes, Hermann B; Steinbach-Rankins, Jill M

    2017-10-05

    Advanced stage cancer treatments are often invasive and painful-typically comprised of surgery, chemotherapy, and/or radiation treatment. Low transport efficiency during systemic chemotherapy may require high chemotherapeutic doses to effectively target cancerous tissue, resulting in systemic toxicity. Nanotherapeutic platforms have been proposed as an alternative to more safely and effectively deliver therapeutic agents directly to tumor sites. However, cellular internalization and tumor penetration are often diametrically opposed, with limited access to tumor regions distal from vasculature, due to irregular tissue morphologies. To address these transport challenges, nanoparticles (NPs) are often surface-modified with ligands to enhance transport and longevity after localized or systemic administration. Here, we evaluate stealth polyethylene-glycol (PEG), cell-penetrating (MPG), and CPP-stealth (MPG/PEG) poly(lactic-co-glycolic-acid) (PLGA) NP co-treatment strategies in 3D cell culture representing hypo-vascularized tissue. Smaller, more regularly-shaped avascular tissue was generated using the hanging drop (HD) method, while more irregularly-shaped masses were formed with the liquid overlay (LO) technique. To compare NP distribution differences within the same type of tissue as a function of different cancer types, we selected HeLa, cervical epithelial adenocarcinoma cells; CaSki, cervical epidermoid carcinoma cells; and SiHa, grade II cervical squamous cell carcinoma cells. In HD tumors, enhanced distribution relative to unmodified NPs was measured for MPG and PEG NPs in HeLa, and for all modified NPs in SiHa spheroids. In LO tumors, the greatest distribution was observed for MPG and MPG/PEG NPs in HeLa, and for PEG and MPG/PEG NPs in SiHa spheroids. Pre-clinical evaluation of PLGA-modified NP distribution into hypo-vascularized tumor tissue may benefit from considering tissue morphology in addition to cancer type.

  11. Multimodal navigated skull base tumor resection using image-based vascular and cranial nerve segmentation: A prospective pilot study.

    Science.gov (United States)

    Dolati, Parviz; Gokoglu, Abdulkerim; Eichberg, Daniel; Zamani, Amir; Golby, Alexandra; Al-Mefty, Ossama

    2015-01-01

    Skull base tumors frequently encase or invade adjacent normal neurovascular structures. For this reason, optimal tumor resection with incomplete knowledge of patient anatomy remains a challenge. To determine the accuracy and utility of image-based preoperative segmentation in skull base tumor resections, we performed a prospective study. Ten patients with skull base tumors underwent preoperative 3T magnetic resonance imaging, which included thin section three-dimensional (3D) space T2, 3D time of flight, and magnetization-prepared rapid acquisition gradient echo sequences. Imaging sequences were loaded in the neuronavigation system for segmentation and preoperative planning. Five different neurovascular landmarks were identified in each case and measured for accuracy using the neuronavigation system. Each segmented neurovascular element was validated by manual placement of the navigation probe, and errors of localization were measured. Strong correspondence between image-based segmentation and microscopic view was found at the surface of the tumor and tumor-normal brain interfaces in all cases. The accuracy of the measurements was 0.45 ± 0.21 mm (mean ± standard deviation). This information reassured the surgeon and prevented vascular injury intraoperatively. Preoperative segmentation of the related cranial nerves was possible in 80% of cases and helped the surgeon localize involved cranial nerves in all cases. Image-based preoperative vascular and neural element segmentation with 3D reconstruction is highly informative preoperatively and could increase the vigilance of neurosurgeons for preventing neurovascular injury during skull base surgeries. Additionally, the accuracy found in this study is superior to previously reported measurements. This novel preliminary study is encouraging for future validation with larger numbers of patients.

  12. Specific Accumulation of Tumor-Derived Adhesion Factor in Tumor Blood Vessels and in Capillary Tube-Like Structures of Cultured Vascular Endothelial Cells

    Science.gov (United States)

    Akaogi, Kotaro; Okabe, Yukie; Sato, Junji; Nagashima, Yoji; Yasumitsu, Hidetaro; Sugahara, Kazuyuki; Miyazaki, Kaoru

    1996-08-01

    Tumor-derived adhesion factor (TAF) was previously identified as a cell adhesion molecule secreted by human bladder carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and tumor tissues. Immunochemical staining with an anti-TAF monoclonal antibody showed that TAF was specifically accumulated in small blood vessels and capillaries within and adjacent to tumor nests, but not in those in normal tissues. Tumor blood vessel-specific staining of TAF was observed in various human cancers, such as esophagus, brain, lung, and stomach cancers. Double immunofluorescent staining showed apparent colocalization of TAF and type IV collagen in the vascular basement membrane. In vitro experiments demonstrated that TAF preferentially bound to type IV collagen among various extracellular matrix components tested. In cell culture experiments, TAF promoted adhesion of human umbilical vein endothelial cells to type IV collagen substrate and induced their morphological change. Furthermore, when the endothelial cells were induced to form capillary tube-like structures by type I collagen, TAF and type IV collagen were exclusively detected on the tubular structures. The capillary tube formation in vitro was prevented by heparin, which inhibited the binding of TAF to the endothelial cells. These results strongly suggest that TAF contributes to the organization of new capillary vessels in tumor tissues by modulating the interaction of endothelial cells with type IV collagen.

  13. Preclinical Evaluation of Radioiodinated Hoechst 33258 for Early Prediction of Tumor Response to Treatment of Vascular-Disrupting Agents

    Directory of Open Access Journals (Sweden)

    Dongjian Zhang

    2018-01-01

    Full Text Available This study aimed to explore the use of 131I-Hoechst 33258 (131I-H33258 for early prediction of tumor response to vascular-disrupting agents (VDAs with combretastatin-A4 phosphate (CA4P as a representative. Necrosis avidity of 131I-H33258 was evaluated in mouse models with muscle necrosis and blocking was used to confirm the tracer specificity. Therapy response was evaluated by 131I-H33258 SPECT/CT imaging 24 h after CA4P therapy in W256 tumor-bearing rats. Radiotracer uptake in tumors was validated ex vivo using γ-counting, autoradiography, and histopathological staining. Results showed that 131I-H33258 had predominant necrosis avidity and could specifically bind to necrotic tissue. SPECT/CT imaging demonstrated that an obvious “hot spot” could be observed in the CA4P-treated tumor. Ex vivo γ-counting revealed 131I-H33258 uptake in tumors was increased 2.8-fold in rats treated with CA4P relative to rats treated with vehicle. Autoradiography and corresponding H&E staining suggested that 131I-H33258 was mainly localized in necrotic tumor area and the higher overall uptake in the treated tumors was attributed to the increased necrosis. These results suggest that 131I-H33258 can be used to image induction of cell necrosis 24 h after CA4P therapy, which support further molecular design of probes based on scaffold H33258 for monitoring of tumor response to VDAs treatment.

  14. Anti-tumor activity of a novel HS-mimetic-vascular endothelial growth factor binding small molecule.

    Directory of Open Access Journals (Sweden)

    Kazuyuki Sugahara

    Full Text Available The angiogenic process is controlled by variety of factors of which the vascular endothelial growth factor (VEGF pathway plays a major role. A series of heparan sulfate mimetic small molecules targeting VEGF/VEGFR pathway has been synthesized. Among them, compound 8 (2-butyl-5-chloro-3-(4-nitro-benzyl-3H-imidazole-4-carbaldehyde was identified as a significant binding molecule for the heparin-binding domain of VEGF, determined by high-throughput-surface plasmon resonance assay. The data predicted strong binding of compound 8 with VEGF which may prevent the binding of VEGF to its receptor. We compared the structure of compound 8 with heparan sulfate (HS, which have in common the functional ionic groups such as sulfate, nitro and carbaldehyde that can be located in similar positions of the disaccharide structure of HS. Molecular docking studies predicted that compound 8 binds at the heparin binding domain of VEGF through strong hydrogen bonding with Lys-30 and Gln-20 amino acid residues, and consistent with the prediction, compound 8 inhibited binding of VEGF to immobilized heparin. In vitro studies showed that compound 8 inhibits the VEGF-induced proliferation migration and tube formation of mouse vascular endothelial cells, and finally the invasion of a murine osteosarcoma cell line (LM8G7 which secrets high levels of VEGF. In vivo, these effects produce significant decrease of tumor burden in an experimental model of liver metastasis. Collectively, these data indicate that compound 8 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of endothelial cell migration and angiogenesis mediated by VEGF. In conclusion, compound 8 may normalize the tumor vasculature and microenvironment in tumors probably by inhibiting the binding of VEGF to its receptor.

  15. PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

    Directory of Open Access Journals (Sweden)

    Mabeta Peace

    2016-09-01

    Full Text Available PF573,228 is a compound that targets focal adhesion kinase (FAK, a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells.

  16. Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Joshua J. Rychak

    2007-09-01

    Full Text Available High-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble ultrasound contrast agents bearing targeting ligands specific for molecular markers of tumor angiogenesis using high-frequency microultrasound imaging. A xenograft tumor model in the mouse was used to image vascular endothelial growth factor receptor 2 (VEGFR-2 expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal antibody or an isotype control. Microultrasound imaging was accomplished at a center frequency of 40 MHz, which provided lateral and axial resolutions of 40 and 90 μm, respectively. The B-mode (two-dimensional mode acoustic signal from microbubbles bound to the molecular target was determined by an ultrasound-based destruction-subtraction scheme. Quantification of the adherent microbubble fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2-targeted microbubbles relative to control-targeted microbubbles. These data demonstrate that contrast-enhanced microultrasound imaging is a useful method for assessing molecular expression of tumor angiogenesis in mice at high resolution.

  17. Tumor vascularity under hypertension induced by intravenous infusion of angiotensin II

    International Nuclear Information System (INIS)

    Kato, Toshio

    1986-01-01

    We studied whether or not the blood flow of tumors was increased by AT-II-induced hypertension in patients. Angiograms of 51 patients before and after intravenous infusion of AT-II were compared carefully from 5 points of view which suggested increased tumor blood flow. These were, 1) Contraction of small arteries feeding normal tissue, 2) Enhanced visualization of tumor vessels, 3) Enhanced visualization of tumor stain, 4) Increase of venous return from tumor-bearing region, and 5) Enhanced visualization of metastatic lymph nodes. The results were as follows. Contractions of small arteries feeding normal tissue [Finding 1)] were observed in 34 cases (66.6 %) and enhanced visualization of tumor vessels, tumor stain and so on [Finding 2)-5] were observed in 18 cases (35.3 %). Concequently, an increase of tumor blood flow was suggested in 40 cases (78.4 %). Blood flow of human tumors and normal tissue during the full course of induced hypertension with AT-II were measures by means of radionuclide angiography ( 99m Tc-RBC) and laser Doppler velocimetry. Activities of the tumor-bearing region and the mid-portion of the thigh (selected as normal tissue) were measured continuously by collimated scintillation detectors. In 26 measurements out of 31 (83.8 %), the activity in the thigh decreased promptly and returned to the baseline synchronously with the rise and fall of blood pressure. In contrast, in 11 measurements (34.4 %) the activity of the tumor-bearing region increased and returned to the baseline accompanying the change of blood pressure. Preliminary observations using laser Doppler velocimetry revealed an increase of blood flow in 5 tumors. In conclusion, the blood flow of human tumors was increased by AT-II, in agreement with the findings in animal tumors. (J.P.N.)

  18. Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

    International Nuclear Information System (INIS)

    Zips, Daniel; Hessel, Franziska; Krause, Mechthild; Schiefer, Yvonne; Hoinkis, Cordelia; Thames, Howard D.; Haberey, Martin; Baumann, Michael

    2005-01-01

    Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD 50 ) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD 50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

  19. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  20. Two Dimensional Mathematical Model of Tumor Angiogenesis: Coupling of Avascular Growth and Vascularization

    Directory of Open Access Journals (Sweden)

    Farideh Hosseini

    2015-09-01

    Full Text Available Introduction As a tumor grows, the demand for oxygen and nutrients increases and it grows further if acquires the ability to induce angiogenesis. In this study, we aimed to present a two-dimensional continuous mathematical model for avascular tumor growth, coupled with a discrete model of angiogenesis. Materials and Methods In the avascular growth model, tumor is considered as a single mass, which uptakes oxygen through diffusion and invades the extracellular matrix (ECM. After the tumor reaches its maximum size in the avascular growth phase, tumor cells may be in three different states (proliferative, quiescent and apoptotic, depending on oxygen availability. Quiescent cells are assumed to secrete tumor angiogenic factors, which diffuse into the surrounding tissue until reaching endothelial cells. The mathematical model for tumor angiogenesis is consisted of a five-point finite difference scheme to simulate the progression of endothelial cells in ECM and their penetration into the tumor. Results The morphology of produced networks was investigated, based on various ECM degradation patterns. The generated capillary networks involved the rules of microvascular branching and anastomosis. Model predictions were in qualitative agreement with experimental observations and might have implications as a supplementary model to facilitate mathematical analyses for anti-cancer therapies. Conclusion Our numerical simulations could facilitate the qualitative comparison between three layers of tumor cells, their TAF-producing abilities and subsequent penetration of micro-vessels in order to determine the dynamics of microvascular branching and anastomosis in ECM and three different parts of the tumor.

  1. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

    2007-02-10

    Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

  2. Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Streb

    2011-04-01

    Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

  3. Optimal interdiction of unreactive Markovian evaders

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory; Hagberg, Aric [Los Alamos National Laboratory; Pan, Feng [Los Alamos National Laboratory

    2008-01-01

    The network interdiction problem arises in a wide variety of areas including military logistics, infectious disease control and counter-terrorism. In the classical formulation one is given a weighted network G(N, E) and the task is to find b nodes (or edges) whose removal would maximally increase the least-cost path from a source node s to a target node r. In practical applications. G represenLs a transportation or activity network; node/edge removal is done by an agent, the 'interdictor' against another agent the 'evader' who wants to traverse G from s to t along the least-cost route. Our work is motivated by cases in which both agents have bounded rationality: e.g. when the authorities set up road blocks to catch bank robbers, neither party can plot its actions with full information about the other. We introduce a novel model of network interdiction in which the motion of (possibly) several evaders i. described by a Markov pr cess on G.We further suppose that the evaden; do not respond to interdiction decisions because of time, knowledge or computational constraint . We prove that this interdiction problem is NP-hard, like the classical formulation, but unlike the classical problem the objective function is submodular. This implies that the solution could be approximated within 1-lie using a greedy algorithm. Exploiting submodularity again. we demonstrate that a 'priority' (or 'lazy') evaluation algorithm can improve performance by orders of magnitude. Taken together, the results bring closer realistic solutions to the interdiction problem on global-scale networks.

  4. Changes in tumor oxygen tension during radiotherapy of uterine cervical cancer: relationships to changes in vascular density, cell density, and frequency of mitosis and apoptosis

    International Nuclear Information System (INIS)

    Lyng, Heidi; Sundfoer, Kolbein; Rofstad, Einar K.

    2000-01-01

    Purpose: Changes in oxygen tension (pO 2 ) during the early phase of fractionated radiotherapy were studied in 22 patients with uterine cervical cancer. The aims were to investigate (a) whether possible changes in pO 2 differed among and within tumors and (b) whether the changes could be attributed to changes in vascular density, cell density, and frequency of mitosis and apoptosis. Methods and Materials: The pO 2 was measured polarographically in four regions of the tumors before treatment and after 2 weeks of radiotherapy. The vascular density, cell density, and frequency of mitosis and apoptosis were determined from biopsies taken from the tumor regions after each pO 2 measurement. Results: The changes in pO 2 during therapy differed among the tumors and were correlated to pO 2 before treatment (p 2 and vice versa. The tumors with increased pO 2 (n = 10) had a large decrease in cell density and a significant increase in apoptotic frequency. In contrast, the tumors with decreased pO 2 (n = 10) had a smaller decrease in cell density (p = 0.014) and no significant increase in apoptotic frequency. Vascular density and mitotic frequency showed no change during therapy; however, vascular damage other than decreased vascular density was observed. Conclusion: These results indicate that the oxygenation of cervix tumors generally changes during the early phase of radiotherapy. The change depends on the balance between the factor leading to an increase and that leading to a decrease in oxygenation; i.e., decreased cell density and vascular damage, respectively. Increased apoptotic frequency may contribute to a large decrease in cell density and hence increased oxygenation during therapy

  5. Influence of vascular normalization on interstitial flow and delivery of liposomes in tumors

    International Nuclear Information System (INIS)

    Ozturk, Deniz; Yonucu, Sirin; Yilmaz, Defne; Unlu, Mehmet Burcin

    2015-01-01

    Elevated interstitial fluid pressure is one of the barriers of drug delivery in solid tumors. Recent studies have shown that normalization of tumor vasculature by anti-angiogenic factors may improve the delivery of conventional cytotoxic drugs, possibly by increasing blood flow, decreasing interstitial fluid pressure, and enhancing the convective transvascular transport of drug molecules. Delivery of large therapeutic agents such as nanoparticles and liposomes might also benefit from normalization therapy since their transport depends primarily on convection. In this study, a mathematical model is presented to provide supporting evidence that normalization therapy may improve the delivery of 100 nm liposomes into solid tumors, by both increasing the total drug extravasation and providing a more homogeneous drug distribution within the tumor. However these beneficial effects largely depend on tumor size and are stronger for tumors within a certain size range. It is shown that this size effect may persist under different microenvironmental conditions and for tumors with irregular margins or heterogeneous blood supply. (paper)

  6. Glutathione regulation of redox-sensitive signals in tumor necrosis factor-α-induced vascular endothelial dysfunction

    International Nuclear Information System (INIS)

    Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.; Chen, J.-W.; Chiang, H.-C.

    2007-01-01

    We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-α)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-α induces various biological effects on vascular cells, TNF-α dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-α concentrations, we adopted the lower TNF-α (0.2 ng/ml) to rule out the possible involvement of other TNF-α-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-α-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-α-induced nuclear factor-kappaB (NF-κB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-α. Inhibition of ERK, JNK, or NF-κB attenuates TNF-α-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-α induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-κB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-α. Although AP-1 activation by the lower TNF-α was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-α-induced adhesion molecule expression

  7. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    National Research Council Canada - National Science Library

    Xia, Mengna

    2005-01-01

    ... spectroscopy and FOXY oxygen sensor simultaneously. The results show that the fitted tumor blood flow and metabolic rate of oxygen showed different responses between oxygen and carbogen interventions by applying our model...

  8. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

    National Research Council Canada - National Science Library

    Xia, Mengna

    2005-01-01

    The goals of the study in the first stage are 1) to develop a mathematic model by which we can derive tumor blood flow and metabolic rate of oxygen from hemoglobin concentration during interventions, 2...

  9. Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.

    Science.gov (United States)

    Hara, Hitomi; Kawamoto, Teruya; Onishi, Yasuo; Fujioka, Hiroyuki; Nishida, Kotaro; Kuroda, Ryosuke; Kurosaka, Masahiro; Akisue, Toshihiro

    2016-01-01

    We report the case of a 32-year-old Japanese female with a giant cell tumor of bone involving multiple midfoot bones. Giant cell tumors of bone account for approximately 5% of all primary bone tumors and most often arise at the ends of long bones. The small bones, such as those of the hands and feet, are rare sites for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more aggressive clinical behavior than those of the long bones. The present patient underwent en bloc tumor excision involving multiple tarsals and metatarsals. We reconstructed the longitudinal arch of the foot with a free vascularized fibular graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor recurrence. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  11. Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure

    Directory of Open Access Journals (Sweden)

    Hanneke W.M. van Laarhoven

    2006-06-01

    Full Text Available For the systemic treatment of colorectal cancer, 5-fluorouracil (FU-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2 may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

  12. Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

    DEFF Research Database (Denmark)

    Müller-Enbergs, Helmut; Hu, Jiong; Popp, Rüdiger

    2012-01-01

    OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted...

  13. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Dominguez, Helena; Storgaard, Heidi; Rask-Madsen, Christian

    2005-01-01

    OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic...... insulin resistance. METHOD AND RESULTS: Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions...... of serotonin, sodium nitroprusside and insulin co-infused with serotonin. Beta-cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly...

  14. The sentinel node in cervical cancer patients: role of tumor size and invasion of lymphatic vascular space.

    Science.gov (United States)

    Zarganis, Petros; Kondi-Pafiti, Agatha; Arapantoni-Dadioti, Petroula; Trivizaki, Erasmia; Velentzas, Konstantinos; Vorgias, George; Fotiou, Stelios

    2009-01-01

    The sentinel lymph node (SLN) technique aims at predicting the absence of regional nodal metastasis and seems promising in the management of cervical cancer patients. Forty patients undergoing surgery for early cervical cancer were submitted to the SLN procedure, using Blue Patente alone in 3, radiocolloid injection alone in 4 and both methods in 33 (82.5%). All patients underwent radical hysterectomy and pelvic lymphadenectomy. The detection rate was as follows: overall 85%, blue dye alone 66%, radiocolloid alone 75%, dual method 87%. Detection was successful in 34 patients, with one false-negative result. No micrometastases were demonstrated during ultrastaging of the sentinels. The detection rate was higher in tumors 0.09). Significant negative correlation between lymphatic vascular space invasion (LVSI) and detection rate was found (p2 cm negatively affect the detection rate and may increase the incidence of false negatives.

  15. Toxicity of Gamma Knife Radiosurgery in the Treatment of Intracranial Tumors in Patients With Collagen Vascular Diseases or Multiple Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Lowell, Dot [Department of Radiation Oncology, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); Tatter, Stephen B. [Department of Neurosurgery, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth E. [Department of Radiation Oncology, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); Ellis, Thomas L. [Department of Neurosurgery, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); Lovato, James F. [Division of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Shaw, Edward G.; Urbanic, James J. [Department of Radiation Oncology, School of Medicine, Wake Forest University, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, School of Medicine, Wake Forest University, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: To assess toxicity in patients with either a collagen vascular disease (CVD) or multiple sclerosis (MS) treated with intracranial radiosurgery. Methods and Materials: Between January 2004 and April 2009, 6 patients with MS and 14 patients with a CVD were treated with Gamma Knife radiosurgery (GKRS) for intracranial tumors. Treated lesions included 15 total brain metastases in 7 patients, 11 benign brain tumors, 1 low grade glioma, and 1 cavernous malformation. Toxicities were graded by the Radiation Therapy Oncology Group Acute/Late Radiation Morbidity Scoring Criteria. 'Rare toxicities' were characterized as those reported in the scientific literature at an incidence of <5%. Results: Median follow-up time was 16 months. Median dose to the tumor margin was 13.0 Gy (range, 12-21 Gy). Median size of tumor was 5.0 cm{sup 3} (range, 0.14-7.8 cm{sup 3}). Of the 14 patients with CVD, none experienced a Grade 3 or 4 toxicity or a toxicity characterized as rare. Of the 6 patients with MS, 3 experienced rare toxicities, and two of these were Grade 3 toxicities. Rare complications included a patient experiencing both communicating hydrocephalus and facial nerve palsy, as well as 2 additional patients with motor cranial nerve palsy. High-grade toxicities included the patient with an acoustic neuroma requiring ventriculoperitoneal shunt placement for obstructive hydrocephalus, and 1 patient with a facial nerve schwannoma who experienced permanent facial nerve palsy. Interval between radiosurgery and high-grade toxicities ranged from 1 week to 4 months. Conclusions: Our series suggests that patients with MS who receive GKRS may be at increased risk of rare and high-grade treatment-related toxicity. Given the time course of toxicity, treatment-related edema or demyelination represent potential mechanisms.

  16. Immunohistochemical expression of vascular endothelial growth factor in keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst: A comparative study.

    Science.gov (United States)

    Khajuria, Nidhi; Metgud, Rashmi; Naik, Smitha; Lerra, Sahul; Tiwari, Priya; Mamta; Katakwar, Payal; Tak, Anirudh

    2016-01-01

    Cyst and tumors arise from tissue remains of odontogenesis, these interactions have been considered to play an important role in the tumorigenesis of odontogenic lesions. The connective tissue stroma has an essential role in the preservation of epithelial tissues and minor alterations in the epithelium are followed by corresponding changes in the stroma, such as angiogenesis. Vascular endothelial growth factor (VEGF) is considered the first factor which maintains its position as the most critical driver of vascular formation and is required to initiate the formation of immature vessels, with this aim, present study was executed to evaluate VEGF expression in kertocystic odontogenic tumor, dentigerous cyst and radicular cyst (RC). A retrospective study was carried out comprising a total of 31 cases; 13 cases of keratocystic odontogenic tumor (KCOT), nine cases of dentigerous cyst (DC) and nine cases of RC. The sections were stained immunohistochemically with VEGF antibody and were evaluated for the presence and intensity of the immuno reactive cells. Statistical analysis was carried out using Chi-square test to inter-compare the VEGF expression between KCOT, DC, and RC. VEGF expression in the epithelium and connective tissue was significantly higher in KCOT compared to dentigerous and RC. One case of KCOT with carcinomatous change also revealed positive results for the VEGF expression in the dysplastic epithelium, tumor islands, and connective tissue. The significant difference was observed on inter-comparison of the VEGF expression in the connective tissue of KCOT and DC, whereas no significant difference was observed in the VEGF expression in the connective tissue of KCOT and DC. The present study data supports the literature finding that angiogenesis can be important in the progression and enlargement of odontogenic cysts similarly to what occurs in neoplastic conditions and further it can be concluded that the higher positivity for VEGF of KCOT could help to

  17. Tumor vascularity of experimentally induced VX2 carcinoma in the rabbit thigh: evaluation with enhanced power doppler sonography and DSA correlated with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hoon; Han, Joon Koo; Chung, Jin Wook; Lee, Kyoung Ho; Kim, Se Hyung; Kim, Seog Joon; Choi, Byung Ihn; Chang, Kee Hyun [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2002-05-01

    To describe findings of enhanced power Doppler sonography and DSA in experimentally induced VX2 carcinomas in rabbit thigh and to correlate the imaging findings with the histopathologic features. A total of 30 VX2 carcinomas were implanted in rabbit thigh, and after conventional and enhanced power Doppler sonography and DSA, histopathologic examination was performed. Enhanced power Doppler sonography and DSA, were used to determine the distribution pattern of tumor vascularity; to assess its grade and the percentage of a tumor area occupied by vessels, conventional and enhanced power Doppler sonography, as well as DSA, were used. The grade of necrosis and the development of fibrovascular stroma and capsule were histopathologically determined. The findings of power Doppler sonography were compared with those of DSA and the imaging features were correlated with the histopathologic features. At enhanced power Doppler sonography, the signal was either avascular (n=9), peripheral (n=15) or diffuse (n=6), while at DSA, the corresponding totals were eight, fourteen and eight. There was statistically significant corelation between enhanced power Doppler sonogrpahy and DSA, both in their depiction of the distribution of patterns of tumor vascularity and as regards their findings of grade and percentage of vascular area. As determined by both conventional and enhanced power Doppler sonogrpahy, and by DSA, grade of necrosis and the development of fibrovascular stroma and a capsule correlated with grade and the percentage of vascular area. Experimentally induced VX2 carcinomas in rabbit thigh demonstrated various patterns of tumor vascularity, and the findings of enhanced power Doppler sonography correlated with those of DSA. Tumor vascularity, as demonstrated by two imaging modalities, correlated closely with grade of necrosis and the development of fibrovascular stroma and a capsule, as revealed by histopathologic examination.

  18. Hypoxia promotes tumor growth in linking angiogenesis to immune escape

    Directory of Open Access Journals (Sweden)

    Salem eCHOUAIB

    2012-02-01

    Full Text Available Despite the impressive progress over the past decade, in the field of tumor immunology, such as the identification of tumor antigens and antigenic peptides as potential targets, there are still many obstacles in eliciting an effective immune response to eradicate cancer. It has become increasingly clear that tumor microenvironment plays a crucial role in the control of immune protection and contains many overlapping mechanisms to evade antigen specific immunotherapy. Obviously, tumors have evolved to utilize hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival and metastasis. Among the hypoxia-induced genes, hypoxia-inducible factor (HIF-1 and vascular endothelial growth factor (VEGF play a determinant role in promoting tumor cell growth and survival. In this regard, hypoxia is emerging as an attractive target for cancer therapy. How the microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions will be discussed.

  19. Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

    Directory of Open Access Journals (Sweden)

    Monika Stimac

    Full Text Available Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET (TS plasmid, in comparison to the plasmid with constitutive promoter (CON plasmid, in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

  20. Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon.

    Science.gov (United States)

    Fernandez-Pineda, Israel; Lopez-Gutierrez, Juan Carlos; Chocarro, Gloria; Bernabeu-Wittel, Jose; Ramirez-Villar, Gema Lucia

    2013-09-01

    . This study aimed to clarify the combinatorial treatment effect of agents as aspirin and ticlopidine associated with vincristine in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor such as kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). . A retrospective review was conducted of medical records of all children with diagnosis of KHE or TA associated with KMP treated with vincristine-aspirin-ticlopidine (VAT) therapy at two different institutions in the same country from 1994 to 2011. Clinical features, response to VAT therapy and outcomes were recorded. . Eleven patients (mean age 11 months, range 0-36), including seven females (64%) and four males (36%), were identified. Seven patients underwent incisional biopsy and two different histologies were found, KHE in four patients and TA in three patients. Tumors were located in the head and neck (n = 5), chest wall (n = 2), arm (n = 2) and retroperitoneum (n = 2). Mean platelet level was 10,200/mm(3) (range 4,000-21,000). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation (63%). All patients underwent VAT therapy. Mean duration of treatment was 3.9 months for vincristine, 13.9 months for aspirin, and 13.4 months for ticlopidine. All patients are alive with a mean follow-up of 4.5 years (range, 2-17). . Antiaggregant therapy is helpful in combination with vincristine in the treatment of KMP associated with KHE and TA. Prognosis is excellent if severe thrombocytopenia is controlled despite failure in reduction of tumor size. Copyright © 2013 Wiley Periodicals, Inc.

  1. Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Gregory J. Baker

    2014-07-01

    Full Text Available As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM, and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients.

  2. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. METHODS: We treated...... mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis...... and proliferation, and circulating angiogenic biomarkers. RESULTS: We show by intravital microscopy that cediranib significantly decreased tumor vessel permeability and diameter. Moreover, cediranib treatment induced normalization of perivascular cell coverage and thinning of the basement membrane, as mirrored...

  3. Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Linfeng, E-mail: zhenglinfeng04@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Li Yujie, E-mail: yujieli01@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Han, E-mail: bingowh@hotmail.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhao Jinglong, E-mail: jinglongz@yahoo.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Xifu, E-mail: wangxiechen001@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Hu Yunsheng, E-mail: springmorninghu@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhang Guixiang, E-mail: guixiangzhang@sina.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China)

    2011-05-15

    Purpose: To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. Methods: We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 {mu}l 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. Results: In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). Conclusion: Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve

  4. Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

    International Nuclear Information System (INIS)

    Ketelsen, Dominik; Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin

    2010-01-01

    We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D Perfusion-CT. Phantom measurements were performed on a 128-slice single source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans

  5. Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

    Science.gov (United States)

    Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin

    2010-01-01

    Objective We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. Materials and Methods An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Results Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Conclusion Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans. PMID:20808699

  6. Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

    Energy Technology Data Exchange (ETDEWEB)

    Ketelsen, Dominik; Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin [University Hospital Tuebingen, Tuebingen (Germany)

    2010-10-15

    We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D Perfusion-CT. Phantom measurements were performed on a 128-slice single source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans

  7. Validation of Dynamic Contrast-Enhanced Magnetic Resonance Imaging-Derived Vascular Permeability Measurements Using Quantitative Autoradiography in the RG2 Rat Brain Tumor Model

    Directory of Open Access Journals (Sweden)

    Moira C. Ferrier

    2007-07-01

    Full Text Available Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI is widely used to evaluate tumor permeability, yet measurements have not been directly validated in brain tumors. Our purpose was to compare estimates of forward leakage Ktrans derived from DCE-MRI to the estimates K obtained using [14C]aminoisobutyric acid quantitative autoradiography ([14C]AIB OAR, an established method of evaluating blood-tumor barrier permeability. Both DCE-MRI and [14C]AIB OAR were performed in five rats 9 to 11 days following tumor implantation. Ktrans in the tumor was estimated from DCE-MRI using the threeparameter general kinetic model and a measured vascular input function. Ki was estimated from OAR data using regions of interest (ROI closely corresponding to those used to estimate Ktrans. Ktrans and Ki correlated with each other for two independent sets of central tumor ROI (R = 0.905, P = .035; R = 0.933, P = .021. In an additional six rats, Ktrans was estimated on two occasions to show reproducibility (intraclass coefficient = 0.9993; coefficient of variance = 6.07%. In vivo blood-tumor permeability parameters derived from DCE-MRI are reproducible and correlate with the gold standard for quantifying blood tumor barrier permeability, [14C]AIB OAR.

  8. Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Axel Kleespies

    2005-10-01

    Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

  9. 17β-estradiol-linked nitro-L-arginine as simultaneous inducer of apoptosis in melanoma and tumor-angiogenic vascular endothelial cells.

    Science.gov (United States)

    Roy, Sayantani; Reddy, Bathula Surendar; Sudhakar, Godeshala; Kumar, Jerald Mahesh; Banerjee, Rajkumar

    2011-04-04

    Aggressive melanoma is commonly associated with rapid angiogenic growth in tumor mass, tumor cells acquiring apoptosis resistance, inhibition of cellular differentiation etc. Designing a single anticancer molecule which will target all these factors simultaneously is challenging. In the pretext of inciting anticancer effect through inhibiting nitric oxide synthase (NOS) via estrogen receptors (ER) in ER-expressing skin cancer cells, we developed an estrogen-linked L-nitro-arginine molecule (ESAr) for inciting anticancer effect in melanoma cells. ESAr showed specific anticancer effect through diminishing aggressiveness and metastatic behavior in melanoma cells and tumor. In comparison, ESAr showed significantly higher antiproliferative effect than parent molecule L-nitroarginine methyl ester (L-NAME, a NOS inhibitor) through induction of prominent apoptosis in melanoma cells. ESAr-pretreated aggressive melanoma cells could not form tumor possibly because of transformation/differentiation into epithelial-type cells. Furthermore, its antiangiogenic effect was demonstrated through ESAr-induced antiproliferation in HUVEC cells and apoptosis-induction in tumor-associated vascular endothelial cells, thereby significantly restricting severe growth in melanoma tumor. The targeting moiety, estrogen, at the therapeutic concentration of ESAr has apparently no effect in tumor-growth reduction. Albeit, no specific NOS-inhibition was observed, but ESAr could simultaneously induce these three cancer-specific antiaggressiveness factors, which the parent molecule could not induce. Our data rationalize and establish a new use of estrogen as a ligand for potentially targeting multiple cellular factors for treating aggressive cancers.

  10. Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin

    Directory of Open Access Journals (Sweden)

    Kerigh Behzad

    2010-01-01

    Full Text Available Background and Aim: Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI bladder tumors is primarily by transurethral resection (TURBT followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. Materials and Methods: A total of 23 patients with bladder transitional cell carcinoma (TCC in stage Ta/T1 or carcinoma insitu (CIS, low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA method was used to obtain VEGF level in samples. Results: Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (P=0.007; but not in urine samples. Conclusion: Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors.

  11. PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation.

    Science.gov (United States)

    Mabeta, Peace

    2016-09-01

    PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells. The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 μmol L-1 and inhibited cell migration with an IC50 of about 0.01 μmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 μmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors.

  12. Curious Vascular Tumor

    Directory of Open Access Journals (Sweden)

    Faissal Jghaimi

    2012-01-01

    Full Text Available Introduction. Sinusoidal hemangioma is a rare variant of acquired cavernous hemangioma predominantly occurring in females. Very few case reports have been described in the literature. Case Report. We present a case of a 46-year-old woman who noticed a slowly growing, cutaneous nodule on the left breast. Local excision of the lesion was performed and histology allowed to find a sinusoidal hemangioma. No recurrence was noticed. Conclusion. The very few reports of such a lesion in the literature reflect either rarity of such lesions or unfamiliarity of this subset among the pathologists.

  13. Curious Vascular Tumor

    Science.gov (United States)

    Jghaimi, Faissal; Baallal, Hasna; Fakhri, Anas; Rais, Hanane; Karbout, Noama; Akhdari, Nadia; Amal, Said; Belaabidia, Badia

    2012-01-01

    Introduction. Sinusoidal hemangioma is a rare variant of acquired cavernous hemangioma predominantly occurring in females. Very few case reports have been described in the literature. Case Report. We present a case of a 46-year-old woman who noticed a slowly growing, cutaneous nodule on the left breast. Local excision of the lesion was performed and histology allowed to find a sinusoidal hemangioma. No recurrence was noticed. Conclusion. The very few reports of such a lesion in the literature reflect either rarity of such lesions or unfamiliarity of this subset among the pathologists. PMID:23227370

  14. Täna algavad Eesti Muusika Päevad

    Index Scriptorium Estoniae

    2004-01-01

    Eesti Muusika Päevade raames toimunud üritustest 21. aprillini: ERSO sümfooniakontserdist Estonia kontserdisaalis, Jüri Reinvere radiofoonilise ooperi "Vastaskallas" esiettekandest Tallinna Linnateatri Hobuveski saalis, kontserdist Kunstihoone Vabaduse väljakul (esitusel Urmas Sisaski uus "Tähistaeva tsükkel" - "Eesti rahvataevas"), lastekontserdist "Kodumaine viis" Estonia kontserdisaalis

  15. Juvenile nasopharyngeal angiofibroma - study of the tumor extension and vascularization through computerized tomography (CT) scan and angiography and the patient's age

    International Nuclear Information System (INIS)

    Sennes, Luiz Ubirajara

    1997-01-01

    The juvenile nasopharyngeal angiofibroma is a rare benign tumor that affects male adolescents. It is a fibro-vascular tumor with an exuberant intra tumor blood flow and irrigated by several arteries. It originates from the lateral and posterior region of the nasal cavity and, due to its characteristic multidirectional growth, widely affects the paranasal sinuses and skull base, sometimes invading the cranial fossa or the cheek. The determinant factors of its growth and vascularisation are unknown. Attempting to clarify them, 33 patients from the University of Sao Paulo Medicine were studied from 1983 to 1995, with complete history and radiological documentation (CT scan and angiography), as well as with histological confirmation of the diagnosis. In order to take only tumors with natural evolution, patients with recidivant tumor and those already submitted to any previous treatment were excluded. The parameters evaluate were: patient age and tumor extension (by classification, degree of invasion and number of compromised sites in CT scan) and vascularisation (by number and degree of participation of bilateral arteries in angiography). The se data were tabled and correlated one with each other. (author)

  16. Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping.

    Science.gov (United States)

    Kim, Jae G; Zhao, Dawen; Song, Yulin; Constantinescu, Anca; Mason, Ralph P; Liu, Hanli

    2003-01-01

    This study investigates the correlation of tumor blood oxygenation and tumor pO(2) with respect to carbogen inhalation. After having refined and validated the algorithms for calculating hemoglobin concentrations, we used near-infrared spectroscopy (NIRS) to measure changes of oxygenated hemoglobin concentration (delta[HbO(2)]) and used an oxygen needle electrode and (19)F MRI for pO(2) measurements in tumors. The measurements were taken from Dunning prostate R3327 tumors implanted in rats, while the anesthetized rats breathed air or carbogen. The NIRS results from tumor measurements showed significant changes in tumor vascular oxygenation in response to carbogen inhalation, while the pO(2) electrode results showed an apparent heterogeneity for tumor pO(2) response to carbogen inhalation, which was also confirmed by (19)F MR pO(2) mapping. Furthermore, we developed algorithms to estimate hemoglobin oxygen saturation, sO(2), during gas intervention based on the measured values of delta[HbO(2)] and pO(2). The algorithms have been validated through a tissue-simulating phantom and used to estimate the values of sO(2) in the animal tumor measurement based on the NIRS and global mean pO(2) values. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive approach to monitoring tumor physiology and is complementary to other techniques, while it also demonstrates the need for an NIR imaging technique to study spatial heterogeneity of tumor vasculature under therapeutic interventions. Copyright 2003 Society of Photo-Optical Instrumentation Engineers

  17. Intercalary Reconstruction after Wide Resection of Malignant Bone Tumors of the Lower Extremity Using a Composite Graft with a Devitalized Autograft and a Vascularized Fibula

    Directory of Open Access Journals (Sweden)

    Koichi Ogura

    2015-01-01

    Full Text Available Introduction. Although several intercalary reconstructions after resection of a lower extremity malignant bone tumor are reported, there are no optimal methods which can provide a long-term reconstruction with fewest complications. We present the outcome of reconstruction using a devitalized autograft and a vascularized fibula graft composite. Materials and Methods. We conducted a retrospective review of 11 patients (7 males, 4 females; median age 27 years undergoing reconstruction using a devitalized autograft (pasteurization (n=6, deep freezing (n=5 and a vascularized fibula graft composite for lower extremity malignant bone tumors (femur (n=10, tibia (n=1. Results. The mean period required for callus formation and bone union was 4.4 months and 9.9 months, respectively. Four postoperative complications occurred in 3 patients: 2 infections (1 pasteurized autograft, 1 frozen autograft and 1 fracture and 1 implant failure (both in pasteurized autografts. Graft removal was required in 2 patients with infections. The mean MSTS score was 81% at last follow-up. Conclusions. Although some complications were noted in early cases involving a pasteurized autograft, our novel method involving a combination of a frozen autograft with a vascularized fibula graft and rigid fixation with a locking plate may offer better outcomes than previously reported allografts or devitalized autografts.

  18. Andrographolide inhibits nuclear factor-κB activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-α-stimulated vascular smooth muscle cells.

    Science.gov (United States)

    Chen, Yu-Ying; Hsu, Ming-Jen; Hsieh, Cheng-Ying; Lee, Lin-Wen; Chen, Zhih-Cherng; Sheu, Joen-Rong

    2014-01-01

    Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

  19. Decline of Tumor Vascular Function as Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Is Associated With Poor Responses to Radiation Therapy and Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang-Hsin; Wang, Chun-Chieh [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital-LinKou, Taoyuan, Taiwan (China); Liu, Ho-Ling [Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fu, Sheng-Yung [Department of Biomedical Engineering and Environmental Sciences, National TsingHua University, Hsinchu, Taiwan (China); Yu, Ching-Fang [Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital-LinKou, Taoyuan, Taiwan (China); Chang, Chen [Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan (China); Chiang, Chi-Shiun [Department of Biomedical Engineering and Environmental Sciences, National TsingHua University, Hsinchu, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital-LinKou, Taoyuan, Taiwan (China)

    2016-08-01

    Purpose: To investigate whether changes in the volume transfer coefficient (K{sup trans}) in a growing tumor could be used as a surrogate marker for predicting tumor responses to radiation therapy (RT) and chemotherapy (CT). Methods and Materials: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was consecutively performed on tumor-bearing mice, and temporal and spatial changes of K{sup trans} values were measured along with tumor growth. Tumor responses to RT and CT were studied before and after observed changes in K{sup trans} values with time. Results: Dynamic changes with an initial increase and subsequent decline in K{sup trans} values were found to be associated with tumor growth. When each tumor was divided into core and peripheral regions, the K{sup trans} decline was greater in core, although neither vascular structure or necrosis could be linked to this spatial difference. Tumor responses to RT were worse if applied after the decline of K{sup trans}, and there was less drug distribution and cell death in the tumor core after CT. Conclusion: The K{sup trans} value in growing tumors, reflecting the changes of tumor microenvironment and vascular function, is strongly associated with tumor responses to RT and CT and could be a potential surrogate marker for predicting the tumor response to these treatments.

  20. Assessment of vascularity and permeability in brain tumor using SPECT and [sup 99m]Tc-DTPA-human serum albumin in relation to [sup 201]Tl SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji; Fukuoka, Seiji; Takahashi, Shuhei; Takahashi, Masaaki; Satoh, Katsuyasu; Suematsu, Katsumi; Nakamura, Jun-ichi (Nakamura Memorial Hospital, Sapporo (Japan))

    1994-02-01

    Single photon emission computed tomography (SPECT) using technetium-99m-DTPA-human serum albumin ([sup 99m]Tc-HSA-D) and thallium-201 chloride ([sup 201]Tl) was simultaneously performed on 25 patients with brain tumors; 10 with brain metastasis, 8 with astrocytoma (Gr. 3) and 7 with meningioma. The early image was obtained 10 minutes after [sup 99m]Tc-HSA-D (740 MBq) injection, and the delayed image was taken 5 hours after the injection. HSA-D index, based on the ratio of [sup 99m]Tc-HSA-D uptake in the tumor versus the cortical area, was calculated on each image, and compared with Tl index (tumor/contralateral cerebrum ratio). HSA-D delayed index was significantly greater than HSA-D early index in all tumor types (p<0.05 by the Wilcoxon ranked sign test). Linear correlation between HSA-D early index and HSA-D delayed index was significant in astrocytoma (GR. 3) (p<0.01) and meningioma (p<0.001), and a linear correlation between HSA-D delayed index and Tl index was significant in astrocytoma (Gr. 3) (p<0.05). It is concluded that HSA-D early index and delayed index could reflect tumor vascularity and permeability, respectively, and provide supplementary information for Tl index. (author).

  1. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  2. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

    International Nuclear Information System (INIS)

    Lee, Hae-June; Yoon, Changhwan; Park, Do Joong; Kim, Yeo-Jung; Schmidt, Benjamin; Lee, Yoon-Jin; Tap, William D.; Eisinger-Mathason, T.S. Karin; Choy, Edwin; Kirsch, David G.; Simon, M. Celeste

    2015-01-01

    Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm 3 within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm 3 for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature

  3. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  4. Inhibition of vascular endothelial growth factor A and hypoxia-inducible factor 1α maximizes the effects of radiation in sarcoma mouse models through destruction of tumor vasculature.

    Science.gov (United States)

    Lee, Hae-June; Yoon, Changhwan; Park, Do Joong; Kim, Yeo-Jung; Schmidt, Benjamin; Lee, Yoon-Jin; Tap, William D; Eisinger-Mathason, T S Karin; Choy, Edwin; Kirsch, David G; Simon, M Celeste; Yoon, Sam S

    2015-03-01

    To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm(3) within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm(3) for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued.

    Science.gov (United States)

    van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I; Lappalainen, Jari P; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J; Verrijp, Kiek; Leenders, William P J

    2016-11-01

    Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells. Such tumor vessel targeting requires the identification of tumor-specific vascular targeting agents (TVTAs).Here we describe a novel TVTA, C-C7, which we identified via in vivo biopanning of a llama nanobody phage display library in an orthotopic mouse model of diffuse glioma. We show that C-C7 recognizes a subpopulation of tumor blood vessels in glioma xenografts and clinical glioma samples. Additionally, C-C7 recognizes macrophages and activated endothelial cells in atherosclerotic lesions. By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified dynactin-1-p150Glued as its binding partner. The interaction was confirmed by co-immunostainings with C-C7 and a commercial anti-dynactin-1-p150Glued antibody, and via co-immunoprecipitation/western blot studies. Normal brain vessels do not express dynactin-1-p150Glued and its expression is reduced under anti-VEGF therapy, suggesting that dynactin-1-p150Glued is a marker for activated endothelial cells.In conclusion, we show that in vivo phage display combined with Y2H screenings provides a powerful approach to identify tumor-targeting nanobodies and their binding partners. Using this combination of methods we identify dynactin-1-p150Glued as a novel targetable protein on activated endothelial cells and macrophages.

  6. Molecular Mechanisms Used bySalmonellato Evade the Immune System.

    Science.gov (United States)

    Bernal-Bayard, Joaquín; Ramos-Morales, Francisco

    2018-01-01

    Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.

  7. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Baba, Masayuki; Sugawara, Toshiyuki; Yashiro, Tomoyasu; Saegusa, Kumiko; Furuno, Aki; Michikawa, Yuichi; Imai, Takashi

    2005-01-01

    Using cultured and nude mouse tumor cell (IA) derived frome a human lung cancer, we studied their radiosensitivity by focusing attention on the dynamics of tumor clonogens. The movement of clonogens in the regrowing IA tumor after X rays irradiation can be divided into three phases: first,: the early and rapid survival recovery (PLD repair) phase, second, the delay phase involving a certain lag in survival change, and third, the repopulation phase consisting of two stagea. Now we compare with the dynamics of tumor clonogens before or after exposure to X rays and carbon-ion beams. PLD repair was not observed in a carbon-ion beam. In relation to radiosensitivity and repair mechanism, we studied the gene expression of the cultured cell and nude tumor with a microarray method using 22K custom oligoallele. (author)

  8. Vascular endothelial growth factor and not cyclooxygenase 2 promotes endothelial cell viability in the pancreatic tumor microenvironment.

    LENUS (Irish Health Repository)

    Toomey, Desmond P

    2010-07-01

    Cyclooxygenase 2 (COX-2) and vascular endothelial growth factor (VEGF), often coexpressed in cancer, are associated with poor prognosis. However, results from pancreatic cancer trials of their inhibitors were disappointing. This study delineated the role of COX-2 and nonsteroidal anti-inflammatory drugs in angiogenesis and VEGF regulation.

  9. Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells

    NARCIS (Netherlands)

    Peverali, F.A.; Mandriota, S.J.; Ciana, P.; Marelli, R.; Quax, P.; Rifkin, D.B.; Della Valle, G.; Mignatti, P.

    1994-01-01

    Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells rapidly up-regulates endothelial cell expression of basic fibroblast growth factor (bFGF) and induces formation of capillary-like structures by vascular endothelial cells grown on three-dimensional fibrin gels (in

  10. Andrographolide Inhibits Nuclear Factor-κB Activation through JNK-Akt-p65 Signaling Cascade in Tumor Necrosis Factor-α-Stimulated Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Yu-Ying Chen

    2014-01-01

    Full Text Available Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α. Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK, Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

  11. A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

    Science.gov (United States)

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

    2016-06-01

    To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

  12. Tumor vascularity evaluated by transrectal color Doppler US in predicting therapy outcome for low-lying rectal cancer

    International Nuclear Information System (INIS)

    Barbaro, Brunella; Valentini, Vincenzo; Coco, Claudio; Mancini, Anna Paola; Gambacorta, Maria Antonietta; Vecchio, Fabio Maria; Bonomo, Lorenzo

    2005-01-01

    Purpose: To evaluate the impact on T downstaging of the vasculature supplying blood flow to rectal cancer evaluated by color Doppler ultrasound. Methods and Materials: Color Doppler images were graded in 29 T3-staged rectal carcinoma patients sonographically just before chemoradiation. Any arterial vessels detected in rectal masses were assigned one of two grades: vascularity was considered as grade 1 for vessels feeding the periphery and as grade 2 for vessels coursing in all rectal masses within its peripheral and central portions. The pulsatility indices (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) were calculated in the central and peripheral portions. Results: The pathologic observations showed a change in stage in 15 of the 23 patients graded 2, positive predictive value 65.2% (p = 0.047), and in one of the six rectal cancers graded 1 (negative predictive value, 83.3%). The minimal peripheral PI values in rectal cancer graded 2 were higher in nonresponding (2.2 ± 1.3) than in responding lesions (1.6 ± 0.7) p = 0.01. Conclusion: Vascularity graded 2 associated with low peripheral PI values are indicators of therapy outcome. Vascularity graded 1 and high peripheral PI values in graded 2 have negative predictive value

  13. Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

    Directory of Open Access Journals (Sweden)

    Väänänen H Kalervo

    2009-10-01

    Full Text Available Abstract Background Prostate cancer metastasizes to regional lymph nodes and distant sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood. Methods We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice. Results VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p p p p Conclusion The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern of lymph node metastasis to an increased proportion of metastases at distant sites.

  14. Vascular neoplasms.

    Science.gov (United States)

    Williams, H B

    1980-07-01

    Vascular neoplasms in the broad sense represent a very common group of tumors or hamartomas that show great variability in gross appearance, microscopic appearance, and clinical course. Generally, neoplasms are composed of one cell type, but vascular neoplasms are collections of endothelial-lined tubes or tubules with connective tissue walls that may contain smooth muscle cells, pericytes, and nerve elements according to the specific tissues of origin. The classification of vascular neoplasms as outlined in this article attempts to delineate each tumor or hamartoma according to its histologic appearance and clinical behavior. The clinical course ranges from completely benign, self-involuting malformations such as the strawberry hemangioma to highly malignant angiosarcomas with their rapid growth and frequent metastases. Defects in the lymphatic system show gradations from simple lymphangiomas through lymphedema and lymphangiectasia, which can probably be explained by faulty embryologic development. Management of these lesions has been discussed, including brief descriptions of most of the currently accepted treatment methods for these frequently encountered clinical problems.

  15. Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

    Directory of Open Access Journals (Sweden)

    Mary E. Peek

    2012-01-01

    Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

  16. The role of vascular endothelial growth factor in proliferation of odontogenic cysts and tumors: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Bhavana Gupta

    2016-01-01

    Conclusion: VEGF expression by the epithelium of odontogenic cysts and tumors may play a role in epithelial proliferation via autocrine mechanism as reflected by increased AgNOR counts. The angiogenic activity via paracrine pathway may be responsible for the difference in growth rate and neoplastic behavior of the lesions.

  17. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    International Nuclear Information System (INIS)

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

  18. In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Hsieh WJ

    2012-06-01

    sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

  19. Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Wong, Kwong-Kwok; Fotopoulou, Christina; Blake, Erin A; Robertson, Sharon E; Pejovic, Tanja; Frimer, Marina; Pardeshi, Vishakha; Hu, Wei; Choi, Jong-Sun; Sun, Charlotte C; Richmond, Abby M; Marcus, Jenna Z; Hilliard, Maren A M; Mostofizadeh, Sayedamin; Mhawech-Fauceglia, Paulette; Abdulfatah, Eman; Post, Miriam D; Saglam, Ozlen; Shahzad, Mian M K; Karabakhtsian, Rouzan G; Ali-Fehmi, Rouba; Gabra, Hani; Roman, Lynda D; Sood, Anil K; Gershenson, David M

    2018-02-01

    To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma. © 2017 Wiley Periodicals, Inc.

  20. Where It?s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

    OpenAIRE

    Elas, Martyna; Hleihel, Danielle; Barth, Eugene D.; Haney, Chad R.; Ahn, Kang-Hyun; Pelizzari, Charles A.; Epel, Boris; Weichselbaum, Ralph R.; Halpern, Howard J.

    2010-01-01

    Purpose Tumor microenvironments show remarkable tumor pO2 heterogeneity, as seen in prior EPR pO2 images (EPROI). pO2 correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO2. Results Quantitative ELISA VEGF concentr...

  1. Role of Vascular Endothelial Growth Factor (VEGF) in Thymus of Mice under Normal Conditions and with Tumor Growth.

    Science.gov (United States)

    Kisseleva, E P; Krylov, A V; Lyamina, I V; Kudryavtsev, I V; Lioudyno, V I

    2016-05-01

    In our study, we for the first time investigated a role for VEGF as a factor regulating transendothelial migration of murine thymocytes in vitro. Effects of VEGF were examined in a model of thymocyte migration across a monolayer of EA.hy 926 endothelial cells. We showed that VEGF enhanced transendothelial migration of murine thymocytes and their adhesion to endothelial cells in a dose-dependent manner. VEGF did not influence thymocytes, but rather acted on endothelial cells by upregulating surface expression of adhesion molecule ICAM-1 and downregulating activity of 5'-nucleotidase. Effects from VEGF were comparable with those from TNF-α. Because it is known that administration of VEGF to intact animals results in thymic atrophy, it was assumed that it might play a role in developing thymic involution during tumor growth. Enhanced egress of thymocytes to the periphery was considered as a plausible mechanism underlying effects of VEGF. However, we revealed no difference in parameters of in vitro transendothelial migration for thymocytes from animals bearing a transplantable hepatoma 22a compared to control animals. VEGF mRNA expression in lysates of thymic stroma was found to be upregulated in mice with grafted tumors, whereas at the protein level the amount of VEGF did not differ. While examining expression of VEGF receptors on thymocytes by flow cytometry, both VEGFR-1 and VEGFR-2 were not detected, whereas the percentage of Nrp-1-positive thymocytes in animals with hepatoma 22a was as high as in the control group. Thus, we were unable to confirm a hypothesis regarding participation of VEGF in developing thymic involution during progression of experimental hepatoma. However, a set of novel data concerning a role for VEGF in stimulating transendothelial migration of thymocytes in vitro was obtained, and it may be of significance for understanding mechanisms underlying thymus functioning as well as a role of this cytokine in preparing endothelial cells for egress

  2. Pursuing an evader through cooperative relaying in multi-agent surveillance networks

    NARCIS (Netherlands)

    Du, Shengli; Sun, Ximing; Cao, Ming; Wang, Wei

    2017-01-01

    We provide a distributed control strategy for each mobile agent in a surveillance network in the plane to cooperatively pursue an evader. The pursuit task is relayed from one agent to another when the evader crosses the boundary of the Voronoi regions divided according to the agents’ positions. The

  3. The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome

    International Nuclear Information System (INIS)

    Wergin, Melanie C.; Roos, Malgorzata; Inteeworn, Nathalie; Laluhova, Dagmar; Allemann, Katrin; Kaser-Hotz, Barbara

    2006-01-01

    Back ground and purpose: Vascular endothelial growth factor (VEGF), a specific pro-angiogenic factor is proposed to be involved in cancer progression and resistance to radiation therapy by promoting angiogenesis and by protecting endothelial cells from radiation induced apoptosis. The aim of this study, was first to assess the influence of ionizing radiation on plasma VEGF concentration in spontaneous canine tumors during fractionated radiation therapy with curative or palliative intent and second to analyze plasma VEGF concentration as predictor for treatment outcome. Patients and methods: For plasma VEGF analysis a human VEGF enzyme linked immunosorbent assay was used. Sixty dogs with various tumor types were included in this study. Dogs were irradiated with either low dose per fx (3-3.5 Gy per fraction, total dose: 42-49 Gy, group A: curative intent) or high dose per fx (6-8 Gy per fraction, total dose: 24-30 Gy, group B: palliative intent). Blood samples were taken before and after dose application at certain time points during therapy. Follow-up evaluation was performed for analysis of time to treatment failure and survival. Results: Repeated measures analysis showed no increase of plasma VEGF in dogs treated with fractionated radiation therapy (group A and B). Dichotomizing baseline plasma VEGF into two groups with high and low plasma VEGF, resulted in shorter time to treatment failure in dogs with high plasma VEGF levels (TTF, group A: P=0.038, group B: P=0.041). Conclusions: This study demonstrated that dogs with a plasma VEGF level higher than 5 pg/ml had a poorer outcome after radiation therapy. It is therefore, suggested, to use plasma VEGF as predictor for treatment outcome in radiation therapy

  4. Evaluation of hepatocellular carcinoma tumor vascularity using contrast-enhanced ultrasonography as a predictor for local recurrence following radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Tomohiro [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.jp [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Hao, Yoshiteru; Doba, Nobutaka; Hara, Koji [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Kondo, Masaaki [Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Maeda, Shin [Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 (Japan)

    2017-04-15

    Purpose: The purpose of this study was to evaluate whether the hypervascularity of hepatocellular carcinomas (HCCs) on contrast-enhanced ultrasonography (CEUS) prior to radiofrequency ablation (RFA) is a significant risk factor for local recurrence after RFA. Materials and methods: Institutional review board approval and informed consent were obtained. Overall, 208 patients (mean age, 71.7 years; range, 50–87 years; 137 men, 71 women) with 282 HCCs treated with RFA were analyzed retrospectively. The mean maximum tumor diameter was 15.7 mm. We compared the abilities of CEUS and contrast-enhanced computed tomography (CECT) to detect hypervascularity in HCCs. We then classified the HCCs into two groups according to the arterial-phase CEUS findings: a “hypervascular group” with whole or partial hypervascular areas within the lesions compared with the surrounding liver parenchyma, and a “non-hypervascular group” with isovascular or hypovascular areas within the lesions. We assessed the cumulative rate of local recurrence after RFA, and we also evaluated the risk factors for local recurrence using a univariate analysis. Results: The detection rate for hypervascular HCCs was significantly higher using CEUS (78%, 221/282) than that using CECT (66%, 186/282) (P < 0.001). Using the CEUS findings, the cumulative rate of local recurrence was significantly higher in the hypervascular group (41.2%, 56/221) than in the non-hypervascular group (18.4%, 6/61) (P = 0.007). A univariate analysis revealed that hypervascularity on CEUS was an independent risk factor for local recurrence (P = 0.010). Conclusion: Hypervascularity in HCCs as observed using CEUS is a significant risk factor for local recurrence after RFA.

  5. Genetically enhanced lysozyme evades a pathogen derived inhibitory protein.

    Science.gov (United States)

    Dostal, Sarah M; Fang, Yongliang; Guerrette, Jonathan C; Scanlon, Thomas C; Griswold, Karl E

    2015-04-17

    The accelerating spread of drug-resistant bacteria is creating demand for novel antibiotics. Bactericidal enzymes, such as human lysozyme (hLYZ), are interesting drug candidates due to their inherent catalytic nature and lack of susceptibility to the resistance mechanisms typically directed toward chemotherapeutics. However, natural antibacterial enzymes have their own limitations. For example, hLYZ is susceptible to pathogen derived inhibitory proteins, such as Escherichia coli Ivy. Here, we describe proof of concept studies demonstrating that hLYZ can be effectively redesigned to evade this potent lysozyme inhibitor. Large combinatorial libraries of hLYZ were analyzed using an innovative screening platform based on microbial coculture in hydrogel microdroplets. Isolated hLYZ variants were orders of magnitude less susceptible to E. coli Ivy yet retained high catalytic proficiency and inherent antibacterial activity. Interestingly, the engineered escape variants showed a disadvantageous increase in susceptibility to the related Ivy ortholog from Pseudomonas aeruginosa as well as an unrelated E. coli inhibitory protein, MliC. Thus, while we have achieved our original objective with respect to escaping E. coli Ivy, engineering hLYZ for broad-spectrum evasion of proteinaceous inhibitors will require consideration of the complex and varied determinants that underlie molecular recognition by these emerging virulence factors.

  6. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report.

    Science.gov (United States)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-07

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  7. ASTAXANTHIN MENURUNKAN KADAR VASCULAR ENDOTHELIAL GROWTH FACTOR, TUMOR NECROSIS FACTOR ALPHA, INTERLEUKIN-6, DAN NITRIC OXIDE PADA NONPROLIFERATIVE DIABETIC RETINOPATHY RINGAN: UJI KLINIS TERKENDALI

    Directory of Open Access Journals (Sweden)

    Ni Made Laksmi Utari

    2015-01-01

    Full Text Available Diabetic Retinopathy (DR merupakan komplikasi mikrovaskular pada Diabetes Mellitus (DM dan penyebab kebutaan paling sering pada usia produktif. Hiperglikemia menyebabkan terjadinya reaksiinflamasi dan stres oksidatif  dalam patogenesis DR dipaparkan oleh beberapa peneliti, namun peran antioksidan dalam mengurangi progresifitas DR masih menjadi perdebatan. Penelitian ini bertujuanuntuk mengetahui pemberian astaxanthin 8 mg dapat menurunkan kadar Vascular Endothelial Growth Factor (VEGF, Tumor Necrosis Factor-alpha (TNF-á, Interleukin-6 (IL-6 dan Nitric Oxide (NO padapenderita Non Proliferative Diabetic Retinopathy (NPDR ringan. Penelitian clinical trial dengan perluasan Randomized, Double Blinded, Placebo-Control, Pre and Posttest Group Design ini dilaksanakanpada bulan Juli 2013 - Desember 2013 di Poliklinik Mata RSUP Sanglah Denpasar Bali. Jumlah sampel yang memenuhi kriteria eligibilitas sebanyak 40 pasien NPDR ringan terbagi menjadi 20 pasien  sebagai kelompok perlakuan yang diberikan astaxanthin 8 mg dan 20 pasien NPDR ringan yang diberikan plasebo sebagai kelompok kontrol. Pengambilan sampel darah vena untuk pemeriksaan dilakukan sebelum dan setelah pemberian astaxanthin 8 mg serta plasebo selama 4 minggu. Perbedaan kadar rerata VEGF, TNF-á, IL-6 dan NO dianalisis dengan uji-t jika distribusi data normal dan uji Mann-whitney jika distribusi data tidak  normal. Hasil penelitian ini diharapkan dapat memberikaninformasi mengenai hubungan VEGF, TNF-á, IL-6, dan NO dalam perkembangan NPDR ringan serta manfaat pemberian astaxanthin dalam perkembangan NPDR ringan. [MEDICINA 2014;45:31-37

  8. Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

    Science.gov (United States)

    Ikonomidis, Ignatios; Papadavid, Evangelia; Makavos, George; Andreadou, Ioanna; Varoudi, Maria; Gravanis, Kostas; Theodoropoulos, Kostas; Pavlidis, George; Triantafyllidi, Helen; Moutsatsou, Paraskevi; Panagiotou, Christina; Parissis, John; Iliodromitis, Efstathios; Lekakis, John; Rigopoulos, Dimitrios

    2017-09-01

    Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment ( P psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857. © 2017 American Heart Association, Inc.

  9. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

    Directory of Open Access Journals (Sweden)

    Wachyu Hadisaputra

    2013-05-01

    Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor

  10. Lung tumorigenesis induced by human vascular endothelial growth factor (hVEGF)-A165 overexpression in transgenic mice and amelioration of tumor formation by miR-16.

    Science.gov (United States)

    Tung, Yu-Tang; Huang, Pin-Wu; Chou, Yu-Ching; Lai, Cheng-Wei; Wang, Hsiu-Po; Ho, Heng-Chien; Yen, Chih-Ching; Tu, Chih-Yen; Tsai, Tung-Chou; Yeh, Dah-Cherng; Wang, Jiun-Long; Chong, Kowit-Yu; Chen, Chuan-Mu

    2015-04-30

    Many studies have shown that vascular endothelial growth factor (VEGF), especially the human VEGF-A165 (hVEGF-A165) isoform, is a key proangiogenic factor that is overexpressed in lung cancer. We generated transgenic mice that overexpresses hVEGF-A165 in lung-specific Clara cells to investigate the development of pulmonary adenocarcinoma. In this study, three transgenic mouse strains were produced by pronuclear microinjection, and Southern blot analysis indicated similar patterns of the foreign gene within the genomes of the transgenic founder mice and their offspring. Accordingly, hVegf-A165 mRNA was expressed specifically in the lung tissue of the transgenic mice. Histopathological examination of the lung tissues of the transgenic mice showed that hVEGF-A165 overexpression induced bronchial inflammation, fibrosis, cysts, and adenoma. Pathological section and magnetic resonance imaging (MRI) analyses demonstrated a positive correlation between the development of pulmonary cancer and hVEGF expression levels, which were determined by immunohistochemistry, qRT-PCR, and western blot analyses. Gene expression profiling by cDNA microarray revealed a set of up-regulated genes (hvegf-A165, cyclin b1, cdc2, egfr, mmp9, nrp-1, and kdr) in VEGF tumors compared with wild-type lung tissues. In addition, overexpressing hVEGF-A165 in Clara cells increases CD105, fibrogenic genes (collagen α1, α-SMA, TGF-β1, and TIMP1), and inflammatory cytokines (IL-1, IL-6, and TNF-α) in the lungs of hVEGF-A165-overexpressing transgenic mice as compared to wild-type mice. We further demonstrated that the intranasal administration of microRNA-16 (miR-16) inhibited lung tumor growth by suppressing VEGF expression via the intrinsic and extrinsic apoptotic pathways. In conclusion, hVEGF-A165 transgenic mice exhibited complex alterations in gene expression and tumorigenesis and may be a relevant model for studying VEGF-targeted therapies in lung adenocarcinoma.

  11. 'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics.

    Science.gov (United States)

    Jenkins, Stuart I; Weinberg, Daniel; Al-Shakli, Arwa F; Fernandes, Alinda R; Yiu, Humphrey H P; Telling, Neil D; Roach, Paul; Chari, Divya M

    2016-02-28

    Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance. As a strategy to overcome this barrier, the use of stealth coatings can reduce immune clearance and prolong circulatory times, thereby enhancing therapeutic capacity. Polyethylene glycol (PEG) is the most widely-used stealth coating and facilitates particle accumulation in the brain. However, once within the brain, the mode of handling of PEGylated particles by the resident immune cells of the brain itself (the 'microglia') is unknown. This is a critical question as it is well established that microglia avidly sequester nanoparticles, limiting their bioavailability and posing a major translational barrier. If PEGylation can be proved to promote evasion of microglia, then this information will be of high value in developing tailored nanoparticle-based therapies for neurological applications. Here, we have conducted the first comparative study of uptake of PEGylated particles by all the major (immune and non-immune) brain cell types. We prove for the first time that PEGylated nanoparticles evade major brain cell populations - a phenomenon which will enhance extracellular bioavailability. We demonstrate changes in protein coronas around these particles within biological media, and discuss how surface chemistry presentation may affect this process and subsequent cellular interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Sissejuhatus Tubinasse : Marianne Kõrveri "Äraoldud päevade summa" / Tõnu Karjatse

    Index Scriptorium Estoniae

    Karjatse, Tõnu

    2005-01-01

    Muusikaline dokumentaalfilm "Äraoldud päevade summa" helilooja Eduard Tubinast : stsenarist ja tekstide autor Jüri Reinvere : režissöör Marianne Kõrver : Exitfilm - Eesti Televisioon - SVT (Rootsi)

  13. Tartu Kevadpäevad 2008 : Nädalajagu muusikat igale maitsele / Signe Tamberg

    Index Scriptorium Estoniae

    Tamberg, Signe

    2008-01-01

    Tartu Kevadpäevad 2008 muusikaprogrammis: 34. tudengilaulu võistlusest 29. apr. Tartu Sadamateatris, öölaulupeost 28. apr. Kassitoome orus, kontsertidest "Rokime!" 2. mail ja "Folgime" 3. mail Raekoja platsil

  14. Pärnus algavad homme Ungari kultuuripäevad / Teet Roossaar

    Index Scriptorium Estoniae

    Roossaar, Teet

    2005-01-01

    Ungari organist Miklos Teleki orelikontsertidest 3. sept. Eliisabeti kirikus ja 4. sept. Pärnu-Jaagupi kirikus ning Pärnu Linnaorkestri hooaja avakontserdist 4. sept. Pärnu kontserdimajas Ungari kultuuripäevade raames

  15. Uudised : Voices of Europe tuleb Pärdi teosega. Puhkpillipäevad Võrus / Ingrid Peek

    Index Scriptorium Estoniae

    Peek, Ingrid

    2000-01-01

    1. sept. Tallinnas Kaarli kirikus toimuvast kontserdist, kus tuleb ettekandele Pärdi teos "Which was the son of...". 15. aug. avatakse Võrus V noorte puhkpillimängijate suvekool ja Võru vaskpillipäevad

  16. Eesti Suusapäevad Jay Peak´is / Peeter Teedla ; fotod: Peeter Teedla

    Index Scriptorium Estoniae

    Teedla, Peeter

    2006-01-01

    märtsikuu esimesel nädalalõpul idaranniku eestlaste suusapäevad, osavõtjaid 156, paljud perekondade ja väikeste lastega, organiseerijaks Kristin Raamot. Peeti murdmaasuusatamise - ja slaalomivõistlused

  17. [Case of law-evading herbs poisoning that induced shock and myocardial damage].

    Science.gov (United States)

    Nakamura, Yoshihiko; Nakano, Minoru; Nakamura, Mitsunobu; Miyazaki, Dai; Okamori, Satoshi; Akuzawa, Hisashi; Yuasa, Masahiro

    2014-12-01

    Law-evading herbs may induce poisoning symptoms, especially when they contain synthetic cannabinoids. However, their detailed pharmacological effects have not yet been clarified. Some reports have previously described symptoms of poisoning, but only a few reports have so far described shock and myocardial damage (MD). We experienced a case of shock and MD in a patient who had smoked law-evading herbs. A 61-year-old male presented at an emergency department 8 hours after smoking law-evading herbs (Rush Trip, High Men Monster) with chest pain. A vasopressor agent was administered to treat shock and antiarrhythmic drugs were administered due to ventricular arrhythmia. The contents of the law-evading herbs were unknown, so an in-hospital follow-up was conducted to treat the patient's symptoms. The follow-up blood test showed an increased level of cardiac enzymes, which thereafter demonstrated a spontaneous remission. The systemic conditions tended to improve and the patient was discharged from the hospital on the 5th hospital day. The contents of the law-evading herbs in question were thereafter,analyzed, and synthetic cannabinoids (JWH-210, JWH-081 and JWH-122) as well as caffeine were detected. The cause for the poisoning symptoms were suspected to be the presence of synthetic cannabinoids and caffeine. Such law-evading herbs may contain synthetic cannabinoids and caffeine which both may induce shock and MD.

  18. Preoperative serum levels of epidermal growth factor receptor, HER2, and vascular endothelial growth factor in malignant and benign ovarian tumors

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla

    2008-01-01

    , and malignant ovarian tumors. Patients and Methods: Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA......). Results: The median EGFR serum level in patients with ovarian cancer was 51 ng/mL, and this was significantly lower than the median serum levels in borderline tumors (P =.0054) and benign ovarian tumors (P ... in patients with ovarian cancer was 10.2 ng/mL and not significantly different from any of the other patient groups. The median VEGF serum level in patients with ovarian cancer was 449 pg/mL and significantly higher than the levels found in borderline tumors (P =.021) and benign tumors (P =.0087) as well...

  19. Vascular Cures

    Science.gov (United States)

    ... vascular disease, such as stroke, aneurysm and pulmonary artery disease. Each one has their own unique story about their battle with vascular disease and their road to recovery. SEE PATIENT STORIES Our Supporters Caring ...

  20. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2013-01-01

    Full Text Available Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET’s anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo.

  1. T-cell mediated anti-tumor immunity after photodynamic therapy: Why does it not always work and how can we improve it?

    Science.gov (United States)

    de Freitas, Lucas Freitas; Hamblin, Michael R

    2015-01-01

    Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients. PMID:26062987

  2. Juvenile nasopharyngeal angiofibroma - study of the tumor extension and vascularization through computerized tomography (CT) scan and angiography and the patient's age; Nasoangiofibroma juvenil - estudo da extensao e vascularizacao do tumor pela tomografia computadorizada e angiografia, e da idade do paciente

    Energy Technology Data Exchange (ETDEWEB)

    Sennes, Luiz Ubirajara

    1997-07-01

    The juvenile nasopharyngeal angiofibroma is a rare benign tumor that affects male adolescents. It is a fibro-vascular tumor with an exuberant intra tumor blood flow and irrigated by several arteries. It originates from the lateral and posterior region of the nasal cavity and, due to its characteristic multidirectional growth, widely affects the paranasal sinuses and skull base, sometimes invading the cranial fossa or the cheek. The determinant factors of its growth and vascularisation are unknown. Attempting to clarify them, 33 patients from the University of Sao Paulo Medicine were studied from 1983 to 1995, with complete history and radiological documentation (CT scan and angiography), as well as with histological confirmation of the diagnosis. In order to take only tumors with natural evolution, patients with recidivant tumor and those already submitted to any previous treatment were excluded. The parameters evaluate were: patient age and tumor extension (by classification, degree of invasion and number of compromised sites in CT scan) and vascularisation (by number and degree of participation of bilateral arteries in angiography). The se data were tabled and correlated one with each other. (author)

  3. Eesti Muusika Päevad 2000 : ECPNMi juhatus Tallinnas / Consuelo Diez ; interv. Evelin Kõrvits

    Index Scriptorium Estoniae

    Diez, Consuelo

    2000-01-01

    28.-30. apr. pidas Tallinnas aastakoosolekut ning külastas Eesti Muusika Päevade kontserte ECPNMi (European Conference of Promoters of New Music) juhatus. ECPNMi juhatuse liikmed räägivad uue muusika üritustest oma riikides, muljeid eesti muusika päevadelt

  4. Why Do Firms Evade Taxes? The Role of Information Sharing and Financial Sector Outreach

    NARCIS (Netherlands)

    Beck, T.H.L.; Lin, C.; Ma, Y.

    2010-01-01

    Informality is a wide-spread phenomenon across the globe. We show that firms in countries with better information sharing systems and greater financial sector outreach evade taxes to a lesser degree, an effect that is stronger for smaller firms, firms in smaller cities and towns, and firms in

  5. Why do firms evade taxes? The role of information sharing and financial sector outreach

    NARCIS (Netherlands)

    Beck, T.H.L.; Lin, C.; Ma, Y.

    2014-01-01

    Tax evasion is a widespread phenomenon across the globe and even an important factor in the ongoing sovereign debt crisis. We show that firms in countries with better credit information–sharing systems and higher branch penetration evade taxes to a lesser degree. This effect is stronger for smaller

  6. Lattice QCD with chemical potential: Evading the fermion-sign problem

    Indian Academy of Sciences (India)

    journal of. December 2004 physics pp. 1211–1224. Lattice QCD with chemical potential: Evading the fermion-sign problem. SOURENDU GUPTA. Department of ... figure 1. In this talk I shall focus on recent attempts to determine the location ..... for the critical end-point are yet to come: the current excitement is that it has been.

  7. Eesti muusika päevad - üks kord aastas, kõigile / Jelena Gandshu

    Index Scriptorium Estoniae

    Gandshu, Jelena

    2008-01-01

    Muusikateadlased Jelena Gandshu ja Gerhard Lock, heliloojad Age Hirv ja Liis Jürgens 3.-10. aprillini toimunud Eesti muusika päevade kontsertidest: kinos Sõprus "Sensatsioon!!!", Kultuuritehases Polymer "Cellissimo", Estonia kontserdisaalis ERSO "Sümfoonilised hääled", Tallinna raekojas Mihkel Poll ja Oliver Kuusik, Katariina kirikus PaukenfEst, Nigulistes Jüri Reinvere autorikontsert. Järgneb

  8. Märtsipäevade valupisaraid peab lastele näitama / Anu Bollverk

    Index Scriptorium Estoniae

    Bollverk, Anu

    2009-01-01

    1949. aasta märtsiküüditamisele pühendatud mälestuspäevast Koeru kultuurimajas ning sealse huviteatri poolt ette kantud Herbert Lasti näidendist "Valupisarais märtsipäevad" (lavastajad Herbert Last ja Uno Aav)

  9. 27 CFR 70.112 - Failure to collect and pay over tax, or attempt to evade or defeat tax.

    Science.gov (United States)

    2010-04-01

    ... Tax, Additional Amounts, and Assessable Penalties § 70.112 Failure to collect and pay over tax, or attempt to evade or defeat tax. Any person required to collect, truthfully account for, and pay over any... account for and pay over such tax, or willfully attempts in any manner to evade or defeat any such tax or...

  10. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued

    NARCIS (Netherlands)

    van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I.; Lappalainen, Jari P.; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J.; Verrijp, Kiek; Leenders, William P J

    2016-01-01

    Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological

  11. Targeting Therapy Resistant Tumor Vessels

    National Research Council Canada - National Science Library

    Ruoslahti, Erkki

    2007-01-01

    .... To achieve this, we have developed tumor models for vascular normalization and are using in vivo phage display and isolation of peptides that specifically home to normalized tumor vessels resistant...

  12. Targeting Therapy Resistant Tumor Vessels

    National Research Council Canada - National Science Library

    Ruoslahti, Erkki

    2008-01-01

    .... To achieve this, we have developed tumor models for vascular normalization and are using in vivo phage display and isolation of peptides that specifically home to normalized tumor vessels resistant...

  13. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  14. Primo Vascular System Accompanying a Blood Vessel from Tumor Tissue and a Method to Distinguish It from the Blood or the Lymph System

    Directory of Open Access Journals (Sweden)

    Jaekwan Lim

    2013-01-01

    Full Text Available A primo vessel was observed in the abdominal cavity in the lung cancer mouse model, and its function as an extra metastatic path was observed. In this work, we found a primo vessel accompanying a blood vessel emanating from a tumor in the skin. We also presented simple and efficient criteria to distinguish a primo vessel from a blood or a lymph vessel and from a nerve. The criteria for using DAPI and Phalloidin will be useful in clinical situations to find and identify the primo vessels among the blood vessels, lymph vessels, or nerves in the tissue surrounding a tumor such as a melanoma or breast cancer.

  15. evad : [luuletused] / Philip Larkin ; inglise keelest tlk. Maarja Kangro

    Index Scriptorium Estoniae

    Larkin, Philip

    2007-01-01

    Sisu: Päevad ; Mitte midagi öelda ; See olgu värss ; Uurimus lugemisharjumustest ; Hommage valitsusele ; Vesi ; Vajakud ; Viige üks koju lastele ; Jutt voodis ; Kõrged aknad ; Sa jätkad elu ; Kui. Orig.: Days ; Nothing to be said ; This be the verse ; A study of reading habits ; Homage to a government ; Water ; Wants ; Take one home for the kiddies ; Talking in bed ; High windows ; Continuing to live ; If

  16. [Drug Dependence and Cytotoxicity of Law-evading Drugs: Their Identities Explored from Basic Research].

    Science.gov (United States)

    Funada, Masahiko

    2016-01-01

      Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

  17. DO PENALTIES AND ENFORCEMENT MEASURES MAKE TAXPAYERS MORE COMPLIANT? THE VIEW OF AUSTRALIAN TAX EVADERS

    OpenAIRE

    Dr Ken Devos

    2013-01-01

    The tax compliance literature indicates that many factors, including, economic, social, psychological and demographic, impact upon the compliance behaviour of individual taxpayers. This study explores the relationship, if any, that exists between selected tax compliance and demographic variables and the compliance behaviour of Australian individual tax evaders. The study employed a mixed method research approach comprising both a survey and interviews. The findings revealed that tax law enfor...

  18. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar

    2017-02-01

    Full Text Available Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

  19. Muusika : Jeremija nutulaulud palmipuudepühal. Jätkub "Musica Grande". Lihavõttetervitus Barcelonast. Rannap "Selges eesti helikeeles". Juba XIII trompetipäevad. III klavessiinipäevad / Jaan-Eik Tulve

    Index Scriptorium Estoniae

    Tulve, Jaan-Eik, 1967-

    2002-01-01

    Vox Clamantise kontsertidest Tartus ja Tallinnas. Jätkub sari "Musica Grande" kontsertidega Tartus ja Tallinnas pealkirjaga "Kontsertlik". Eestisse sõidab esinema üks Hispaania tippkoore Coral Cantiga Barcelonast. Rein Rannapi tänavusest suurprojektist, klaveriõhtust "Selges eesti helikeeles". 1. - 7. aprillini toimuvad EMA rahvusvahelised trompetipäevad. 4. - 7. aprillini korraldab Eesti Klavessiinisõprade Tsunft III klavessiinipäevad

  20. Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

    Science.gov (United States)

    2010-01-01

    Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3) and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium), although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating endothelial cells, and the cross

  1. Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Stacker Steven A

    2010-07-01

    Full Text Available Abstract Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3 and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium, although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating

  2. [The Characteristics of Law-evading Drug Users and Effective Approaches].

    Science.gov (United States)

    Kondo, Ayumi

    2016-01-01

      The increasing number of law-evading drug users in Japan is becoming a serious social problem. Previous studies have shown that law-evading drug users are younger, more educated, and less antisocial than methamphetamine users. They also tend to have some type of psychiatric disorder before starting drug use; therefore one of the reasons that they start using drugs may be to alleviate certain psychiatric symptoms. Furthermore, if drug users are successful in avoiding arrest, they often lack the motivation to stop, which makes treatment difficult. Therapists are required to be non-confrontational, to keep pace with their patients, and to take their patients' other existing disorders into account. Recently, the Matrix Model has shown promise as a new treatment strategy for drug abusers in Japan. The Matrix Model, which was originally developed in response to the 1980s cocaine epidemic in the USA, is an intensive outpatient treatment approach for drug abuse and dependence. The Matrix Model integrates cognitive-behavioral therapy, contingency management, motivational interviewing, 12-step facilitation, family involvement, and so on, with a directive, non-confrontational approach, and this style of therapy seems to fit with law-evading drug users. A Matrix Model-based treatment program was first established in Japan in 2006. The aim of this report is to introduce and assess the benefits of the TAMA Mental Health and Welfare Center Relapse Prevention Program, a Matrix Model-based treatment program established at the Tama Mental Health and Welfare Center in 2007.

  3. Vascular dementia

    African Journals Online (AJOL)

    Adele

    2003-12-10

    Dec 10, 2003 ... ischaemic VaD includes multiple lacunes and subcortical arteriosclerotic encephalopathy (Binswanger's disease) and imaging shows multiple deep ... culitis, multiple sclerosis, acute demyelinating encephalomy- ... Table I. The NINDS-AIREN criteria for the diagnosis of Vascular Dementia. 12. Require both ...

  4. VASCULAR SURGERY

    African Journals Online (AJOL)

    2016-06-02

    Jun 2, 2016 ... with the literature from South Africa over the last four decades, and reflects the high rate of interpersonal violence in the country.14,15 As expected, cervical ... via the intact circle of Willis in young patients is the most likely explanation for the lack of strokes. Five patients were referred to the Durban vascular ...

  5. Ultrasound -- Vascular

    Science.gov (United States)

    ... waves from passing into your body. The sonographer (ultrasound technologist) or radiologist then places the transducer on the ... is specialized and is best performed by a technologist and physician with experience in vascular ultrasound imaging. top of page Additional Information and Resources ...

  6. The Effect of Aerobic Training and Arbotin on Cardiac Nitric Oxide, Tumor Necrosis Factor alpha, and Vascular Endothelial Growth Factor in Male Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Rahemeh Jahangiri Jahangiri

    2017-07-01

    Full Text Available Background and Objectives: Diabetes is one of the most important metabolic diseases, which its incidence rate has increased in recent years. In this disease, the insulin function is impaired, leading to several complications. Physical exercise and medicinal plants are considered as a way to control diabetes along with nutrition and medicine. The present study was conducted with the purpose of determining the effect of aerobic training and use of arbutin on cardiac nitric oxide, tumor necrosis factor-α and vessel endothelial growth factor in male diabetic rats. Methods: In this experimental study, 42 male adult Wistar rats (age, 8 weeks; weight, 190-220g, were randomly divided into 6 groups of 7 each (control, arbutin, diabetic, diabetic+training, diabetic+arbutin, and diabetic+training+arbutin. Training programs included 5 days of swimming per week for 6 weeks. Sampling from the heart was performed 72 hours after the last training session and arbutin consumption to analyze NO, TNF-α and VEGF. Data were analyzed using one-way ANOVA at the significance level p≤0.05. Results: Aerobic training along with use of arbutin led to increased levels of NO and VEGF and decreased level of TNF-α in cardiac tissue of diabetic rats (p<0.001. Conclusion: The results indicated that a period of regular aerobic training and use of arbutin can be considered as an appropriate non-medicinal method to control diabetes mellitus type 2 through decrease in inflammatory factors.

  7. Glucocorticoid receptor knockdown decreases the antioxidant protection of B16 melanoma cells: an endocrine system-related mechanism that compromises metastatic cell resistance to vascular endothelium-induced tumor cytotoxicity.

    Science.gov (United States)

    Obrador, Elena; Valles, Soraya L; Benlloch, María; Sirerol, J Antoni; Pellicer, José A; Alcácer, Javier; Coronado, Javier Alcácer-F; Estrela, José M

    2014-01-01

    We previously reported an interorgan system in which stress-related hormones (corticosterone and noradrenaline), interleukin-6, and glutathione (GSH) coordinately regulate metastatic growth of highly aggressive B16-F10 melanoma cells. Corticosterone, at levels measured in tumor-bearing mice, also induces apoptotic cell death in metastatic cells with low GSH content. In the present study we explored the potential role of glucocorticoids in the regulation of metastatic cell death/survival during the early stages of organ invasion. Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in metastatic cells in vivo independent of the tumor location (liver, lung, or subcutaneous). The decrease in γ-GCS activity was associated with lower intracellular GSH levels. Nrf2- and p53-dependent down-regulation of γ-GCS was associated with a decrease in the activities of superoxide dismutase 1 and 2, catalase, glutathione peroxidase, and glutathione reductase, but not of the O2--generating NADPH oxidase. The GCR knockdown-induced decrease in antioxidant protection caused a drastic decrease in the survival of metastatic cells during their interaction with endothelial cells, both in vitro and in vivo; only 10% of cancer cells attached to the endothelium survived compared to 90% survival observed in the controls. This very low rate of metastatic cell survival was partially increased (up to 52%) in vivo by inoculating B16-F10 cells preloaded with GSH ester, which enters the cell and delivers free GSH. Taken together, our results indicate that glucocorticoid signaling influences the survival of metastatic cells during their interaction with the vascular endothelium.

  8. An Audit of the Clinicopathological Spectrum of Benign Vascular ...

    African Journals Online (AJOL)

    Background: Vascular tumors of the female genital tract (FGT) are very rare. The aim of this study was to analyze the spectrum of vascular tumors in FGT and to correlate their clinicopathological features. Materials and Methods: A retrospective study of 15years, including clinical features, imaging studies, gross and ...

  9. [Drug Dependence and Toxicity of Law-Evading Drugs: Their Mechanisms Explored from Basic Research].

    Science.gov (United States)

    Funada, Masahiko

    2016-10-01

    The number of law-evading chemical substances that pose serious health risks to humans is increasing worldwide, including Japan and the Western world, and their abuse is becoming a serious social problem. Analysis of the chemical substances in these herbal products revealed the presence of synthetic cannabinoids. This review summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids as a group of chemical substances contained in these products. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids by using animals and cell cultures. In a place-conditioning study, the synthetic cannabinoids produced a significant conditioned-place preference. The rewarding effects of synthetic cannabinoids were completely suppressed by a cannabinoid CB1 receptor antagonist. Administration of synthetic cannabinoids to primary striatal culture caused cell death in a dose-dependent manner. Our findings show that the CB1 receptor might be involved in the expression of synthetic cannabinoid-induced rewarding effect. These behavioral data indicate that synthetic cannabinoids have a psychic-dependence liability. Furthermore, our data from primary striatal culture indicate that synthetic cannabinoids have strong neurotoxicity. These behavioral and neurochemical data indicate that synthetic cannabinoids might have strong adverse effects and a psychic-dependence liability.

  10. How do K-RAS-activated cells evade cellular defense mechanisms?

    Science.gov (United States)

    Lee, Y-S; Bae, S-C

    2016-02-18

    Lung adenocarcinomas, like other cancers, develop through the accumulation of epigenetic and genetic alterations. Numerous studies have shown that K-RAS mutation is among the most important early events in carcinogenesis of the lung. However, it is also well established that growth-stimulating signals feed back into growth-suppressing pathways, and any imbalance in these signaling networks will cause the cell to exit the cell cycle, thereby preventing uncontrolled cell growth. How, then, do K-RAS-activated cells evade cellular defense mechanisms? To answer this question, it is necessary to identify the molecular event(s) responsible for the development of early dysplastic lesions that are unable to defend against aberrant oncogene activation. Lineage-determining transcriptional regulators govern differentiation status during normal lung development, as well as in lung adenocarcinoma. Among the genes involved in K-RAS-induced lung tumorigenesis, RUNX3 is unique: inactivation of Runx3 in mouse lung induces lung adenoma and abrogates the ARF-p53 pathway. This observation raises the possibility of intimate cross-talk between the differentiation program and oncogene surveillance. In this review, we summarized evidences suggesting that K-RAS-activated cells do not evade cellular defense mechanisms per se; instead, cells with K-RAS mutations are selected only if they occur in cells in which defense mechanism is abrogated.

  11. Vascular ultrasound.

    Science.gov (United States)

    Pilcher, D B; Ricci, M A

    1998-04-01

    Surgeon-interpreted diagnostic ultrasound has become the preferred screening test and often the definitive test for the diagnosis of arterial stenosis, aneurysm, and venous thrombosis. As a modality for surveillance, its noninvasive quality makes it particularly appealing as the test of choice to screen patients for abdominal aortic aneurysms or to perform follow-up examinations on those patients with a carotid endartectomy or in situ bypass grafts. The increasing reliance on intraoperative duplex imaging of vascular procedures demands that the surgeon learn the skills to perform the studies without a technologist or radiologist to interpret the examination.

  12. Evading the pulsar constraints on the cosmic string tension in supergravity inflation

    International Nuclear Information System (INIS)

    Kamada, Kohei; Miyamoto, Yuhei; Yokoyama, Jun'ichi

    2012-04-01

    The cosmic string is a useful probe of the early Universe and may give us a clue to physics at high energy scales where any artificial particle accelerators cannot reach. Although one of the most promising tools is the cosmic microwave background, the constraint from gravitational waves is becoming so stringent that one may not hope to detect its signatures in the cosmic microwave background. In this paper, we construct a scenario that contains cosmic strings observable in the cosmic microwave background while evading the constraint imposed by the recent pulsar timing data. We argue that cosmic strings with relatively large tension are allowed by delaying the onset of the scaling regime. We also show that this scenario is naturally realized in the context of chaotic inflation in supergravity, where the phase transition is governed by the Hubble induced mass.

  13. [Vascular anomalies in the neonatal period].

    Science.gov (United States)

    Bejarano, M; Vicario, F; Soria, A; Parri, F J; Albert, A

    2017-07-20

    Vascular anomalies in the neonatal period are a diagnostic challenge for the lack of evident signs, symptoms and follow-up, and the convenience of restricting aggressive diagnostic tests. The aim of this work is to review the characteristics of neonatal cases presented to our Vascular Anomalies Unit in the last 5 years. All cases of suspected vascular anomaly presented to our unit before 1 month of age between 2010 and 2015 were reviewed, diagnostic tests and treatments carried out with chronology were analyzed. Presumptive diagnosis and final diagnosis (when available) were compared. Fifteen vascular tumors were found, 2 with visceral involvement: 6 infantile hemangiomas (IH), 3 NICH, 4 RICH, 1 tufted hemangioma, 1 unspecified liver vascular tumor, 3 venous malformations (2 equivocal MRI and a hyperkeratotic venous malformation), 4 lymphatic malformations, 3 of them macrocystic, and 2 vascular lesions that were diagnosed of fibrosarcoma and sclerema neonatorum and they were not vascular anomalies. Only 3 patients with macrocystic lymphatic malformations had prenatal diagnosis. Accurate diagnosis of vascular anomalies during the first month of life is difficult, even with MRI. Only in a few cases early treatment is needed, so it is worth taking time to follow-up. Different types of treatment (observation, propranolol, biopsy, laser, embolization, and resection) will depend on the condition to be treated. A continuous observation can avoid unnecessary procedures and risks.

  14. 26 CFR 301.6672-1 - Failure to collect and pay over tax, or attempt to evade or defeat tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Failure to collect and pay over tax, or attempt... § 301.6672-1 Failure to collect and pay over tax, or attempt to evade or defeat tax. Any person required to collect, truthfully account for, and pay over any tax imposed by the Code who willfully fails to...

  15. Tallinna Merepäevade turismikonverents käsitles mere ja linna kohtumispaiga arenguid ja arendamist / Ain Hinsberg

    Index Scriptorium Estoniae

    Hinsberg, Ain

    2013-01-01

    Tallinna Sadama, linnavalitsuse, Viking Line ja EHTE poolt 12. juulil Admiraliteedi basseiniääres Merepäevade paviljonis korraldatud konverentsist "Mere ja linna kohtumispaik kui linnaruum ja sihtkoht", kus esinesid Allan Kiil, Tiit Kask, Duncan Frazer Inglismaalt, Satu Lehtonen Soomest, Anu Hallik-Jürgenstein, Peeter Pere, Heikki Mäki, Evelyn Sepp ja Ahto Ader

  16. Lübecki filmipäevad 1999 ja Thomas Manni ekraniseering 1923 / Lauri Kärk

    Index Scriptorium Estoniae

    Kärk, Lauri, 1954-

    1999-01-01

    4.-7. novembrini Lübeckis toimunud Põhjamaade filmipäevade 41. Nordische Filmtage huvitavamatest filmidest, nagu Thomas Manni "Buddenbrookide" ekraniseering 1923. aastast (režissöör Gerhard Lamprecht) ja Rasmus Gerlachi dokumentaal "Operaator Kaufman" Dziga Vertovist ja tema kahest, samuti kino alal tegutsenud vennast

  17. The new deal: a potential role for secreted vesicles in innate immunity and tumor progression.

    Science.gov (United States)

    Benito-Martin, Alberto; Di Giannatale, Angela; Ceder, Sophia; Peinado, Héctor

    2015-01-01

    Tumors must evade the immune system to survive and metastasize, although the mechanisms that lead to tumor immunoediting and their evasion of immune surveillance are far from clear. The first line of defense against metastatic invasion is the innate immune system that provides immediate defense through humoral immunity and cell-mediated components, mast cells, neutrophils, macrophages, and other myeloid-derived cells that protect the organism against foreign invaders. Therefore, tumors must employ different strategies to evade such immune responses or to modulate their environment, and they must do so prior metastasizing. Exosomes and other secreted vesicles can be used for cell-cell communication during tumor progression by promoting the horizontal transfer of information. In this review, we will analyze the role of such extracellular vesicles during tumor progression, summarizing the role of secreted vesicles in the crosstalk between the tumor and the innate immune system.

  18. Imaging evaluation of fetal vascular anomalies

    International Nuclear Information System (INIS)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal; Adams, Denise M.; Gupta, Anita; Lim, Foong-Yen

    2015-01-01

    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  19. Imaging evaluation of fetal vascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal [MLC 5031 Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Adams, Denise M. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics and Hemangioma and Vascular Malformation Center, Cincinnati, OH (United States); Gupta, Anita [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Pediatric Surgery and Fetal Center of Cincinnati, Cincinnati, OH (United States)

    2015-08-15

    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  20. Close, but no cigar: certain cigars are pseudo-cigarettes designed to evade regulation.

    Science.gov (United States)

    Delnevo, Cristine D; Hrywna, Mary; Giovenco, Daniel P; Miller Lo, Erin J; O'Connor, Richard J

    2017-05-01

    An abundance of evidence suggests that the tobacco industry's response to increased regulation imposed on cigarettes has been the development of little cigars and filtered cigars which are tobacco products that are merely cigarettes in disguise. Emphasising these products' physical attributes, the tobacco industry has offered cigar products to its consumers as pseudo-cigarettes. For decades, tobacco manufacturers' response to increased cigarette regulation and taxation has been to exploit policy loopholes by offering these little cigars and filtered cigars pseudo-cigarettes that are exempted from this regulatory oversight. As a result, in spite of increased regulations and taxes on cigarettes, smokers can purchase cigars that are almost physically indistinguishable from their cigarettes at a lower cost. This commentary describes the recent evolution of the cigar market in response to federal regulation, and highlights historical cigar industry attempts to evade taxation, capitalise on product features that are off-limits to cigarettes, and capture the shrinking market of cigarette smokers. We present the case that little cigars and filtered cigars, differing very little physically from cigarettes, are products deserving the same regulatory scrutiny. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Evading plant immunity: feedback control of the T3SS inPseudomonas syringae.

    Science.gov (United States)

    Waite, Christopher; Schumacher, Jörg; Jovanovic, Milija; Bennett, Mark; Buck, Martin

    2017-03-17

    Microbes are responsible for over 10% of the global yield losses in staple crops such as wheat, rice, and maize. Understanding the decision-making strategies that enable bacterial plant pathogens to evade the host immune system and cause disease is essential for managing their ever growing threat to food security. Many utilise the needle-like type III secretion system (T3SS) to suppress plant immunity, by injecting effector proteins that inhibit eukaryotic signalling pathways into the host cell cytoplasm. Plants can in turn evolve resistance to specific pathogens via recognition and blocking of the T3SS effectors, so leading to an ongoing co-evolutionary 'arms race' between pathogen and host pairs. The extracytoplasmic function sigma factor HrpL co-ordinates the expression of the T3SS regulon in the leaf-dwelling Pseudomonas syringae and similar pathogens. Recently, we showed that association of HrpL with a target promoter directly adjacent to the hrpL gene imposes negative autogenous control on its own expression level due to overlapping regulatory elements. Our results suggest that by down-regulating T3SS function, this fine-tuning mechanism enables P. syringae to minimise effector-mediated elicitation of plant immunity.

  2. Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response

    Directory of Open Access Journals (Sweden)

    Megan L. Shaw

    2009-12-01

    Full Text Available Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the host interferon (IFN response is conferred by the P gene. The henipavirus P gene encodes four proteins; the P, V, W and C proteins, which have all been described to inhibit the antiviral response. Further studies have revealed that these proteins have overlapping but unique properties which enable the virus to block multiple signaling pathways in the IFN response. The best characterized of these is the JAK-STAT signaling pathway which is targeted by the P, V and W proteins via an interaction with the transcription factor STAT1. In addition the V and W proteins can both limit virus-induced induction of IFN but they appear to do this via distinct mechanisms that rely on unique sequences in their C-terminal domains. The ability to generate recombinant Nipah viruses now gives us the opportunity to determine the precise role for each of these proteins and address their contribution to pathogenicity. Additionally, the question of whether these multiple anti-IFN strategies are all active in the different mammalian hosts for henipaviruses, particularly the fruit bat reservoir, warrants further exploration.

  3. A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway.

    Science.gov (United States)

    Wang, Kathy K; Stone, Laura K; Lieberman, Tami D; Shavit, Michal; Baasov, Timor; Kishony, Roy

    2016-02-01

    Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid's components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae

    Directory of Open Access Journals (Sweden)

    Christopher Waite

    2017-03-01

    Full Text Available Microbes are responsible for over 10% of the global yield losses in staple crops such as wheat, rice, and maize. Understanding the decision-making strategies that enable bacterial plant pathogens to evade the host immune system and cause disease is essential for managing their ever growing threat to food security. Many utilise the needle-like type III secretion system (T3SS to suppress plant immunity, by injecting effector proteins that inhibit eukaryotic signalling pathways into the host cell cytoplasm. Plants can in turn evolve resistance to specific pathogens via recognition and blocking of the T3SS effectors, so leading to an ongoing co-evolutionary ‘arms race’ between pathogen and host pairs. The extracytoplasmic function sigma factor HrpL co-ordinates the expression of the T3SS regulon in the leaf-dwelling Pseudomonas syringae and similar pathogens. Recently, we showed that association of HrpL with a target promoter directly adjacent to the hrpL gene imposes negative autogenous control on its own expression level due to overlapping regulatory elements. Our results suggest that by down-regulating T3SS function, this fine-tuning mechanism enables P. syringae to minimise effector-mediated elicitation of plant immunity.

  5. Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

    Science.gov (United States)

    Kotagiri, Nalinikanth; Kim, Jin-Woo

    2014-01-01

    Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such “stealth” CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering. PMID:24872705

  6. Evading Quantum Mechanics: Engineering a Classical Subsystem within a Quantum Environment

    Directory of Open Access Journals (Sweden)

    Mankei Tsang

    2012-09-01

    Full Text Available Quantum mechanics is potentially advantageous for certain information-processing tasks, but its probabilistic nature and requirement of measurement backaction often limit the precision of conventional classical information-processing devices, such as sensors and atomic clocks. Here we show that, by engineering the dynamics of coupled quantum systems, it is possible to construct a subsystem that evades the measurement backaction of quantum mechanics, at all times of interest, and obeys any classical dynamics, linear or nonlinear, that we choose. We call such a system a quantum-mechanics-free subsystem (QMFS. All of the observables of a QMFS are quantum-nondemolition (QND observables; moreover, they are dynamical QND observables, thus demolishing the widely held belief that QND observables are constants of motion. QMFSs point to a new strategy for designing classical information-processing devices in regimes where quantum noise is detrimental, unifying previous approaches that employ QND observables, backaction evasion, and quantum noise cancellation. Potential applications include gravitational-wave detection, optomechanical-force sensing, atomic magnetometry, and classical computing. Demonstrations of dynamical QMFSs include the generation of broadband squeezed light for use in interferometric gravitational-wave detection, experiments using entangled atomic-spin ensembles, and implementations of the quantum Toffoli gate.

  7. Influence of WR-2721 on metastatic tumor spread after irradiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.; Jernigan, M.C.; Yuhas, J.M.

    1975-01-01

    The Line 1 alveolar cell carcinoma is a transplantable murine tumor which, unlike most others, kills the host by means of metastatic spread. Attempts to cure this tumor with localized radiation therapy often fail, in spite of local tumor control, because the metastases evade the treatment. These facts suggest that host-tumor interactions may play a particularly important role in determining the ultimate survival of the tumor bearing animal. In order to initially evaluate the possible importance of normal regional tissues in host-tumor interactions the influence of WR-2721, a radioprotective drug, was examined for local tumor control and subsequent survival of the tumor bearing animal after localized radiation. Results indicated that WR-2721 can decrease metastasis. (U.S.)

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  9. Vasculogenic mimicry and tumor metastasis.

    Science.gov (United States)

    Zhang, Jingxin; Qiao, Lili; Liang, Ning; Xie, Jian; Luo, Hui; Deng, Guodong; Zhang, Jiandong

    2016-01-01

    Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion. In addition, hypoxia, cancer stem cells (CSCs) and epithelial-mesenehymal transition (EMT) are regarded as significant factors in VM formation and tumor metastasis. Due to the important effects of VM on tumor progression, a review was carried out in the present study, to synthetically analyze the relationship between VM and tumor metastasis.

  10. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  11. Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?

    Science.gov (United States)

    Connolly, Gregory N; Alpert, Hillel R

    2014-03-01

    Under the Family Smoking Prevention and Tobacco Control Act (FSPTCA), the Food and Drug Administration (FDA) banned the use of "Lights" descriptors or similar terms on tobacco products that convey messages of reduced risk. Manufacturers eliminated terms explicitly stated and substituted colour name descriptors corresponding to the banned terms. This paper examines whether the tobacco industry complied with or circumvented the law and potential FDA regulatory actions. Philip Morris retailer manuals, manufacturers' annual reports filed with the Massachusetts Department of Public Health, a national public opinion survey, and market-wide cigarette sales data were examined. Manufacturers substituted "Gold" for "Light" and "Silver" for "Ultra-light" in the names of Marlboro sub-brands, and "Blue", "Gold", and "Silver" for banned descriptors in sub-brand names. Percent filter ventilation levels, used to generate the smoke yield ranges associated with "Lights" categories, appear to have been reassigned to the new colour brand name descriptors. Following the ban, 92% of smokers reported they could easily identify their usual brands, and 68% correctly named the package colour associated with their usual brand, while sales for "Lights" cigarettes remained unchanged. Tobacco manufacturers appear to have evaded a critical element of the FSPTCA, the ban on misleading descriptors that convey reduced health risk messages. The FPSTCA provides regulatory mechanisms, including banning these products as adulterated (Section 902). Manufacturers could then apply for pre-market approval as new products and produce evidence for FDA evaluation and determination whether or not sales of these products are in the public health interest.

  12. CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma

    NARCIS (Netherlands)

    C. Zhu (Changbin); I. Chrifi (Ihsan); D.A.M. Mustafa (Dana); M.M. van der Weiden (Marcel); P.J. Leenen (Pieter); D.J.G.M. Duncker (Dirk); J.M. Kros (Johan); C. Cheng (Caroline)

    2017-01-01

    textabstractGlioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein

  13. Realizing the Potential of Vascular Targeted Therapy: The Rationale for Combining Vascular Disrupting Agents and Anti-Angiogenic Agents to Treat Cancer

    DEFF Research Database (Denmark)

    Siemann, D W; Chaplin, D J; Horsman, M R

    2017-01-01

    Vascular targeted therapies (VTTs) are agents that target tumor vasculature and can be classified into two categories: those that inhibit angiogenesis and those that directly interfere with established tumor vasculature. Although both the anti-angiogenic agents (AAs) and the vascular disrupting a...

  14. Author's view: radiation and immunotherapy as systemic therapy for solid tumors.

    Science.gov (United States)

    Seyedin, Steven N; Tang, Chad; Welsh, James W

    2015-01-01

    The ability of tumors to evade detection by the immune system via inducing immunosuppression prompted the therapeutic development of immune checkpoint inhibitors. In our recent review, we discussed findings from preclinical and clinical investigations of these agents utilized in combination with radiation inducing abscopal (systemic) antitumor effects.

  15. Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as Angiogenesis

    OpenAIRE

    Nagy, Janice A.; Vasile, Eliza; Feng, Dian; Sundberg, Christian; Brown, Lawrence F.; Detmar, Michael J.; Lawitts, Joel A.; Benjamin, Laura; Tan, Xiaolian; Manseau, Eleanor J.; Dvorak, Ann M.; Dvorak, Harold F.

    2002-01-01

    Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A164, we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A–expressing tumors. We now...

  16. Imaging and therapeutic approach of hemangiomas and vascular malformations in the pediatric age group

    International Nuclear Information System (INIS)

    Dubois, J.; Garel, L.

    1999-01-01

    Terminology regarding the vascular lesions of the soft tissues remains confusing. A single classification is necessary in order to decide on the proper investigation and the best treatment. At the Workshop on Vascular Anomalies in Rome in June 1996, the membership accepted the Mulliken and Glowacki classification, which differentiates vascular lesions into vascular tumors, including hemangiomas and vascular malformations. At Sainte-Justine, we have set up a multidisciplinary clinic for the discussion of problem patients with vascular anomalies, both in terms of diagnosis and treatment. In this review, we present our experience regarding the classification, the imaging modalities and the treatment of vascular anomalies. In our experience, Doppler ultrasound should be the initial imaging modality for recognizing vascular tumors from vascular malformations. CT scan or magnetic resonance imaging is best to evaluate the extent of the lesions prior to treatment. A multidisciplinary approach is essential to establish a correct diagnosis and define accordingly the appropriate treatment and follow-up. (orig.)

  17. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  18. Tumor-Penetrating Peptides

    Science.gov (United States)

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  19. Programmed Death Ligand 1 (PD-L1 Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Gerardo Botti

    2017-02-01

    Full Text Available Triple Negative Breast Cancers (TNBC subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1 is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs, to define its real prognostic value, optimizing immunohistochemistry method with an “approved for diagnostic assay” antibody. PD-L1 expression directly correlated with proliferation index (Ki-67, glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan–Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS but not correlated with overall survival (OS. Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.

  20. Mediastinal tumor

    Science.gov (United States)

    Thymoma - mediastinal; Lymphoma - mediastinal ... mediastinal tumors in adults occur in the anterior mediastinum. They are usually cancerous (malignant) lymphomas, germ cell tumors, or thymomas. These tumors are ...

  1. Collagen vascular disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

  2. Vascular Anomalies in Pediatrics.

    Science.gov (United States)

    Foley, Lisa S; Kulungowski, Ann M

    2015-08-01

    A standardized classification system allows improvements in diagnostic accuracy. Multidisciplinary vascular anomaly centers combine medical, surgical, radiologic, and pathologic expertise. This collaborative approach tailors treatment and management of vascular anomalies for affected individuals.

  3. Peripheral Vascular Disease

    Science.gov (United States)

    ... Topics FAQs Peripheral Vascular Disease Peripheral vascular disease (PVD) involves damage to or blockage in the blood ... the organs in and below your stomach area. PVD may also affect the arteries leading to your ...

  4. Diagnostic dilemma in vascular mal-formation of the upper lip: a ...

    African Journals Online (AJOL)

    Background: Vascular lesions are broad term used for a wide range of conditions that results in abnormal number, structure, or position of blood vessels now widely divided in two groups; vascular tumors and vascular malformations. These lesions could be clinically diagnosed with 90% accuracy, however radiographic ...

  5. A prospective, comparative study on the early effects of local and remote radiation therapy on carotid intima-media thickness and vascular cellular adhesion molecule-1 in patients with head and neck and prostate tumors.

    Science.gov (United States)

    Pereira Lima, Marta N; Biolo, Andréia; Foppa, Murilo; da Rosa, Priscila Raupp; Rohde, Luis Eduardo P; Clausell, Nadine

    2011-12-01

    To investigate early vascular changes related to carotid atherosclerotic injury post-radiation therapy (RT), we studied carotid intima-media thickness (IMT) and vascular cellular adhesion molecule (VCAM)-1 at two time-points after RT and compared local and remote irradiation effects in patients with head and neck (HNC) and prostate cancer (PC), respectively. We prospectively studied patients beginning RT for HNC or PC, performing carotid ultrasound before RT, early after and six months after treatment to measure carotid IMT. Blood samples were simultaneously collected to study VCAM-1 by ELISA. We studied 19 patients with HNC and 24 with PC. Patients with HNC were younger (55 ± 10 years) than PC patients (68 ± 8 years). Early post-RT only HNC patients had an increase in IMT compared to baseline measurements (0.73 ± 0.04 mm vs. 0.80 ± 0.05 mm, p=0.029). On the other hand, VCAM-1 levels decreased in PC patients, remaining unchanged in HNC patients. Late post-RT (six months from previous assessment), neither IMT nor VCAM-1 values changed in both groups. Local and remote RT seem to exert differential early effects regarding vascular-related changes: (1) local RT seems to affect vascular structure and increase IMT and (2) RT for PC is associated with reduction in VCAM levels, suggesting systemic modulation of cancer-related factors. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Two opposing roles of O-glycans in tumor metastasis

    Science.gov (United States)

    Tsuboi, Shigeru; Hatakeyama, Shingo; Ohyama, Chikara; Fukuda, Minoru

    2012-01-01

    Despite the high prevalence and poor outcome of patients with metastatic cancers, the processes of tumor metastasis still remain poorly understood. It has been shown that cell-surface carbohydrates attached to proteins through the amino acids serine or threonine (O-glycans) are involved in tumor metastasis, with the roles of O-glycans varying depending on their structures. Core2 O-glycans allow tumor cells to evade natural killer (NK) cells of the immune system and survive longer in the circulatory system, thereby promoting tumor metastasis. Core3 O-glycans or O-mannosyl glycans suppress tumor formation and metastasis by modulating integrin-mediated signaling. Here, we highlight recent advances in our understanding of the detailed molecular mechanisms by which O-glycans promote or suppress tumor metastasis. PMID:22425488

  7. Tumors of the optic nerve

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Heegaard, Steffen

    2009-01-01

    A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... atrophy, but less than one-tenth of these tumors are confined to the optic nerve or its sheaths. No signs or symptoms are pathognomonic for tumors of the optic nerve. The tumors of the optic nerve may originate from the optic nerve itself (primary tumors) as a proliferation of cells normally present...... in the nerve (e.g., astrocytes and meningothelial cells). The optic nerve may also be invaded from tumors originating elsewhere (secondary tumors), invading the nerve from adjacent structures (e.g., choroidal melanoma and retinoblastoma) or from distant sites (e.g., lymphocytic infiltration and distant...

  8. Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes.

    Science.gov (United States)

    Voyich, Jovanka M; Sturdevant, Daniel E; Braughton, Kevin R; Kobayashi, Scott D; Lei, Benfang; Virtaneva, Kimmo; Dorward, David W; Musser, James M; DeLeo, Frank R

    2003-02-18

    Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis. Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections. We discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Importantly, the irr gene was highly expressed during human GAS pharyngitis. We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease. The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.

  9. The PCa Tumor Microenvironment.

    Science.gov (United States)

    Sottnik, Joseph L; Zhang, Jian; Macoska, Jill A; Keller, Evan T

    2011-12-01

    The tumor microenvironment (TME) is a very complex niche that consists of multiple cell types, supportive matrix and soluble factors. Cells in the TME consist of both host cells that are present at tumor site at the onset of tumor growth and cells that are recruited in either response to tumor- or host-derived factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME. Crosstalk results in an orchestrated evolution of both the tumor and microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble factors as well as direct interaction with PCa cells. In return, the TME produces soluble factors, structural support and direct contact interactions that influence the establishment and progression of PCa. In this review, we focus on the host side of the equation to provide a foundation for understanding how different aspects of the TME contribute to PCa progression. We discuss immune effector cells, specialized niches, such as the vascular and bone marrow, and several key protein factors that mediate host effects on PCa. This discussion highlights the concept that the TME offers a potentially very fertile target for PCa therapy.

  10. Vascular abnormalities associated with acute hypoxia in human melanoma xenografts

    International Nuclear Information System (INIS)

    Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

    2012-01-01

    Background and purpose: The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts. Materials and methods: Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy. Results: R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells. Conclusion: The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.

  11. Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

    Science.gov (United States)

    Ramírez-Toloza, Galia; Ferreira, Arturo

    2017-01-01

    American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote) and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68), T. cruzi complement regulatory protein (TcCRP), trypomastigote decay-accelerating factor (T-DAF), C2 receptor inhibitor trispanning (CRIT) and T. cruzi calreticulin (TcCRT). Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH) and plasma membrane-derived vesicles (PMVs). All these proteins inhibit different steps of the classical (CP), alternative (AP) or lectin pathways (LP). Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host-parasite interplay

  12. Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

    Directory of Open Access Journals (Sweden)

    Galia Ramírez-Toloza

    2017-09-01

    Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host

  13. Vascularity in thyroid neoplasms

    DEFF Research Database (Denmark)

    Larsen, Karen Kjaer; Andersen, Niels Frost; Melsen, Flemming

    2006-01-01

    The aim of the present study was to evaluate the reliability of four different methods (vascular grading, Chalkley count, microvessel density (MVD) and stereological estimation) for quantifying intratumoral microvascularity in thyroid neoplasms, by comparing the variability within and between...... count should be the preferred method for assessing microvascularity in thyroid neoplasms. The diagnostic evaluation revealed a tendency towards higher degree of vascularity in FA compared to both FC and PC for all methods. No statistically significant association was seen between vascular density...

  14. Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Central nervous system (CNS primitive neuroectodermal tumors (PNETs are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall survival. To achieve efficient killing of tumor cells, however, immunotherapy has to overcome cancer-associated strategies to evade the cytotoxic immune response. Whether CNS-PNETs can evade the immune response remains unknown.We examined by immunohistochemistry the immune response and immune evasion strategies in pediatric CNS-PNETs.Here, we show that CD4+, CD8+, γδ-T-cells, and Tregs can infiltrate pediatric CNS-PNETs, although the activation status of cytotoxic cells is variable. Pediatric CNS-PNETs evade immune recognition by downregulating cell surface MHC-I and CD1d expression. Intriguingly, expression of SERPINB9, SERPINB1, and SERPINB4 is acquired during tumorigenesis in 29%, 29%, and 57% of the tumors, respectively.We show for the first time that brain tumors express direct granzyme inhibitors (serpins as a potential mechanism to overcome cellular cytotoxicity, which may have consequences for cellular immunotherapy.

  15. Contributing Factors of Temozolomide Resistance in MCF-7 Tumor Xenograft Models

    OpenAIRE

    Kato, Yoshinori; Okollie, Baasil; Raman, Venu; Vesuna, Farhad; Zhao, Ming; Baker, Sharyn D.; Bhujwalla, Zaver M.; Artemov, Dmitri

    2007-01-01

    Vasculature mediated drug resistance in tumors was studied in female SCID mice bearing wild type MCF-7 and adriamycin resistant MCF-7/ADR xenograft using temozolomide (TMZ). A strong tumor growth inhibitory effect of TMZ treatment was observed in MCF-7 tumors during the initial treatment phase with subsequent relapse, but not in MCF-7/ADR tumors. Non-invasive MRI measurements of tumor vascular volume and vascular permeability-surface area product (PS) demonstrated significant reduction of PS ...

  16. Trapping effect on a small molecular drug with vascular-disrupting agent CA4P in rodent H22 hepatic tumor model: in vivo magnetic resonance imaging and postmortem inductively coupled plasma atomic emission spectroscopy.

    Science.gov (United States)

    Gao, Meng; Yao, Nan; Huang, Dejian; Jiang, Cuihua; Feng, Yuanbo; Li, Yue; Lou, Bin; Peng, Fei; Sun, Ziping; Ni, Yicheng; Zhang, Jian

    2015-06-01

    The aim of the present study is to verify the trapping effect of combretastatin A-4-phosphate (CA4P) on small molecular drugs in rodent tumors. Mice with H22 hepatocarcinoma were randomized into groups A and B. Magnetic resonance imaging (MRI) of T1WI, T2WI, and DWI was performed as baseline. Mice in group A were injected with Gd-DTPA and PBS. Mice in group B were injected with Gd-DTPA and CA4P. All mice undergo CE-T1WI at 0 h, 3 h, 6 h, 12 h, and 24 h. Enhancing efficacy of the two groups on CE-T1WI was compared with the signal-to-noise ratio (SNR) calculated. Concentrations of gadolinium measured by ICP-AES in the tumor were compared between groups. On the early CE-T1WI, tumors were equally enhanced in both groups. On the delayed CE-T1WI, the enhancing effect of group A was weaker than that of group B. The SNR and the concentration of gadolinium within the tumor of group A were lower than that of group B at 6 h, 12 h, and 24 h after administration. This study indicates that CA4P could improve the retention of Gd-DTPA in the tumor and MRI allowed dynamically monitoring trapping effects of CA4P on local retention of Gd-DTPA as a small molecular drug.

  17. NF1 Signal Transduction and Vascular Dysfunction

    Science.gov (United States)

    2014-05-01

    the effects of losing a second allele of NF1 in the vascular endothelium of the adult mouse. This will be the first model of NF1 loss in the... adult endothelium and can serve as a model system for investigation of both cardiovascular effects and the tumor microenvironment. Body: Aim 1...would be to try and determine if there were defects in TGF-b signaling (Smad activation/EndMT) prior to doing a wholesale catalog of all the

  18. Vascular disease: Hemorrhage

    International Nuclear Information System (INIS)

    Norman, D.

    1987-01-01

    An understanding of the role of magnetic resonance (MR) in detection and characterization of vascular lesions is evolving. Improvements in spatial detail suggest great promise in delineation of structural vascular lesions, and insights into the appearance of evolving intraparenchymal hematoma have broadened the applications

  19. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...... impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  20. Function of miR-146a-5p in Tumor Cells As a Regulatory Switch between Cell Death and Angiogenesis: Macrophage Therapy Revisited

    Directory of Open Access Journals (Sweden)

    Elina Simanovich

    2018-01-01

    Full Text Available Tumors survive and progress by evading killing mechanisms of the immune system, and by generating a tumor microenvironment (TME that reprograms macrophages in situ to produce factors that support tumor growth, angiogenesis, and metastasis. We have previously shown that by blocking the translation of the enzyme inducible nitric oxide synthase (iNOS, miR-146a-5p inhibits nitric oxide (NO production in a mouse renal carcinoma cell line (RENCA, thereby endowing RENCA cells with resistance to macrophage-induced cell death. Here, we expand these findings to the mouse colon carcinoma CT26 cell line and demonstrate that neutralizing miR-146a-5p’s activity by transfecting both RENCA and CT26 cells with its antagomir restored iNOS expression and NO production and enhanced susceptibility to macrophage-induced cell death (by 48 and 25%, respectively, p < 0.001. Moreover, miR-146a-5p suppression simultaneously inhibited the expression of the pro-angiogenic protein EMMPRIN (threefolds, p < 0.001, leading to reduced MMP-9 and vascular endothelial growth factor secretion (twofolds and threefolds, respectively, p < 0.05, and reduced angiogenesis, as estimated by in vitro tube formation and scratch assays. When we injected tumors with pro-inflammatory-stimulated RAW 264.7 macrophages together with i.v. injection of the miR-146a-5p antagomir, we found inhibited tumor growth (sixfolds, p < 0.001 and angiogenesis (twofolds, p < 0.01, and increased apoptosis (twofolds, p < 0.01. This combination therapy increased nitrites and reduced TGFβ concentrations in tumor lysates, alleviated immune suppression, and allowed enhanced infiltration of cytotoxic CD8+ T cells. Thus, miR-146a-5p functions as a control switch between angiogenesis and cell death, and its neutralization can manipulate the crosstalk between tumor cells and macrophages and profoundly change the TME. This strategy can be therapeutically utilized in combination with the macrophage

  1. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2017-12-01

    Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

  2. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    Science.gov (United States)

    Zhang, Bo; Hu, Yu; Pang, Zhiqing

    2017-01-01

    Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

  3. Neuroradiological findings in vascular dementia

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali; Miaux, Yves; Suhy, Joyce; Pauls, Jon; Lopez, Ria [Synarc, Inc., Department of Radiology Services, San Francisco, CA (United States); Rovira-Canellas, Alex [Hospital General Universitari Vall d' Hebron, Unita de Resonancia Magnetica, Barcelona (Spain); Posner, Holly [Eisai, Inc., Teaneck, NJ (United States)

    2007-01-15

    There are multiple diagnostic criteria for vascular dementia (VaD) that may define different populations. Utilizing the criteria of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) has provided improved consistency in the diagnosis of VaD. The criteria include a table listing brain imaging lesions associated with VaD. The different neuroradiological aspects of the criteria are reviewed based on the imaging data from an ongoing large-scale clinical trial testing a new treatment for VaD. The NINDS-AIREN criteria were applied by a centralized imaging rater to determine eligibility for enrollment in 1,202 patients using brain CT or MRI. Based on the above data set, the neuroradiological features that are associated with VaD and that can result from cerebral small-vessel disease with extensive leukoencephalopathy or lacunae (basal ganglia or frontal white matter), or may be the consequence of single strategically located infarcts or multiple infarcts in large-vessel territories, are illustrated. These features may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage, or other mechanisms such as genetically determined arteriopathies. Neuroimaging confirmation of cerebrovascular disease in VaD provides information about the topography and severity of vascular lesions. Neuroimaging may also assist with the differential diagnosis of dementia associated with normal pressure hydrocephalus, chronic subdural hematoma, arteriovenous malformation or tumoral diseases. (orig.)

  4. Vascular Growth in Health and Disease

    Directory of Open Access Journals (Sweden)

    Anja eBondke Persson

    2011-08-01

    Full Text Available Vascular growth forms the first functional organ system during development, and continues into adult life, wherein it is often associated with disease states. Genetically determined vasculogenesis produces a primary vascular plexus in ontogenesis. Angiogenesis, occuring e.g. in response to metabolic stress within hypoxic tissues, enhances tissue capillarization. Arteriogenesis denotes the adaptive outgrowth of preexistent collateral arteries to bypass arterial stenoses in response to hemodynamic changes. It has been debated whether vasculogenesis occurs in the adult, and whether or not circulating progenitor cells structurally contribute to vessel regeneration. Secondly, the major determinants of vascular growth - genetic predisposition, metabolic factors (hypoxia and hemodynamics - cannot be assigned in a mutually exclusive fashion to vasculogenesis, angiogenesis and arteriogenesis, respectively; rather, mechanisms overlap. Lastly, all three mechanisms of vessel growth seem to contribute to physiological embryogenesis as well as adult adaptive vascularization as occurs in tumors or to circumvent arterial stenosis. Thus, much conceptual and terminological confusion has been created, while therapies targetting neovascularization have yielded promising results in the lab, but failed randomised studies when taken to the bedside. Therefore, this review article aims at providing an exact definition of the mechanisms of vascular growth and their contribution to embryonic development as well as adult adaptive revascularization. We have been looking for potential reasons for why clinical trials have failed, how vitally the application of appropriate methods of measuring and assessment influences study outcomes, and how relevant e.g. results gained in models of vascular occlusive disease may be for antineoplastic startegies, advocating a reverse bedside-to-bench approach, which may hopefully yield successful approaches to therapeutically targetting

  5. Pediatric vascular access

    International Nuclear Information System (INIS)

    Donaldson, James S.

    2006-01-01

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  6. Vascular Access in Children

    International Nuclear Information System (INIS)

    Krishnamurthy, Ganesh; Keller, Marc S.

    2011-01-01

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the “expert procedural pyramid” is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  7. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  8. Imaging tumors of the patella

    Energy Technology Data Exchange (ETDEWEB)

    Casadei, R., E-mail: roberto.casadei@ior.it [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Kreshak, J., E-mail: j.kreshak@yahoo.com [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Rinaldi, R. [Department of Radiology, Istituto Ortopedico Rizzoli, Bologna (Italy); Rimondi, E., E-mail: eugenio.rimondi@ior.it [Department of Radiology, Istituto Ortopedico Rizzoli, Bologna (Italy); Bianchi, G., E-mail: giuseppe.bianchi@ior.it [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Alberghini, M., E-mail: marco.alberghini@ior.it [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Ruggieri, P. [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Vanel, D., E-mail: daniel.vanel@ior.it [Department of Radiology, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy)

    2013-12-01

    Background: Patellar tumors are rare; only a few series have been described in the literature and radiographic diagnosis can be challenging. We reviewed all patellar tumors at one institution and reviewed the literature. Materials and methods: In an evaluation of the database at one institution from 1916 to 2009, 23,000 bone tumors were found. Of these, 41 involved the patella. All had imaging studies and microscopic diagnostic confirmation. All medical records, imaging studies, and pathology were reviewed. Results: There were 15 females and 26 males, ranging from 8 to 68 years old (average 30). There were 30 benign tumors; eight giant cell tumors, eight chondroblastomas, seven osteoid osteomas, two aneurysmal bone cysts, two ganglions, one each of chondroma, exostosis, and hemangioma. There were 11 malignant tumors: five hemangioendotheliomas, three metastases, one lymphoma, one plasmacytoma, and one angiosarcoma. Conclusion: Patellar tumors are rare and usually benign. As the patella is an apophysis, the most frequent lesions are giant cell tumor in the adult and chondroblastoma in children. Osteoid osteomas were frequent in our series and easily diagnosed. Metastases are the most frequent malignant diagnoses in the literature; in our series malignant vascular tumors were more common. These lesions are often easily analyzed on radiographs. CT and MR define better the cortex, soft tissue extension, and fluid levels. This study presents the imaging patterns of the more common patellar tumors in order to help the radiologist when confronted with a lesion in this location.

  9. Vascular malformations in pediatrics

    International Nuclear Information System (INIS)

    Reith, W.; Shamdeen, M.G.

    2003-01-01

    Vascular malformations are the cause of nearly all non-traumatic intracranial hemorrhage in children beyond the neonatal stage. Therefore, any child presenting with spontaneous intracranial hemorrhage should be evaluated for child abuse and for vascular malformations. Intracerebral malformations of the cerebral vasculature include vein of Galen malformations, arteriovenous malformation (AVM), cavernomas, dural arteriovenous fistulas, venous anomalies (DVA), and capillary teleangiectasies. Although a few familial vascular malformation have been reported, the majority are sporadic. Clinical symptoms, diagnostic and therapeutic options are discussed. (orig.) [de

  10. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  11. Muusikamaailm : Festivalil Schwetzingenis. Ellingtoni sajandi tähistamine. Linz saab uue ooperimaja. Isaac Stern viiulita Saksamaal. Muusikapäevad Luksemburgis / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    30. apr.-7. juunini toimuvast muusikafestivalist Schwetzingenis. D. Ellingtoni 100. sünniaastapäeva tähistamisest maailmas. Valmis Linzi uue ooperimaja planeering. I. Stern juhatas kümnepäevast seminari Kölni Kõrgema Muusikakooli juures. Rahvusvahelise Nüüdismuusika Ühingu (ISCM) iga-aastased maailma muusikapäevad toimuvad 2000. aastal Luksemburgis

  12. Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

    Science.gov (United States)

    Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

    2017-06-01

    Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Congenital Vascular Malformation

    Science.gov (United States)

    ... surgery or less invasive therapy of the enlarged superficial veins can also be helpful. T he V ascular D isease F oundation Established in 1998, t he Vascular Disease Foundation (VDF) develops educational information and initiatives for patients, ...

  14. Uterine Vascular Lesions

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  15. Heart and vascular services

    Science.gov (United States)

    ... maintain body temperature, among other things. CARDIOVASCULAR MEDICINE Cardiovascular medicine refers to the branch of health care that specializes in the treatment of diseases or conditions dealing with the heart and vascular systems. Common ...

  16. Vascular Access Procedures

    Science.gov (United States)

    ... vascular access catheters: A peripherally inserted central catheter (PICC) is a long catheter that extends from an ... central catheter may be larger caliber than a PICC, and is designed to be placed via a ...

  17. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.

    Science.gov (United States)

    Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun

    2018-02-13

    Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  18. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Sharon K. Kuss-Duerkop

    2018-02-01

    Full Text Available Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  19. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  20. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  1. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  2. Application Study on Isotope Tracing RRL Tumor Angiogenesis Imaging

    Directory of Open Access Journals (Sweden)

    WANG Rong-fu

    2015-11-01

    Full Text Available Angiogenesis plays crucial roles in the progress of tumor growth, progression and metastases. The new tumor blood vessel tracer RRL can be targeted to the VEGFR-2 receptor on tumor vascular endothelial cells, Tracing with radioisotopes different types of tumor and angiogenesis in malignant tumor tissues with different invasive ability will provide the important information on the diagnosis, treatment and evaluated prognosis of malignant tumor. In this review, the recent study and progresses on molecular imaging with the peptide RRL in tumor angiogenesis will be summarized.

  3. Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade Caenorhabditis elegans avoidance behavioral defenses

    Science.gov (United States)

    Peng, Donghai; Luo, Xiaoxia; Zhang, Ni; Guo, Suxia; Zheng, Jinshui; Chen, Ling

    2018-01-01

    Abstract Pathogen avoidance behavior protects animal hosts against microbial pathogens. Pathogens have evolved specific strategies during coevolution in response to such host defenses. However, these strategies for combatting host avoidance behavioral defenses remain poorly understood. Here, we used Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis as a model and determined that small RNA (sRNA)-mediated Cry toxin silencing allowed pathogens to evade host avoidance behavioral defenses. The B. thuringiensis strain YBT-1518, which encodes three nematicidal cry genes, is highly toxic to C. elegans. However, the expression of the most potent toxin, Cry5Ba, was silenced in this strain when YBT-1518 was outside the host. Cry5Ba silencing was due to the sRNA BtsR1, which bound to the RBS site of the cry5Ba transcript via direct base pairing and inhibited Cry5Ba expression. Upon ingestion by C. elegans, Cry5Ba was expressed in vivo by strain YBT-1518. Cry5Ba silencing may allow B. thuringiensis to avoid nematode behavioral defenses and then express toxins once ingested to kill the host and gain a survival advantage. Our work describes a novel model of sRNA-mediated regulation to aid pathogens in combating host avoidance behavioral defenses. PMID:29069426

  4. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    Energy Technology Data Exchange (ETDEWEB)

    Hoenen, Antje [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Gillespie, Leah [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia); Morgan, Garry; Heide, Peter van der [Institute for Molecular Bioscience, University of Queensland, Brisbane (Australia); Khromykh, Alexander [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Australian Infectious Diseases Research Centre, University of Queensland, Brisbane (Australia); Mackenzie, Jason, E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia)

    2014-01-05

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.

  5. Escape and evade control policies for ensuring the physical security of nonholonomic, ground-based, unattended mobile sensor nodes

    Science.gov (United States)

    Mascarenas, David; Stull, Christopher; Farrar, Charles

    2011-06-01

    In order to realize the wide-scale deployment of high-endurance, unattended mobile sensing technologies, it is vital to ensure the self-preservation of the sensing assets. Deployed mobile sensor nodes face a variety of physical security threats including theft, vandalism and physical damage. Unattended mobile sensor nodes must be able to respond to these threats with control policies that facilitate escape and evasion to a low-risk state. In this work the Precision Immobilization Technique (PIT) problem has been considered. The PIT maneuver is a technique that a pursuing, car-like vehicle can use to force a fleeing vehicle to abruptly turn ninety degrees to the direction of travel. The abrupt change in direction generally causes the fleeing driver to lose control and stop. The PIT maneuver was originally developed by law enforcement to end vehicular pursuits in a manner that minimizes damage to the persons and property involved. It is easy to imagine that unattended autonomous convoys could be targets of this type of action by adversarial agents. This effort focused on developing control policies unattended mobile sensor nodes could employ to escape, evade and recover from PIT-maneuver-like attacks. The development of these control policies involved both simulation as well as small-scale experimental testing. The goal of this work is to be a step toward ensuring the physical security of unattended sensor node assets.

  6. Cooperative option of pursuit game with two pursuers and one evader. A strong stability of division variety

    Directory of Open Access Journals (Sweden)

    Viktor D. Shiryayev

    2017-06-01

    Full Text Available Introduction: The article deals with a simple differential game on the plane of pursuit with two consistently active players and one evader E; the game is considered in the form of the characteristic function. Materials and Methods: The geometric constructions and methods are used for solving the problem. The security zone of the escapee is bounded by the Apollonius circle, the pursuit team uses a strategy of parallel approach. Results: A method of finding the optimal players strategies and the optimal players’ trajectory is proposed. The way of forming the characteristic function is provided. All the variety of division is considered as a solution. However, the use of the results of cooperative theory of differential games is impossible without solving the problems associated with the specifics of differential equations of motion. Foremost, it is the problem of dynamic stability of optimality principles. The article introduces an auxiliary function of making the redistribution of winnings in time, keeping his total winnings throughout the game. The dynamic stability of the cooperative solution is determined with the help of this function. Strong dynamic stability of the entire set of solutions is shown. Discussion and Conclusions: The obtained results are consistent with similar research of other authors. Further research in this field can be used in the development of methods for “regularization” of optimality principles, for which the condition of dynamic stability is always fulfilled.

  7. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release

    Science.gov (United States)

    Escudero, Claudia A.; Lazo, Oscal M.; Galleguillos, Carolina; Parraguez, Jose I.; Lopez-Verrilli, Maria A.; Cabeza, Carolina; Leon, Luisa; Saeed, Uzma; Retamal, Claudio; Gonzalez, Alfonso; Marzolo, Maria-Paz; Carter, Bruce D.; Court, Felipe A.; Bronfman, Francisca C.

    2014-01-01

    ABSTRACT The p75 neurotrophin receptor (p75, also known as NGFR) is a multifaceted signalling receptor that regulates neuronal physiology, including neurite outgrowth, and survival and death decisions. A key cellular aspect regulating neurotrophin signalling is the intracellular trafficking of their receptors; however, the post-endocytic trafficking of p75 is poorly defined. We used sympathetic neurons and rat PC12 cells to study the mechanism of internalisation and post-endocytic trafficking of p75. We found that p75 internalisation depended on the clathrin adaptor protein AP2 and on dynamin. More surprisingly, p75 evaded the lysosomal route at the level of the early endosome, instead accumulating in two different types of endosomes, Rab11-positive endosomes and multivesicular bodies (MVBs) positive for CD63, a marker of the exosomal pathway. Consistently, depolarisation by KCl induced the liberation of previously endocytosed full-length p75 into the extracellular medium in exosomes. Thus, p75 defines a subpopulation of MVBs that does not mature to lysosomes and is available for exosomal release by neuronal cells. PMID:24569882

  8. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    International Nuclear Information System (INIS)

    Hoenen, Antje; Gillespie, Leah; Morgan, Garry; Heide, Peter van der; Khromykh, Alexander; Mackenzie, Jason

    2014-01-01

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV KUN ) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV KUN particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV KUN under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV KUN assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV KUN assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition

  9. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  10. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  11. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  12. Venous Thromboembolism in Pediatric Vascular Anomalies

    Directory of Open Access Journals (Sweden)

    Taizo A. Nakano

    2017-07-01

    Full Text Available The presence of a vascular anomaly suggests that capillaries, veins, arteries, and/or lymphatic vessels have demonstrated abnormal development and growth. Often dilated and misshaped, these vessels augment normal flow of blood and lymphatic fluids that increases the overall risk to develop intralesional thrombosis. Abnormal endothelial and lymphoendothelial cells activate hemostasis and hyperfibrinolytic pathways through poorly understood mechanisms, which contribute to the development of localized intravascular coagulopathy. Vascular malformations, tumors, and complex combined syndromes demonstrate varying degrees of prothrombotic activity and consumptive coagulopathy depending on the vessels involved and the pattern and extent of abnormal growth. The clinical impact of venous thromboembolism in pediatric vascular anomalies varies from painful syndromes that disrupt quality of life to life-threatening embolic disease. There remains little literature on the study, evaluation, and treatment of thrombosis in pediatric vascular anomalies. However, there have been great advances in our ability to image complex lesions, to surgically and interventionally augment disease, and to provide enhanced supportive care including patient education, compression therapy, and strategic use of anticoagulation.

  13. Vascular anomalies of the cerebellopontine angle

    International Nuclear Information System (INIS)

    Papanagiotou, P.; Grunwald, I.Q.; Politi, M.; Struffert, T.; Ahlhelm, F.; Reith, W.

    2006-01-01

    Vascular anomalies of the cerebellopontine angle are rare compared to tumors in this area. Irritation of the trigeminal, facial, or vestibulocochlear nerve may cause trigeminal neuralgia, hemifacial spasm and vertigo, or tinnitus accordingly. Vessel loops in the cerebellopontine cisterns may cause compression at the root entry or exit zone of the cranial nerves V, VII, and VIII, a phenomenon which is called ''vascular loop syndrome.'' Megadolichobasilar artery and aneurysms of the vertebrobasilar system can also lead to dislocation and compression of the cranial nerves and brain stem. Three-dimensional CISS MR imaging and MR angiography are useful in the detection of neurovascular compression. Microvascular decompression is an effective surgical procedure in the management of compression syndromes of the cranial nerves V, VII, and VIII. (orig.) [de

  14. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  15. Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    International Nuclear Information System (INIS)

    Okamoto, Yuko; Kawamoto, Hirofumi; Takaki, Akinobu; Ishida, Etsuji; Ogawa, Tsuneyoshi; Kuwaki, Kenji; Kobayashi, Yoshiyuki; Sakaguchi, Kohsaku; Shiratori, Yasushi

    2007-01-01

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (κ coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063). Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors

  16. Inferior vena cava leiomyosarcoma: vascular reconstruction is not ...

    African Journals Online (AJOL)

    Leiomyosarcoma (LMS) of inferior vena cava is a rare and aggressive tumor, arising from the smooth muscle cells in the vessel wall. A large complete surgical resection is the essential treatment. The need of vascular reconstruction is not always mandatory. It's above all to understand the place of the reconstruction with ...

  17. Tumores neonatales bucomaxilofaciales Neonatal buccomaxillofacial tumors

    Directory of Open Access Journals (Sweden)

    Zoila del S. López Díaz

    2007-12-01

    Full Text Available Se realiza un estudio descriptivo, lineal y retrospectivo por un período de 10 años, de 11 recién nacidos (edad 0-30 días, quienes al nacer presentan en la región bucomaxilofacial un tumor que les ocasiona de manera determinante compromiso para la ventilación y/o alimentación, por lo que se hace necesario realizarles a todos de manera inmediata, tratamiento quirúrgico para preservarles la vida. Se analizaron las variables edad, sexo, color de la piel, diagnóstico, tumoraciones que se presentaron con mayor frecuencia, compromiso para la ventilación y/o alimentación, procederes y mortalidad. Los datos se recogieron en una planilla confeccionada al efecto, lo que permitió establecer resultados y confeccionar tablas. Se concluye que en nuestro estudio este tipo de tumoración afectó con mayor frecuencia al sexo femenino y a niños de piel blanca; y el tipo de tumoración observada con mayor frecuencia fueron las malformaciones vasculares de tipo linfático (linfangiomas gigantes o higromas quísticos, así como y los teratomas bucofaríngeos, con una mortalidad de alrededor del 27,3 % en estas edades neonatales.A descriptive, lineal and retrospective study of 11 newborn infants aged 0-30 days was conducted. They presented a tumor in the buccomaxillofacial region that compromised their ventilation and/or nutrition, which made necessary to immediately perform surgery to preserve their lives. The following variables were analyzed: age, sex, colour of the skin, diagnosis, the most common tumours, compromise for ventilation and/or nutrition, procedures and mortality. Data were collected in a form that allowed to establish results and to make tables. It was concluded that this type of tumor affected mostly females and white children. The most commonly observed tumors were vascular lymphatic malformations (giant lymphangiomas or cystic hygromas, as well as buccopharyngeal teratomas, with a mortality around 27.3 % at these neonatal ages.

  18. Chemokines in tumor proximal fluids.

    Science.gov (United States)

    Kotyza, Jaromir

    2017-03-01

    Chemokines are chemotactic cytokines produced by leukocytes and other types of cells including tumor cells. Their action is determined by the expression of cognate receptors and subsequent signaling in target cells, followed by the modulation of cytoskeletal proteins and the induction of other responses. In tumors, chemokines produced by neoplastic/stroma cells control the leukocyte infiltrate influencing tumor growth and progression. Tumor cells also express functional chemokine receptors responding to chemokine signals, promoting cell survival, proliferation and metastasis formation. Chemokines may be detected in serum of cancer patients, but due to the paracrine nature of these molecules, more significant concentrations are found in the tumor adjacent, non-vascular fluids, collectively called tumor proximal fluids. This review summarizes the expression of CC and CXC chemokines in these fluids, namely in interstitial fluid, pleural, ascitic, and cyst fluids, but also in urine, saliva, cerebrospinal fluid, cervical secretions and bronchoalveolar lavage fluid. Most comparative clinical studies reveal increased chemokine levels in high-grade tumor proximal fluids rather than in low-grade tumors and benign conditions, indicating shorter survival periods. The data confirm peritumoral fluid chemokines as sensitive diagnostic and prognostic markers, as well as offer support for chemokines and their receptors as potential targets for antitumor therapy.

  19. Knee glomangioma: a rare location for a glomus tumor

    Directory of Open Access Journals (Sweden)

    Ricardo Gonçalves

    2014-12-01

    Full Text Available Glomus tumor is a rare, benign neoplasm rising from the glomus apparatus of the skin. It occurs most frequently on fingers and toes and accounts for 1.6% of all soft tissue tumors. Clinical diagnosis may prove difficult if the tumor occurs on an extra digital location. We report a case of a vascular-type glomus tumor (glomangioma found in an atypical location, namely the lateral aspect of the knee joint.

  20. Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.

    Science.gov (United States)

    Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

    2013-10-01

    The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

  1. Testing the ability of viral haemorrhagic septicaemia virus to evade the protective immune response induced in rainbow trout by DNA vaccination

    DEFF Research Database (Denmark)

    Sepulveda, Dagoberto; Lorenzen, Niels

    2013-01-01

    Viral haemorrhagic septicaemia virus, a negative strand RNA virus belonging to the genus Novirhabdovirus within the family Rhabdoviridae, is the causative agent of VHS, which is a serious disease in rainbow trout and other economically important fish species. The DNA vaccine encoding the viral......, this work aims to evaluate whether VHSV is able to evade the protective immune response induced by the DNA vaccination. Earlier studies have demonstrated that VHSV can evade the neutralizing effect of monoclonal antibodies by mutations in the glycoprotein gene. One approach of the present study is therefore...... to try to isolate VHSV variants which can escape the neutralizing activity of serum from fish immunized with the DNA vaccine. To do so, a highly pathogenic VHSV isolate (DK3592B) will be repeatedly passaged in fish cell cultures in the presence of neutralizing fish serum. Another approach comprises...

  2. Nonenhancing spinal subdural metastatic tumor

    International Nuclear Information System (INIS)

    Sirakov, S.; Penev, L.; Georgieva-Kozarova, G.

    2012-01-01

    Full text: We describe a case of a spinal subdural metastatic tumor that became rapidly symptomatic after a minor trauma, as a result of severe cord compression and cord haemorrhage. Spinal subdural hematomas are most commonly caused by anticoagulant therapy, lumbar puncture, blood dyscrasias, spinal trauma, or spinal vascular malformations. Subdural metastatic tumors are very uncommon, and their presentation as spinal subdural hematomas is exceedingly rare. We describe a case of 59 years old woman with quadriparesis and her preoperative findings on MRI and the follow up

  3. Differentiation and definition of vascular-targeted therapies.

    Science.gov (United States)

    Siemann, Dietmar W; Bibby, Michael C; Dark, Graham G; Dicker, Adam P; Eskens, Ferry A L M; Horsman, Michael R; Marmé, Dieter; Lorusso, Patricia M

    2005-01-15

    The therapeutic potential of targeting the tumor vascular supply is now widely recognized. Intense research and development activity has resulted in a variety of investigational agents, a number of which are currently in clinical development. As these novel agents are quite distinct from the cytotoxic drugs conventionally used in the treatment of solid tumors, it will be particularly important to ensure early differentiation of these vascular-targeted therapies in order to encourage widespread understanding of their potential benefits and application in the clinic. Two distinct groups of vascular-targeted therapies have evolved: antiangiogenic agents and vascular-disrupting approaches. These differ in three key respects: their physiologic target, the type or extent of disease that is likely to be susceptible, and the treatment scheduling. Inhibitors of angiogenesis interfere with new vessel formation and therefore have a preventative action, require chronic administration, and are likely to be of particular benefit in early-stage or asymptomatic metastatic disease. Vascular-disrupting agents target the established tumor blood vessels, resulting in tumor ischemia and necrosis. These agents are therefore given acutely, show more immediate effects, and may have particular efficacy against advanced disease. It is essential that these agents can be readily distinguished from conventional therapies and that an understanding of key differences between the two types of vascular-targeted therapies is fostered. Here, a simple taxonomy and nomenclature is proposed in anticipation that the therapeutic potential of this novel class can be realized as these approaches advance in clinical settings and a new anticancer strategy becomes available in the clinic.

  4. Uudised : Üheteistkümnendad trompetipäevad. Eesti Muusikanõukogus. Tüüri "Motus I" Londonis / Kadri Ruudi

    Index Scriptorium Estoniae

    Ruudi, Kadri

    2000-01-01

    4.-15. apr. toimuvad EMA XI trompetipäevad. 14.-19. märtsil viibis Eestis IMC asepresident F. Müller-Heuser, 22. märtsil toimus EMN juhatuse koosolek. 19. märtsil andis Londoni South Bank Centre'is kontserdi P. Carneiro, kes tõi Inglismaal esiettekandele ka E.-S. Tüüri teose "Motus I"

  5. Overexpression of thrombospondin-1 reduces growth and vascular index but not perfusion in glioblastoma

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Tenan, Mirna

    2002-01-01

    growth, vascularity, and perfusion. Persistence of TSP-1 overexpression was confirmed after three serial s.c. passages of small xenografted tumor blocks of cells stably transfected with TSP-1 cDNA (clones C9 and E7) or vector controls (pooled clones A7-A9) in immunodeficient nu/nu mice. The tumor...... growth. In size-matched tumors (approximately 300 mm(3)), the blood volume and the histological vessel scores were lower in the TSP-1-transfected tumors than in controls, and this effect was more pronounced in tumors derived from the clone with the highest TSP-1 expression (clone E9). Despite this clear...... and a reduced vascular index at sacrifice are observed in TSP-1-transfected tumors, this did not affect perfusion when size-matched comparisons were performed. Given the increased time needed to reach equal size, it indicates that a fixed rate of perfusion must be maintained in the tumor to allow for growth...

  6. Overexpression of thrombospondin-1 reduces growth and vascular index but not perfusion in glioblastoma

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Tenan, Mirna

    2002-01-01

    Little is known about the effects of antiangiogenic therapy on perfusion of human tumors and the mechanisms by which tumors can adapt to these treatments and recur. Here, we examined the effects of serial passaging of LN-229 human glioma xenografts overexpressing thrombospondin (TSP)-1 on tumor...... growth, vascularity, and perfusion. Persistence of TSP-1 overexpression was confirmed after three serial s.c. passages of small xenografted tumor blocks of cells stably transfected with TSP-1 cDNA (clones C9 and E7) or vector controls (pooled clones A7-A9) in immunodeficient nu/nu mice. The tumor...... vascularity was estimated by noninvasive near infrared spectroscopy measuring blood volume at 800 +/- 10 nm and by histological vessel scores in CD31-immunostained cryosections. The tumor perfusion was assessed by noninvasive laser Doppler flowmetry. Overexpression of TSP-1 significantly inhibited tumor...

  7. Color coded duplex sonography. Interdisciplinary vascular ultrasonography

    International Nuclear Information System (INIS)

    Kubale, R.; Stiegler, H.

    2002-01-01

    An interdisciplinary team of experts impart the state of the art in color coded duplex sonography applied for examination of all anatomic areas. Detailed information is given for every vascular area, describing the examination procedure, possible origins of mistakes or faults, and means to avoid them. In addition to the classical applications, eg. for examination of the extra- and intracranial vessels, vessels of the limbs, visceral vessels and the vessels of liver and kidney, there are chapters devoted to: haemodialysis shunts, arteriovenous malformations, duplex sonography of the penis, tumor vascularisation. (orig./CB) [de

  8. Vascular responses to radiotherapy and androgendeprivation therapy in experimental prostate cancer

    LENUS (Irish Health Repository)

    2012-05-23

    AbstractBackgroundRadiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC.MethodsUsing mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI.ResultsCompared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after

  9. tion of vascular malformations

    African Journals Online (AJOL)

    Imaging is only required in cases where there is diag- nostic uncertainty or where interven- tion is required. Ultrasound (with doppler) will rapidly distinguish solid haemangiomas from vascular malfor- mations. Computed tomography. (CT) and magnetic resonance imag- ing (MRI) will help to assess the depth and extent of ...

  10. Acupuncture for vascular dementia.

    Science.gov (United States)

    Peng, W N; Zhao, H; Liu, Z S; Wang, S

    2007-04-18

    Dementia is a widespread condition characterized by acquired global impairment of intellect, memory and personality, but with no impairment of consciousness. There is no definitive medical or surgical treatment for vascular dementia. Acupuncture is an ancient Chinese method which has been used for both the prevention and treatment of diseases for over three thousand years. Preliminary searches revealed more than 105 studies of acupuncture for treating vascular dementia. Benefit was reported in up to 70-91% of the treatment group. Body acupuncture and electroacupuncture were the most commonly used techniques. A comparison of electroacupuncture and acupuncture therapy alone suggested that the former was more effective in promoting the recovery of cognitive function. The objective is to assess the efficacy and possible adverse effects of acupuncture therapy for treating vascular dementia. The trials were identified from a search of the Cochrane Dementia and Cognitive Improvement group's Specialized Register on 2 February 2007 which contains records from all major health care databases and many ongoing trials databases. In addition the Allied and Complementary Medicine Database was searched and the web was searched using the search engine Copernic. Randomized controlled trials testing acupuncture therapy in the treatment of vascular dementia were included regardless of language and publication types. The intervention and control group had to receive identical treatment apart from the acupuncture intervention. In view of possible confounding, studies in which acupuncture was combined with other treatments were subjected to subgroup analyses. Titles and abstracts identified from the searches were checked by two reviewers. If it was clear that the study did not refer to a randomized controlled trial in vascular dementia, it was excluded. If it was not clear from the abstract and title, then the full text of study was obtained for an independent assessment by two reviewers

  11. Mesohepatectomy for Centrally Located Tumors in Children.

    Science.gov (United States)

    Amesty, Maria Virginia; Chocarro, Gloria; Vilanova Sánchez, Alejandra; Nuñez Cerezo, Vanesa; de la Torre, C A; Encinas, Jose Luis; Gamez Arance, Manuel; Hernández, Francisco; Lopez Santamaria, Manuel

    2016-02-01

    Central hepatectomy or mesohepatectomy (MH) is a complex surgical technique rarely used in children. It is indicated in central tumors to preserve functioning liver mass avoiding an extended right hepatectomy. The purpose of this article is to analyze our experience with this technique. We reviewed five patients who underwent MH in the period from 2008 to 2014. Diagnoses were hepatoblastoma PRETEXT III (two cases), hepatic embryonal sarcoma (one case), focal nodular hyperplasia (one case), and vascular tumor with rapid growth in a newborn causing an acute liver failure, compartment syndrome, and multiple organ failure (one case). In all cases, the tumor was centrally located, including the segment IVb, with large displacement of the hepatic pedicle in two cases. MH was standard in three cases and under total vascular exclusion in two cases. All children are alive with a mean follow-up of 38 (6-70) months. None of the children required reoperation because of bleeding. One child developed a biliary fistula in the cutting area that closed spontaneously. The newborn with the vascular tumor required the placement of a Gore-Tex patch (W. L. Gore & Associates, Inc, Flagstaff, Arizona, United States) to relieve the compartment syndrome. He subsequently underwent partial embolization of the tumor and MH under vascular exclusion. In selected patients, MH is an alternative to trisegmentectomy and should be available in advanced pediatric hepatobiliary units. Georg Thieme Verlag KG Stuttgart · New York.

  12. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  13. Evading the Boomerang Effect

    DEFF Research Database (Denmark)

    Laursen, Keld; Moreira, Solon; Reichstein, Toke

    2017-01-01

    Technology licensing agreements potentially can create future appropriability problems. Drawing on the appropriability literature, we argue that the inclusion of a grant-back clause in technology licensing agreements is an attempt to balance the gains from and protection of the focal firms’ techn...... the hypotheses on a sample of 397 licensed technologies. This method allows us to model the choice to include a grant-back clause as nested in the decision about which technologies to license out. We find broad support for our theoretical arguments....

  14. Evading death by vacuum

    OpenAIRE

    Barroso, A.; Ferreira, P. M.; Ivanov, I. P.; Santos, Rui; Silva, João P.

    2012-01-01

    In the Standard Model, the Higgs potential allows only one minimum at tree-level. But the open possibility that there might be two scalar doublets enriches the vacuum structure, allowing for the risk that we might now be in a metastable state, which we dub the panic vacuum. Current experiments at the LHC are probing the Higgs particle predicted as a result of the spontaneous symmetry breaking. Remarkably, in the two Higgs model with a softly broken U(1) symmetry, the LHC experiments already p...

  15. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  16. Benign vascular lesions of bone: radiologic and pathologic features

    International Nuclear Information System (INIS)

    Wenger, D.E.; Wold, L.E.

    2000-01-01

    The benign vascular tumors of bone represent a diverse group of tumors that can present with a broad spectrum of clinical signs and symptoms. They can also present a significant diagnostic challenge due to their widely variable radiographic imaging and histologic features. Some of the tumors manifest as clearly benign lesions with tissue-specific diagnostic imaging features, while others have non-specific imaging features that may simulate malignant neoplasm. This article will provide a review of the nomenclature and the characteristic radiographic and pathologic features of the benign vascular lesions of bone. The information will aid in improving our diagnostic accuracy and enhance our understanding of the biologic potential of this diverse group of osseous lesions. (orig.)

  17. Real time laser speckle imaging monitoring vascular targeted photodynamic therapy

    Science.gov (United States)

    Goldschmidt, Ruth; Vyacheslav, Kalchenko; Scherz, Avigdor

    2017-02-01

    Laser speckle imaging is a technique that has been developed to non-invasively monitor in vivo blood flow dynamics and vascular structure, at high spatial and temporal resolution. It can record the full-field spatio-temporal characteristics of microcirculation and has therefore, often been used to study the blood flow in tumors after photodynamic therapy (PDT). Yet, there is a paucity of reports on real-time laser speckle imaging (RTLSI) during PDT. Vascular-targeted photodynamic therapy (VTP) with WST11, a water-soluble bacteriochlorophyll derivative, achieves tumor ablation through rapid occlusion of the tumor vasculature followed by a cascade of events that actively kill the tumor cells. WST11-VTP has been already approved for treatment of early/intermediate prostate cancer at a certain drug dose, time and intensity of illumination. Application to other cancers may require different light dosage. However, incomplete vascular occlusion at lower light dose may result in cancer cell survival and tumor relapse while excessive light dose may lead to toxicity of nearby healthy tissues. Here we provide evidence for the feasibility of concomitant RTLSI of the blood flow dynamics in the tumor and surrounding normal tissues during and after WST11-VTP. Fast decrease in the blood flow is followed by partial mild reperfusion and a complete flow arrest within the tumor by the end of illumination. While the primary occlusion of the tumor feeding arteries and draining veins agrees with previous data published by our group, the late effects underscore the significance of light dose control to minimize normal tissue impairment. In conclusion- RTSLI application should allow to optimize VTP efficacy vs toxicity in both the preclinical and clinical arenas.

  18. Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models

    Science.gov (United States)

    Poleszczuk, Jan; Hahnfeldt, Philip; Enderling, Heiko

    2015-01-01

    Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target. PMID:25785600

  19. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

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

  20. Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Emre Kumral

    2017-03-01

    Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

  1. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  2. Carcinoid Tumors

    Science.gov (United States)

    ... spread to other parts of the body. Doctors don't know what causes the mutations that can lead to carcinoid tumors. But they know that carcinoid tumors develop in neuroendocrine cells. Neuroendocrine cells are found in various organs throughout the body. They perform some nerve cell ...

  3. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  4. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  5. Vascular Thoracic Outlet Syndrome.

    Science.gov (United States)

    Hussain, Mohamad Anas; Aljabri, Badr; Al-Omran, Mohammed

    2016-01-01

    Two distinct terms are used to describe vascular thoracic outlet syndrome (TOS) depending on which structure is predominantly affected: venous TOS (due to subclavian vein compression) and arterial TOS (due to subclavian artery compression). Although the venous and arterial subtypes of TOS affect only 3% and <1% of all TOS patients respectively, the diagnostic and management approaches to venous and arterial TOS have undergone considerable evolution due to the recent emergence of minimally invasive endovascular techniques such as catheter-directed arterial and venous thrombolysis, and balloon angioplasty. In this review, we discuss the anatomical factors, etiology, pathogenesis and clinical presentation of vascular TOS patients. In addition, we use the most up to date observational evidence available to provide a contemporary approach to the diagnosis and management of venous TOS and arterial TOS patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  7. Engineered vascularized bone grafts

    OpenAIRE

    Tsigkou, Olga; Pomerantseva, Irina; Spencer, Joel A.; Redondo, Patricia A.; Hart, Alison R.; O’Doherty, Elisabeth; Lin, Yunfeng; Friedrich, Claudia C.; Daheron, Laurence; Lin, Charles P.; Sundback, Cathryn A.; Vacanti, Joseph P.; Neville, Craig

    2010-01-01

    Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. W...

  8. Imatinib disrupts lymphoma angiogenesis by targeting vascular pericytes.

    Science.gov (United States)

    Ruan, Jia; Luo, Min; Wang, Chunjie; Fan, Lei; Yang, Shao Ning; Cardenas, Mariano; Geng, Huimin; Leonard, John P; Melnick, Ari; Cerchietti, Leandro; Hajjar, Katherine A

    2013-06-27

    Pericytes and vascular smooth muscle cells (VSMCs), which are recruited to developing blood vessels by platelet-derived growth factor BB, support endothelial cell survival and vascular stability. Here, we report that imatinib, a tyrosine kinase inhibitor of platelet-derived growth factor receptor β (PDGFRβ), impaired growth of lymphoma in both human xenograft and murine allograft models. Lymphoma cells themselves neither expressed PDGFRβ nor were growth inhibited by imatinib. Tumor growth inhibition was associated with decreased microvascular density and increased vascular leakage. In vivo, imatinib induced apoptosis of tumor-associated PDGFRβ(+) pericytes and loss of perivascular integrity. In vitro, imatinib inhibited PDGFRβ(+) VSMC proliferation and PDGF-BB signaling, whereas small interfering RNA knockdown of PDGFRβ in pericytes protected them against imatinib-mediated growth inhibition. Fluorescence-activated cell sorter analysis of tumor tissue revealed depletion of pericytes, endothelial cells, and their progenitors following imatinib treatment. Compared with imatinib, treatment with an anti-PDGFRβ monoclonal antibody partially inhibited lymphoma growth. Last, microarray analysis (Gene Expression Omnibus database accession number GSE30752) of PDGFRβ(+) VSMCs following imatinib treatment showed down-regulation of genes implicated in vascular cell proliferation, survival, and assembly, including those representing multiple pathways downstream of PDGFRβ. Taken together, these data indicate that PDGFRβ(+) pericytes may represent a novel, nonendothelial, antiangiogenic target for lymphoma therapy.

  9. Pulmonary vascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fedullo, P.F.; Shure, D.

    1987-03-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

  10. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  11. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

  12. Podocalyxin expression in malignant astrocytic tumors

    International Nuclear Information System (INIS)

    Hayatsu, Norihito; Kaneko, Mika Kato; Mishima, Kazuhiko; Nishikawa, Ryo; Matsutani, Masao; Price, Janet E.; Kato, Yukinari

    2008-01-01

    Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that has been implicated in the development of aggressive forms of cancer. Podocalyxin is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that highly sulfated KS or another mucin-like transmembrane sialoglycoprotein podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this study is to examine the relationship between podocalyxin expression and malignant progression of astrocytic tumors. In this study, 51 astrocytic tumors were investigated for podocalyxin expression using immunohistochemistry, Western blot analysis, and quantitative real-time PCR. Immunohistochemistry detected podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed only in vascular endothelial cells. Podocalyxin might be associated with the malignant progression of astrocytic tumors, and be a useful prognostic marker for astrocytic tumors

  13. Tumor-penetrating nanosystem strongly suppresses breast tumor growth

    Science.gov (United States)

    Sharma, Shweta; Kotamraju, Venkata Ramana; Mölder, Tarmo; Tobi, Allan; Teesalu, Tambet; Ruoslahti, Erkki

    2018-01-01

    Antiangiogenic and vascular disrupting compounds have shown promise in cancer therapy, but tend to be only partially effective. We previously reported a potent theranostic nanosystem that was highly effective in glioblastoma and breast cancer mouse models, retarding tumor growth and producing some cures [Agemy et al. 2011,2013]. The nanosystem consists of iron oxide NPs (“nanoworms”) coated with a composite peptide with tumor-homing and pro-apoptotic domains. The homing component targets tumor vessels by binding to p32/gC1qR at the surface or tumor endothelial cells. We sought to further improve the efficacy nanosystem by searching for an optimally effective homing peptide that would also incorporate a tumor-penetrating function. To this effect, we tested a panel of candidate p32 binding peptides with a sequence motif that conveys tumor-penetrating activity (CendR motif). We identified a peptide designated as Linear TT1 (Lin TT1) (sequence: AKRGARSTA) as most effective in causing tumor homing and penetration of the nanosystem. This peptide had the lowest affinity for p32 among the peptides tested. The low affinity may have moderated the avidity effect from the multivalent presentation on nanoparticles (NPs), such that the NPs avoid getting trapped by the so called “binding-site barrier”, which can hinder tissue penetration of compounds with a high affinity for their receptors. Treatment of breast cancer mice with the LinTT1 nanosystem showed greatly improved efficacy compared to the original system. These results identify a promising treatment modality and underscore the value of tumor penetration effect in improving the efficacy tumor treatment. PMID:28178415

  14. Aberrant internal carotid artery presenting as a retrotympanic vascular mass

    International Nuclear Information System (INIS)

    Nicolay, Simon; De Foer, Bert; Bernaerts, Anja; Van Dinther, Joost; Parizel, Paul M

    2014-01-01

    We report a case of a young woman with an aberrant right internal carotid artery (ICA) presenting as a retrotympanic reddish mass. This variant of the ICA represents the collateral pathway that is formed as a result of an embryological agenesis of the cervical segment of the ICA. The embryonic inferior tympanic artery is recruited to bypass the absent carotid segment. This hypertrophied vessel may be seen otoscopically and wrongfully considered to be a vascular middle ear tumor. Informing the otorhinolaryngologist of this important vascular variant not only obviates biopsy but also helps in careful preoperative planning of eventual middle ear procedures

  15. Generalities of anomalous CT chest non tumoral

    International Nuclear Information System (INIS)

    Dibarboure, L.

    2012-01-01

    This presentation is about the generalities of multidetector CT in the pulmonary, the diaphragmatic, the pleural and the mediastinum pathology.These techniques as well as the virtual endoscopy allow visualize volumetric thorax reconstructions, brain diseases, opacities, radiolucent images, respiratory and vascular diseases, pneumonia, embolism, AIDS stage, tuberculosis, tumors, etc

  16. Pathophysiological Basis for the Formation of the Tumor Microenvironment

    DEFF Research Database (Denmark)

    Horsman, Michael R; Vaupel, Peter

    2016-01-01

    Poor microenvironmental conditions are a characteristic feature of solid tumors. Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing...

  17. Effects of hyperthermia, radiotherapy and thermoradiotherapy on tumor microvasculature

    International Nuclear Information System (INIS)

    Fujiwara, Kouji

    1987-01-01

    The therapeutic effects of hyperthermia (immersion of tumor-bearing leg in a water bath at 46 deg C for 60 min), radiotherapy (500 rad or 1000 rad) and thermoradiotherapy on VX-2 tumors of the rabbits were studied morphologically. Especially, vascular morphological changes and vascular permeability to ferritin after treatment were investigated by electron microscopy. As assessed by decrease in tumor volume, local hyperthermia potentiated the destructive effect of radiotherapy. The light microscopic pictures invariably suggested prolonged necrotic tendency of tumor cells following thermoradiotherapy. Electron microscopically, 1 day and 3 days after thermoradiotherapy, small blood vessels in the tumors showed swelling and protrusion of endothelial cells in the lumen. Similar morphological changes were obtained only at 3 days after radiotherapy. When vascular permeability to ferritin was examined by electron microscopy, an increase in tumor vascular permeability was occured at 1 day after hyperthermia or thermoradiotherapy, while at 3 days after radiotherapy. These results suggest that the early reaction of tumor microvasculature may be a contributing factor to delayed cell death in tumors after hyperthermia or thermoradiotherapy. (author)

  18. Radionuclidr diagnosis of brain tumors, brain inflammatory and traumatic lesions

    International Nuclear Information System (INIS)

    Badmaev, K.N.; Mel'kishev, V.F.; Dement'ev, E.V.; Svetlova, N.L.

    1982-01-01

    A complex of problems of radionuclide diagnosis of central nervous system diseases including tumors, traumas, vascular lessons, inflammatory processes is considered. The principles, technique and results of radionuclide xintigraphy of a tumor, depending on its localization are given. Radioindication of brain tumours in the operation is given

  19. Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma

    OpenAIRE

    1995-01-01

    Vascular cell adhesion molecule 1 (VCAM-1) mediates extravasation of circulating leukocytes into inflamed tissues, and presumably, plays a role in the immigration of cytotoxic effector lymphocytes into tumor metastases. Since metastases are rarely cleared by blood-borne cells from the immune system, we asked whether the tumor may escape host defense by interfering with the mechanism of effector cell extravasation. Here we show that in mice and humans, VCAM-1 expression is repressed on tumor-i...

  20. Tumor Markers

    Science.gov (United States)

    ... only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results. Although tumor markers are extremely useful in ...

  1. Tumor Grade

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... may require immediate or more aggressive treatment. The importance of tumor grade in planning treatment and determining ...

  2. Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas

    NARCIS (Netherlands)

    van Laarhoven, H. W. M.; Gambarota, G.; Heerschap, A.; Lok, J.; Verhagen, I.; Corti, A.; Toma, S.; Gallo Stampino, C.; van der Kogel, A.; Punt, C. J. A.

    2006-01-01

    TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the

  3. Change in the in vivo hyperthermic response resulting from the metabolic effects of temporary vascular occlusion

    International Nuclear Information System (INIS)

    Stewart, J.R.; Gibbs, F.A. Jr.; Lehman, C.M.; Peck, J.W.; Egger, M.J.

    1983-01-01

    Previous workers have reported that clamping of animal tumors in vivo enhanced the effect of hyperthermia; the enhancement has been attributed to pH and nutritional effects of vascular occlusion. It has not been clear, however, the degree to which improved heating patterns or effects on the tumor cells and vasculature from the clamping procedure itself might have contributed to the observed effect. In the experiments herein reported, care was taken to insure comparable heating of C3H mouse mammary tumors transplanted on the flank whether clamped or unclamped. Clamping for one hour with hyperthermia during the final 30 minutes caused a marked thermosensitization as measured by tumor control. The temperature at 30 minutes heating to control 50% of the tumors for 120 days (TCT 50-120) was reduced from 46.8 degrees C in controls to 43.5 degrees C in clamped tumors, a difference of 3.3 +/- 0.09 degrees C. No cytotoxicity from the clamping alone was evident by assessment of subsequent tumor growth and no lasting vascular effects could be detected by 133 Xe washout and tumor growth. Since the techniques used produced essentially identical heating patterns, we conclude that the striking enhancement in hyperthermic response in clamped tumors can be attributed to the metabolic consequences of temporary vascular occlusion

  4. Primo Vascular System in the Lymph Vessel from the Inguinal to the Axillary Nodes

    Directory of Open Access Journals (Sweden)

    Seung Hwan Lee

    2013-01-01

    Full Text Available The primo vascular system (PVS in a lymph system was observed mostly in large caliber ducts around the caudal vena cava of rabbits, rats, and mice. This required a severe surgery with laparectomy and massive removal of fat tissues in the abdomen to expose the lymph vessel. In the current brief report, we presented a new method to evade these shortcomings by observing the PVS in a less large caliber duct in the skin, that is, the lymph vessel from the inguinal to the axillary nodes. The Alcian blue injection into the inguinal node revealed the desired primo vessel in the target lymph vessel. This opened a new perspective for the investigation of the lymphatic PVS without severe damage to subject animals and for monitoring of the PVS in a long period of time.

  5. Hepatic benign vascular tumor in infancy: correlative imaging

    International Nuclear Information System (INIS)

    Rosen, P.R.; Mewborne, E.B.; Macpherson, R.I.; Nusynowitz, M.L.

    1982-01-01

    The use of multiple imaging modalities to diagnose hepatic hemangioendothelioma in a neonate is demonstrated. This approach avoided operative intervention to establish the diagnosis. Tc-99m sulfur colloid and Tc-99m PIPIDA scintigraphy was used to define the nature of sonographic hypoechoic structures in the liver, and angiography was employed to confirm the suspected diagnosis

  6. Imaging tumor vascularization for detection and diagnosis of breast cancer

    NARCIS (Netherlands)

    Heijblom, M.; Klaase, J. M.; van den Engh, F. M.; van Leeuwen, T. G.; Steenbergen, W.; Manohar, S.

    2011-01-01

    Breast cancer is one of the major causes of morbidity and mortality in western women. Current screening and diagnostic imaging modalities, like x-ray mammography and ultrasonography, focus on morphological changes of breast tissue. However, these techniques still miss some cancers and often falsely

  7. Vascular Tumors in Nigeria Middle Belt: A Histopathological Survey ...

    African Journals Online (AJOL)

    Seventy-five dentists (96.2%) claimed acrylic denture was always provided as against metal denture, fixed denture and maxillofacial prostheses that were never or occasionally provided. The most frequently mentioned suggestion to improving prosthetics dentistry specialty popularity were adequate supply of materials and ...

  8. Vascular Tumors in Nigeria Middle Belt: A Histopathological Survey ...

    African Journals Online (AJOL)

    Introduction: Prosthetic Dentistry pertains to provision of artificial substitutes for missing oral structures. It was reported as an unpopular dental specialty in Nigeria, which necessitated the current follow up research. Objective: To assess the level of acceptability and interest in Prosthetic Dentistry, highlight major factors ...

  9. The radiological diagnosis of bone tumors

    International Nuclear Information System (INIS)

    Freyschmidt, J.

    1979-01-01

    Since the definitive diagnosis of very many bone tumors is not only histological but also radiological it is important that the latter examination be of high quality. Prior to biopsy the differential diagnosis should be narrowed down as far as possible radiologically. The radiological procedures include conventional X-ray examination in two projections, tomography, angiography, and computerized tomography. Tomography can reveal the borders of the tumor and minute clacifications within the tumor. Angiography may show atypically vascularized areas and thus be helpful in choosing the best site for biopsy and in making a prognosis. It might reveal, for example, unusual vascularization or penetration of tumor into blood vessels. Computerized tomography allows precise delineation of the intraosseous and extraosseous borders of the tumor, and is particularly useful in this respect in regions in which angiography has its technical limitations, such as the pelvis and the spine. The radiological assessment of a tumor or tumor-like lesion should take account of the structural changes, the site of the lesion, and the age and sex of the patient. The report should include a statement about the malignancy of the lesion. (orig.) [de

  10. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    Search Menu Facebook Twitter YouTube Flickr Instagram LinkedIn Brain Tumor Information | News & Blog Our Mission Our History Mission Leadership & Staff Financials Careers News & Blog Contact Us Donate Now Our Impact Our Impact Recent News News & ...

  11. Interventional vascular radiology

    International Nuclear Information System (INIS)

    Yune, H.Y.

    1984-01-01

    The papers published during this past year in the area of interventional vascular radiology presented some useful modifications and further experiences both in the area of thromboembolic therapy and in dilation and thrombolysis, but no new techniques. As an introductory subject, an excellent monograph reviewing the current spectrum of pharmacoangiography was presented in Radiographics. Although the presented material is primarily in diagnostic application of various pharmacologic agents used today to facilitate demonstration of certain diagnostic criteria of various disease processes, both vasodilatory and vasoconstrictive reaction to these agents are widely used in various therapeutic vascular procedures. This monograph should be reviewed by every angiographer whether or not he or she performs interventional procedures, and it would be very convenient to have this table available in the angiography suite. In a related subject, Bookstein and co-workers have written an excellent review concerning pharmacologic manipulations of various blood coagulative parameters during angiography. Understanding the proper method of manipulation of the bloodclotting factors during angiography, and especially during interventional angiography, is extremely important. Particularly, the method of manipulating the coagulation with the use of heparin and protamine and modification of the platelet activity by using aspirin and dipyridamole are succinctly reviewed. The systemic and selective thrombolytic activities of streptokianse are also discussed

  12. Spinal vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Krings, Timo [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); University Hospital Aachen, Department of Neurosurgery, Aachen (Germany); Mull, Michael; Thron, Armin [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); Gilsbach, Joachim M. [University Hospital Aachen, Department of Neurosurgery, Aachen (Germany)

    2005-02-01

    Spinal vascular malformations are rare diseases that consist of true inborn cavernomas and arteriovenous malformations (including perimedullary fistulae, glomerular and juvenile AVMs) and presumably acquired dural arteriovenous fistulae. This review article gives an overview of the imaging features both on MRI and angiography, the differential diagnoses, the clinical symptomatology and the potential therapeutic approaches to these diseases. It is concluded that MRI is the diagnostic modality of first choice in suspected spinal vascular malformation and should be complemented by selective spinal angiography. Treatment in symptomatic patients offers an improvement in the prognosis, but should be performed in specialized centers. Patients with spinal cord cavernomas and perimedullary fistulae type I are surgical candidates. Dural arteriovenous fistulae can either be operated upon or can be treated by an endovascular approach, the former being a simple, quick and secure approach to obliterate the fistula, while the latter is technically demanding. In spinal arteriovenous malformations, the endovascular approach is the method of first choice; in selected cases, a combined therapy might be sensible. (orig.)

  13. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  14. Targeting the tumor microenvironment for cancer therapy.

    Science.gov (United States)

    Sounni, Nor Eddine; Noel, Agnès

    2013-01-01

    With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix. © 2012 American Association for Clinical Chemistry

  15. Mediastinal tumors

    International Nuclear Information System (INIS)

    Canizares, Claudio; Araujo, Ivan; Rodriguez, Amparo; Robles, Wilson; Simba, Catalina

    2005-01-01

    In our practice the mediastinal tumors are infrequent. The mediastinum is the portion of the thoracic cavity that contains numerous organs and structures which makes a crossroad for the diagnostic process. Within which congenital cysts, inflammatory and benign tumors, malignant neoplasms may develop. In the superior compartment are found: thymoma and thymic cysts, germ cell tumors, thyroid lesions, parathyroid adenomas, malignant lymphomas, paragangliomas, hemangiomas, lipomas, and inflammatory lesions such as fibrosing mediastinitis. In the middle portion: pericardial cysts, bronchial cysts, malignant lymphomas. In the posterior region: neurogenic tumors such as Shawnomas, neurofibromas, ganglioneuroblastomas, neuroblastomas, paragangliomas, and gastro enteric cysts. We describe two cases. One of a female patient with a prominent tumor in the anterior compartment of the mediastinum, detected by the x-ray films. Initially a cardiac lesion was excluded by echographic, angiographic studies. The biopsy exhibited a prominent fibrosis that suggested fibrosing mediastinitis (sclerosing). Whoever the immunohistochemical phenotype was positive for lambda chains, determining the diagnosis of lymphoma. The other case is of a young male with a thymoma associated to a pure red cell aplasia, which was the initial clinical symptom. Computerized tomography and thyroid scintigraphy was used. (The author)

  16. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    Five patients with non-viable limbs had the vessel ligated. Conclusions. A TIVS in the damage control setting is both life- and limb-saving. These shunts can be inserted safely in a facility without access to a surgeon with vascular surgery experience if there is uncontrollable bleeding or the delay to definitive vascular surgery ...

  17. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  18. [Glomus jugulare tumor: perioperative management].

    Science.gov (United States)

    Ferrando, A; Fraile, J R; Bermejo, L; de Miguel, A; Aristegui, M; Hervías, M; Quirós, P

    1996-12-01

    Surgical treatment of glomus jugulare tumors yields high rates of perioperative morbidity and mortality for several reasons, among them neuroendocrine secretory activity, a high degree of vascularization, intracranial extension, duration of surgery and cranial nerve lesion. Secretory activity (e.g. catecholamines and serotonin) should be investigated before surgery and treated appropriately. Carotid arteriography (and ball occlusion) are useful to assess vascularization of the tumor and determine the need to clamp the carotid artery during the procedure. Potential complications such as hemodynamic alterations (bleeding or endocrine response), pulmonary embolism (air or thrombotic), hypothermia, facial nerve lesion, should be monitored for during surgery. After surgery cranial nerve involvement, which can lead to dysphagia and bronchoaspiration, must be looked for; the risk of cerebro-spinal fluid fistula is also high. We report the case of a woman who underwent surgery for a non secreting glomus jugulare tumor with extradural intracranial invasion. The main complications during surgery were bleeding with hemodynamic repercussions, pulmonary embolism, lesions in the VII, VIII and X cranial nerves, and opening of the dura mater (which required insertion of an intradural drain to prevent formation of a fistula). After surgery oral intake was delayed until intestinal function was established and glottic sphincter competence was verified by fiberoptic laryngoscopy. The only complication presenting at this time was cephalea, which disappeared upon removal of the drain on day 4. The patient was released on day 10.

  19. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  20. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  1. Digital subtraction angiography in evaluation of vascular supply of head and neck paragangliomas

    International Nuclear Information System (INIS)

    Juszkat, R.; Szyfter, P.; Zarzecka, A.

    2008-01-01

    Paragangliomas (PGs) of the head and neck are relatively rare and represent 0.6% of all head and neck tumors and 0.03% of all tumors. There are four groups of head and neck PGs: carotid body tumors, vagal PGs, jugular PGs, and tympanic PGs. The resection of head and neck PGs carries an inherent risk of injury to cranial nerves and vascular structures which may lead to excessive bleeding. To plan the surgical strategy for PGs, detailed information about the vascular supply of the tumor is required. Between January 1998 and April 2007, 41 tumors of the head and neck were identified in 37 patients (20 females, 17 males, mean age: 38.4 years). Single tumors were observed in 33 patients, two head and neck PGs were identified in 3 patients, and 1 patient presented 3 PGs, one of which was located laterally to the aortic arch. There were 21 PGs located at the carotid bifurcation, 10 in the jugular foramen, 6 in the tympanic cavity, and 4 along the course of the vagus nerve. In all the cases of PGs located in the head and neck, the vascular supply came from branches of the external carotid artery. Vascular supply from the internal carotid and the vertebral arteries was not seen in any of the patients. The most common vascular supply in the cases of carotid body tumors and jugular PGs was the pharyngeal ascending artery. In the cases of vagal PGs it was the pharyngeal ascending artery and the posterior auricular artery and in the case of tympanic PGs the posterior auricular artery. DSA is an important tool in the diagnosis of head and neck PGs. The evaluation of its vascularization is essential in planning further treatment, both endovascular and surgical. (author)

  2. Congenital tumors of the central nervous system

    International Nuclear Information System (INIS)

    Severino, Mariasavina; Schwartz, Erin S.; Thurnher, Majda M.; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

    2010-01-01

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease

  3. Congenital tumors of the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Severino, Mariasavina [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); Schwartz, Erin S. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Thurnher, Majda M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Rydland, Jana [MR Center, St. Olav' s Hospital HF, Trondheim (Norway); Nikas, Ioannis [Agia Sophia Children' s Hospital, Imaging Department, Athens (Greece); Rossi, Andrea [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); G. Gaslini Children' s Hospital, Department of Pediatric Neuroradiology, Genoa (Italy)

    2010-06-15

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors

  4. Peripheral vascular injuries

    Directory of Open Access Journals (Sweden)

    Celal Yavuz

    2009-01-01

    Full Text Available Aim: To determine etiology and management in patients with peripheral vascular trauma.Materials and Methods: From 2005 to 2006 with a diagnosis of peripheral artery injury, 69 cases admitted to Diyarbakır State Hospital Department of Cardiovascular surgery.Results: These cases have been respectively reviewed. The causes of injuries were; penetrating injuries in 60 cases (87%, blunt trauma in seven cases (10% and gunshot injuries in two cases (3%. In 53 cases (74% upper extremity, in 15 cases (21% lower extremity was involved. As a surgical procedure, in 34 cases (47% end-to-end anastomosis, in 28 cases (39% lateral suture, in five cases (7% venous graft interposition, in five cases (7% ligation was performed.Conclusion: Early intervention, transfusion of fluid and blood, systemic anticoagulation, preoperative and postoperative detailed debridement decreased the morbidity and mortality rates.

  5. Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies

    DEFF Research Database (Denmark)

    Horsman, Michael Robert; Siemann, D.W.

    2006-01-01

    A functional vascular supply is critical for the continued growth and development of solid tumors. It also plays a major role in metastatic spread of tumor cells. This importance has led to the concept of targeting the vasculature of the tumor as a form of cancer therapy. Two major types of vascu...... on the tumor response to more conventional therapies. This review aims to discuss the pathophysiologic changes induced by VTAs and the implications of these effects on the potential use of VTAs in combined modality therapy....... successful in the clinic they will need to be combined with more conventional therapies. However, by affecting the tumor vascular supply, these VTAs should induce pathophysiologic changes in variables, such as blood flow, pH, and oxygenation. Such changes could have negative or positive influences......A functional vascular supply is critical for the continued growth and development of solid tumors. It also plays a major role in metastatic spread of tumor cells. This importance has led to the concept of targeting the vasculature of the tumor as a form of cancer therapy. Two major types...

  6. The vascular secret of Klotho

    DEFF Research Database (Denmark)

    Lewin, Ewa; Olgaard, Klaus

    2015-01-01

    Klotho is an evolutionarily highly conserved protein related to longevity. Increasing evidence of a vascular protecting effect of the Klotho protein has emerged and might be important for future treatments of uremic vascular calcification. It is still disputed whether Klotho is locally expressed ...

  7. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings

    2012-01-01

    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  8. Diagnostic criteria for vascular dementia

    NARCIS (Netherlands)

    Scheltens, P.; Hijdra, A. H.

    1998-01-01

    The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria

  9. Vascular Structure Identification in Intraoperative 3D Contrast-Enhanced Ultrasound Data

    Science.gov (United States)

    Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Lindner, Dirk; Cruz-Aceves, Ivan; Arlt, Felix; Chalopin, Claire

    2016-01-01

    In this paper, a method of vascular structure identification in intraoperative 3D Contrast-Enhanced Ultrasound (CEUS) data is presented. Ultrasound imaging is commonly used in brain tumor surgery to investigate in real time the current status of cerebral structures. The use of an ultrasound contrast agent enables to highlight tumor tissue, but also surrounding blood vessels. However, these structures can be used as landmarks to estimate and correct the brain shift. This work proposes an alternative method for extracting small vascular segments close to the tumor as landmark. The patient image dataset involved in brain tumor operations includes preoperative contrast T1MR (cT1MR) data and 3D intraoperative contrast enhanced ultrasound data acquired before (3D-iCEUSstart) and after (3D-iCEUSend) tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUSstart and 3D-iCEUSend data. The method was validated by using three similarity measures (Normalized Gradient Field, Normalized Mutual Information and Normalized Cross Correlation). Tests were performed on data obtained from ten patients overcoming a brain tumor operation and it succeeded in nine cases. Despite the small size of the vascular structures, the artifacts in the ultrasound images and the brain tissue deformations, blood vessels were successfully identified. PMID:27070610

  10. NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238, VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936 AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569 GENES IN AGERELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    A. V. Shevchenko

    2017-01-01

    Full Text Available Age-related macular degeneration is one of the most widespread multifactorial eye diseases. Polymorphic functional alleles of vascular endothelial growth factor (VEGF combined with matrix metalloproteinase (MMP gene and tumor necrosis factor (TNF gene variants may influence the development of disease. We have performed frequency analysis of their polymorphisms in regulatory regions of VEGF (rs 699947, rs 3025039, ММР2 (rs 2438650, ММР3 (rs 3025058, ММР9 (rs 3918242, TNFα (rs1800630, rs1800629, rs 361525 genes, and their combinations in a group of patients with age-related macular degeneration (MD. Frequencies of TNFα (rs1800629 genotypes significantly differed for the MD patients and control group. Upon the combined genotype analysis, we have revealed six constellations of VEGF-ММР genes that were positively associated with the disease development. Five of them included minor homozygous genotype VEGF-2578АА. A combined analysis of VEGF – TNFα genes polymorphisms has shown presence of both positive and negative complex genotypes. The most significant differences have been detected by comparative analysis of the complex genotypes frequencies which included 8 polymorphic regulatory gene regions of all genes studied. In most genetic complexes associated with the disease development, homozygous TNFα-863СС, homozygous MMP2-1306 ТТ, and MMP9-1562СС genotypes have been detected, together with the combination of homozygous VEGFA+936СС genotype in the same patients. We can assume that harboring allelic variants, which may contribute to angiogenesis prorcesses is typical for the genome of patients with macular degeneration, along with low-level production of pro-inflammatory regulatory factors and enzymes participating in degradation of extracellular matrix. Analysis of complex genetic factors, procing some factors taking part at the pathological process being the regulators of production for each other, is more informative when

  11. Ultrasonography and computed tomography in the study of orbital tumors and pseudo-tumoral lesions

    International Nuclear Information System (INIS)

    Marins, J.L.C.; Pereira, R.M.; Prando, A.; Selos Moreira, A.R. de

    1987-01-01

    The computerized tomography and the ultrasonography in the ocular and orbital patologies were considered as complementary each other. the ultrasonography method as choice for the detection of the eye lesions in the adult, particularly of vascular origin and in the follow-up of inflammatory and pseudo-tumoral lesions was chosen. (L.M.J.) [pt

  12. Selected biological markers in various vascular lesions of the head and neck

    Directory of Open Access Journals (Sweden)

    Zuzanna Gronkiewicz

    2014-10-01

    Full Text Available Vascular anomalies are divided according to the contemporary system of classification into two groups: tumors and malformations. However, there is no consensus on juvenile angiofibroma’s place in that system. The general characteristics of selected markers of angiogenesis and tissue remodeling are presented in the series in the context of current knowledge in the field of pathophysiology of vascular lesions. The mentioned markers are currently the subjects of multidirectional studies in oncology, as they take part in the process of neoangiogenesis and proliferation of tumors. Nevertheless, they have not been widely examined in vascular lesions. The indirect goal of that series is to indicate the possible research direction on vascular lesions to determine their molecular profile, to create a more specific system of classification, and above all to develop new diagnostic and treatment methods.

  13. Social media in vascular surgery.

    Science.gov (United States)

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  14. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-01-01

    Full Text Available Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial.

  15. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  16. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  17. A study of spinal cord tumors by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio.

    1989-01-01

    We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author)

  18. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    Directory of Open Access Journals (Sweden)

    Theodore S. Johnson

    2012-01-01

    Full Text Available Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

  19. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

    2005-01-01

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

  20. Poikiloderma vasculare atrophicans: A distinct clinical entity?

    Directory of Open Access Journals (Sweden)

    Vikram K Mahajan

    2015-01-01

    Full Text Available This paper describes a typical case of poikiloderma vasculare atrophicans (PVA in a 48-year-old female. Histologically, the features were suggestive of PVA with the absence of Pautrier′s microabscess or atypical lymphoid cells. The biopsy specimen was positive for cluster of differentiation (CD 8 on immunohistochemical staining. Its exact pathogenesis remains obscure, and it remains unclear whether PVA actually is mycosis fungoides (MF, a forme fruste of MF, or a distinct and benign dermatosis with CD8+ phenotype that can perhaps be labeled as PVA. However, it has a long benign clinical course without progression to tumor stage of MF in most cases, and its status within the spectrum of cutaneous T-cell lymphoma remains poorly understood. Yet it is imperative to distinguish PVA from poikilodermic MF.

  1. Vascular Targeting of a Gold Nanoparticle to Breast Cancer Metastasis.

    Science.gov (United States)

    Peiris, Pubudu M; Deb, Partha; Doolittle, Elizabeth; Doron, Gilad; Goldberg, Amy; Govender, Priya; Shah, Shruti; Rao, Swetha; Carbone, Sarah; Cotey, Thomas; Sylvestre, Meilyn; Singh, Sohaj; Schiemann, William P; Lee, Zhenghong; Karathanasis, Efstathios

    2015-08-01

    The vast majority of breast cancer deaths are due to metastatic disease. Although deep tissue targeting of nanoparticles is suitable for some primary tumors, vascular targeting may be a more attractive strategy for micrometastasis. This study combined a vascular targeting strategy with the enhanced targeting capabilities of a nanoparticle to evaluate the ability of a gold nanoparticle (AuNP) to specifically target the early spread of metastatic disease. As a ligand for the vascular targeting strategy, we utilized a peptide targeting alpha(v) beta(3) integrin, which is functionally linked to the development of micrometastases at a distal site. By employing a straightforward radiolabeling method to incorporate Technetium-99m into the AuNPs, we used the high sensitivity of radionuclide imaging to monitor the longitudinal accumulation of the nanoparticles in metastatic sites. Animal and histological studies showed that vascular targeting of the nanoparticle facilitated highly accurate targeting of micrometastasis in the 4T1 mouse model of breast cancer metastasis using radionuclide imaging and a low dose of the nanoparticle. Because of the efficient targeting scheme, 14% of the injected AuNP deposited at metastatic sites in the lungs within 60 min after injection, indicating that the vascular bed of metastasis is a viable target site for nanoparticles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Effect of SPG (Sonifilan) immunotherapy and PDT on murine tumor

    International Nuclear Information System (INIS)

    Korbelik, M.; Krosl, G.; Dougherty, G.J.; Chaplin, D.J.

    1992-01-01

    PhotoDynamic Therapy of solid tumors is unique in eliciting a strong host immune response unparalleled in other cancer therapies. This immune response is manifested as an acute inflammatory reaction, and can be readily seen as redness and edema around the treated area. Destruction of typical solid tumor cannot be accomplished solely by direct phototoxic action. This was shown to be the case even with drugs more potent in this direct killing effect than Photofrin, the photosensitizer presently used in clinical PDT. Limiting factors seem to be regional insufficiencies in supply of molecular oxygen, needed for generation of phototoxic species. They can be ascribed to the existence of chronically and acute hypoxic tumor regions, oxygen consumption by the photodynamic process, and vascular shutdown induced during PDT. The remaining tumor mass is eradicated by an indirect effect, necrosis induced by destruction of tumor vasculature. Since most events in PDT treated tumor that lead to vascular collapse are, in fact, typical inflammatory manifestations, it was suggested that PDT-induced acute inflammatory reaction actually leads to vascular damage. In a related report characteristics are shown of cellular inflammatory infiltrate in PDT-treated murine tumor. This work examines the effect of combining PDT with immunotherapy, in an attempt to investigate a possibility of amplification of immune reaction to PDT and its direction towards more pervasive destruction of treated tumors. (authors). 6 refs

  3. Peritoneal vascular density assessment using narrow-band imaging and vascular analysis software, and cytokine analysis in women with and without endometriosis.

    Science.gov (United States)

    Kuroda, Keiji; Kitade, Mari; Kikuchi, Iwaho; Kumakiri, Jun; Matsuoka, Shozo; Kuroda, Masako; Takeda, Satoru

    2010-01-01

    The development and onset of endometriosis is associated with angiogenesis and angiogenic factors including cytokines. We analyzed intrapelvic conditions in women with endometriosis via vascular density assessment of grossly normal peritoneum and determination of cytokine levels in peritoneal fluid. Seventy-three patients underwent laparoscopic surgery because of gynecologic disease including endometriosis in our department using a narrow-band imaging system. Each patient was analyzed for peritoneal vascular density using commercially available vascular analysis software (SolemioENDO ProStudy; Olympus Corp, Tokyo, Japan). Each patient was also subjected to analysis of interleukin 6 (IL-6), IL-8, tumor necrosis factor-alpha, and vascular endothelial growth factor concentrations in peritoneal fluid. We defined 4 groups as follows: group 1, endometriosis: gonadotropin-releasing hormone (GnRH) agonist administration group (n=27); group 2, endometriosis: GnRH agonist nonadministration group (n=15); group 3, no endometriosis: GnRH agonist administration group (n=18); and group 4, no endometriosis: GnRH agonist nonadministration group (n=13). No significant differences in peritoneal vascular density between the 4 groups were found under conventional light; however, under narrow-band light, vascular density in the endometriosis groups (groups 1 and 2) was significantly higher. Cytokine analysis of the 4 groups determined that IL-6 and IL-8 concentrations were significantly higher compared with the no endometriosis groups (groups 3 and 4). Tumor necrosis factor-alpha and vascular endothelial growth factor concentrations were not significantly different between groups. In endometriosis, peritoneal vascular density was significantly higher as assessed using the narrow-band imaging system and SolemioENDO ProStudy, whereas GnRH agonist did not obviously decrease vascular density but IL-6 concentration was lower in the GnRH agonist administration group. Copyright (c) 2010 AAGL

  4. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Vascular disease in cocaine addiction.

    Science.gov (United States)

    Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-07-01

    Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step. Georg Thieme Verlag KG Stuttgart · New York.

  7. Tumor angiogenesis assessment using multi-fluorescent scans on murine slices by Markov random field framework

    Science.gov (United States)

    Laifa, Oumeima; Le Guillou-Buffello, Delphine; Racoceanu, Daniel

    2017-11-01

    The fundamental role of vascular supply in tumor growth makes the evaluation of the angiogenesis crucial in assessing effect of anti-angiogenic therapies. Since many years, such therapies are designed to inhibit the vascular endothelial growth factor (VEGF). To contribute to the assessment of anti-angiogenic agent (Pazopanib) effect on vascular and cellular structures, we acquired data from tumors extracted from a murine tumor model using Multi- Fluorescence Scanning. In this paper, we implemented an unsupervised algorithm combining the Watershed segmentation and Markov Random Field model (MRF). This algorithm allowed us to quantify the proportion of apoptotic endothelial cells and to generate maps according to cell density. Stronger association between apoptosis and endothelial cells was revealed in the tumors receiving anti-angiogenic therapy (n = 4) as compared to those receiving placebo (n = 4). A high percentage of apoptotic cells in the tumor area are endothelial. Lower density cells were detected in tumor slices presenting higher apoptotic endothelial areas.

  8. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

    Directory of Open Access Journals (Sweden)

    Wang Wen-Quan

    2012-11-01

    Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

  9. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    Science.gov (United States)

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  10. HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits.

    Science.gov (United States)

    Xu, Weifeng; Santini, Paul A; Sullivan, John S; He, Bing; Shan, Meimei; Ball, Susan C; Dyer, Wayne B; Ketas, Thomas J; Chadburn, Amy; Cohen-Gould, Leona; Knowles, Daniel M; Chiu, April; Sanders, Rogier W; Chen, Kang; Cerutti, Andrea

    2009-09-01

    Contact-dependent communication between immune cells generates protection but also facilitates viral spread. Here we found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type 1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine-exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients with Nef-deficient virions, our data suggest that HIV-1 exploits intercellular 'highways' as a 'Trojan horse' to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry.

  11. Role of preoperative vascular ultrasonography in hemodialysis vascular access operation.

    Science.gov (United States)

    Siribumrungwong, Boonying; Tomtitchong, Prakitpunthu; Kanpirom, Kitti

    2010-12-01

    Preoperative vascular mapping increase rate of successful hemodialysis vascular access operation. Several studies recommend using this procedure routinely. But some studies recommend using this procedure in selected patients. So this study aims to determine the impacts of preoperative vascular mapping in unfavorable-examined patients. 55 patients were studied retrospectively from August 2006 to October 2009. Before April 2008, the operative plans were based on physical examination (group 1). After April 2008, the surgeon did preoperative vascular mapping prior to the operation in unfavorable-examined patients (group 2). The results were compared. There were high maturation rates in favorable-examined patients. In unfavorable-examined patients, preoperative vascular mapping can identified nonpalpable favorable vein which successful maturation of 18.75%. Complementary duplex scan decrease rate of unsuccessful operation significantly (p = 0.037) but does not increase maturation rate. Careful physical examination is important part before operation. Preoperative vascular mapping has benefit only in patients with unfavorable-examined patients. It finds some nonpalpable favorable vein and decrease unsuccessful exploration.

  12. Trauma vascular, visión del cirujano vascular

    Directory of Open Access Journals (Sweden)

    Dr. D. Cristián Salas

    2011-09-01

    Full Text Available El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesiones de vasos torácicos y abdominales requieren de imágenes de apoyo, siempre que el paciente se encuentre estabilizado, generalmente tomografía axial computada. La mayoría de las lesiones vasculares son por trauma penetrante, comprometiendo principalmente las extremidades. Con el desarrollo de los procedimientos invasivos vasculares en los últimos años se ha observado un aumento de lesiones vasculares iatrogénicas. Hoy en día muchos pacientes con trauma vascular son manejados por vía endovascular.

  13. Vascular injuries during gynecological laparoscopy: the vascular surgeon's advice

    Directory of Open Access Journals (Sweden)

    Marcello Barbosa Barros

    Full Text Available CONTEXT: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services. CASES: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period. DISCUSSION: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

  14. IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity

    Science.gov (United States)

    Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N.; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S.

    2012-01-01

    Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15–transduced NKT cells. PMID:22565311

  15. IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity.

    Science.gov (United States)

    Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S

    2012-06-01

    Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15-transduced NKT cells.

  16. Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy.

    Directory of Open Access Journals (Sweden)

    Rickson C Mesquita

    Full Text Available Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively. However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

  17. Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy.

    Science.gov (United States)

    Mesquita, Rickson C; Han, Sung Wan; Miller, Joann; Schenkel, Steven S; Pole, Andrew; Esipova, Tatiana V; Vinogradov, Sergei A; Putt, Mary E; Yodh, Arjun G; Busch, Theresa M

    2012-01-01

    Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

  18. MRI of orbital tumors. Usefulness of dynamic MRI

    International Nuclear Information System (INIS)

    Kawanishi, Masayuki; Kotake, Fumio; Abe, Kimihiko

    1998-01-01

    MRI is very useful for the diagnosis of orbital tumors, bus T1 and T2-weighted images and contrast T1-weighted image are often insufficient for accurate diagnosis. In the present study, we conducted dynamic MRI for the diagnosis of orbital tumors and evaluated its usefulness. 19 patients with 20 lesions were included in the present study: vascular tumors, schwannomas, orbital lymphoid tumors, meningiomas, lacrimal tumors, metastatic orbital tumors, leukemic infiltration of the orbit and post operative granuloma. Dynamic MRIs were acquired by the SE method at TR 100/TE 26 msec at 30 sec intervals starting immediately after iv injection of 0.1 mmol/kg of Gd-DTPA. Time intensity curves (TIC) were drawn after setting regions interest in tumorous areas. TICs obtained were classified into 5 types: Type 1 (rapid increase and rapid decrease), Type 2 (rapid increase and gradual decrease), Type 3 (rapid increase and no decrease), Type 4 (gradual increase), Type 5 (no changes). TIC was of Type 1 in 2 patients, Type 2 in 8, Type 3 in 3, Type 4 in 3, Type 5 in 3. The presence or absence of correlation between the TIC types and types of tumor was evaluated. TIC made it possible to make differential diagnosis of vascular tumors and schwannoma and to differentiate benign and malignant lacrimal tumors, suggesting that it is useful for qualitative diagnosis of these disease. (author)

  19. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  20. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  1. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  2. ( Elaeis guineensis Jacq ) vascular wilt

    African Journals Online (AJOL)

    Effet de la jachére sur l'expérimentation de la fusariose vasculaire du palmier à huile ( Elaeis guineensis Jacq ) : Effects of the fallow in the expression of oil-palm ( Elaeis guineensis Jacq ) vascular wilt.

  3. Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal

    Directory of Open Access Journals (Sweden)

    Enriqueta M. Serafini

    2013-02-01

    Full Text Available La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.

  4. Histopathological studies on the irradiated brain tumors

    International Nuclear Information System (INIS)

    Narita, Tadao

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy. (J.P.N.)

  5. High efficiency diffusion molecular retention tumor targeting.

    Directory of Open Access Journals (Sweden)

    Yanyan Guo

    Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

  6. Vascular lesions of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Drape, Jean-Luc [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France)]. E-mail: jean-luc.drape@cch.ap-hop-paris.fr; Feydy, Antoine [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Guerini, Henri [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Desmarais, Eric [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Godefroy, Didier [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Viet, Dominique Le [Institut de la main, Paris (France); Chevrot, Alain [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France)

    2005-12-15

    The vascular malformations are not uncommon on the hand and offer diagnostic and therapeutic challenges. Enjolras and Mulliken's classification is exposed. Their depiction and pretreatment assessment may benefit from non-invasive imaging as color-Doppler ultrasound and MRI combined with magnetic resonance angiography (MRA). Some chronic traumatic vascular injuries as the hypothenar hammer syndrome may also take advantage of these imaging modalities.

  7. Hemimegalencephaly, hemihypertrophy and vascular lesions.

    Science.gov (United States)

    Cristaldi, A; Vigevano, F; Antoniazzi, G; di Capua, M; Andreuzzi, A; Morselli, G; Iorio, F; Fariello, G; Trasimeni, G; Gualdi, G F

    1995-02-01

    We report on two children with hemihypertrophy and ipsilateral hemimegalencephaly. Vascular lesions in one were consistent with a diagnosis of the Klippel-Trénaunay-Weber Syndrome. MRI performed in the first days of life and at 1 month of age revealed the presence of the neuronal anomaly. The occurrence of hemimegalencephaly in our patients indicates that hemihypertrophy and vascular dysplasia are pathogenetically related phenomena of a continuous spectrum in which this brain disorder may appear.

  8. Facial vascular malformations in children

    International Nuclear Information System (INIS)

    Brunelle, F.O.; Lallemand, D.; Chaumont, P.; Teillac, D.; Manach, Y.

    1988-01-01

    The authors present their experience with conventional and digital angiography of vascular malformations of the head and neck in children. 22 hemangioendotheliomas, 8 venous angiomas, and 3 arteriovenous fistula were studied. 22 patients were embolised. DSA offers many advantages during the diagnostic as well as during the therapeutic phase of angiography. Embolization appears to have a major role in treatment of such vascular malformations. (orig.)

  9. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... vasculature may affect the retinal response to potential vascular disease in later life....

  10. Choroid plexus papilloma of the third ventricle: A rare infantile brain tumor

    OpenAIRE

    Gupta, Pankaj; Sodhi, Kushaljit Singh; Mohindra, Sandeep; Saxena, Akshay Kumar; Das, Ashim; Khandelwal, Niranjan

    2013-01-01

    Choroid plexus papilloma (CPP) represents an uncommon pediatric brain tumor with an overall incidence less than 1% of all intracranial tumors. Most of these tumors occur in the lateral ventricles in neonates. Third ventricular location is uncommon, limited to a few case reports. These highly vascular tumors retain the physiological function of choroid plexus and thus lead to overproduction of cerebrospinal fluid (CSF), besides obstructing the CSF pathway. Imaging is fairly sensitive and speci...

  11. Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact.

    Science.gov (United States)

    Takara, Kazuhiro; Eino, Daisuke; Ando, Koji; Yasuda, Daisuke; Naito, Hisamichi; Tsukada, Yohei; Iba, Tomohiro; Wakabayashi, Taku; Muramatsu, Fumitaka; Kidoya, Hiroyasu; Fukuhara, Shigetomo; Mochizuki, Naoki; Ishii, Satoshi; Kishima, Haruhiko; Takakura, Nobuyuki

    2017-08-29

    Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6). In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact

    Directory of Open Access Journals (Sweden)

    Kazuhiro Takara

    2017-08-01

    Full Text Available Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1–6. In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation.

  13. Angiogenesis, Cancer, and Vascular Aging

    Directory of Open Access Journals (Sweden)

    Junji Moriya

    2017-10-01

    Full Text Available Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

  14. A Rare Tumor of Nasal Cavity: Glomangiopericytoma

    Directory of Open Access Journals (Sweden)

    Aysegul Verim

    2014-01-01

    Full Text Available Glomangiopericytoma is a rare vascular neoplasm characterized by a pattern of prominent perivascular growth. A 72-year-old woman was admitted to our clinic complaining of nasal obstruction, frequent epistaxis, and facial pain. A reddish tumor filling the left nasal cavity was observed on endoscopy and treated with endoscopic excision. Microscopically, closely packed cells interspersed with numerous thin-walled, branching staghorn vessels were seen. Glomangiopericytoma is categorized as a borderline low malignancy tumor by WHO classification. Long-term follow-up with systemic examination is necessary due to high risk of recurrence.

  15. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents1

    Science.gov (United States)

    Galiè, Mirco; D'Onofrio, Mirko; Montani, Maura; Amici, Augusto; Calderan, Laura; Marzola, Pasquina; Benati, Donatella; Merigo, Flavia; Marchini, Cristina; Sbarbati, Andrea

    2005-01-01

    Abstract Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 µm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes. PMID:15967105

  16. Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

    International Nuclear Information System (INIS)

    Li, Rong; Zhang, Xu; Zhang, Zhuo; Zhang, Xiao; Ran, Bing; Wu, Jianbo; Ren, Meiping; Chen, Ni; Luo, Mao; Deng, Xin; Xia, Jiyi; Yu, Guang; Liu, Jinbo; He, Bing

    2014-01-01

    Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA. Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation. Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis

  17. Reconstruction of lower end of radius using vascularized upper end of fibula

    Directory of Open Access Journals (Sweden)

    Koul Ashok

    2007-01-01

    Full Text Available Background: Giant cell tumor is a fairly common locally invasive tumor in young adults. The lower end of the radius is the second commonest site for this tumor. The most common treatment for this tumor is curettage with or without bone grafting but it carries a significant rate of recurrence. Excision is the treatment of choice, especially for cases in which the cortex has been breached. After excision of the distal end of the radius, different procedures have been described to reconstruct the defect of distal radius. These include partial arthrodesis and hemiarthroplasty using the upper end of the fibula. The upper end of the fibula has a morphological resemblance to the lower end of the radius and has been used to replace the latter. Traditionally it was used as a ′free′ (non-vascularized graft. More recently the upper end of the fibula has been transferred as a vascularized transfer for the same purpose. Though vascularized transfer should be expected to be more physiological, its superiority over the technically simpler non-vascularized transfer has not been conclusively proven. Materials and Methods: Two patients are presented who had giant cell tumor of distal radius. They underwent wide local excision and reconstruction with free vascularized upper end of the fibula. Result: Follow-up period was two and a half years and 12 months respectively. Both patients have returned to routine work. One patient has excellent functional result and the other has a good result. Conclusion: Vascularized upper end of fibula transfer is a reliable method of reconstruction for loss of the distal end of the radius that restores local anatomy and physiology.

  18. Identification of a characteristic vascular belt zone in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jakob Nikolas Kather

    Full Text Available Intra-tumoral blood vessels are of supreme importance for tumor growth, metastasis and therapy. Yet, little is known about spatial distribution patterns of these vessels. Most experimental or theoretical tumor models implicitly assume that blood vessels are equally abundant in different parts of the tumor, which has far-reaching implications for chemotherapy and tumor metabolism. In contrast, based on histological observations, we hypothesized that blood vessels follow specific spatial distribution patterns in colorectal cancer tissue. We developed and applied a novel computational approach to identify spatial patterns of angiogenesis in histological whole-slide images of human colorectal cancer.In 33 of 34 (97% colorectal cancer primary tumors blood vessels were significantly aggregated in a sharply limited belt-like zone at the interface of tumor tissue to the intestinal lumen. In contrast, in 11 of 11 (100% colorectal cancer liver metastases, a similar hypervascularized zone could be found at the boundary to surrounding liver tissue. Also, in an independent validation cohort, we found this vascular belt zone: 22 of 23 (96% samples of primary tumors and 15 of 16 (94% samples of liver metastases exhibited the above-mentioned spatial distribution.We report consistent spatial patterns of tumor vascularization that may have far-reaching implications for models of drug distribution, tumor metabolism and tumor growth: luminal hypervascularization in colorectal cancer primary tumors is a previously overlooked feature of cancer tissue. In colorectal cancer liver metastases, we describe a corresponding pattern at the invasive margin. These findings add another puzzle piece to the complex concept of tumor heterogeneity.

  19. Laparoscopic partial nephrectomy for multiple (four tumors

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    Lessandro Curcio

    Full Text Available ABSTRACT Background Nephron sparing surgery (NSS is well established as the standard of care for most surgical small renal tumors when technically feasible. While the majority of sporadic renal tumors are solitary, multifocal tumors have been reported in 5.4% to 25% of patients with tumors smaller than 5cm. We present a video where we approach, through laparoscopy, four tumors on the same kidney. Case study Male, 58y, went through a routine abdominal ultrasound which showed a 5cm left kidney nodule. His MRI pointed a total of 4 nodules on his left kidney. The aspect suggested a papillary cancer due to high cellularity and low vascularization. The patient was submitted to partial nephrectomy under ischemia to remove the two largest tumors (inferior pole and a resection without clamping of the other two ipsilateral tumors. Result We performed the surgery in 2 stages. In the first one, we approached the 2 tumors located on the inferior pole inducing warm ischemia, whereas in the second stage we resected the 2 remaining tumors using the technique without clamping. The surgery lasted 220 minutes, with 800mL of blood loss, not requiring blood transfusion. Ischemia time was 35 minutes. The histopathological analysis confirmed that the 4 tumors were papillary cancer, with free margins. Conclusion NSS can be performed and should be tried in patients with multiple kidney tumors, preferably through laparoscopy or assisted by robot. It can be made either using or not clamping of the pedicle, depending on the RENAL score.

  20. Effect of tumor shape and size on drug delivery to solid tumors

    Directory of Open Access Journals (Sweden)

    Soltani M

    2012-04-01

    Full Text Available Abstract Tumor shape and size effect on drug delivery to solid tumors are studied, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for predefined tumor geometries. The governing equations are solved using a numerical method, the element-based finite volume method. Interstitial fluid pressure and velocity are used to show the details of drug delivery in a solid tumor, under an assumption that drug particles flow with the interstitial fluid. Drug delivery problems have been most extensively researched in spherical tumors, which have been the simplest to examine with the analytical methods. With our numerical method, however, more complex shapes of the tumor can be studied. The numerical model of fluid flow in solid tumors previously introduced by our group is further developed to incorporate and investigate non-spherical tumors such as prolate and oblate ones. Also the effects of the surface area per unit volume of the tissue, vascular and interstitial hydraulic conductivity on drug delivery are investigated.

  1. Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

    Directory of Open Access Journals (Sweden)

    Qishan Chen

    2013-01-01

    Full Text Available Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs, and vascular smooth muscle cells (VSMCs and its interaction with extracellular matrix (ECM play a critical role in the processes. Matrix metalloproteinases (MMPs, well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

  2. [The impact of Glut-1 marker application on the diagnosis and treatment of congenital vascular anomalies].

    Science.gov (United States)

    López Gutiérrez, J C; Tovar, J A; Patrón, M

    2005-07-01

    Hemangiomas of infancy have a unique vascular phenotype demonstrated by glucose transporter 1 (GLUT-1) staining marker. Since its first description by P. E. North in 2000 its use has become widely spread by clinicians and researchers in the field of vascular anomalies. We prospectively and retrospectively used GLUT-1 marker on 90 patients divided in five groups over a two years period. Grupo I: Hemangiomas under 1 year of age. Grupo II: Hemangiomas between 1 and 15 years of age. Grupo III: Misdiagnosed angiomas in patients older than 15 years. Grupo IV: Patients with low and high flow vascular malformations Grupo V: Vascular tumors other than hemangiomas. As a result of the study, significant improvement has been noticed by the authors in appropiate vascular anomalies classification by primary care physicians involved in the study. Angioma is not anymore synonym of vascular birthmark. In addition the management of the newborn with a vascular tumour benefit from a more appropriate antiangiogenic therapy. Patients with RICH (rapidly involuting congenital hemangioma) or NICH (non involuting congenital hemangioma) pattern after biopsy and inmunohistochemical study did not receive any pharmacological agent as a part of their treatment. Finally GLUT-1 helped multidisciplinary vascular anomalies team development by promoting clinical, radiological and histopathologic correlations between different specialists.

  3. Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis.

    Science.gov (United States)

    Kitahara, Shuji; Suzuki, Yasuhiro; Morishima, Masae; Yoshii, Asuka; Kikuta, Sachiko; Shimizu, Kazuhiko; Morikawa, Shunichi; Sato, Yasufumi; Ezaki, Taichi

    2014-05-04

    Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice. ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed. We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine. We propose that VASH2 may modulate the onset of tumors in

  4. Immune Consequences of Decreasing Tumor Vasculature with Antiangiogenic Tyrosine Kinase Inhibitors in Combination with Therapeutic Vaccines

    Science.gov (United States)

    Farsaci, Benedetto; Donahue, Renee N.; Coplin, Michael A.; Grenga, Italia; Lepone, Lauren M.; Molinolo, Alfredo A.; Hodge, James W.

    2014-01-01

    This study investigated the effects on the tumor microenvironment of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in 2 murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using 3 endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating T lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight junctions, and pressure, leading to vascular normalization and increased tumor oxygenation. This combination therapy also increased TILs, including tumor antigen-specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals. The improved antitumor activity induced by combining antiangiogenic TKIs with vaccine may be the result of activated lymphoid and myeloid cells in the tumor microenvironment, resulting from vascular normalization, decreased tumor-cell density, and the consequent improvement in vascular perfusion and oxygenation. Therapies that alter tumor architecture can thus have a dramatic impact on the effectiveness of cancer immunotherapy. PMID:25092771

  5. Obesity in Indian subjects with Vascular Dementia

    OpenAIRE

    Chandra, Mina; Anand, Kuljeet Singh Anand

    2015-01-01

    ABSTRACT Background: Obesity is considered a public health challenge in South Asia. Obesity is an independent risk factor in vascular dementia. It also contributes to other risk factors of vascular dementia like hypertension, coronary artery disease, dyslipidaemia and diabetes. As the rate of obesity in Indian subjects with vascular dementia is not known, we decided to assess obesity in subjects with vascular dementia. Methods: Subjects with vascular dementia presenting to Mem...

  6. Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.

    Science.gov (United States)

    Patel, Himadri; Nilendu, Pritish; Jahagirdar, Devashree; Pal, Jayanta K; Sharma, Nilesh Kumar

    2018-01-02

    The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.

  7. PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization.

    Science.gov (United States)

    Goldbrunner, Roland H; Bendszus, Martin; Wood, Jeanette; Kiderlen, Michael; Sasaki, Masato; Tonn, Jörg-Christian

    2004-08-01

    The aim of this study was to test the efficacy of PTK787/ZK222584, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, on VEGF-dependent glioma vascularization and growth. C6 rat glioma cells were transfected with VEGF(164) in a sense (V(+)) or antisense (V(-)) direction. Spheroids generated from V(+) or V(-) cells were implanted orthotopically into 60 rat brains. Expression of VEGF and fetal liver kinase-1 (VEGF receptor 2) was assessed immunohistochemically. Animals with V(+) gliomas received orally administered PTK787/ZK222584 on postoperative Day (POD) 1 to 12 or POD 7 to 12. Untreated animals served as negative controls, and animals with V(-) gliomas served as positive controls. Growth and vascularization were evaluated by magnetic resonance imaging and immunohistochemistry. Flk-1 expression was positive within tumor vessels in V(+) gliomas, whereas all C6 clones were negative for fetal liver kinase-1 in vitro. Early (POD 1-12) and delayed (POD 7-12) application of PTK787/ZK222584 in V(+) glioma-bearing animals resulted in a significant reduction of tumor size (71% and 36%, P new tool in malignant glioma therapy.

  8. Idiopathic sudden sensorineural hearing loss: vascular or viral?

    Science.gov (United States)

    Linthicum, Fred H; Doherty, Joni; Berliner, Karen I

    2013-12-01

    To demonstrate that sudden sensorineural hearing loss is possibly of viral origin rather than vascular. The histopathologic morphology in 7 temporal bones with known vascular impairment due to surgical interventions was compared with that of 11 bones with a history of idiopathic sudden sensorineural hearing loss (ISSNHL). Attention was paid to the spiral ligament, stria vascularis, organ of Corti hair cells, tectorial membrane, ganglion cell population, and degree of perilymph fibrosis and the auditory nerve. A temporal bone laboratory that has been in operation for more than 50 years and includes a database consisting of clinical and histopathological information that facilitates quantitative and qualitative analysis. Eight hundred forty-nine individuals who pledged their temporal bones for scientific study, of which 18 were selected for this study by means of the database criteria of sudden sensorineural hearing loss and postmiddle fossa and retro sigmoid sinus tumor removal or vestibular nerve section. Sudden sensorineural hearing loss bones exhibited no perilymph fibrosis compared with 6 of 7 vascular cases with fibrosis (P ≤ .001), exhibited less loss of ganglion cells (P ≤ .026), exhibited greater survival of spiral ligament (P ≤ .029), and averaged twice the survival of hair cells and more widespread tectorial membrane abnormalities. Analysis of human temporal bones from patients with a sudden sensorineural hearing loss does not support a vascular insufficiency but is more suggestive of a viral etiology.

  9. Vascular anomalies: A pictorial review of nomenclature, diagnosis and treatment

    Science.gov (United States)

    Nosher, John L; Murillo, Philip G; Liszewski, Mark; Gendel, Vyacheslav; Gribbin, Christopher E

    2014-01-01

    Vascular anomalies, including vascular malformations and tumors, are frequently straightforward to detect; however, accurate diagnosis and appropriate treatment are often challenging. Misdiagnosis of these lesions can lead clinicians in the wrong direction when treating these patients, which can have unfavorable results. This review presents an overview of the classification systems that have been developed for the diagnosis of vascular lesions with a focus on the imaging characteristics. Pictorial examples of each lesion on physical examination, as well as non-invasive and minimally invasive imaging are presented. An overview of the endovascular treatment of these lesions is also given. In some cases, vascular anomalies may be associated with an underlying syndrome and several of the most commonly encountered syndromes are discussed. Understanding of the classification systems, familiarity with the treatment options and knowledge of the associated syndromes are essential for all physicians working with this patient population. The approach to the described entities necessitates an organized multi-disciplinary team effort, with diagnostic imaging playing an increasingly important role in the proper diagnosis and a combined interventional radiologic and surgical treatment method showing promising results. PMID:25276311

  10. The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment.

    Science.gov (United States)

    Hendry, Shona A; Farnsworth, Rae H; Solomon, Benjamin; Achen, Marc G; Stacker, Steven A; Fox, Stephen B

    2016-01-01

    Recently developed cancer immunotherapy approaches including immune checkpoint inhibitors and chimeric antigen receptor T cell transfer are showing promising results both in trials and in clinical practice. These approaches reflect increasing recognition of the crucial role of the tumor microenvironment in cancer development and progression. Cancer cells do not act alone, but develop a complex relationship with the environment in which they reside. The host immune response to tumors is critical to the success of immunotherapy; however, the determinants of this response are incompletely understood. The immune cell infiltrate in tumors varies widely in density, composition, and clinical significance. The tumor vasculature is a key component of the microenvironment that can influence tumor behavior and treatment response and can be targeted through the use of antiangiogenic drugs. Blood vascular and lymphatic endothelial cells have important roles in the trafficking of immune cells, controlling the microenvironment, and modulating the immune response. Improving access to the tumor through vascular alteration with antiangiogenic drugs may prove an effective combinatorial strategy with immunotherapy approaches and might be applicable to many tumor types. In this review, we briefly discuss the host's immune response to cancer and the treatment strategies utilizing this response, before focusing on the pathological features of tumor blood and lymphatic vessels and the contribution these might make to tumor immune evasion.

  11. Trauma vascular, visión del cirujano vascular

    OpenAIRE

    Dr. D. Cristián Salas

    2011-01-01

    El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesi...

  12. Acidente vascular cerebral e demência vascular no idoso

    OpenAIRE

    Ionel, Cristina

    2015-01-01

    Trabalho final de mestrado integrado em Medicina, apresentado à Faculdade de Medicina da Universidade de Coimbra. Em consequência de um fenómeno global de envelhecimento populacional, é expectável um aumento na prevalência de demência. A demência vascular é a segunda causa mais comum de demência, depois da doença de Alzheimer. Trata-se de uma entidade clínica bastante heterogénea, sendo o acidente vascular cerebral (AVC) um dos seus mecanismos subjacentes. No entanto, nem todos os doentes ...

  13. Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Peng Fang; Wang Jin; Zou Yi; Bao Yong; Huang Wenlin; Chen Guangming; Luo Xianrong; Chen Ming

    2011-01-01

    Objective: To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods: Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results: Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. (authors)

  14. Jugular foramen tumors: diagnosis and treatment.

    Science.gov (United States)

    Ramina, Ricardo; Maniglia, Joao Jarney; Fernandes, Yvens Barbosa; Paschoal, Jorge Rizzato; Pfeilsticker, Leopoldo Nizan; Neto, Mauricio Coelho; Borges, Guilherme

    2004-08-15

    Jugular foramen tumors are rare skull base lesions that present diagnostic and complex management problems. The purpose of this study was to evaluate a series of patients with jugular foramen tumors who were surgically treated in the past 16 years, and to analyze the surgical technique, complications, and outcomes. The authors retrospectively studied 102 patients with jugular foramen tumors treated between January 1987 and May 2004. All patients underwent surgery with a multidisciplinary method combining neurosurgical and ear, nose, and throat techniques. Preoperative embolization was performed for paragangliomas and other highly vascularized lesions. To avoid postoperative cerebrospinal fluid (CSF) leakage and to improve cosmetic results, the surgical defect was reconstructed with specially developed vascularized flaps (temporalis fascia, cervical fascia, sternocleidomastoid muscle, and temporalis muscle). A saphenous graft bypass was used in two patients with tumor infiltrating the internal carotid artery (ICA). Facial nerve reconstruction was performed with grafts of the great auricular nerve or with 12th/seventh cranial nerve anastomosis. Residual malignant and invasive tumors were irradiated after partial removal. The most common tumor was paraganglioma (58 cases), followed by schwannomas (17 cases) and meningiomas (10 cases). Complete excision was possible in 45 patients (77.5%) with paragangliomas and in all patients with schwannomas. The most frequent and also the most dangerous surgical complication was lower cranial nerve deficit. This deficit occurred in 10 patients (10%), but it was transient in four cases. Postoperative facial and cochlear nerve paralysis occurred in eight patients (8%); spontaneous recovery occurred in three of them. In the remaining five patients the facial nerve was reconstructed using great auricular nerve grafts (three cases), sural nerve graft (one case), and hypoglossal/facial nerve anastomosis (one case). Four patients (4

  15. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation.

    Science.gov (United States)

    Takano, Shingo

    2012-04-01

    Glioblastomas are highly vascular tumors. Recent preclinical and clinical investigations have revealed that agents targeting angiogenesis may have efficacy against this type of tumor. Antibodies to vascular endothelial growth factor are being studied in this patient population. Unfortunately, treatment inevitably fails. This review provides an update on recent research on the mechanisms by which tumor cells acquire resistance, and discusses recent preclinical and experimental development of novel new-generation anti-angiogenic agents that overcome this problem, especially those based on the molecular mechanisms of tumor vessel formation. The tumor vasculature not only nourishes glioblastomas, but also provides a specialized microenvironment for tumor stem-like cells and for the brain tumor. The factors, pathways, and interactions described in this review provide information about the cell biology of glioblastomas which may ultimately result in new modes of treatment.

  16. Coupled Hybrid Continuum-Discrete Model of Tumor Angiogenesis and Growth.

    Directory of Open Access Journals (Sweden)

    Jie Lyu

    Full Text Available The processes governing tumor growth and angiogenesis are codependent. To study the relationship between them, we proposed a coupled hybrid continuum-discrete model. In this model, tumor cells, their microenvironment (extracellular matrixes, matrix-degrading enzymes, and tumor angiogenic factors, and their network of blood vessels, described by a series of discrete points, were considered. The results of numerical simulation reveal the process of tumor growth and the change in microenvironment from avascular to vascular stage, indicating that the network of blood vessels develops gradually as the tumor grows. Our findings also reveal that a tumor is divided into three regions: necrotic, semi-necrotic, and well-vascularized. The results agree well with the previous relevant studies and physiological facts, and this model represents a platform for further investigations of tumor therapy.

  17. Scintigraphic and radiologic aspects of two exceptional tumors at knee

    International Nuclear Information System (INIS)

    Lescout, J.M.; Bussy, E.; Tourrette, J.H.; Dussau, J.P.; Gadea, J.; Camelli, M.

    1997-01-01

    We present two cases of rare vascular tumors of knee which in the frame of the pre-surgery extension examination were successfully explored by the Osseous Scintigraphy (OS) and Magnetic Resonance Imagery (MRI). The first case was a young girl 17 years old accusing since two years a mechanical pain in the left knee, without radiographic or biologic anomalies. Early profile incidence of OS indicates an articular hyperemia of geometrical shape which later disappeared totally, what evoked the absence of osteoblastic activity of a hyper-vascularized lesion. The MRI showed the existence of an extraosseous tumor in the retro-patellar loge. The histologic analysis led to the diagnosis of synovial hemangioma, a rare benign tumor which benefited by a complete extirpation followed by rapid remission of walking. The second case was a male 53 years old which presented a painful right sub-patellar tumefaction with a major osteolysis of 1/3 upper tibia, by standard radiography. The OS in two phases indicated a unique hyper-vascularized very active osseous affliction. The MRI has confirmed the well circumscribed afflicted zone of the tibia's proximal metaphysis and showed an invasion of the soft parts. The pathologist concluded on a epithelial hemangioma-endothelioma, a vascular tumor of intermediate malignity which benefited by an extirpation with osseous graft showing no negative evolution after one year. In the vast frame of the skeletal tumors these exceptional vascular peri-articular afflictions allow illustrating the complementarity of OS and MRI which give to the surgery all the information useful for their extension on their more or less vascularized character and on their osteoblastic component

  18. Melanoma Exosomes Enable Tumor Tolerance in Lymph Nodes

    OpenAIRE

    Hood, Joshua L.

    2016-01-01

    Melanoma preferentially spreads via lymph nodes. Melanoma exosomes can induce angiogenesis and immune suppression. However, a role for melanoma exosomes in facilitating tumor tolerance in lymph nodes has not been considered. Herein, the hypothesis that melanoma exosome mediated induction of vascular endothelial cell (VEC) derived TNF-α results in lymphatic endothelial cell (LEC) mediated tumor tolerance is explored. To support this hypothesis, experiments involving ex vivo lymph node associat...

  19. [Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic].

    Science.gov (United States)

    Liu, Han-Min

    2013-10-01

    Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

  20. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  1. Modeling human endothelial cell transformation in vascular neoplasias.

    Science.gov (United States)

    Wen, Victoria W; MacKenzie, Karen L

    2013-09-01

    Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia.

  2. Bilateral carotid body tumor resection in a female patient

    Directory of Open Access Journals (Sweden)

    Alfred Burgess

    Full Text Available Introduction: Carotid body tumors also called carotid paragangliomas are rare neuroendocrine neoplasms derived from neural crest cells, approximately 3% of all paragangliomas occur in the head and neck area (Xiao and She, 2015; although they represent 65% of the head and neck paragangliomas (Georgiadis et al., 2008. Presentation of case: We present the therapeutic management of a 65-year-old woman with bilateral carotid body tumors. The patient presented to medical clinic for unrelated signs and symptoms of weight loss, dyspepsia, and epigastric pain. Physical examination showed bilateral non-tender neck masses for which imaging studies were ordered resulting in the diagnosis of bilateral carotid tumor. Surgical resection was staged with one week of distance between each tumor resection. Discussion: Carotid Body Tumors can arise from the paraganglia located within the adventitia of the medial aspect of the carotid bifurcation.Resection is the only curative treatment. Carotid body tumors resection represents a special challenge due to potential neurovascular complications. Conclusions: Surgical resection of carotid body tumors represents a special challenge to the surgeon because of the complex anatomical location of the tumor, including close relationship with the cranial nerves, involvement of the carotid vessels and large vascularization of the tumor. With the advance of diagnosis and improvement in surgical techniques as well as the understanding of biological behavior of tumors, surgical treatment has become a safer alternative for treating these tumors. Keywords: Carotid body tumor, Bilateral, Paraganglioma, Resection

  3. Urologic surgery laparoscopic access: vascular complications.

    Science.gov (United States)

    Branco, Anibal Wood

    2017-01-01

    Vascular injury in accidental punctures may occur in large abdominal vessels, it is known that 76% of injuries occur during the development of pneumoperitoneum. The aim of this video is to demonstrate two cases of vascular injury occurring during access in laparoscopic urologic surgery. The first case presents a 60-year old female patient with a 3cm tumor in the superior pole of the right kidney who underwent a laparoscopic partial nephrectomy. After the Verres needle insertion, output of blood was verified. During the evaluation of the cavity, a significant hematoma in the inferior vena cava was noticed. After the dissection, a lesion in the inferior vena cava was identified and controlled with a prolene suture, the estimated bloos loss was 300ml. The second case presents a 42-year old female live donor patient who had her right kidney selected to laparoscopic live donor nephrectomy. After the insertion of the first trocar, during the introduction of the 10mm scope, an active bleeding from the mesentery was noticed. The right colon was dissected and an inferior vena cava perforation was identified; a prolene suture was used to control the bleeding, the estimated blood loss was 200mL, in both cases the patients had no previous abdominal surgery. Urologists must be aware of this uncommon, serious, and potentially lethal complication. Once recognized and in the hands of experienced surgeons, some lesions may be repaired laparoscopically. Whenever in doubt, the best alternative is the immediate conversion to open surgery to minimize morbidity and mortality. Copyright® by the International Brazilian Journal of Urology.

  4. Imaging after vascular gene therapy

    International Nuclear Information System (INIS)

    Manninen, Hannu I.; Yang, Xiaoming

    2005-01-01

    Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy

  5. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale

    2011-01-01

    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  6. Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-12-15

    Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

  7. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor...

  8. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  9. Targeted Brain Tumor Treatment: Current Perspectives

    Directory of Open Access Journals (Sweden)

    Ningaraj N.S

    2007-01-01

    Full Text Available Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (KCa channels, and high grade glioma express specific KCa channel gene (gBK splice variants, and mutant epidermal growth factor receptors (EGFRvIII. These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.

  10. Targeted Brain Tumor Treatment-Current Perspectives

    Directory of Open Access Journals (Sweden)

    N.S. Ningaraj

    2007-01-01

    Full Text Available Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (K Ca channels, and high grade glioma express specific K Ca channel gene (gBK splice variants, and mutant epidermal growth factor receptors (EGFRvIII. These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.

  11. Vascular injuries caused by acupuncture.

    Science.gov (United States)

    Bergqvist, D

    2008-08-01

    To systematically review the literature on vascular injuries caused by acupuncture. Systematic literature search in Medline and PubMed. Twentyone cases were identified and the majority developed symptoms in direct connection with the acupuncture treatment. Three patients died, two from pericardial tamponade and one from an aortoduodenal fistula. There were five more tamponades, seven pseudoaneurysms, two with ischaemia, two with venous thrombosis, one with compartment syndrome and one with bleeding. The two patients with ischaemia had remaining sequeleae. Information on follow-up was suboptimal with no information in nine patients. Vascular injuries are rare, bleeding and pseudoaneurysm dominating. Follow-up is insufficient in the hitherto published papers.

  12. Vascular endothelial growth factor expression and angiogenesis in various grades and subtypes of meningioma

    Directory of Open Access Journals (Sweden)

    Priya Dharmalingam

    2013-01-01

    Full Text Available Background: Vascular endothelial growth factor (VEGF expression has been extensively studied in astrocytoma, whereas relatively less literature exists on VEGF expression in meningioma. Materials and Methods: Patients operated for meningioma from 2006 to 2011 (n = 46 were included. Tumor was subtyped and graded as per WHO grading. Immunohistochemistry was performed for MIB labeling index, VEGF, and CD 34 staining. The patterns of VEGF expression in various histological subtypes and grades and its correlation with microvascular density were analyzed. Results: This series consisted of 40 Grade I meningioma, 4 Grade II tumors, and 2 Grade III tumors. While 14 (30.4% tumors showed no staining with VEGF antibody, 32 (69.6% were positive for VEGF. Sixty five percent of Grade I tumors showed VEGF positivity, while 100% of Grade II and Grade III tumors were VEGF positive (P = 0.157. The mean microvascular density in VEGF-negative tumors was 9.00, while that of VEGF-positive tumors was 17.81(P = 0.013. There was a gradual increase in microvascular density from tumors which are negative for VEGF to tumors which expressed moderate to strong VEGF, the difference being statistically significant (P = 0.009. Conclusions: VEGF expression correlated with the microvascular density in meningioma irrespective of tumor grade, with a gradual increase in microvascular density in relation to the VEGF score.

  13. Vascular malforma- tions part 1 — normal and abnormal vascular ...

    African Journals Online (AJOL)

    Enrique

    Ang2 with VEGF produces loss of adhesion of endothelial cells allowing their migration to occur. 3. Fibroblast growth factor : (aFGF, bFGF). •. Are potent stimulators of endothelial cell migration, proliferation, sprouting and tube formation. •. Are mainly involved with vascular maintenance and repair. 4. Platelet derived factor ...

  14. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer.In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294].Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  15. Computed tomography of the orbital tumors

    International Nuclear Information System (INIS)

    Choi, Jai Korl; Lee, Hwang Bok; Kang, Eun Young; Seol, Hae Young; Suh, Won Hyuck; Ahn, Byeong Yeob

    1987-01-01

    The development of computed tomography (CT) provided a noninvasive safe technique for imaging the orbit in any plane exquisitely demonstrating its normal anatomy as well as its pathologic process. The orbit is an ideal structure to be examined by CT because of large difference of absorption values between the intraorbital fat, muscle, optic nerve and vessels. In this study, the authors reviewed CT findings of 66 pathologically proven orbital tumors and tumorous conditions among the total of 98 cases who had taken orbital CT scan because if exophthalmos, ocular pain, diplopia and other ophthalmologic symptoms suggesting orbital masses during the period of 3 years. For the analysis of characteristic CT findings of the orbital lesions, all lesions are divided into 4 groups according to the site of origin, i.e., tumors arising in the eyeball (group 1); from intraconal space (group 2); from extraconal space (group 3); and from extraorbital regions (group 4). The results are as follows; 1.Extra tumor detection and localization was possible in 63 cases. Thus the detection rate was 95% with CT scan. 2.Among 36 males and 30 females, their age ranged from 10 months to 72 years. 3.Intraocular tumors (group 1) were 10 cases. Retinoblastoma occurred wholly in the young children under 5 years and combined with calcification in 57%. Choroidal melanoma occurred wholly in adults. 4.Intraconal tumors (group 2) were 9 cases. Vascular tumors (7 cases) were the most frequent and well enhancing mass. 5.The tumors arising in the extraconal region (group 3) were pseudotumor (12 cases), lymphoma (3 cases), dermoid cyst (4 cases), metastasis (2 cases), adenoid cystic carcinoma (1 case) and teratoma (1 case). A case of lymphoma demonstrating retrobulbar ill defined mass with scleral l thickening could not be differentiated from the pseudotumor which showing similar finding. 6.The lesions arising from extraorbital region (group 4) were PNS cancer (9 cases), mucocele (3 cases), lid cancer (4

  16. Malignant bone tumors of the pelvis and of the extremities

    International Nuclear Information System (INIS)

    Gullotta, U.; Reiser, M.; Feuerbach, S.; Biehl, T.; Technische Univ. Muenchen

    1981-01-01

    Bone tumors of the extremities are usually diagnosed by conventional radiography. A good angiogram may render information not only about intra- and extraosseous extension of the tumor, but often also about the biological dignity. CT is usually not necessary, especially since it is sometimes difficult to define the extraosseous borders of these extremity tumors with this method. In bone tumors of the pelvis, however, neither conventional radiography nor angiography render reliable information about the extent of the tumor, which CT is very well able to do. Therefore CT is primarily indicated for evaluation of bone tumors in this region. Angiography is done only for preoperative evaluation of the vascular architecture or for potential therapeutic embolisation. (orig.) [de

  17. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  18. Pericyte–fibroblast transition promotes tumor growth and metastasis

    Science.gov (United States)

    Hosaka, Kayoko; Yang, Yunlong; Seki, Takahiro; Fischer, Carina; Dubey, Olivier; Fredlund, Erik; Hartman, Johan; Religa, Piotr; Ishii, Yoko; Sasahara, Masakiyo; Larsson, Ola; Cossu, Giulio; Cao, Renhai; Lim, Sharon; Cao, Yihai

    2016-01-01

    Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB–activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB–induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB–promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis. PMID:27608497

  19. Cross-border reproductive care for law evasion: should physicians be allowed to help infertility patients evade the law of their own country?

    Science.gov (United States)

    Van Hoof, Wannes; Pennings, Guido; De Sutter, Petra

    2016-07-01

    There are fundamental differences between countries with regard to legislation on assisted reproduction. Many infertility patients are looking to evade the law of their own country and make use of reproductive services abroad. The role of the local physician in cross-border reproductive care for law evasion has been characterized as "channeling local patients to foreign medical establishments" and "against the spirit and essence of the law". The logical view is that by supporting CBRC for law evasion, physicians are essentially supporting immoral behavior. We will tackle this position on two levels. First, we will argue that governments should generally be tolerant toward people with different positions on assisted reproduction. Second, we will show that contributing to cross-border reproductive care for law evasion is not necessarily immoral, because the prima facie wrongness of complicity in law evasion can be outweighed by the fact that physicians should act in the best interest of the patient. Several countries have tried to prevent local physicians from helping patients to make use of reproductive services abroad, but they should rather leave it up to the individual physicians to decide whether or not to support a particular patient. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Association of tumor angiogenesis with bone marrow micrometastases in breast cancer patients.

    Science.gov (United States)

    Fox, S B; Leek, R D; Bliss, J; Mansi, J L; Gusterson, B; Gatter, K C; Harris, A L

    1997-07-16

    The microscopic detection of tumor cells (micrometastases) in bone marrow and the extent of blood vessel formation (angiogenesis) in primary tumor specimens are recognized as independent prognostic markers in patients with breast cancer. Since micrometastases occur as a consequence of interaction between the neoplastic cells and the tumor neovasculature, we have examined the relationship between these markers to determine whether the degree of angiogenesis is related to the presence of micrometastases. Micrometastases were identified in bone marrow aspirates collected from multiple sites in 214 breast cancer patients prior to surgery (mastectomy or lumpectomy). Tumor cells were detected through an examination of epithelial membrane antigen expression and an analysis of cell morphology. Tumor vascularity was graded semiquantitatively or quantitatively (Chalkley point count) after immunohistochemical staining of the CD31 antigen expressed by the endothelial cells. The reproducibility and accuracy of the vascular grading were validated by use of kappa statistics. Associations between micrometastases and clinicopathologic characteristics, including angiogenesis, were examined using chi-squared and logistic regression techniques. All tests of statistical significance were two-sided. Of the 214 patients, 42 (20%) were positive for bone marrow micrometastases and 75 (35%) had tumors of high vascular grade. There was 86% agreement between vascular grades assessed twice for 35 tumors (kappa statistic = 0.66); for 22 evaluated tumors, there was absolute concordance between vascular grade and Chalkley point count. There were significant positive associations between tumor angiogenesis and micrometastasis (P = .01), tumor grade (P = .003), and estrogen receptor expression (P = .007); however, no significant associations were observed with tumor size (P = .9), lymph node status (P = .33), vascular invasion (peritumoral blood or lymph vessels) (P = .9), menopausal status (P

  1. A poly(l-glutamic acid)-combretastatin A4 conjugate for solid tumor therapy: Markedly improved therapeutic efficiency through its low tissue penetration in solid tumor.

    Science.gov (United States)

    Liu, Tianzhou; Zhang, Dawei; Song, Wantong; Tang, Zhaohui; Zhu, Jiaming; Ma, Zhiming; Wang, Xudong; Chen, Xuesi; Tong, Ti

    2017-04-15

    Combretastatin A4 (CA4) is a leading agent in vascular disrupting strategies for tumor therapy. Although many small-molecule prodrugs of CA4 have been developed to improve its solubility, the overall therapeutic efficiency is moderate. A key reason for this is the reversible effect that CA4 has on tubulin as well as its rapid clearance from plasma and tissues. In this study, we proposed a poly(l-glutamic acid)-CA4 conjugate (PLG-CA4) nanomedicine to fulfill the requirements for fully liberating the potential of CA4 on tumor therapy. Enhanced accumulation and retention of CA4 in tumor tissue, especially, high distribution and gradual release around tumor blood vessels resulted in prolonged vascular disruption and markedly enhanced therapeutic efficiency. We examined and compared the therapeutic effect of PLG-CA4 and commercial combretastatin-A4 phosphate (CA4P) in a murine colon C26 tumor. PLG-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, the PLG-CA4 was mainly distributed around the tumor vessels because of its low tissue penetration in solid tumor. Pathology tests showed that PLG-CA4 treatment resulted in persistent vascular disruption and tumor damage 72h after a single injection, this in contrast to CA4P treatment, which showed quick relapse at an equal dose. Tumor suppression tests showed that PLG-CA4 treatment resulted in a tumor suppression rate of 74%, which indicates a significant advantage when compared to tumor suppression rate of the CA4P group, which was 24%. This is the first time that an advantage of the polymeric CA4 nanomedicine with low tissue penetration for solid tumor therapy has been shown. Thus, the results presented in this study provide a new idea for enhancing the tumor therapeutic effect of vascular disrupting agents. Nanomedicine usually has low tissue penetration in solid tumors, which limits the efficacy of nanomedicine in most cases. But herein, we demonstrate a nanosized vascular disruptive

  2. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Energy Technology Data Exchange (ETDEWEB)

    Stagg, Brian C., E-mail: briancstagg@gmail.com; Uehara, Hironori; Lambert, Nathan; Rai, Ruju; Gupta, Isha; Radmall, Bryce; Bates, Taylor; Ambati, Balamurali K. [John A Moran Eye Center, University of Utah, Salt Lake City, UT, 65 Mario Capecchi Drive, Salt Lake City, UT 84132 (United States)

    2014-11-26

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

  3. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  4. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  5. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  6. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  7. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  8. Tumor necrosis factor induces tumor promoting and anti-tumoral effects on pancreatic cancer via TNFR1.

    Directory of Open Access Journals (Sweden)

    Martin Chopra

    Full Text Available Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5%, TNF deficient (12.5%, and TNFR2 deficient mice (22.2% were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4(+ T cells and CD4(+ forkhead box P3 (FoxP3(+ regulatory T cells (Treg but reduced numbers of CD8(+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8(+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.

  9. Vascular cognitive impairment in dementia.

    Science.gov (United States)

    Etherton-Beer, Christopher D

    2014-10-01

    Vascular risk factors and cerebrovascular disease are common causes of dementia. Shared risk factors for vascular dementia and Alzheimer's disease, as well as frequent coexistence of these pathologies in cognitively impaired older people, suggests convergence of the aetiology, prevention and management of the commonest dementias affecting older people. In light of this understanding, the cognitive impairment associated with cerebrovascular disease is an increasingly important and recognised area of the medicine of older people. Although the incidence of cerebrovascular events is declining in many populations, the overall burden associated with brain vascular disease will continue to increase associated with population ageing. A spectrum of cognitive disorders related to cerebrovascular disease is now recognised. Cerebrovascular disease in older people is associated with specific clinical and imaging findings. Although prevention remains the cornerstone of management, the diagnosis of brain vascular disease is important because of the potential to improve clinical outcomes through clear diagnosis, enhanced control of risk factors, lifestyle interventions and secondary prevention. Specific pharmacological intervention may also be indicated for some patients with cognitive impairment and cerebrovascular disease. However the evidence base to guide intervention remains relatively sparse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Vascular involvement in tuberous sclerosis.

    Science.gov (United States)

    Salerno, Ann E; Marsenic, Olivera; Meyers, Kevin E C; Kaplan, Bernard S; Hellinger, Jeffrey C

    2010-08-01

    Vascular involvement in tuberous sclerosis (TS) is rare. Central and peripheral aneurysms and large and medium size arterial stenotic-occlusive disease have been reported in patients with TS. We present here three pediatric patients with TS and severe vascular abnormalities, followed by a review of the literature. The three cases include a 14-month-old girl with polycystic kidneys and cerebral tubers who had a large asymptomatic abdominal aortic aneurysm, a 2-year-old boy with multiple features of TS who had hypertension and was found to have mid-aortic syndrome with bilateral renal artery stenosis, and an 18-year-old girl with abdominal pain and TS features who had greater than 70% celiac artery stenosis. In all cases, noninvasive vascular imaging modalities were utilized for either initial diagnosis, surveillance, or both. These cases highlight the collaborative roles of the pediatric nephrologist and cardiovascular imager in the diagnosis and management of the vascular complications in TS patients. Appropriate care can only be made through a high index of suspicion.

  11. Postprandial lipaemia and vascular disease.

    Science.gov (United States)

    Kolovou, Genovefa; Ooi, Teik Chye

    2013-07-01

    In this review we discuss the postprandial pathophysiological mechanisms that promote vascular disease, the evidence for a role of postprandial lipaemia (PPL) in vascular disease and the effect of modifiable and nonmodifiable factors in PPL. PPL refers to the dynamic changes in serum lipids and lipoproteins (mainly in serum triglycerides) that occur after a fat load or a meal. Recent data indicate that postprandial or nonfasting triglyceride levels are better predictors of cardiovascular risk, suggesting that efficiency of postprandial handling of triglyceride-rich lipoproteins plays a role in the causation of vascular disease. The recent finding that postprandial serum triglyceride levels are even better than fasting serum triglyceride levels as predictors of vascular disease indicate that it is better to measure an index of triglyceride-rich lipoproteins (in most cases serum triglyceride levels) in the postprandial period than in the postabsorptive fasting state. Moreover, by the time the postabsorptive state is reached, some of these proatherogenic triglyceride-rich lipoprotein changes may be missed in the measurement.

  12. Peripheral vascular imaging and intervention

    International Nuclear Information System (INIS)

    Kim, D.; Orron, D.E.

    1990-01-01

    This reference addresses the entire clinical approach to the vascular system from the diagnosis of pathology to surgery or interventional radiological management. All diagnostic imaging modalities currently available are included with specific information on how to interpret various results. It features discussions of the latest therapeutic techniques, including laser angioplasty, intravascular stents, and transluminal embolization

  13. Limb vascular function in women

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Gliemann, Lasse

    2018-01-01

    tone and oxidative stress and thereby functions such as oxygen delivery and blood pressure. The acute hormonal fluctuations do not substantially impact health, but their influence should be considered with regard to measurements of vascular function. The chronic hormonal change with menopause strongly...

  14. FOTOPROTECCION EN PLANTAS VASCULARES ANTARTICAS.

    OpenAIRE

    PEREZ TORRES, EDUARDO; PEREZ TORRES, EDUARDO

    2006-01-01

    Colobanthus quitensis y Deschampsia antarctica son las únicas plantas vasculares que han colonizado de manera natural la Antártida Marítima, donde resisten episodios de alta intensidad lumínica y baja temperatura, condiciones que combinadas suelen causar 83p.

  15. Image Quality in Vascular Radiology

    International Nuclear Information System (INIS)

    Vanhavere, F.; Struelens, L.

    2005-01-01

    In vascular radiology, the radiologists use the radiological image to diagnose or treat a specific vascular structure. From literature, we know that related doses are high and that large dose variability exists between different hospitals. The application of the optimization principle is therefore necessary and is obliged by the new legislation. So far, very little fieldwork has been performed and no practical instructions are available to do the necessary work. It's indisputable that obtaining quantitative data is of great interest for optimization purposes. In order to gain insight into these doses and the possible measures for dose reduction, we performed a comparative study in 7 hospitals. Patient doses will be measured and calculated for specific procedures in vascular radiology and evaluated against their most influencing parameters. In view of optimization purposes, a protocol for dose audit will be set-up. From the results and conclusions in this study, experimentally based guidelines will be proposed, in order to improve clinical practice in vascular radiology

  16. Blocking Blood Flow to Solid Tumors by Destabilizing Tubulin: An Approach to Targeting Tumor Growth.

    Science.gov (United States)

    Pérez-Pérez, María-Jesús; Priego, Eva-María; Bueno, Oskía; Martins, Maria Solange; Canela, María-Dolores; Liekens, Sandra

    2016-10-13

    The unique characteristics of the tumor vasculature offer the possibility to selectively target tumor growth and vascularization using tubulin-destabilizing agents. Evidence accumulated with combretastatin A-4 (CA-4) and its prodrug CA-4P support the therapeutic value of compounds sharing this mechanism of action. However, the chemical instability and poor solubility of CA-4 demand alternative compounds that are able to surmount these limitations. This Perspective illustrates the different classes of compounds that behave similar to CA-4, analyzes their binding mode to αβ-tubulin according to recently available structural complexes, and includes described approaches to improve their delivery. In addition, dissecting the mechanism of action of CA-4 and analogues allows a closer insight into the advantages and drawbacks associated with these tubulin-destabilizing agents that behave as vascular disrupting agents (VDAs).

  17. A proposed grading system for standardizing tumor consistency of intracranial meningiomas.

    Science.gov (United States)

    Zada, Gabriel; Yashar, Parham; Robison, Aaron; Winer, Jesse; Khalessi, Alexander; Mack, William J; Giannotta, Steven L

    2013-12-01

    Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency

  18. Obesity-induced vascular inflammation involves elevated arginase activity.

    Science.gov (United States)

    Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

    2017-11-01

    Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-( S )-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

  19. MRI of mediastinal tumor in children

    International Nuclear Information System (INIS)

    Inuzuka, Michiko; Aida, Noriko; Nishi, Toshiji; Nishihira, Hirokazu; Odagiri, Kunio; Katsumata, Yasushi.

    1994-01-01

    We reviewed MRI findings in 15 children with mediastinal tumors before operation or biopsy. Their pathological diagnosis were: 4 neuroblastomas, 3 bronchogenic cysts, 2 mature teratomas, 2 malignant lymphomas, an immature teratoma, a PNET, a BPFM and a ganglioneuroblastoma. We evaluated the usefulness and the limits of MRI. MRI was not more useful than CT for the pathological differential diagnosis of tumors with the exception of cystic lesion. MRI was useful in distinguishing the interface between tumor and spine, and the vascular system. Therefore, it was very efficient before treatment including surgery. Two cases were followed up after operation, chemotherapy and radiation. We believe that MRI will replace invasive imaging modalities such as angiography and myelography. (author)

  20. Tumors of the spinal cord and canal

    International Nuclear Information System (INIS)

    Karlsson, U.L.; Brady, L.W.

    1987-01-01

    Most spine (primary and secondary) neoplasms should receive curative or palliative radiation therapy. Data from the literature support its use as a beneficial treatment modality. Meningiomas and neurofibromas should be resected and irradiated postoperatively if removed subtotally or if the histopathology is malignant. The prognosis for patients with these tumors is generally good. Intramedullary tumors should be biopsied and irradiated when neoplastic histology has been established. The prognosis for these patients is unsatisfactory for high-grade astrocytomas but is more reasonable for ependymomas and vascular malformations. A favorable exception may be the myxopapillary ependymoma in the lumbosacral region. It should be maximally resected with sparing of cauda equina function but then irradiated postoperatively. The primary intent should be to eradicate the tumor. Radiation therapy is the main treatment modality, with steroid medication, in cases of cord compression

  1. Molecular, colloidal and cellular approaches to attack tumor vasculature

    NARCIS (Netherlands)

    Fens, M.H.A.M.

    2009-01-01

    This thesis is focused on improvement of blood vessel disruption. New systems have been developed that effectuate tumor blood vessel disruption at the molecular, colloidal and cellular level. Vascular disrupting agents (VDAs) are generally small molecular weight drugs that bind to cytoskeletal

  2. PTEN hamartoma tumor syndrome and Gorham-Stout phenomenon

    NARCIS (Netherlands)

    Hopman, Saskia M. J.; van Rijn, Rick R.; Eng, Charis; Bras, Johannes; Alders, Marielle; van der Horst, Chantal M.; Hennekam, Raoul C. M.; Merks, Johannes H. M.

    2012-01-01

    PTEN hamartoma tumor syndrome (PHTS) is a group of syndromes caused by mutations in PTEN. GorhamStout phenomenon (GSP) is a rare condition characterized by proliferation of vascular structures in bones, resulting in progressive osteolysis. Here we present a 1-year-old boy with PHTS and GSP. The

  3. Combination of nanotechnology with vascular targeting agents for effective cancer therapy.

    Science.gov (United States)

    Jahanban-Esfahlan, Rana; Seidi, Khaled; Banimohamad-Shotorbani, Behnaz; Jahanban-Esfahlan, Ali; Yousefi, Bahman

    2018-04-01

    As a young science, nanotechnology promptly integrated into the current oncology practice. Accordingly, various nanostructure particles were developed to reduce drug toxicity and allow the targeted delivery of various diagnostic and therapeutic compounds to the cancer cells. New sophisticated nanosystems constantly emerge to improve the performance of current anticancer modalities. Targeting tumor vasculature is an attractive strategy to fight cancer. Though the idea was swiftly furthered from basic science to the clinic, targeting tumor vasculature had a limited potential in patients, where tumors relapse due to the development of multiple drug resistance and metastasis. The aim of this review is to discuss the advantages of nanosystem incorporation with various vascular targeting agents, including (i) endogen anti-angiogenic agents; (ii) inhibitors of angiogenesis-related growth factors; (iii) inhibitors of tyrosine kinase receptors; (iv) inhibitors of angiogenesis-related signaling pathways; (v) inhibitors of tumor endothelial cell-associated markers; and (vi) tumor vascular disrupting agents. We also review the efficacy of nanostructures as natural vascular targeting agents. The efficacy of each approach in cancer therapy is further discussed. © 2017 Wiley Periodicals, Inc.

  4. Radiolabeling of VEGF(165) with Tc-99m to evaluate VEGFR expression in tumor angiogenesis

    NARCIS (Netherlands)

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Agostinelli, Enzo; Dierckx, Rudi A. J. O.; Signore, Alberto

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool

  5. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-07-15

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  6. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor...... (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...

  7. Pediatric central nervous system vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Ezra A. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Orbach, Darren B. [Boston Children' s Hospital, Neurointerventional Radiology, Boston, MA (United States)

    2015-09-15

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  8. Pediatric central nervous system vascular malformations

    International Nuclear Information System (INIS)

    Burch, Ezra A.; Orbach, Darren B.

    2015-01-01

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  9. ESRD QIP - Vascular