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Sample records for tumor-associated blood vessels

  1. Tumor Blood Vessel Dynamics

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    Munn, Lance

    2009-11-01

    ``Normalization'' of tumor blood vessels has shown promise to improve the efficacy of chemotherapeutics. In theory, anti-angiogenic drugs targeting endothelial VEGF signaling can improve vessel network structure and function, enhancing the transport of subsequent cytotoxic drugs to cancer cells. In practice, the effects are unpredictable, with varying levels of success. The predominant effects of anti-VEGF therapies are decreased vessel leakiness (hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence perfusion of the vessel network, inducing flow in regions that were previously sluggish or stagnant. Unfortunately, when anti-VEGF therapies affect vessel structure and function, the changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization ``window'' during which perfusion and subsequent drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to network structural changes in clinical trials or animal studies. We have developed a mathematical model to calculate blood flow in complex tumor networks imaged by two-photon microscopy. The model incorporates the necessary and sufficient components for addressing the problem of normalization of tumor vasculature: i) lattice-Boltzmann calculations of the full flow field within the vasculature and within the tissue, ii) diffusion and convection of soluble species such as oxygen or drugs within vessels and the tissue domain, iii) distinct and spatially-resolved vessel hydraulic conductivities and permeabilities for each species, iv) erythrocyte particles advecting in the flow and delivering oxygen with real oxygen release kinetics, v) shear stress-mediated vascular remodeling. This model, guided by multi-parameter intravital imaging of tumor vessel structure

  2. Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

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    Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

    2017-12-01

    Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

  3. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

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    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  4. Molecular imaging of tumor blood vessels in prostate cancer.

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    Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

    2009-05-01

    In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

  5. Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip

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    Guo, Peng; Huang, Jing; Moses, Marsha A.

    2018-02-01

    Angiogenesis, the formation of new blood vessels from existing ones, is a biological process that has an essential role in solid tumor growth, development, and progression. Recent advances in Lab-on-a-Chip technology has created an opportunity for scientists to observe endothelial cell (EC) behaviors during the dynamic process of angiogenesis using a simple and economical in vitro platform that recapitulates in vivo blood vessel formation. Here, we use quantitative phase imaging (QPI) microscopy to continuously and non-invasively characterize the dynamic process of tumor cell-induced angiogenic sprout formation on a microfluidic chip. The live tumor cell-induced angiogenic sprouts are generated by multicellular endothelial sprouting into 3 dimensional (3D) Matrigel using human umbilical vein endothelial cells (HUVECs). By using QPI, we quantitatively measure a panel of cellular morphological and behavioral parameters of each individual EC participating in this sprouting. In this proof-of-principle study, we demonstrate that QPI is a powerful tool that can provide real-time quantitative analysis of biological processes in in vitro 3D biomimetic devices, which, in turn, can improve our understanding of the biology underlying functional tissue engineering.

  6. Antibody-linked drug destroys tumor cells and tumor blood vessels in many types of cancer | Center for Cancer Research

    Science.gov (United States)

    A team led by Brad St. Croix, Ph.D., Senior Associate Scientist, Mouse Cancer Genetics Program, has developed an antibody-drug conjugate (ADC) that destroys both tumor cells and the blood vessels that nourish them. The drug significantly shrank breast tumors, colon tumors and several other types of cancer and prolonged survival. Learn more...  

  7. 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

  8. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

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    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  9. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

    International Nuclear Information System (INIS)

    Wang, Q.; Deng, Z. S.; Liu, J.

    2012-01-01

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  10. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

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    Wang, Q. [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China); Deng, Z. S. [Chinese Academy of Sciences, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry (China); Liu, J., E-mail: jliubme@tsinghua.edu.cn [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China)

    2012-07-15

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  11. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

    Science.gov (United States)

    Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

    2016-10-04

    Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

  12. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

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    McKeage, Mark J; Baguley, Bruce C

    2010-04-15

    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

  13. Aminopeptidase A is a functional target in angiogenic blood vessels.

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    Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A; Hajitou, Amin; Ozawa, Michael G; Trepel, Martin; Giordano, Ricardo J; Nanus, David M; Dijkman, Henri B P M; Oosterwijk, Egbert; Sidman, Richard L; Cooper, Max D; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

    2004-02-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.

  14. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

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    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  15. Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    International Nuclear Information System (INIS)

    Nigg, D.W.

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  16. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

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    Mirco Galiè

    2005-05-01

    Full Text Available 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.

  17. Gene expression analysis in human breast cancer associated blood vessels.

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    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  18. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents1

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    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

  19. Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

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    Lin CY

    2012-04-01

    Full Text Available Chung-Yin Lin1*, Hsiao-Ching Tseng1*, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US sonication with microbubbles (MBs has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage with PLD 6 (or 4 mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1 US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2 for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3 with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4 for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg, the tumor size still increased for several days and then decreased (a biphasic pattern; (5 MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood

  20. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads

    International Nuclear Information System (INIS)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-01-01

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes

  1. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

    Science.gov (United States)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-05-21

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

  2. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

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    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  3. Quantitative ex-vivo micro-computed tomographic imaging of blood vessels and necrotic regions within tumors.

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    Downey, Charlene M; Singla, Arvind K; Villemaire, Michelle L; Buie, Helen R; Boyd, Steven K; Jirik, Frank R

    2012-01-01

    Techniques for visualizing and quantifying the microvasculature of tumors are essential not only for studying angiogenic processes but also for monitoring the effects of anti-angiogenic treatments. Given the relatively limited information that can be gleaned from conventional 2-D histological analyses, there has been considerable interest in methods that enable the 3-D assessment of the vasculature. To this end, we employed a polymerizing intravascular contrast medium (Microfil) and micro-computed tomography (micro-CT) in combination with a maximal spheres direct 3-D analysis method to visualize and quantify ex-vivo vessel structural features, and to define regions of hypoperfusion within tumors that would be indicative of necrosis. Employing these techniques we quantified the effects of a vascular disrupting agent on the tumor vasculature. The methods described herein for quantifying whole tumor vascularity represent a significant advance in the 3-D study of tumor angiogenesis and evaluation of novel therapeutics, and will also find potential application in other fields where quantification of blood vessel structure and necrosis are important outcome parameters.

  4. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?

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    Donnem, Tom; Hu, Jiangting; Ferguson, Mary; Adighibe, Omanma; Snell, Cameron; Harris, Adrian L; Gatter, Kevin C; Pezzella, Francesco

    2013-08-01

    Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10-30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.

  5. Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

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    Mathivet, Thomas; Bouleti, Claire; Van Woensel, Matthias; Stanchi, Fabio; Verschuere, Tina; Phng, Li-Kun; Dejaegher, Joost; Balcer, Marly; Matsumoto, Ken; Georgieva, Petya B; Belmans, Jochen; Sciot, Raf; Stockmann, Christian; Mazzone, Massimiliano; De Vleeschouwer, Steven; Gerhardt, Holger

    2017-12-01

    Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  6. Aminopeptidase A is a functional target in angiogenic blood vessels.

    NARCIS (Netherlands)

    Marchio, S.; Lahdenranta, J.; Schlingemann, R.O.; Valdembri, D.; Wesseling, P.; Arap, M.A.; Hajitou, A.; Ozawa, M.G.; Trepel, M.; Giordano, R.J.; Nanus, D.M.; Dijkman, H.B.P.M.; Oosterwijk, E.; Sidman, R.L.; Cooper, M.D.; Bussolino, F.; Pasqualini, R.; Arap, W.

    2004-01-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

  7. Aminopeptidase A is a functional target in angiogenic blood vessels

    NARCIS (Netherlands)

    Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O.; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A.; Hajitou, Amin; Ozawa, Michael G.; Trepel, Martin; Giordano, Ricardo J.; Nanus, David M.; Dijkman, Henri B. P. M.; Oosterwijk, Egbert; Sidman, Richard L.; Cooper, Max D.; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

    2004-01-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

  8. Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

    International Nuclear Information System (INIS)

    Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

    1984-01-01

    Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

  9. Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.

    Science.gov (United States)

    Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Park, Jung Hee; Yan, Hong Hua; Fang, Zhenghuan; Kang, Yeo Wool; Han, Boreum; Lim, Joo Han; Hong, Soon-Sun

    2017-09-10

    Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply.

    Science.gov (United States)

    Yang, Zhigang; Yao, Hong; Fei, Fei; Li, Yuwei; Qu, Jie; Li, Chunyuan; Zhang, Shiwu

    2018-04-01

    During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels. In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia. An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.

  11. Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

    Science.gov (United States)

    Itkin, Tomer; Rafii, Shahin

    2017-09-11

    In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

  12. Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer

    Directory of Open Access Journals (Sweden)

    Pohida Thomas J

    2006-03-01

    Full Text Available Abstract Background A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. Methods Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method. Results Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. Conclusion We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.

  13. Non-invasive assessment of vessel morphology and function in tumors by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kiessling, Fabian; Jugold, Manfred; Woenne, Eva C.; Brix, Gunnar

    2007-01-01

    The switch to an angiogenic phenotype is an important precondition for tumor growth, invasion and spread. Since newly formed vessels are characterized by structural, functional and molecular abnormalities, they offer promising targets for tumor diagnosis and therapy. Previous studies indicate that MRI is valuable to assess vessel morphology and function. It can be used to distinguish between benign and malignant lesions and to improve delineation of proliferating areas within heterogeneous tumors. In addition, tracer kinetic analysis of contrast-enhanced image series allows the estimation of well-defined physiological parameters such as blood volume, blood flow and vessel permeability. Frequently, changes of these parameters during cytostatic, anti-angiogenic and radiation therapy precede tumor volume reduction. Moreover, target-specific MRI techniques can be used to elucidate the expression of angiogenic markers at the molecular level. This review summarizes strategies for non-invasive characterization of tumor vascularization by functional and molecular MRI, hereby introducing representative preclinical and clinical applications. (orig.)

  14. An integrated 3-D image of cerebral blood vessels and CT view of tumor

    International Nuclear Information System (INIS)

    Suetens, P.; Baert, A.L.; Gybels, J.; Haegemans, S.; Jansen, P.; Oosterlinck, A.; Wilms, G.

    1984-01-01

    The authors developed a method that yields an integrated three-dimensional image of cerebral blood vessels and CT view of tumor. This method allows the neurosurgeon to choose any electrode trajectory that looks convenient to him, without imminent danger of causing a hemorrhage. Besides offering more safety to stereotactic interventions, this integrated 3-D image also has other applications. First, it gives a better characterization of most focal mass lesions seen by CT. Second, it allows high dose focal irradiation to be effected in such a way as to avoid arteries and veins. Third, it provides useful information for planning the strategy of open surgery

  15. Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels.

    Science.gov (United States)

    Mahal, Katharina; Resch, Marcus; Ficner, Ralf; Schobert, Rainer; Biersack, Bernhard; Mueller, Thomas

    2014-04-01

    Two analogues of the discontinued tumor vascular-disrupting agent verubulin (Azixa®, MPC-6827, 1) featuring benzo-1,4-dioxan-6-yl (compound 5 a) and N-methylindol-5-yl (compound 10) residues instead of the para-anisyl group on the 4-(methylamino)-2-methylquinazoline pharmacophore, were prepared and found to exceed the antitumor efficacy of the lead compound. They were antiproliferative with single-digit nanomolar IC50 values against a panel of nine tumor cell lines, while not affecting nonmalignant fibroblasts. Indole 10 surpassed verubulin in seven tumor cell lines including colon, breast, ovarian, and germ cell cancer cell lines. In line with docking studies indicating that compound 10 may bind the colchicine binding site of tubulin more tightly (Ebind =-9.8 kcal mol(-1) ) than verubulin (Ebind =-8.3 kcal mol(-1) ), 10 suppressed the formation of vessel-like tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic membrane of fertilized chicken eggs at nanomolar concentrations. When applied to nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor, compound 10 displayed pronounced vascular-disrupting effects that led to hemorrhages and extensive central necrosis in the tumor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation.

    Science.gov (United States)

    Le, Catherine T K; Laidlaw, Grace; Morehouse, Christopher A; Naiman, Brian; Brohawn, Philip; Mustelin, Tomas; Connor, Jane R; McDonald, Donald M

    2015-11-01

    Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findings demonstrate that Ang2 and TNF are essential and synergistic drivers of remodeling of blood vessels and lymphatics during the initial stage of inflammation after infection. Inhibition of Ang2 and TNF together results in widespread suppression of the inflammatory response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. The impact of including spatially longitudinal heterogeneities of vessel oxygen content and vascular fraction in 3D tumor oxygenation models on predicted radiation sensitivity.

    Science.gov (United States)

    Lagerlöf, Jakob H; Kindblom, Jon; Bernhardt, Peter

    2014-04-01

    from 0% to 97%, and a maximal D99 increment of 57%. Only minor differences were observed between different vessel architectures, i.e., CVF vs VVF. In the smallest tumor with a low necrotic fraction, the D99 strictly decreased with increasing blood velocity. Increasing blood velocity also decreased the necrotic fraction in all tumor sizes. VF had the most profound influence on both the necrotic fraction and on D99. Our present analysis of necrotic formation and the impact of tumor oxygenation on D99 demonstrated the importance of including longitudinal variations in vessel oxygen content in tumor models. For small tumors, radiosensitivity was particularly dependent on VF and slightly dependent on the blood velocity and vessel arrangement. These dependences decreased with increasing tumor size, because the necrotic fraction also increased, thereby decreasing the number of viable tumor cells that required sterilization. The authors anticipate that the present model will be useful for estimating tumor oxygenation and radiation response in future detailed studies. © 2014 American Association of Physicists in Medicine.

  18. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE).

    Science.gov (United States)

    Kos, Bor; Voigt, Peter; Miklavcic, Damijan; Moche, Michael

    2015-09-01

    Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated. The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy. Output of the numerical treatment planning method shows that a 19.9 cm3 irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months. Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-02-18

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  1. Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

    International Nuclear Information System (INIS)

    Akabani, G.; Poston, J.W. Sr.

    1992-01-01

    At present, absorbed dose calculations for radionuclides in the human circulatory system use relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, Monte Carlo calculations were performed using the code Electron Gamma Shower (EGS4). Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessel sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was or cross fire between blood vessels was assumed. Results are useful in assessing the doses to blood and blood vessel walls for different nuclear medicine procedures

  2. Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

    International Nuclear Information System (INIS)

    Akabani, G.; Poston, J.W.

    1991-05-01

    At present, absorbed dose calculations for radionuclides in the human circulatory system used relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, EGS4 Monte Carlo calculations were performed. Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessels sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was assumed nor cross fire between vessel was assumed. Results are useful in assessing the dose in blood and blood vessel walls for different nuclear medicine procedures. 6 refs., 6 figs., 5 tabs

  3. Estimation of center line and diameter of brain blood vessel using three-dimensional blood vessel matching method with head three-dimensional CTA image

    International Nuclear Information System (INIS)

    Maekawa, Masashi; Shinohara, Toshihiro; Nakayama, Masato; Nakasako, Noboru

    2010-01-01

    To support and automate the brain blood vessel disease diagnosis, a novel method to obtain the center line and the diameter of a blood vessel is proposed with a three-dimensional head computed tomographic angiography (CTA) image. Although the line thinning processing with distance transform or gray information is generally used to obtain the blood vessel center line, this method is not essentially one to obtain the center line and tends to yield extra lines depending on CTA images. In this study, the center line of the blood vessel is obtained by tracing the vessel. The blood vessel is traced by sequentially estimating the center point and direction of the blood vessel. The center point and direction of the blood vessel are estimated by taking the correlation between the blood vessel and a solid model of the blood vessel that is designed by considering noise influence. In addition, the vessel diameter is also estimated by correlating the blood vessel and the blood vessel model of which the diameter is variable. The validity of the proposed method is confirmed by experimentally applied the proposed method to an actual three-dimensional head CTA image. (author)

  4. Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

    Science.gov (United States)

    Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2016-01-01

    Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  5. Gamma-secretase inhibitor treatment promotes VEGF-A-driven blood vessel growth and vascular leakage but disrupts neovascular perfusion.

    Directory of Open Access Journals (Sweden)

    Mattias Kalén

    Full Text Available The Notch signaling pathway is essential for normal development due to its role in control of cell differentiation, proliferation and survival. It is also critically involved in tumorigenesis and cancer progression. A key enzyme in the activation of Notch signaling is the gamma-secretase protein complex and therefore, gamma-secretase inhibitors (GSIs--originally developed for Alzheimer's disease--are now being evaluated in clinical trials for human malignancies. It is also clear that Notch plays an important role in angiogenesis driven by Vascular Endothelial Growth Factor A (VEGF-A--a process instrumental for tumor growth and metastasis. The effect of GSIs on tumor vasculature has not been conclusively determined. Here we report that Compound X (CX, a GSI previously reported to potently inhibit Notch signaling in vitro and in vivo, promotes angiogenic sprouting in vitro and during developmental angiogenesis in mice. Furthermore, CX treatment suppresses tumor growth in a mouse model of renal carcinoma, leads to the formation of abnormal vessels and an increased tumor vascular density. Using a rabbit model of VEGF-A-driven angiogenesis in skeletal muscle, we demonstrate that CX treatment promotes abnormal blood vessel growth characterized by vessel occlusion, disrupted blood flow, and increased vascular leakage. Based on these findings, we propose a model for how GSIs and other Notch inhibitors disrupt tumor blood vessel perfusion, which might be useful for understanding this new class of anti-cancer agents.

  6. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

  7. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

  8. NMR blood vessel imaging method and apparatus

    International Nuclear Information System (INIS)

    Riederer, S.J.

    1988-01-01

    A high speed method of forming computed images of blood vessels based on measurements of characteristics of a body is described comprising the steps of: subjecting a predetermined body area containing blood vessels of interest to, successively, applications of a short repetition time (TR) NMR pulse sequence during the period of high blood velocity and then to corresponding applications during the period of low blood velocity for successive heart beat cycles; weighting the collected imaging data from each application of the NMR pulse sequence according to whether the data was acquired during the period of high blood velocity or a period of low blood velocity of the corresponding heart beat cycle; accumulating weighted imaging data from a plurality of NMR pulse sequences corresponding to high blood velocity periods and from a plurality of NMR pulse sequences corresponding to low blood velocity periods; subtracting the weighted imaging data corresponding to each specific phase encoding acquired during the high blood velocity periods from the weighted imaging data for the same phase encoding corresponding to low blood velocity periods in order to compute blood vessel imaging data; and forming an image of the blood vessels of interest from the blood vessel imaging data

  9. Primo vessel inside a lymph vessel emerging from a cancer tissue.

    Science.gov (United States)

    Lee, Sungwoo; Ryu, Yeonhee; Cha, Jinmyung; Lee, Jin-Kyu; Soh, Kwang-Sup; Kim, Sungchul; Lim, Jaekwan

    2012-10-01

    Primo vessels were observed inside the lymph vessels near the caudal vena cava of a rabbit and a rat and in the thoracic lymph duct of a mouse. In the current work we found a primo vessel inside the lymph vessel that came out from the tumor tissue of a mouse. A cancer model of a nude mouse was made with human lung cancer cell line NCI-H460. We injected fluorescent nanoparticles into the xenografted tumor tissue and studied their flow in blood, lymph, and primo vessels. Fluorescent nanoparticles flowed through the blood vessels quickly in few minutes, and but slowly in the lymph vessels. The bright fluorescent signals of nanoparticles disappeared within one hour in the blood vessels but remained much longer up to several hours in the case of lymph vessels. We found an exceptional case of lymph vessels that remained bright with fluorescence up to 24 hours. After detailed examination we found that the bright fluorescence was due to a putative primo vessel inside the lymph vessel. This rare observation is consistent with Bong-Han Kim's claim on the presence of a primo vascular system in lymph vessels. It provides a significant suggestion on the cancer metastasis through primo vessels and lymph vessels. Copyright © 2012. Published by Elsevier B.V.

  10. Ionizing radiations and blood vessels

    International Nuclear Information System (INIS)

    Vorob'ev, E.I.; Stepanov, R.P.

    1985-01-01

    Data on phenomeology of radiation changes of blood vessels are systemized and the authors' experience is generalyzed. A critical analysis of modern conceptions on processes resulting in vessel structure damage after irradiation, is given. Special attention is paid to reparation and compensation of radiation injury of vessels

  11. A method for increasing the homogeneity of the temperature distribution during magnetic fluid hyperthermia with a Fe-Cr-Nb-B alloy in the presence of blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yundong [College of Physics and Information Engineering, Fuzhou University, Fuzhou 350116 (China); Flesch, Rodolfo C.C. [Departamento de Automação e Sistemas, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Jin, Tao, E-mail: jintly@fzu.edu.cn [College of Electrical Engineering and Automation, Fuzhou University, Fuzhou 350116 (China)

    2017-06-15

    Highlights: • The effects of blood vessels on temperature field distribution are investigated. • The critical thermal energy of hyperthermia is computed by the Finite Element Analysis. • A treatment method is proposed by using the MNPs with low Curie temperature. • The cooling effects due to the blood flow can be controlled. - Abstract: Magnetic hyperthermia ablates tumor cells by absorbing the thermal energy from magnetic nanoparticles (MNPs) under an external alternating magnetic field. The blood vessels (BVs) within tumor region can generally reduce treatment effectiveness due to the cooling effect of blood flow. This paper aims to investigate the cooling effect of BVs on the temperature field of malignant tumor regions using a complex geometric model and numerical simulation. For deriving the model, the Navier-Stokes equation for blood flow is combined with Pennes bio-heat transfer equation for human tissue. The effects on treatment temperature caused by two different BV distributions inside a mammary tumor are analyzed through numerical simulation under different conditions of flow rate considering a Fe-Cr-Nb-B alloy, which has low Curie temperature ranging from 42 °C to 45 °C. Numerical results show that the multi-vessel system has more obvious cooling effects than the single vessel one on the temperature field distribution for hyperthermia. Besides, simulation results show that the temperature field within tumor area can also be influenced by the velocity and diameter of BVs. To minimize the cooling effect, this article proposes a treatment method based on the increase of the thermal energy provided to MNPs associated with the adoption of low Curie temperature particles recently reported in literature. Results demonstrate that this approach noticeably improves the uniformity of the temperature field, and shortens the treatment time in a Fe-Cr-Nb-B system, thus reducing the side effects to the patient.

  12. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  13. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  14. Bone marrow blood vessels: normal and neoplastic niche

    Directory of Open Access Journals (Sweden)

    Saeid Shahrabi

    2016-11-01

    Full Text Available Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016 of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases.

  15. Ionizing radiations and blood vessels

    International Nuclear Information System (INIS)

    Vorob'ev, E.I.; Stepanov, R.P.

    1985-01-01

    Data on phenomenology of radiation-induced changes in blood vessels are systematized and authors' experience is generalized. Modern concepts about processes leading to vessel structure injury after irradiation is critically analyzed. Special attention is paid to reparation and compensation of X-ray vessel injury, consideration of which is not yet sufficiently elucidated in literature

  16. Acrolein generation stimulates hypercontraction in isolated human blood vessels

    International Nuclear Information System (INIS)

    Conklin, D.J.; Bhatnagar, A.; Cowley, H.R.; Johnson, G.H.; Wiechmann, R.J.; Sayre, L.M.; Trent, M.B.; Boor, P.J.

    2006-01-01

    Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H 2 O 2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca 2+ to hypercontraction. Acrolein or allylamine but not H 2 O 2 , benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca 2+ -free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension

  17. Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels.

    Science.gov (United States)

    Ruiz-Saurí, Amparo; García-Bustos, V; Granero, E; Cuesta, S; Sales, M A; Marcos, V; Llombart-Bosch, A

    2017-07-01

    To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.

  18. Trends in Tissue Engineering for Blood Vessels

    Directory of Open Access Journals (Sweden)

    Judee Grace Nemeno-Guanzon

    2012-01-01

    Full Text Available Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

  19. Accuracy of geometrical modelling of heat transfer from tissue to blood vessels

    NARCIS (Netherlands)

    Leeuwen, van G.M.J.; Kotte, A.N.T.J.; Bree, de J.; Koijk, van der J.F.; Crezee, J.; Lagendijk, J.J.W.

    1997-01-01

    We have developed a thermal model in which blood vessels are described as geometrical objects, 3D curves with associated diameters. Here the behaviour of the model is examined for low resolutions compared with the vessel diameter and for strongly curved vessels. The tests include a single straight

  20. Effect of fluid friction on interstitial fluid flow coupled with blood flow through solid tumor microvascular network.

    Science.gov (United States)

    Sefidgar, Mostafa; Soltani, M; Raahemifar, Kaamran; Bazmara, Hossein

    2015-01-01

    A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

  1. 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

  2. A contrast enhancement and scanning techniques for CT angiography of head and neck. One phase injection method for simultaneous imaging of vessels and tumor

    International Nuclear Information System (INIS)

    Morita, Yasuhiko; Indo, Hiroko; Noikura, Takenori

    1999-01-01

    We report on a method of CT-Angiography useful for examining lesion of the head and neck using three-dimensional images and measured CT value. This study focused on some of the important blood vessels in the head and neck. The aim of this method was to obtain high-contrast enhancement for both vessels and tumors at same time. A total amount of 100 ml nonionic contrast media (Omnipaque 240, 240 mg iodine per milliliter, Daiichi seiyaku, Tokyo, Japan) was injected intravenously with a flow of 1.5 ml/sec. Spiral scans, 24 rotations with 24 seconds, were started at a time when remaining amount of contrast media had become 30 to 20 ml. All CT scans were performed using double speed spiral scan technique with a slice thickness of 2 to 3 mm and table speeds from 3 to 5 mm/rotation. The patients populations consisted of 9 men and 6 women who ranged in age from 37 to 85 years. Sixteen CT-angiography were performed according to this method. Mean CT values of major blood vessels were measured in order to find out threshold at the level of submandibular gland in 13 examinations for 12 subjects. Important vessels like the common, internal, and the external artery, internal and external jugular vein were clearly visible in all subjects. Three dimensional images of these vessels could also be reconstructed for 15 of the subjects. Mean CT values were 211 Hounsfield units (HU) and 209 HU for the right and left internal carotid artery, respectively, and 204 HU and 206 HU for the right and left external carotid artery, respectively. Mean CT values for right and left internal jugular vein were 195 HU and 194 HU respectively. Measured CT values at each important blood vessels showed this method could yields acceptable enhancements. Good enhancement effect of tumor and blood vessels in the same scan seems to be mutually incompatible. One very important trade-off is the early enhancement effect at blood vessels versus the late enhancement effect at tumors. The other important trade

  3. Erratum to: Ungersma SE, Pacheco G, Ho C, Yee SF, Ross J, van Bruggen N, Peale FV Jr, Ross S, Carano RA. Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis. Magn Reson Med 2010;63:1637–1647.

    Science.gov (United States)

    Ungersma, Sharon E; Pacheco, Glenn; Ho, Calvin; Yee, Sharon Fong; Ross, Jed; van Bruggen, Nicholas; Peale, Franklin V; Ross, Sarajane; Carano, Richard A D

    2011-03-01

    Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density (Q). Here, this technique is validated with direct comparisons to ex vivo micro-computed tomography angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and Q by two antiangiogenic therapeutics [anti-vascular endothelial growth factor (anti-VEGF) and anti-neuropilin-1] on an HM7 colorectal tumor model. Anti-vascular endothelial growth factor reduced blood volume by 36±3% (p<0.0001) and Q by 52±3% (p<0.0001) at 48 h post-treatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18±6% (p<0.05) and a reduction in Q of 33±5% (p<0.05) at 48 h post-treatment.

  4. Blood vessel-based liver segmentation through the portal phase of a CT dataset

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Moriyama, Noriyuki; Utsunomiya, Toru; Shimada, Mitsuo

    2013-02-01

    Blood vessels are dispersed throughout the human body organs and carry unique information for each person. This information can be used to delineate organ boundaries. The proposed method relies on abdominal blood vessels (ABV) to segment the liver considering the potential presence of tumors through the portal phase of a CT dataset. ABV are extracted and classified into hepatic (HBV) and nonhepatic (non-HBV) with a small number of interactions. HBV and non-HBV are used to guide an automatic segmentation of the liver. HBV are used to individually segment the core region of the liver. This region and non-HBV are used to construct a boundary surface between the liver and other organs to separate them. The core region is classified based on extracted posterior distributions of its histogram into low intensity tumor (LIT) and non-LIT core regions. Non-LIT case includes normal part of liver, HBV, and high intensity tumors if exist. Each core region is extended based on its corresponding posterior distribution. Extension is completed when it reaches either a variation in intensity or the constructed boundary surface. The method was applied to 80 datasets (30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI data) including 60 datasets with tumors. Our results for the MICCAI-test data were evaluated by sliver07 [1] with an overall score of 79.7, which ranks seventh best on the site (December 2013). This approach seems a promising method for extraction of liver volumetry of various shapes and sizes and low intensity hepatic tumors.

  5. A method for increasing the homogeneity of the temperature distribution during magnetic fluid hyperthermia with a Fe-Cr-Nb-B alloy in the presence of blood vessels

    Science.gov (United States)

    Tang, Yundong; Flesch, Rodolfo C. C.; Jin, Tao

    2017-06-01

    Magnetic hyperthermia ablates tumor cells by absorbing the thermal energy from magnetic nanoparticles (MNPs) under an external alternating magnetic field. The blood vessels (BVs) within tumor region can generally reduce treatment effectiveness due to the cooling effect of blood flow. This paper aims to investigate the cooling effect of BVs on the temperature field of malignant tumor regions using a complex geometric model and numerical simulation. For deriving the model, the Navier-Stokes equation for blood flow is combined with Pennes bio-heat transfer equation for human tissue. The effects on treatment temperature caused by two different BV distributions inside a mammary tumor are analyzed through numerical simulation under different conditions of flow rate considering a Fe-Cr-Nb-B alloy, which has low Curie temperature ranging from 42 °C to 45 °C. Numerical results show that the multi-vessel system has more obvious cooling effects than the single vessel one on the temperature field distribution for hyperthermia. Besides, simulation results show that the temperature field within tumor area can also be influenced by the velocity and diameter of BVs. To minimize the cooling effect, this article proposes a treatment method based on the increase of the thermal energy provided to MNPs associated with the adoption of low Curie temperature particles recently reported in literature. Results demonstrate that this approach noticeably improves the uniformity of the temperature field, and shortens the treatment time in a Fe-Cr-Nb-B system, thus reducing the side effects to the patient.

  6. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  7. A numerical analysis on the curved bileaflet Mechanical Heart Valve (MHV) : leaflet motion and blood flow in an elastic blood vessel

    International Nuclear Information System (INIS)

    Bang, Jin Seok; Kim, Chang Nyung; Choi, Choeng Ryul

    2005-01-01

    In blood flow passing through the Mechanical Heart Valve (MHV) and elastic blood vessel, hemolysis and platelet activation causing thrombus formation can be seen owing to the shear stress in the blood. Also, fracture and deformation of leaflets can be observed depending on the shape and material properties of the leaflets which is opened and closed in a cycle. Hence, comprehensive study is needed on the hemodynamics which is associated with the motion of leaflet and elastic blood vessel in terms of fluid-structure interaction. In this paper, a numerical analysis has been performed for a three-dimensional pulsatile blood flow associated with the elastic blood vessel and curved bileaflet for multiple cycles in light of fluid-structure interaction. From this analysis fluttering phenomenon and rebound of the leaflet have been observed and recirculation and regurgitation have been found in the flow fields of the blood. Also, the pressure distribution and the radial displacement of the elastic blood vessel have been obtained. The motion of the leaflet and flow fields of the blood have shown similar tendency compared with the previous experiments carried out in other studies. The present study can contribute to the design methodology for the curved bileaflet mechanical heart valve. Furthermore, the proposed fluid-structure interaction method will be effectively used in various fields where the interaction between fluid flow and structure are involved

  8. Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

    International Nuclear Information System (INIS)

    Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

    2013-01-01

    Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

  9. Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Cao Wei, E-mail: cawe-001@163.com [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Li Jing, E-mail: lijing02@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Burn and Plastic Surgery (China); Wu Zhiqun, E-mail: zhiqunwu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Zhou Changxi, E-mail: changxizhou@163.com [Chinese PLA General Hospital, Department of Respiratory Disease (China); Liu Xi, E-mail: xiliu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China); Wan Yi, E-mail: yiwan@163.com [The Fourth Military Medical University, Department of Health Statistics, Institute for Health Informatics (China); Duan Yunyou, E-mail: yunyouduan@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China)

    2013-06-15

    Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

  10. Automatic segmentation of blood vessels from retinal fundus images ...

    Indian Academy of Sciences (India)

    The retinal blood vessels were segmented through color space conversion and color channel .... Retinal blood vessel segmentation was also attempted through multi-scale operators. A few works in this ... fundus camera at 35 degrees field of view. The image ... vessel segmentation is available from two human observers.

  11. Melanopsin mediates light-dependent relaxation in blood vessels.

    Science.gov (United States)

    Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

    2014-12-16

    Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

  12. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Science.gov (United States)

    Soltani, M; Chen, P

    2013-01-01

    Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  13. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Directory of Open Access Journals (Sweden)

    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  14. Arterial displacement by the tumor demonstrated by magnetic resonance CT

    International Nuclear Information System (INIS)

    Tsuchiya, Kazuhiro; Yoshikawa, Kohki; Machida, Tohru; Iio, Masahiro.

    1985-01-01

    MR-CT permits visualization of blood vessels non-invasively. Major blood vessels in scan slices are demonstrated as structures with low or no signal intensity. In this report, two cases with brain tumor and spinal tumor are presented in which arterial displacement by the tumor was visualized by MR-CT. MR-CT is considered to be an effective method in detecting blood vessel abnormalities. (author)

  15. CD4+ and Perivascular Foxp3+ T Cells in Glioma Correlate with Angiogenesis and Tumor Progression

    Directory of Open Access Journals (Sweden)

    Luyan Mu

    2017-11-01

    Full Text Available BackgroundAngiogenesis and immune cell infiltration are key features of gliomas and their manipulation of the microenvironment, but their prognostic significance remains indeterminate. We evaluate the interconnection between tumor-infiltrating lymphocyte (TIL and tumor blood-vasculatures in the context of glioma progression.MethodsPaired tumor tissues of 44 patients from three tumor-recurrent groups: diffuse astrocytomas (DA recurred as DA, DA recurred as glioblastomas (GBM, and GBM recurred as GBM were evaluated by genetic analysis, immunohistochemistry for tumor blood vessel density, TIL subsets, and clinical outcomes. These cells were geographically divided into perivascular and intratumoral TILs. Associations were examined between these TILs, CD34+ tumor blood vessels, and clinical outcomes. To determine key changes in TIL subsets, microarray data of 15-paired tumors from patients who failed antiangiogenic therapy- bevacizumab, and 16-paired tumors from chemo-naïve recurrent GBM were also evaluated and compared.ResultsUpon recurrence in primary gliomas, similar kinetic changes were found between tumor blood vessels and each TIL subset in all groups, but only CD4+ including Foxp3+ TILs, positively correlated with the density of tumor blood vessels. CD4 was the predominant T cell population based on the expression of gene-transcripts in primary GBMs, and increased activated CD4+ T cells were revealed in Bevacizumab-resistant recurrent tumors (not in chemo-naïve recurrent tumors. Among these TILs, 2/3 of them were found in the perivascular niche; Foxp3+ T cells in these niches not only correlated with the tumor vessels but were also an independent predictor of shortened recurrence-free survival (RFS (HR = 4.199, 95% CI 1.522–11.584, p = 0.006.ConclusionThe minimal intratumoral T cell infiltration and low detection of CD8 transcripts expression in primary GBMs can potentially limit antitumor response. CD4+ and perivascular Foxp3

  16. Recovery of testicular blood flow following ligation of testicular vessels

    International Nuclear Information System (INIS)

    Pascual, J.A.; Villanueva-Meyer, J.; Salido, E.; Ehrlich, R.M.; Mena, I.; Rajfer, J.

    1989-01-01

    To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133-xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach

  17. Blood vessel growth blocker may treat AIDS-related Kaposi’s sarcoma

    Science.gov (United States)

    Patients with an AIDS-associated cancer, Kaposi's sarcoma (KS), showed improvement after receiving the combination of bevacizumab, a cancer drug that blocks the growth of new blood vessels, and highly active antiretroviral therapy (HAART).

  18. Application of morphological bit planes in retinal blood vessel extraction.

    Science.gov (United States)

    Fraz, M M; Basit, A; Barman, S A

    2013-04-01

    The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree.

  19. Fluid and mass transport in a single lymphatic blood vessel

    International Nuclear Information System (INIS)

    Bestman, A.R.

    1987-08-01

    The problem considers the single blood vessel model in pulmonary circulation in the presence of gravitation and mass transfer. The tissue surrounding the blood vessel is modelled as a permeable medium distinct from the blood vessel which is a normal free space. On the assumption that the mass concentration varies slowly at the interface between the blood vessel and the tissue, the problem is tackled by asymptotic approximation. A crucial point of the analysis is the dependence of the flow variables on the permeability K of the tissue in a completely arbitrary manner. A primary conjecture of the study is the intimacy of the pathological pulmonary edema and the parameter K. (author). 4 refs

  20. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    Directory of Open Access Journals (Sweden)

    Scott D. Packard

    2003-07-01

    Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

  1. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry.

    Science.gov (United States)

    Chen, Yuanyuan; Li, Donghai; Li, Yongjian; Wan, Jiandi; Li, Jiang; Chen, Haosheng

    2017-11-10

    Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.

  3. Immersive volume rendering of blood vessels

    Science.gov (United States)

    Long, Gregory; Kim, Han Suk; Marsden, Alison; Bazilevs, Yuri; Schulze, Jürgen P.

    2012-03-01

    In this paper, we present a novel method of visualizing flow in blood vessels. Our approach reads unstructured tetrahedral data, resamples it, and uses slice based 3D texture volume rendering. Due to the sparse structure of blood vessels, we utilize an octree to efficiently store the resampled data by discarding empty regions of the volume. We use animation to convey time series data, wireframe surface to give structure, and utilize the StarCAVE, a 3D virtual reality environment, to add a fully immersive element to the visualization. Our tool has great value in interdisciplinary work, helping scientists collaborate with clinicians, by improving the understanding of blood flow simulations. Full immersion in the flow field allows for a more intuitive understanding of the flow phenomena, and can be a great help to medical experts for treatment planning.

  4. Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

    Science.gov (United States)

    Prisby, Rhonda D.

    2014-01-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

  5. Interstitial Cells of Blood Vessels

    Directory of Open Access Journals (Sweden)

    Vladimír Pucovský

    2010-01-01

    Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

  6. Regional cerebral blood flow in the patient with brain tumor

    International Nuclear Information System (INIS)

    Tsuchida, Shohei

    1993-01-01

    Regional cerebral blood flow (rCBF) was measured with xenon-enhanced CT (Xe-CT) in 21 cases of intracranial tumors (13 meningiomas, 5 gliomas, 3 metastatic brain tumors). Peritumoral edema was graded as mild, moderate or severe based on the extent of edema on CT and MRI. According to intratumoral blood flow distribution patterns, three patterns were classified as central type with relatively high blood flow at the center of the tumor, homogeneous type with an almost homogeneous blood flow distribution, and marginal type with relatively high blood flow at the periphery of the tumor. High grade astrocytoma and metastatic brain tumor showed marginal type blood flow and moderate or severe edema except in one case. Five meningiomas with severe peritumoral edema revealed marginal type blood flow and four with mild peritumoral edema showed central type blood flow, except for one case. No correlation was found between the extent of peritumoral edema and histological subtype, tumor size, location, duration of clinical history, vascularization on angiogram, and mean blood flow in the tumor. These results suggest that blood flow distribution patterns within the tumor may affect the extension of peritumoral edema. Pre- and postoperative rCBFs were evaluated with Xe-CT and IMP-SPECT in 7 cases, mean rCBF of peritumoral edema was 6.2 ml/100 g/min preoperatively, and discrepancy between rCBF on Xe-CT and that on IMP-SPECT was shown in the remote cortical region ipsilateral to the tumor. Postoperative rCBF revealed an improved blood flow in both adjacent and remote areas, suggesting that the decreased blood flow associated with brain tumors might be relieved after surgery. (author) 53 refs

  7. Depiction of blood vessels by x-ray phase contrast

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Atsushi [School of Engineering, University of Tokyo, Tokyo (Japan); Takeda, Tohoru; Itai, Yuji [Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki (Japan)

    2001-04-01

    Blood vessels in livers of a mouse and a rat were depicted by phase-contrast x-ray imaging with an x-ray interferometer without using contrast agents. X-ray interference patterns were converted to image mapping x-ray phase shift caused by the livers using the technique of phase-shifting x-ray interferometry. The arteries and veins to and from the livers were tied before excision in order to prevent blood from flowing out of the liver. The x-ray phase shift caused by blood was substantially different from that caused by other soft sues, and consequently trees of blood vessels were revealed in the images. Vessels of diameter smaller than 0.1 mm were detected. This result suggests new possibilities for investigating vascular systems. (author)

  8. ICG-assisted blood vessel detection during stereotactic neurosurgery: simulation study on excitation power limitations due to thermal effects in human brain tissue.

    Science.gov (United States)

    Rühm, Adrian; Göbel, Werner; Sroka, Ronald; Stepp, Herbert

    2014-09-01

    Intraoperative blood vessel detection based on intraluminal indocyanin-green (ICG) would allow to minimize the risk of blood vessel perforation during stereotactic brain tumor biopsy. For a fiber-based approach compatible with clinical conditions, the maximum tolerable excitation light power was derived from simulations of the thermal heat load on the tissue. Using the simulation software LITCIT, the temperature distribution in human brain tissue was calculated as a function of time for realistic single-fiber probes (0.72mm active diameter, numerical aperture 0.35, optional focusing to 0.29mm diameter) and for the optimum ICG excitation wavelength of 785nm. The asymptotic maximum temperature in the simulated tissue region was derived for different radiant fluxes at the distal fiber end. Worst case values were assumed for all other parameters. In addition to homogeneous (normal and tumor) brain tissue with homogeneous blood perfusion, models with localized extra blood vessels incorporated ahead of the distal fiber end were investigated. If one demands that destruction of normal brain tissue must be excluded by limiting the tissue heating to 42°C, then the radiant flux at the distal fiber end must be limited to 33mW with and 43mW without focusing. When considering extra blood vessels of 0.1mm diameter incorporated into homogeneously perfused brain tissue, the tolerable radiant flux is reduced to 22mW with and 32mW without focusing. The threshold value according to legal laser safety regulations for human skin tissue is 28.5mW. For the envisaged modality of blood vessel detection, light power limits for an application-relevant fiber configuration were determined and found to be roughly consistent with present legal regulations for skin tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. The influence of P-glycoprotein expression and its inhibitors on the distribution of doxorubicin in breast tumors

    International Nuclear Information System (INIS)

    Patel, Krupa J; Tannock, Ian F

    2009-01-01

    Anti-cancer drugs access solid tumors via blood vessels, and must penetrate tumor tissue to reach all cancer cells. Previous studies have demonstrated steep gradients of decreasing doxorubicin fluorescence with increasing distance from blood vessels, such that many tumor cells are not exposed to drug. Studies using multilayered cell cultures show that increased P-glycoprotein (PgP) is associated with better penetration of doxorubicin, while PgP inhibitors decrease drug penetration in tumor tissue. Here we evaluate the effect of PgP expression on doxorubicin distribution in vivo. Mice bearing tumor sublines with either high or low expression of PgP were treated with doxorubicin, with or without pre-treatment with the PgP inhibitors verapamil or PSC 833. The distribution of doxorubicin in relation to tumor blood vessels was quantified using immunofluorescence. Our results indicate greater uptake of doxorubicin by cells near blood vessels in wild type as compared to PgP-overexpressing tumors, and pre-treatment with verapamil or PSC 833 increased uptake in PgP-overexpressing tumors. However, there were steeper gradients of decreasing doxorubicin fluorescence in wild-type tumors compared to PgP overexpressing tumors, and treatment of PgP overexpressing tumors with PgP inhibitors led to steeper gradients and greater heterogeneity in the distribution of doxorubicin. PgP inhibitors increase uptake of doxorubicin in cells close to blood vessels, have little effect on drug uptake into cells at intermediate distances, and might have a paradoxical effect to decrease doxorubicin uptake into distal cells. This effect probably contributes to the limited success of PgP inhibitors in clinical trials

  10. Did antepartum hypoxic insult caused by fetal vessel thrombosis influence the procalcitonin level in umbilical blood? A case report.

    Science.gov (United States)

    Kaneko, Masatoki; Yamauchi, Aya; Yamashita, Rie; Sato, Yuichiro; Kodama, Yuki; Sameshima, Hiroshi

    2015-11-01

    We report a case of marked elevation of the procalcitonin level in umbilical blood and neonatal blood at birth. The mother did not perceive fetal motion. Antepartum fetal heart rate monitoring showed a loss of variability and absence of acceleration. No fetal breathing movement, fetal movement, or fetal tone were observed by ultrasonography. The female neonate was delivered by cesarean section at 25 weeks of gestation, with birthweight 774 g. The umbilical arterial pH value at birth was 7.29. Mild elevation in interleukin-6 and tumor necrosis factor-α in umbilical blood were observed. Cytochrome c showed a high level in umbilical and neonatal blood at birth. Placental histopathology revealed multiple fetal vessel thrombosis in the large stem villi and chorionic vessels. The neonate showed no infectious signs throughout the neonatal period. Computed tomography at 3 months of age revealed atrophy in the cerebrum and cerebellum. At 1 year after birth, the infant showed spastic quadriplegia. In this case, antepartum asphyxia due to fetal vessel thrombosis may have influenced the elevation of procalcitonin level in umbilical blood and neonatal blood at birth. © 2015 Japan Society of Obstetrics and Gynecology.

  11. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish

    Science.gov (United States)

    2012-01-01

    Background Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish. Methods Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR. Results Two polysaccharide fractions, P4 (50000 D 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4. Conclusion The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. PMID:22357377

  12. Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

    International Nuclear Information System (INIS)

    Siraj, Ahsan; Gonin, Julie; Radu, Aurelian; Ghinea, Nicolae; Desestret, Virginie; Antoine, Martine; Fromont, Gaëlle; Huerre, Michel; Sanson, Marc; Camparo, Philippe; Pichon, Christophe; Planeix, François

    2013-01-01

    The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors

  13. Juvenile nasopharyngeal angiofibroma: vascular determinates for operative complications and tumor recurrence.

    Science.gov (United States)

    Chan, Kenny H; Gao, Dexiang; Fernandez, Patrick G; Kingdom, Todd T; Kumpe, David A

    2014-03-01

    Operative complications and tumor recurrence in juvenile nasopharyngeal angiofibroma (JNA) are measurable and meaningful outcomes. This study aimed to assess the association of these two outcomes to various clinical indices and in particular, vascular determinates. Retrospective cohort study. An 18-year retrospective chart review of an academic tertiary center was undertaken. Data from clinical notes, imaging studies, and arteriograms were analyzed. Thirty-seven male (mean age, 14.4 years) patients were included in the study. Tumor stages included: IA (three), IB (three), IIA (14), IIB (three), IIC (five), IIIA (five), and IIIB (four). Four complications (cerebrospinal fluid leak, cerebral vascular accident, and two transient ocular defects) occurred. Eight recurrences occurred within 24 months following surgery. Complications were associated with estimated intraoperative blood loss (EBL) (P = .045). Tumor recurrence was associated with feeding vessels from the contralateral internal carotid artery (ICA) (P = .017). EBL was significantly associated with surgical technique used. EBL, tumor stage, and tumor vascular supply were significantly associated with each other. Vascular factors were associated with JNA complication and tumor recurrence. EBL might affect complications, and contralateral ICA as a feeding vessel might affect recurrence. EBL was influenced by procedure choice and was interrelated to size and vascular supply of the tumor. This study bolsters the need to decrease intraoperative blood loss by preoperative embolization and use of endoscopic removal techniques. Furthermore, when branches of the ICA are found to be feeding vessels, greater surgical attention for a dry surgical field is encouraged. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile.

    Science.gov (United States)

    Dreischalück, Johannes; Schwöppe, Christian; Spieker, Tilmann; Kessler, Torsten; Tiemann, Klaus; Liersch, Ruediger; Schliemann, Christoph; Kreuter, Michael; Kolkmeyer, Astrid; Hintelmann, Heike; Mesters, Rolf M; Berdel, Wolfgang E

    2010-12-01

    tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.

  15. Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression

    International Nuclear Information System (INIS)

    Koskinen, Walter J.; Bono, Petri; Leivo, Ilmo; Vaheri, Antti; Aaltonen, Leena-Maija; Joensuu, Heikki

    2005-01-01

    Background and purpose: Early stage vocal cord carcinomas are usually cured by radiation therapy despite the use of portals that exclude the cervical lymph nodes. We investigated whether the lymphatic vessel density (LVD) of vocal cord carcinomas differs from that of other head and neck carcinomas. Patients and methods: Deparaffinized tissue from tumors of 60 patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were immunostained for LYVE-1, a novel lymphatic vessel marker. Twenty-two had vocal cord carcinoma. Tumor blood vessel density (BVD) was assessed using immunostaining for CD31. Results: Tumor overall LVD, including both intra- and peritumoral lymph vessels, was 10-fold lower than the BVD (5 counts/mm 2 vs. 52 mm -2 , respectively). A high LVD was associated with a high BVD (P=.002), but neither was associated with the tumor size. Both tumor LVD and BVD were lower in vocal cord carcinomas than in HNSCCs arising at other sites (median, 0 vs. 7 mm -2 , P=.016; and median, 36 vs. 52 mm -2 , P=.006, respectively). Only one vocal cord carcinoma was associated with a regional metastasis at the time of the diagnosis. Among the rest of the cases tumor size was a better predictor for the presence of regional metastases than tumor BVD or LVD in a logistic regression model (odds ratio 2.2, 95% CI 1.1-4.5). Conclusion: Vocal cord carcinomas have a low lymph vessel density as compared with HNSCCs arising at other sites

  16. “Data characterizing microfabricated human blood vessels created via hydrodynamic focusing”

    Directory of Open Access Journals (Sweden)

    Kyle A. DiVito

    2017-10-01

    Full Text Available This data article provides further detailed information related to our research article titled “Microfabricated Blood Vessels Undergo Neovascularization” (DiVito et al., 2017 [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF. Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into ‘bullseye-like” cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016 [2–6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.

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

    Science.gov (United States)

    2009-12-01

    diabetic retinopathy . Therefore, se- lectively targeting existing blood vessels (vascular- disrupting therapy) and/or inhibiting the forma- tion of new...adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at...tumor sections (Fig. 4). However, viable tumor cells were commonly detected at tumor periphery. Because of the existence of viable peripheral tumor cells

  18. Effect of variable heat transfer coefficient on tissue temperature next to a large vessel during radiofrequency tumor ablation

    Directory of Open Access Journals (Sweden)

    Pinheiro Cleber

    2008-07-01

    Full Text Available Abstract Background One of the current shortcomings of radiofrequency (RF tumor ablation is its limited performance in regions close to large blood vessels, resulting in high recurrence rates at these locations. Computer models have been used to determine tissue temperatures during tumor ablation procedures. To simulate large vessels, either constant wall temperature or constant convective heat transfer coefficient (h have been assumed at the vessel surface to simulate convection. However, the actual distribution of the temperature on the vessel wall is non-uniform and time-varying, and this feature makes the convective coefficient variable. Methods This paper presents a realistic time-varying model in which h is a function of the temperature distribution at the vessel wall. The finite-element method (FEM was employed in order to model RF hepatic ablation. Two geometrical configurations were investigated. The RF electrode was placed at distances of 1 and 5 mm from a large vessel (10 mm diameter. Results When the ablation procedure takes longer than 1–2 min, the attained coagulation zone obtained with both time-varying h and constant h does not differ significantly. However, for short duration ablation (5–10 s and when the electrode is 1 mm away from the vessel, the use of constant h can lead to errors as high as 20% in the estimation of the coagulation zone. Conclusion For tumor ablation procedures typically lasting at least 5 min, this study shows that modeling the heat sink effect of large vessels by applying constant h as a boundary condition will yield precise results while reducing computational complexity. However, for other thermal therapies with shorter treatment using a time-varying h may be necessary.

  19. Development of glia and blood vessels in the internal capsule of rats.

    Science.gov (United States)

    Earle, K L; Mitrofanis, J

    1998-02-01

    microglia are seen in the thalamus. In summary, our results indicate that all three types of glia in the internal capsule are associated closely with the vasculature, suggesting they may play a role in the development of the blood-brain barrier among the vessels in this white matter region of the forebrain.

  20. Blood Vessels in Allotransplantation.

    Science.gov (United States)

    Abrahimi, P; Liu, R; Pober, J S

    2015-07-01

    Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Application of blood-pool agents in visualization of peripheral vessels

    International Nuclear Information System (INIS)

    Giovagnoni, A.; Catalano, C.

    2007-01-01

    Effective arterial imaging is essential in patients with peripheral arterial disease (PAD) in whom a revascularization procedure is planned. Digital subtraction angiography (DSA) has traditionally been regarded as the gold standard for imaging in peripheral arterial disease, but this technique is subject to certain limitations, such as the risks of adverse reactions associated with arterial catheterization and iodinated contrast agents. Contrast-enhanced magnetic resonance angiography is now recommended as an effective and useful imaging technique in peripheral arterial disease, since it offers high enhanced contrast between blood and stationary tissue and fast acquisition times. However, extracellular gadolinium contrast agents rapidly diffuse into the interstitial spaces, and thus are suitable only for first-pass imaging. This limitation can be overcome by the use of blood-pool (intravascular) contrast agents, such as gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which are retained within the blood vessels and hence facilitate both first-pass and steady-state imaging with high spatial resolution. Blood-pool agents, therefore, offer improved imaging, particularly of distal vessels, compared with extracellular contrast agents. Examples of first-pass and steady-state imaging with gadofosveset are presented. (orig.)

  2. Predictive simulation of bidirectional Glenn shunt using a hybrid blood vessel model.

    Science.gov (United States)

    Li, Hao; Leow, Wee Kheng; Chiu, Ing-Sh

    2009-01-01

    This paper proposes a method for performing predictive simulation of cardiac surgery. It applies a hybrid approach to model the deformation of blood vessels. The hybrid blood vessel model consists of a reference Cosserat rod and a surface mesh. The reference Cosserat rod models the blood vessel's global bending, stretching, twisting and shearing in a physically correct manner, and the surface mesh models the surface details of the blood vessel. In this way, the deformation of blood vessels can be computed efficiently and accurately. Our predictive simulation system can produce complex surgical results given a small amount of user inputs. It allows the surgeon to easily explore various surgical options and evaluate them. Tests of the system using bidirectional Glenn shunt (BDG) as an application example show that the results produc by the system are similar to real surgical results.

  3. Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

    Science.gov (United States)

    Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi

    2017-11-01

    The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

  4. Laparoscopic prototype for optical sealing of renal blood vessels

    Science.gov (United States)

    Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

    2017-02-01

    Energy-based, radiofrequency and ultrasonic devices provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternative for vessel sealing with less collateral thermal damage. Previous studies demonstrated vessel sealing in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices in surgical use was developed, and tests were conducted on porcine renal blood vessels. The 5-mm-OD prototype featured a traditional Maryland jaw configuration. Laser energy was delivered through a 550-μm-core fiber and side-delivery from the lower jaw, with beam dimensions of 18-mm-length x 1.2-mm-width. The 1470-nm diode laser delivered 68 W with 3 s activation time. A total of 69 porcine renal vessels with mean diameter of 3.3 +/- 1.7 mm were tested, ex vivo. Vessels smaller than 5 mm were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038 +/- 474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174 +/- 221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7 +/- 0.8, 3.4 +/- 0.7, and 1.0 +/- 0.4 mm. A novel optical laparoscopic prototype with 5-mm- OD shaft integrated within a standard Maryland jaw design consistently sealed vessels less than 5 mm with minimal thermal spread. Further in vivo studies are planned to test performance across a variety of vessels and tissues.

  5. Vessel Sampling and Blood Flow Velocity Distribution With Vessel Diameter for Characterizing the Human Bulbar Conjunctival Microvasculature.

    Science.gov (United States)

    Wang, Liang; Yuan, Jin; Jiang, Hong; Yan, Wentao; Cintrón-Colón, Hector R; Perez, Victor L; DeBuc, Delia C; Feuer, William J; Wang, Jianhua

    2016-03-01

    This study determined (1) how many vessels (i.e., the vessel sampling) are needed to reliably characterize the bulbar conjunctival microvasculature and (2) if characteristic information can be obtained from the distribution histogram of the blood flow velocity and vessel diameter. Functional slitlamp biomicroscope was used to image hundreds of venules per subject. The bulbar conjunctiva in five healthy human subjects was imaged on six different locations in the temporal bulbar conjunctiva. The histograms of the diameter and velocity were plotted to examine whether the distribution was normal. Standard errors were calculated from the standard deviation and vessel sample size. The ratio of the standard error of the mean over the population mean was used to determine the sample size cutoff. The velocity was plotted as a function of the vessel diameter to display the distribution of the diameter and velocity. The results showed that the sampling size was approximately 15 vessels, which generated a standard error equivalent to 15% of the population mean from the total vessel population. The distributions of the diameter and velocity were not only unimodal, but also somewhat positively skewed and not normal. The blood flow velocity was related to the vessel diameter (r=0.23, Psampling size of the vessels and the distribution histogram of the blood flow velocity and vessel diameter, which may lead to a better understanding of the human microvascular system of the bulbar conjunctiva.

  6. Heritability of retinal vessel diameters and blood pressure

    DEFF Research Database (Denmark)

    Taarnhøj, Nina C B B; Larsen, Michael; Sander, Birgit

    2006-01-01

    PURPOSE: To assess the relative influence of genetic and environmental effects on retinal vessel diameters and blood pressure in healthy adults, as well as the possible genetic connection between these two characteristics. METHODS: In 55 monozygotic and 50 dizygotic same-sex healthy twin pairs......%-80%) for CRAE, 83% (95% CI: 73%-89%) for CRVE, and 61% (95% CI: 44%-73%) for mean arterial blood pressure (MABP). Retinal artery diameter decreased with increasing age and increasing arterial blood pressure. Mean vessel diameters in the population were 165.8 +/- 14.9 microm for CRAE, 246.2 +/- 17.7 microm...... for CRVE, and 0.67 +/- 0.05 microm for AVR. No significant influence on artery or vein diameters was found for gender, smoking, body mass index (BMI), total cholesterol, fasting blood glucose, or 2-hour oral glucose tolerance test values. CONCLUSIONS: In healthy young adults with normal blood pressure...

  7. Mural cell associated VEGF is required for organotypic vessel formation.

    Directory of Open Access Journals (Sweden)

    Lasse Evensen

    Full Text Available BACKGROUND: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. METHODS AND FINDINGS: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. CONCLUSIONS: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation.

  8. Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Vannucchi, Alessandro M; Migliaccio, Anna Rita

    2007-01-01

    BACKGROUND AND OBJECTIVES: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from...

  9. Improvement of retinal blood vessel detection by spur removal and Gaussian matched filtering compensation

    Science.gov (United States)

    Xiao, Di; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi

    2016-03-01

    Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. In this paper, we proposed approaches for improving the quality of blood vessel detection based on our initial blood vessel detection methods. A blood vessel spur pruning method has been developed for removing the blood vessel spurs both on vessel medial lines and binary vessel masks, which are caused by artifacts and side-effect of Gaussian matched vessel enhancement. A Gaussian matched filtering compensation method has been developed for removing incorrect vessel branches in the areas of low illumination. The proposed approaches were applied and tested on the color fundus images from one publicly available database and our diabetic retinopathy screening dataset. A preliminary result has demonstrated the robustness and good performance of the proposed approaches and their potential application for improving retinal blood vessel detection.

  10. Regulation of cellular communication by signaling microdomains in the blood vessel wall.

    Science.gov (United States)

    Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

  11. Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

    Science.gov (United States)

    Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

  12. HIFU procedures at moderate intensities-effect of large blood vessels

    International Nuclear Information System (INIS)

    Hariharan, P; Myers, M R; Banerjee, R K

    2007-01-01

    A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams

  13. HIFU procedures at moderate intensities-effect of large blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Hariharan, P [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States); Myers, M R [Division of Solid and Fluid Mechanics, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 62, Silver Spring, MD 20993-0002 (United States); Banerjee, R K [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States)

    2007-07-21

    A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams.

  14. THE ALGORITHM OF DETERMINATION OF EYE FUNDUS VESSELS BLOOD FLOW CHARACTERISTICS ON VIDEOSEQUENCE

    Directory of Open Access Journals (Sweden)

    O. V. Nedzvedz

    2018-01-01

    Full Text Available The method of determination of the dynamic characteristics like the vessel diameter change, the linear and volume blood velocities in the vessels of the eye fundus is considered. Such characteristics allow to determine blood flow changes in the microvasculature affecting the blood flow in the brain, kidneys and coronary vessels. Developed algorithm includes four stages: the video sequence stabilization, the vessels segmentation with the help of a neural network, the determination of the instantaneous velocity in the vessels based on the optical flow and the analysis of the results.

  15. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. New algorithm for detecting smaller retinal blood vessels in fundus images

    Science.gov (United States)

    LeAnder, Robert; Bidari, Praveen I.; Mohammed, Tauseef A.; Das, Moumita; Umbaugh, Scott E.

    2010-03-01

    About 4.1 million Americans suffer from diabetic retinopathy. To help automatically diagnose various stages of the disease, a new blood-vessel-segmentation algorithm based on spatial high-pass filtering was developed to automatically segment blood vessels, including the smaller ones, with low noise. Methods: Image database: Forty, 584 x 565-pixel images were collected from the DRIVE image database. Preprocessing: Green-band extraction was used to obtain better contrast, which facilitated better visualization of retinal blood vessels. A spatial highpass filter of mask-size 11 was applied. A histogram stretch was performed to enhance contrast. A median filter was applied to mitigate noise. At this point, the gray-scale image was converted to a binary image using a binary thresholding operation. Then, a NOT operation was performed by gray-level value inversion between 0 and 255. Postprocessing: The resulting image was AND-ed with its corresponding ring mask to remove the outer-ring (lens-edge) artifact. At this point, the above algorithm steps had extracted most of the major and minor vessels, with some intersections and bifurcations missing. Vessel segments were reintegrated using the Hough transform. Results: After applying the Hough transform, both the average peak SNR and the RMS error improved by 10%. Pratt's Figure of Merit (PFM) was decreased by 6%. Those averages were better than [1] by 10-30%. Conclusions: The new algorithm successfully preserved the details of smaller blood vessels and should prove successful as a segmentation step for automatically identifying diseases that affect retinal blood vessels.

  17. Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

    Directory of Open Access Journals (Sweden)

    Ali Zarina S

    2008-02-01

    Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

  18. Improvement of retinal blood vessel detection using morphological component analysis.

    Science.gov (United States)

    Imani, Elaheh; Javidi, Malihe; Pourreza, Hamid-Reza

    2015-03-01

    Detection and quantitative measurement of variations in the retinal blood vessels can help diagnose several diseases including diabetic retinopathy. Intrinsic characteristics of abnormal retinal images make blood vessel detection difficult. The major problem with traditional vessel segmentation algorithms is producing false positive vessels in the presence of diabetic retinopathy lesions. To overcome this problem, a novel scheme for extracting retinal blood vessels based on morphological component analysis (MCA) algorithm is presented in this paper. MCA was developed based on sparse representation of signals. This algorithm assumes that each signal is a linear combination of several morphologically distinct components. In the proposed method, the MCA algorithm with appropriate transforms is adopted to separate vessels and lesions from each other. Afterwards, the Morlet Wavelet Transform is applied to enhance the retinal vessels. The final vessel map is obtained by adaptive thresholding. The performance of the proposed method is measured on the publicly available DRIVE and STARE datasets and compared with several state-of-the-art methods. An accuracy of 0.9523 and 0.9590 has been respectively achieved on the DRIVE and STARE datasets, which are not only greater than most methods, but are also superior to the second human observer's performance. The results show that the proposed method can achieve improved detection in abnormal retinal images and decrease false positive vessels in pathological regions compared to other methods. Also, the robustness of the method in the presence of noise is shown via experimental result. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Evaluation of RGD-targeted albumin carriers for specific delivery of auristatin E to tumor blood vessels

    NARCIS (Netherlands)

    Temming, Kai; Meyer, Damon L.; Zabinski, Roger; Dijkers, Eli C. F.; Poelstra, Klaas; Molema, Grietje; Kok, Robbert J.

    2006-01-01

    Induction of apoptosis in endothelial cells is considered an attractive strategy to therapeutically interfere with a solid tumor's blood supply. In the present paper, we constructed cytotoxic conjugates that specifically target angiogenic endothelial cells, thus preventing typical side effects of

  20. Angiogenesis and blood vessel stability in inflammatory arthritis.

    LENUS (Irish Health Repository)

    Kennedy, Aisling

    2012-02-01

    OBJECTIVE: To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo. METHODS: Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity\\/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)\\/alpha-smooth muscle actin (alpha-SMA). NCAM and 8-oxo-7,8-dihydro-2\\'-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay. RESULTS: A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO(2) levels in the inflamed joint (median [range] 22.8 [3.2-54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and alpha-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC-pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO(2) (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O(2) (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). CONCLUSION: Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC-pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.

  1. Migraine aura pathophysiology: the role of blood vessels and microembolisation

    OpenAIRE

    Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A

    2010-01-01

    Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...

  2. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT and that of New Blood Vessels (CD105+ in Patients with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Micu Gianina Viorica

    2016-06-01

    Full Text Available Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells and CD 105 (for new vessels. Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

  3. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  4. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    International Nuclear Information System (INIS)

    Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

    2008-01-01

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOα on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOα at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 ± 4.7 mg and 34.9 ± 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

  5. A reason for intermittent fasting to suppress the awakening of dormant breast tumors.

    Science.gov (United States)

    Lankelma, Jan; Kooi, Bob; Krab, Klaas; Dorsman, Josephine C; Joenje, Hans; Westerhoff, Hans V

    2015-01-01

    For their growth, dormant tumors, which lack angiogenesis may critically depend on gradients of nutrients and oxygen from the nearest blood vessel. Because for oxygen depletion the distance from the nearest blood vessel to depletion will generally be shorter than for glucose depletion, such tumors will contain anoxic living tumor cells. These cells are dangerous, because they are capable of inducing angiogenesis, which will "wake up" the tumor. Anoxic cells are dependent on anaerobic glucose breakdown for ATP generation. The local extracellular glucose concentration gradient is determined by the blood glucose concentration and by consumption by cells closer to the nearest blood vessel. The blood glucose concentration can be lowered by 20-40% during fasting. We calculated that glucose supply to the potentially hazardous anoxic cells can thereby be reduced significantly, resulting in cell death specifically of the anoxic tumor cells. We hypothesize that intermittent fasting will help to reduce the incidence of tumor relapse via reducing the number of anoxic tumor cells and tumor awakening. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Childhood Vascular Tumors Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood vascular tumors form from cells that make blood vessels or lymph vessels. They can be benign (not cancer) or malignant (cancer). Get information about the symptoms, tests to diagnose, prognosis, and treatment of the most common type of vascular tumor, infantile hemangioma, and other vascular tumors in this expert-reviewed summary.

  7. Automatic detection of blood vessels in retinal images for diabetic retinopathy diagnosis.

    Science.gov (United States)

    Raja, D Siva Sundhara; Vasuki, S

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively.

  8. Subconjunctival Hemorrhage (Broken Blood Vessel in Eye)

    Science.gov (United States)

    Subconjunctival hemorrhage (broken blood vessel in eye) Overview A subconjunctival hemorrhage (sub-kun-JUNK-tih-vul HEM-uh-ruj) ... may not even realize you have a subconjunctival hemorrhage until you look in the mirror and notice ...

  9. CT diagnosis and differentiation of benign and malignant varieties of solitary fibrous tumor of the pleura.

    Science.gov (United States)

    You, Xiaofang; Sun, Xiwen; Yang, Chunyan; Fang, Yong

    2017-12-01

    To investigate computed tomography (CT) characteristics of benign and malignant solitary fibrous tumors of the pleura (SFTPs).Preoperative CTs for 60 SFTP cases (49 benign and 11 malignant) with subsequently confirmed diagnoses were retrospectively analyzed.Tumor morphologies included mounded or mushroom umbrella-shape (19 cases, 31.7%), quasi-circular or oval-shape (30 cases, 50%), and growth resembling a casting mould (12 cases, 20%). Maximum tumor diameters were 1.1 to 18.9 cm (average: 6.4 ± 4.8 cm). Fifty-seven cases had clear boundaries, and 3 had partially coarse boundaries. Twenty-seven cases showed homogeneous density; 33, "geographic"-patterned inhomogeneous density; 6, calcifications; 12, intratumor blood vessels; and 3, thick nourishing peritumoral blood vessels. Pleural thickening (regular and irregular) was found adjacent to tumors in 4, compression of adjacent ribs with absorption and cortical sclerosis in 2, and location adjacent to ribs with bony destruction in 1. Four cases had a small amount of lung tissue enfolded along the boundary, 2 had multiple peritumoral pulmonary bullae, and 9 had small ipsilateral pleural effusions. Compared with benign and malignant SFTPs were larger (P < .001), had inhomogeneous density, and were more commonly associated with intratumor blood vessels and pleural effusions (P < .01).CT revealed characteristic patterns in SFTPs, including casting mould-like growth, rich blood supply, and "geographic"-patterned enhancement. In addition, larger tumor size, inhomogeneous intensities, abundant intratumor blood vessels, and pleural effusions were more common with malignancy. Lastly, multislice CT angiography can reveal feeding arteries and help guide surgical management.

  10. Polymer-based blood vessel models with micro-temperature sensors in EVE

    Science.gov (United States)

    Mizoshiri, Mizue; Ito, Yasuaki; Hayakawa, Takeshi; Maruyama, Hisataka; Sakurai, Junpei; Ikeda, Seiichi; Arai, Fumihito; Hata, Seiichi

    2017-04-01

    Cu-based micro-temperature sensors were directly fabricated on poly(dimethylsiloxane) (PDMS) blood vessel models in EVE using a combined process of spray coating and femtosecond laser reduction of CuO nanoparticles. CuO nanoparticle solution coated on a PDMS blood vessel model are thermally reduced and sintered by focused femtosecond laser pulses in atmosphere to write the sensors. After removing the non-irradiated CuO nanoparticles, Cu-based microtemperature sensors are formed. The sensors are thermistor-type ones whose temperature dependences of the resistance are used for measuring temperature inside the blood vessel model. This fabrication technique is useful for direct-writing of Cu-based microsensors and actuators on arbitrary nonplanar substrates.

  11. A reason for intermittent fasting to suppress the awakening of dormant breast tumors.

    NARCIS (Netherlands)

    Lankelma, J.; Kooi, B.W.; Krab, K.; Dorsman, J.C.; Joenje, H.; Westerhoff, H.V.

    2015-01-01

    For their growth, dormant tumors, which lack angiogenesis may critically depend on gradients of nutrients and oxygen from the nearest blood vessel. Because for oxygen depletion the distance from the nearest blood vessel to depletion will generally be shorter than for glucose depletion, such tumors

  12. A reason for intermittent fasting to suppress the awakening of dormant breast tumors

    NARCIS (Netherlands)

    Lankelma, J.; Kooi, B.; Krab, K.; Dorsman, J.C.; Joenje, H.; Westerhoff, H.V.

    2015-01-01

    For their growth, dormant tumors, which lack angiogenesis may critically depend on gradients of nutrients and oxygen from the nearest blood vessel. Because for oxygen depletion the distance from the nearest blood vessel to depletion will generally be shorter than for glucose depletion, such tumors

  13. Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

    Science.gov (United States)

    Cobec, Ionut Marcel; Sas, Ioan; Pirtea, Laurențiu; Cimpean, Anca Maria; Moatar, Aurica Elisabeta; Ceaușu, Raluca Amalia; Raica, Marius

    2016-10-01

    Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. X-ray phase contrast with injected gas for tumor microangiography

    International Nuclear Information System (INIS)

    Lundström, U; Larsson, D H; Burvall, A; Hertz, H M; Westermark, U K; Henriksson, M Arsenian

    2014-01-01

    We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas–tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research. (paper)

  15. Does Physical Fitness Buffer the Relationship between Psychosocial Stress, Retinal Vessel Diameters, and Blood Pressure among Primary Schoolchildren?

    Science.gov (United States)

    Endes, Katharina; Herrmann, Christian; Colledge, Flora; Brand, Serge; Donath, Lars; Faude, Oliver; Pühse, Uwe; Hanssen, Henner; Zahner, Lukas

    2016-01-01

    Background. Strong evidence exists showing that psychosocial stress plays an important part in the development of cardiovascular diseases. Because physical inactivity is associated with less favourable retinal vessel diameter and blood pressure profiles, this study explores whether physical fitness is able to buffer the negative effects of psychosocial stress on retinal vessel diameters and blood pressure in young children. Methods. 325 primary schoolchildren (51% girls, Mage = 7.28 years) took part in this cross-sectional research project. Retinal arteriolar diameters, retinal venular diameters, arteriolar to venular ratio, and systolic and diastolic blood pressure were assessed in all children. Interactions terms between physical fitness (performance in the 20 m shuttle run test) and four indicators of psychosocial stress (parental reports of critical life events, family, peer and school stress) were tested in a series of hierarchical regression analyses. Results. Critical life events and family, peer, and school-related stress were only weakly associated with retinal vessel diameters and blood pressure. No support was found for a stress-buffering effect of physical fitness. Conclusion. More research is needed with different age groups to find out if and from what age physical fitness can protect against arteriolar vessel narrowing and the occurrence of other cardiovascular disease risk factors. PMID:27795958

  16. Regulation of blood vessels by prolactin and vasoinhibins.

    Science.gov (United States)

    Clapp, Carmen; Thebault, Stéphanie; Macotela, Yazmín; Moreno-Carranza, Bibiana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2015-01-01

    Prolactin (PRL) stimulates the growth of new blood vessels (angiogenesis) either directly through actions on endothelial cells or indirectly by upregulating proangiogenic factors like vascular endothelial growth factor (VEGF). Moreover, PRL acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects. In view of the opposing actions of PRL and vasoinhibins, the regulation of the proteases responsible for specific PRL cleavage represents an efficient mechanism for controlling blood vessel growth and function. This review briefly describes the vascular actions of PRL and vasoinhibins, and addresses how their interplay could help drive biological effects of PRL in the context of health and disease.

  17. Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment

    OpenAIRE

    Kirkpatrick, Nathaniel D.; Chung, Euiheon; Cook, Daniel C.; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L.; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.

    2012-01-01

    The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion...

  18. An approach to localize the retinal blood vessels using bit planes and centerline detection.

    Science.gov (United States)

    Fraz, M M; Barman, S A; Remagnino, P; Hoppe, A; Basit, A; Uyyanonvara, B; Rudnicka, A R; Owen, C G

    2012-11-01

    The change in morphology, diameter, branching pattern or tortuosity of retinal blood vessels is an important indicator of various clinical disorders of the eye and the body. This paper reports an automated method for segmentation of blood vessels in retinal images. A unique combination of techniques for vessel centerlines detection and morphological bit plane slicing is presented to extract the blood vessel tree from the retinal images. The centerlines are extracted by using the first order derivative of a Gaussian filter in four orientations and then evaluation of derivative signs and average derivative values is performed. Mathematical morphology has emerged as a proficient technique for quantifying the blood vessels in the retina. The shape and orientation map of blood vessels is obtained by applying a multidirectional morphological top-hat operator with a linear structuring element followed by bit plane slicing of the vessel enhanced grayscale image. The centerlines are combined with these maps to obtain the segmented vessel tree. The methodology is tested on three publicly available databases DRIVE, STARE and MESSIDOR. The results demonstrate that the performance of the proposed algorithm is comparable with state of the art techniques in terms of accuracy, sensitivity and specificity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

    Science.gov (United States)

    Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

    2015-09-01

    Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

  20. Feasibility of Using the Marginal Blood Vessels as Reference Landmarks for CT Colonography

    Science.gov (United States)

    Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Dwyer, Andrew J.; Pickhardt, Perry J.; Nowinski, Wieslaw L.; Summers, Ronald M.

    2015-01-01

    OBJECTIVE The purpose of this study was to show the spatial relationship of the colonic marginal blood vessels and the teniae coli on CT colonography (CTC) and the use of the marginal blood vessels for supine-prone registration of polyps and for determination of proper connectivity of collapsed colonic segments. MATERIALS AND METHODS We manually labeled the marginal blood vessels on 15 CTC examinations. Colon segmentation, centerline extraction, teniae detection, and teniae identification were automatically performed. For assessment of their spatial relationships, the distances from the marginal blood vessels to the three teniae coli and to the colon were measured. Student t tests (paired, two-tailed) were performed to evaluate the differences among these distances. To evaluate the reliability of the marginal vessels as reference points for polyp correlation, we analyzed 20 polyps from 20 additional patients who underwent supine and prone CTC. The average difference of the circumferential polyp position on the supine and prone scans was computed. Student t tests (paired, two-tailed) were performed to evaluate the supine-prone differences of the distance. We performed a study on 10 CTC studies from 10 patients with collapsed colonic segments by manually tracing the marginal blood vessels near the collapsed regions to resolve the ambiguity of the colon path. RESULTS The average distances (± SD) from the marginal blood vessels to the tenia mesocolica, tenia omentalis, and tenia libera were 20.1 ± 3.1 mm (95% CI, 18.5–21.6 mm), 39.5 ± 4.8 mm (37.1–42.0 mm), and 36.9 ± 4.2 mm (34.8–39.1 mm), respectively. Pairwise comparison showed that these distances to the tenia libera and tenia omentalis were significantly different from the distance to the tenia mesocolica (p marginal blood vessels to the colon wall was 15.3 ± 2.0 mm (14.2–16.3 mm). For polyp localization, the average difference of the circumferential polyp position on the supine and prone scans was 9

  1. Intestinal Ischaemia Associated with Carcinoid Tumor: A Case Report with Review of the Pathogenesis

    Directory of Open Access Journals (Sweden)

    Oktay Yener

    2013-01-01

    Full Text Available Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that are often indolent and may not become clinically apparent until there is a metastatic spread or evidence of carcinoid syndrome.  A 44-year-old man presented to our clinic department with a history of previous left colon cancer operation, chronic crampy left lower quadrant pain, mass and severe anemia.  A MR scan was obtained which demonstrated a calcified mesenteric mass 12×8×10 cm diameter with surrounding left colon mesenteric infiltration. The liver was normal. A case of ischaemic ileal necrosis is reported. It was associated with elastic vascular sclerosis produced by mesenteric metastases of an ileal carcinoid tumor. It is postulated that intestinal ischaemia may be of more importance in the production of abdominal pain by carcinoid tumors than has been generally accepted, and that it is the result of functional and structural changes in and around the mesenteric blood vessels, caused by substances secreted by the carcinoid tumor.

  2. Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

  3. Customizable engineered blood vessels using 3D printed inserts.

    Science.gov (United States)

    Pinnock, Cameron B; Meier, Elizabeth M; Joshi, Neeraj N; Wu, Bin; Lam, Mai T

    2016-04-15

    Current techniques for tissue engineering blood vessels are not customizable for vascular size variation and vessel wall thickness. These critical parameters vary widely between the different arteries in the human body, and the ability to engineer vessels of varying sizes could increase capabilities for disease modeling and treatment options. We present an innovative method for producing customizable, tissue engineered, self-organizing vascular constructs by replicating a major structural component of blood vessels - the smooth muscle layer, or tunica media. We utilize a unique system combining 3D printed plate inserts to control construct size and shape, and cell sheets supported by a temporary fibrin hydrogel to encourage cellular self-organization into a tubular form resembling a natural artery. To form the vascular construct, 3D printed inserts are adhered to tissue culture plates, fibrin hydrogel is deposited around the inserts, and human aortic smooth muscle cells are then seeded atop the fibrin hydrogel. The gel, aided by the innate contractile properties of the smooth muscle cells, aggregates towards the center post insert, creating a tissue ring of smooth muscle cells. These rings are then stacked into the final tubular construct. Our methodology is robust, easily repeatable and allows for customization of cellular composition, vessel wall thickness, and length of the vessel construct merely by varying the size of the 3D printed inserts. This platform has potential for facilitating more accurate modeling of vascular pathology, serving as a drug discovery tool, or for vessel repair in disease treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effect of non-Newtonian characteristics of blood on magnetic particle capture in occluded blood vessel

    Science.gov (United States)

    Bose, Sayan; Banerjee, Moloy

    2015-01-01

    Magnetic nanoparticles drug carriers continue to attract considerable interest for drug targeting in the treatment of cancer and other pathological conditions. Magnetic carrier particles with surface-bound drug molecules are injected into the vascular system upstream from the desired target site, and are captured at the target site via a local applied magnetic field. Herein, a numerical investigation of steady magnetic drug targeting (MDT) using functionalized magnetic micro-spheres in partly occluded blood vessel having a 90° bent is presented considering the effects of non-Newtonian characteristics of blood. An Eulerian-Lagrangian technique is adopted to resolve the hemodynamic flow and the motion of the magnetic particles in the flow using ANSYS FLUENT. An implantable infinitely long cylindrical current carrying conductor is used to create the requisite magnetic field. Targeted transport of the magnetic particles in a partly occluded vessel differs distinctly from the same in a regular unblocked vessel. Parametric investigation is conducted and the influence of the insert configuration and its position from the central plane of the artery (zoffset), particle size (dp) and its magnetic property (χ) and the magnitude of current (I) on the "capture efficiency" (CE) is reported. Analysis shows that there exists an optimum regime of operating parameters for which deposition of the drug carrying magnetic particles in a target zone on the partly occluded vessel wall can be maximized. The results provide useful design bases for in vitro set up for the investigation of MDT in stenosed blood vessels.

  5. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  6. Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

    Science.gov (United States)

    Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

    2015-12-04

    Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

  7. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  8. Intravenous contrast-enhanced cone beam computed tomography (IVCBCT of intrahepatic tumors and vessels

    Directory of Open Access Journals (Sweden)

    Cynthia L. Eccles, BSc

    2016-01-01

    Conclusions: Intravenous-CBCT may enhance the visibility of hepatic vessels and tumor in CBCT scans obtained during breath hold. Optimization of IV contrast timing and reduction of artifacts to improve tumor visualization warrant further investigation.

  9. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  10. Mechanism of brain tumor headache.

    Science.gov (United States)

    Taylor, Lynne P

    2014-04-01

    Headaches occur commonly in all patients, including those who have brain tumors. Using the search terms "headache and brain tumors," "intracranial neoplasms and headache," "facial pain and brain tumors," "brain neoplasms/pathology," and "headache/etiology," we reviewed the literature from the past 78 years on the proposed mechanisms of brain tumor headache, beginning with the work of Penfield. Most of what we know about the mechanisms of brain tumor associated headache come from neurosurgical observations from intra-operative dural and blood vessel stimulation as well as intra-operative observations and anecdotal information about resolution of headache symptoms with various tumor-directed therapies. There is an increasing overlap between the primary and secondary headaches and they may actually share a similar biological mechanism. While there can be some criticism that the experimental work with dural and arterial stimulation produced head pain and not actual headache, when considered with the clinical observations about headache type, coupled with improvement after treatment of the primary tumor, we believe that traction on these structures, coupled with increased intracranial pressure, is clearly part of the genesis of brain tumor headache and may also involve peripheral sensitization with neurogenic inflammation as well as a component of central sensitization through trigeminovascular afferents on the meninges and cranial vessels. © 2014 American Headache Society.

  11. Towards cavitation-enhanced permeability in blood vessel on a chip

    Science.gov (United States)

    De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

    2017-08-01

    The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

  12. Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Qingyi [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Qing, Yong, E-mail: qingyongxy@yahoo.co.jp [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Yang [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Hu, Xiaojuan; Jiang, Lei [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Xiaohua, E-mail: wuxh@scu.edu.cn [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China)

    2014-12-01

    Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of dioscin. We showed that dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied by obvious blood vessel decrease within solid tumors. We also found dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF-induced blood vessel formation in vivo. We also identified that dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied by the increase of phosphorylated P38MAPK. The results potently suggest that dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways. - Highlights: • Dioscin inhibits tumor growth in vivo and does not exhibit any toxicity. • Dioscin inhibits angiogenesis within solid tumors. • Dioscin inhibits the proliferation, migration, invasion, and tube formation of HUVECs. • Dioscin inhibits VEGF–induced blood vessel formation in vivo. • Dioscin inhibits VEGFR2 signaling pathway as well as AKT/MAPK pathway.

  13. Regional cerebral blood flow measurement in brain tumors

    International Nuclear Information System (INIS)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-01-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of 133 Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors. (author)

  14. Regional cerebral blood flow measurement in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-10-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of /sup 133/Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors.

  15. A thresholding based technique to extract retinal blood vessels from fundus images

    Directory of Open Access Journals (Sweden)

    Jyotiprava Dash

    2017-12-01

    Full Text Available Retinal imaging has become the significant tool among all the medical imaging technology, due to its capability to extract many data which is linked to various eye diseases. So, the accurate extraction of blood vessel is necessary that helps the eye care specialists and ophthalmologist to identify the diseases at the early stages. In this paper, we have proposed a computerized technique for extraction of blood vessels from fundus images. The process is conducted in three phases: (i pre-processing where the image is enhanced using contrast limited adaptive histogram equalization and median filter, (ii segmentation using mean-C thresholding to extract retinal blood vessels, (iii post-processing where morphological cleaning operation is used to remove isolated pixels. The performance of the proposed method is tested on and experimental results show that our method achieve an accuracies of 0.955 and 0.954 on Digital retinal images for vessel extraction (DRIVE and Child heart and health study in England (CHASE_DB1 databases respectively.

  16. Wide-field absolute transverse blood flow velocity mapping in vessel centerline

    Science.gov (United States)

    Wu, Nanshou; Wang, Lei; Zhu, Bifeng; Guan, Caizhong; Wang, Mingyi; Han, Dingan; Tan, Haishu; Zeng, Yaguang

    2018-02-01

    We propose a wide-field absolute transverse blood flow velocity measurement method in vessel centerline based on absorption intensity fluctuation modulation effect. The difference between the light absorption capacities of red blood cells and background tissue under low-coherence illumination is utilized to realize the instantaneous and average wide-field optical angiography images. The absolute fuzzy connection algorithm is used for vessel centerline extraction from the average wide-field optical angiography. The absolute transverse velocity in the vessel centerline is then measured by a cross-correlation analysis according to instantaneous modulation depth signal. The proposed method promises to contribute to the treatment of diseases, such as those related to anemia or thrombosis.

  17. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K. Kartini

    2015-04-01

    Full Text Available Background Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. Methods An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. Results Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. Conclusion The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  18. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K Kartini

    2016-02-01

    Full Text Available BACKGROUND Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. METHODS An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. RESULTS Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. CONCLUSION The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  19. Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review.

    Science.gov (United States)

    Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

    2016-09-01

    Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

  20. Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

    Science.gov (United States)

    Azimipour, Mehdi; Atry, Farid; Pashaie, Ramin

    2015-05-15

    In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

  1. Blood Vessel-Derived Acellular Matrix for Vascular Graft Application

    Directory of Open Access Journals (Sweden)

    Luigi Dall’Olmo

    2014-01-01

    Full Text Available To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm blood vessels, this study aimed to develop acellular matrix- (AM- based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm. The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels.

  2. Tracking blood vessels in human forearms using visual servoing

    DEFF Research Database (Denmark)

    Savarimuthu, Thiusius Rajeeth; Ellekilde, Lars-Peter; Hansen, Morten

    compensation. By using images taken with near-infrared light to locate the blood vessels in a human forearm and using the same images to detects movements of the arm, this paper shows that it is possible make a robot arm, potentially equipped with a needle for drawing the blood, compensate for the movements......Drawing an average of more than 2 blood sample per Danish citizen per year increases the demand for an automatic blood sampling method. This paper presents a proof of concept to one of the main challenges in making a fully automated blood sampling procedure, namely: the patient movement...

  3. Acute effect of gamma-irradiation on blood vessels of the eye

    International Nuclear Information System (INIS)

    Matsushima, Hideno

    1977-01-01

    Radiation injuries to the eye were studied by examining the alteration of fine vasculature of irradiated rabbit eyes, by referring to the usual clinical findings, fundus photography, microangiography, and histological sections. These experiments were performed by using white rabbits whose eyes were locally irradiated with a single dose of 500, 1000, 2000, 3000, and 5000 R of 60 Co-γ-ray. The eyes were observed periodically for a period up to 10 weeks after irradiation, and the following results were obtained: 1) Radiation damage to the blood vessels was maximum around 6 weeks after irradiation for doses less than 2000 R, and the damage appeared to be reversible. 2) When given more than 3000 R irradiation, alteration of the blood vessels continued increasing for 10 weeks with no evidence of recovery. Experimental evidence from these studies supports the hypothesis that the degree of radiation injury of the eye depends highly on the damage to blood vessels serving each structure of the eye. (auth.)

  4. [Large vessel vasculitis with myelodysplastic syndrome: A rare association].

    Science.gov (United States)

    Galland, J; Kawski, H; Guichard, J-F; Maurier, F

    2017-07-01

    The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare. A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm 3 ). Radiological examinations found thoracic aortitis and carotid vasculitis. Treatment in the form of steroids and azacitidine was instituted. The lack of control of both RAEB-2 and vasculitis was responsible for the death of the patient. Myelodysplastic syndrome and large vessels vasculitis is a rare but serious association disease. The lack of efficiency of corticosteroids seems to be common. Prognosis depends on the haematological treatment effectiveness. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Detection of tumor-associated cells in cryopreserved peripheral blood mononuclear cell samples for retrospective analysis.

    Science.gov (United States)

    Zhu, Peixuan; Stanton, Melissa L; Castle, Erik P; Joseph, Richard W; Adams, Daniel L; Li, Shuhong; Amstutz, Platte; Tang, Cha-Mei; Ho, Thai H

    2016-07-02

    Cryopreserved peripheral blood mononuclear cells (PBMCs) are commonly collected in biobanks. However, little data exist regarding the preservation of tumor-associated cells in cryopreserved collections. The objective of this study was to determine the feasibility of using the CellSieve™ microfiltration assay for the isolation of circulating tumor cells (CTCs) and circulating cancer-associated macrophage-like cells (CAMLs) from cryopreserved PBMC samples. Blood samples spiked with breast (MCF-7), prostate (PC-3), and renal (786-O) cancer cell lines were used to establish analytical accuracy, efficiency, and reproducibility after cryopreservation. The spiked samples were processed through Ficoll separation, and cryopreservation was followed by thawing and microfiltration. MCF-7 cells were successfully retrieved with recovery efficiencies of 90.5 % without cryopreservation and 87.8 and 89.0 %, respectively, on day 7 and day 66 following cryopreservation. The corresponding recovery efficiencies of PC-3 cells were 83.3 % without cryopreservation and 85.3 and 84.7 %, respectively, after cryopreservation. Recovery efficiencies of 786-O cells were 92.7 % without cryopreservation, and 82.7 and 81.3 %, respectively, after cryopreservation. The recovered cells retained the morphologic characteristics and immunohistochemical markers that had been observed before freezing. The protocols were further validated by quantitation of CAMLs in blood samples from two patients with renal cell carcinoma (RCC). The recovery rates of CTCs and CAMLs from cryopreserved samples were not statistically significant different (P > 0.05) from matched fresh samples. To our knowledge, this is the first report that CAMLs could be cryopreserved and analyzed after thawing with microfiltration technology. The application of microfiltration technology to cryopreserved samples will enable much greater retrospective study of cancer patients in relation to long-term outcomes.

  7. Tumor blood flow and pH changes after glucose administration

    International Nuclear Information System (INIS)

    Thistlethwaite, A.J.; Tupchong, L.; Leeper, D.B.

    1987-01-01

    The authors used a laser doppler technique to correlate blood flow changes with pH changes in human tumors after glucose ingestion. Three PTs with large superficial tumors ingested 100 gm glucose. A 21g needle pH electrode (Micro-electrodes, Inc.) and a 21g ''Laserflo'' fiberoptic laser doppler blood flow probe (TSI, Minneapolis, MN) were used at the same location. Blood glucose was measured by finger stick every 7.5 min. One PT with a squamous cell CA with extensive necrosis had only a small increase in blood glucose and an increase in tumor pH. Blood flow readings were within 6.4-18.4ml/100g/min. Another PT with a squamous CA had a drop in tumor pH (7.46 to 7.05) as blood glucose increased from 85 to 137 mg/dl by 55 min. Blood flow remained in a range of 7.7-13.8 ml/100g/min with a mean of 11.4. The third PT with a sarcoma had tumor pH and blood glucose measurements on two occasions, with similar results. Blood glucose rose from approx. 100 to 150 mg/dl by 52.5 min with a drop in tumor pH from approx. 7.4 to 7.25. On the second trial, tumor blood flow was measured and, while erratic (6.4-24.9ml/100g/min), decreased by approx. 50%. These preliminary data show that the laser doppler blood flow technique is quite sensitive to movement artifact and interference by free hemoglobin. Currently, it is inconclusive whether blood flow is altered with blood glucose and tumor pH changes. Further studies may prove this to be a valuable tool in predicting tumor response to hyperthermia

  8. Comparison of the Blood and Lymphatic Microvessel Density of Pleomorphic Adenoma and Basal Cell Adenoma

    Directory of Open Access Journals (Sweden)

    Andresa Borges Soares

    2015-01-01

    Full Text Available Background Pleomorphic adenoma (PA is the most common tumor of the salivary gland, while basal cell adenoma (BCA is an uncommon neoplasm. Blood and lymphatic vessels are crucial for tumor metabolism. The aim of this study was to compare the blood and lymphatic vascular density and vascular and endothelial growth factor (VEGF expression in PA and BCA tumors. In addition, cell proliferation was evaluated in these tumors. Methods Blood and lymphatic vessel content, VEGF expression, and cell proliferation were analyzed in 30 cases of PA and 13 cases of BCA by immu-nohistochemistry using antibodies for CD34, CD105, D2-40, VEGF, and Mcm -2. Results Regarding CD34 and CD105 expression, PA demonstrated a high vascularity and a low number of positive vessels, respectively. D2-40-positive lymphatic vessels were mainly located in the tumor capsules, with small intratumoral lymphatic vessels observed occasionally. VEGF expression revealed a remarkably heterogeneous immunoreactivity, alternating from weak or negative to positive or intense. BCA presented significantly higher CD34, CD34, CD105, D2-40, and VEGF expression compared to PA. No significant difference was found in cell proliferation between the tumors. Conclusion Although PA and BCA are considered part of the same spectrum of differentiation, this study showed that the blood and lymphatic vascularization of these tumors is different.

  9. 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.

  10. Blood vessel damage correlated with irradiance for in vivo vascular targeted photodynamic therapy

    Science.gov (United States)

    Zhang, Jinde; Tan, Zou; Niu, Xiangyu; Lin, Linsheng; Lin, Huiyun; Li, Buhong

    2016-10-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely utilized for the prevention or treatment of vascular-related diseases, including age-related macular degeneration, port-wine stains and prostate cancer. In order to quantitative assessment the blood vessel damage during V-PDT, nude mice were implanted with Titanium dorsal skin window chambers for in vivo V-PDT studies. For treatments, various irradiances including 50, 75, 100 and 200 mW/cm2 provided by a 532 nm semiconductor laser were performed with the same total light dose of 30 J/cm2 after the mice were intravenously injection of Rose Bengal for 25 mg/Kg body weight. Laser speckle imaging and microscope were used to monitor blood flow dynamics and vessel constriction during and after V-PDT, respectively. The V-PDT induced vessel damages between different groups were compared. The results show that significant difference in blood vessel damage was found between the lower irradiances (50, 75 and 100 mW/cm2) and higher irradiance (200 mW/cm2), and the blood vessel damage induced by V-PDT is positively correlated with irradiance. This study implies that the optimization of irradiance is required for enhancing V-PDT therapeutic efficiency.

  11. Mathematical modelling for trajectories of magnetic nanoparticles in a blood vessel under magnetic field

    International Nuclear Information System (INIS)

    Sharma, Shashi; Katiyar, V.K.; Singh, Uaday

    2015-01-01

    A mathematical model is developed to describe the trajectories of a cluster of magnetic nanoparticles in a blood vessel for the application of magnetic drug targeting (MDT). The magnetic nanoparticles are injected into a blood vessel upstream from a malignant tissue and are captured at the tumour site with help of an applied magnetic field. The applied field is produced by a rare earth cylindrical magnet positioned outside the body. All forces expected to significantly affect the transport of nanoparticles were incorporated, including magnetization force, drag force and buoyancy force. The results show that particles are slow down and captured under the influence of magnetic force, which is responsible to attract the magnetic particles towards the magnet. It is optimized that all particles are captured either before or at the centre of the magnet (z≤0) when blood vessel is very close proximity to the magnet (d=2.5 cm). However, as the distance between blood vessel and magnet (d) increases (above 4.5 cm), the magnetic nanoparticles particles become free and they flow away down the blood vessel. Further, the present model results are validated by the simulations performed using the finite element based COMSOL software. - Highlights: • A mathematical model is developed to describe the trajectories of magnetic nanoparticles. • The dominant magnetic, drag and buoyancy forces are considered. • All particles are captured when distance between blood vessel and magnet (d) is up to 4.5 cm. • Further increase in d value (above 4.5 cm) results the free movement of magnetic particles

  12. Imaging Blood Vessel Morphology in Skin

    DEFF Research Database (Denmark)

    Schuh, Sandra; Holmes, Jon; Ulrich, Martina

    2017-01-01

    Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine...... practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight...... into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel...

  13. Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

    Science.gov (United States)

    Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann

    2016-01-01

    Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

  14. Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

    Science.gov (United States)

    Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

    2016-01-01

    Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept “bio-adaption” between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed. PMID:27698548

  15. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Kyle C. Kern

    2017-05-01

    Full Text Available Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1 identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2 compare this relationship across blood pressure groups, and (3 relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

  16. DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis.

    Science.gov (United States)

    Choi, Hyeong Sim; Lee, Kangwook; Kim, Min Kyoung; Lee, Kang Min; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2016-04-19

    Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.

  17. Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

    Science.gov (United States)

    Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

    2011-09-01

    Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

  18. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

    2013-01-01

    The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform

  19. Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

    2013-02-01

    Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

  20. Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Yahalom, J; Biran, S; Fuks, Z; Vlodavsky, I [Hadassah University Hospital, Jerusalem (Israel). Dept. of Radiation and Clinical Oncology; Eldor, A [Hadassah University Hospital, Jerusalem (Israel). Dept. of Hematology

    1985-04-01

    Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. This requires adhesion of blood-borne cells to the luminal surface of the vascular endothelium, invasion through the endothelial cell layer and local dissolution of the subendothelial basement membrane. The authors studied the interaction of platelets and tumor cells with cultured vascular endothelial cells and their secreted basement membrane-like extracellular matrix (ECM). Interaction of platelets with this ECM was associated with platelet activation, aggregation and degradation of heparan sulfate in the ECM by means of the platelet heparitinase. Biochemical and scanning electron microscopy (SEM) studies have demonstrated that platelets may detect even minor gaps between adjacent endothelial cells and degrade the ECM heparan sulfate. Platelets were also shown to recruit lymphoma cells into minor gaps in the vascular endothelium. It is suggested that the platelet heparitinase is involved in the impairment of the integrity of the vessel wall and thus play a role in tumor cell metastasis.

  1. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

    International Nuclear Information System (INIS)

    Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

    1991-01-01

    The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

  2. Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment.

    Science.gov (United States)

    Kirkpatrick, Nathaniel D; Chung, Euiheon; Cook, Daniel C; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L; Padera, Timothy P; Fukumura, Dai; Jain, Rakesh K

    2012-01-01

    The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors. However, traditional multiphoton microscopy suffers from inherently slow imaging rates-only a few frames per second, thus unable to capture more rapid events such as blood flow, lymphatic flow, and cell movement within vessels. Here, we report the development and implementation of a video-rate multiphoton microscope (VR-MPLSM) based on resonant galvanometer mirror scanning that is capable of recording at 30 frames per second and acquiring intravital multispectral images. We show that the design of the system can be readily implemented and is adaptable to various experimental models. As examples, we demonstrate the utility of the system to directly measure flow within tumors, capture metastatic cancer cells moving within the brain vasculature and cells in lymphatic vessels, and image acute responses to changes in a vascular network. VR-MPLSM thus has the potential to further advance intravital imaging and provide new insight into the biology of the tumor microenvironment.

  3. Evaluation of RGD-targeted albumin carriers for specific delivery of auristatin E to tumor blood vessels.

    Science.gov (United States)

    Temming, Kai; Meyer, Damon L; Zabinski, Roger; Dijkers, Eli C F; Poelstra, Klaas; Molema, Grietje; Kok, Robbert J

    2006-01-01

    Induction of apoptosis in endothelial cells is considered an attractive strategy to therapeutically interfere with a solid tumor's blood supply. In the present paper, we constructed cytotoxic conjugates that specifically target angiogenic endothelial cells, thus preventing typical side effects of apoptosis-inducing drugs. For this purpose, we conjugated the potent antimitotic agent monomethyl-auristatin-E (MMAE) via a lysosomal cleavable linker to human serum albumin (HSA) and further equipped this drug-albumin conjugate with cyclic c(RGDfK) peptides for multivalent interaction with alphavbeta3-integrin. The RGD-peptides were conjugated via either an extended poly(ethylene glycol) linker or a short alkyl linker. The resulting drug-targeting conjugates RGDPEG-MMAE-HSA and RGD-MMAE-HSA demonstrated high binding affinity and specificity for alphavbeta3-integrin expressing human umbilical vein endothelial cells (HUVEC). Both types of conjugates were internalized by endothelial cells and killed the target cells at low nM concentrations. Furthermore, we observed RGD-dependent binding of the conjugates to C26 carcinoma. Upon i.v. administration to C26-tumor bearing mice, both drug-targeting conjugates displayed excellent tumor homing properties. Our results demonstrate that RGD-modified albumins are suitable carriers for cell selective intracellular delivery of cytotoxic compounds, and further studies will be conducted to assess the antivascular and tumor inhibitory potential of RGDPEG-MMAE-HSA and RGD-MMAE-HSA.

  4. Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors

    Directory of Open Access Journals (Sweden)

    Tian Yufeng

    2010-06-01

    Full Text Available Abstract Background New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic. Results In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization. Conclusion Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.

  5. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  6. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  7. Inflammatory angiomyolipoma of the liver: a rare hepatic tumor

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2012-09-01

    Full Text Available Abstract Angiomyolipoma (AML is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370

  8. A Computational Model Predicting Disruption of Blood Vessel Development

    Science.gov (United States)

    Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...

  9. Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors.

    Science.gov (United States)

    Ojha, Tarun; Pathak, Vertika; Shi, Yang; Hennink, Wim E; Moonen, Chrit T W; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2017-09-15

    The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Classic beta-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease.

    Science.gov (United States)

    Armstrong, Richard A

    2006-11-01

    Various hypotheses could explain the relationship between beta-amyloid (Abeta) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of Abeta deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Abeta and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (>10 microm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.

  11. A novel vascular-targeting peptide for gastric cancer delivers low-dose TNFα to normalize the blood vessels and improve the anti-cancer efficiency of 5-fluorouracil.

    Science.gov (United States)

    Lu, Lan; Li, Zhi Jie; Li, Long Fei; Shen, Jing; Zhang, Lin; Li, Ming Xing; Xiao, Zhan Gang; Wang, Jian Hao; Cho, Chi Hin

    2017-11-01

    Various vascular-targeted agents fused with tumor necrosis factor α (TNFα) have been shown to improve drug absorption into tumor tissues and enhance tumor vascular function. TCP-1 is a peptide selected through in vivo phage library biopanning against a mouse orthotopic colorectal cancer model and is a promising agent for drug delivery. This study further investigated the targeting ability of TCP-1 phage and peptide to blood vessels in an orthotopic gastric cancer model in mice and assessed the synergistic anti-cancer effect of 5-fluorouracil (5-FU) with subnanogram TNFα targeted delivered by TCP-1 peptide. In vivo phage targeting assay and in vivo colocalization analysis were carried out to test the targeting ability of TCP-1 phage/peptide. A targeted therapy for improvement of the therapeutic efficacy of 5-FU and vascular function was performed through administration of TCP-1/TNFα fusion protein in this model. TCP-1 phage exhibited strong homing ability to the orthotopic gastric cancer after phage injection. Immunohistochemical staining suggested that and TCP-1 phage/TCP-1 peptide could colocalize with tumor vascular endothelial cells. TCP-1/TNFα combined with 5-FU was found to synergistically inhibit tumor growth, induce apoptosis and reduce cell proliferation without evident toxicity. Simultaneously, subnanogram TCP-1/TNFα treatment normalized tumor blood vessels. Targeted delivery of low-dose TNFα by TCP-1 peptide can potentially modulate the vascular function of gastric cancer and increase the drug delivery of chemotherapeutic drugs. Copyright © 2017. Published by Elsevier Inc.

  12. Optics based signal processing methods for intraoperative blood vessel detection and quantification in real time (Conference Presentation)

    Science.gov (United States)

    Chaturvedi, Amal; Shukair, Shetha A.; Le Rolland, Paul; Vijayvergia, Mayank; Subramanian, Hariharan; Gunn, Jonathan W.

    2016-03-01

    Minimally invasive operations require surgeons to make difficult cuts to blood vessels and other tissues with impaired tactile and visual feedback. This leads to inadvertent cuts to blood vessels hidden beneath tissue, causing serious health risks to patients and a non-reimbursable financial burden to hospitals. Intraoperative imaging technologies have been developed, but these expensive systems can be cumbersome and provide only a high-level view of blood vessel networks. In this research, we propose a lean reflectance-based system, comprised of a dual wavelength LED, photodiode, and novel signal processing algorithms for rapid vessel characterization. Since this system takes advantage of the inherent pulsatile light absorption characteristics of blood vessels, no contrast agent is required for its ability to detect the presence of a blood vessel buried deep inside any tissue type (up to a cm) in real time. Once a vessel is detected, the system is able to estimate the distance of the vessel from the probe and the diameter size of the vessel (with a resolution of ~2mm), as well as delineate the type of tissue surrounding the vessel. The system is low-cost, functions in real-time, and could be mounted on already existing surgical tools, such as Kittner dissectors or laparoscopic suction irrigation cannulae. Having been successfully validated ex vivo, this technology will next be tested in a live porcine study and eventually in clinical trials.

  13. Estimation of vessel diameter and blood flow dynamics from laser speckle images

    DEFF Research Database (Denmark)

    Postnov, Dmitry D.; Tuchin, Valery V.; Sosnovtseva, Olga

    2016-01-01

    Laser speckle imaging is a rapidly developing method to study changes of blood velocity in the vascular networks. However, to assess blood flow and vascular responses it is crucial to measure vessel diameter in addition to blood velocity dynamics. We suggest an algorithm that allows for dynamical...

  14. [Markers of angiogenesis in tumor growth].

    Science.gov (United States)

    Nefedova, N A; Kharlova, O A; Danilova, N V; Malkov, P G; Gaifullin, N M

    2016-01-01

    Angiogenesis is a process of new blood vessels formation. The role of angiogenesis in growth, invasion and metastasis of malignant tumours is nowdays universally recognized. Though, investigation of mechanisms of blood vessels formation and elaboration methods for assessment of tumour angiogenesis are still up-dated. Another important concern are different aspects of usage of immunohistochemical markers of blood vessels endothelium (CD31 and CD34) for assessment of tumour aggressiveness and prognosis. The problems of malignant lymphangiogenesis are also up-to-date. The focus is on methods of immunohistochemical visualization of forming lymphatic vessels, role of podoplanin, the most reliable marker of lymphatic vessels, in their identification, and formulization of the main criteria for lymphangiogenesis estimation, its correlation with metastatic activity and prognostic potential. Studying of angiogenesis and lymph angiogenesis in malignant tumors is important and challenging direction for researching tumour progression and invention of antiangiogenic therapy.

  15. Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

    Directory of Open Access Journals (Sweden)

    Mohsen Mehrabi

    2012-01-01

    Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

  16. An Experimental Study to Replace the Thoracic Descending Aorta for Pigs with a Self-Made Sutureless Blood Vessel

    Directory of Open Access Journals (Sweden)

    Fenglin Song

    2014-01-01

    Full Text Available To simplify the procedure of blood vessel replacement operation and shorten the vascular anastomosis time, we developed a special artificial blood vessel which can be connected to native blood vessels without suture. The self-made sutureless blood vessel (SMSBV was made from two titanium connectors and a Gore-Tex graft. To investigate blood compatibility and histocompatibility of the SMSBV, we carried thoracic descending aorta replacement using either SMSBV or Gore-Tex, respectively, in pigs. The aortic clamp time and the operative blood loss in the experimental group (using SMSBV were less than those in the control group (using Gore-Tex. The whole blood hematocrit, platelet count, plasma soluble P-selectin, plasma free hemoglobin, and interleukins 2, 6 at each time point were not different significantly between the two groups. Light microscopy and transmission electron microscopy examination showed there were layers of vascular smooth muscle cells and endothelial cells adhered in the inner wall of artificial blood vessel without any signs of thrombosis. Based on the result, we have drawn the conclusion that the application of SMSBV can significantly shorten the vascular anastomosis time, reduce operative blood loss, and show good blood and tissue compatibility.

  17. Continuum mathematical modelling of pathological growth of blood vessels

    Science.gov (United States)

    Stadnik, N. E.; Dats, E. P.

    2018-04-01

    The present study is devoted to the mathematical modelling of a human blood vessel pathological growth. The vessels are simulated as the thin-walled circular tube. The boundary value problem of the surface growth of an elastic thin-walled cylinder is solved. The analytical solution is obtained in terms of velocities of stress strain state parameters. The condition of thinness allows us to study finite displacements of cylinder surfaces by means of infinitesimal deformations. The stress-strain state characteristics, which depend on the mechanical parameters of the biological processes, are numerically computed and graphically analysed.

  18. Waves and fluid-solid interaction in stented blood vessels

    Science.gov (United States)

    Frecentese, S.; Argani, L. P.; Movchan, A. B.; Movchan, N. V.; Carta, G.; Wall, M. L.

    2018-01-01

    This paper focuses on the modelling of fluid-structure interaction and wave propagation problems in a stented artery. Reflection of waves in blood vessels is well documented in the literature, but it has always been linked to a strong variation in geometry, such as the branching of vessels. The aim of this work is to detect the possibility of wave reflection in a stented artery due to the repetitive pattern of the stents. The investigation of wave propagation and possible blockages under time-harmonic conditions is complemented with numerical simulations in the transient regime.

  19. Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries

    NARCIS (Netherlands)

    van Leeuwen, G. M.; Kotte, A. N.; Crezee, J.; Lagendijk, J. J.

    1997-01-01

    We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some

  20. Automatic segmentation of blood vessels from retinal fundus images ...

    Indian Academy of Sciences (India)

    The retinal blood vessels were segmented through color space conversion and color channel extraction, image pre-processing, Gabor filtering, image postprocessing, feature construction through application of principal component analysis, k-means clustering and first level classification using Naïve–Bayes classification ...

  1. 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.)

  2. Fluid Dynamics of Magnetic Nanoparticles in Simulated Blood Vessels

    Science.gov (United States)

    Blue, Lauren; Sewell, Mary Kathryn; Brazel, Christopher S.

    2008-11-01

    Magnetic nanoparticles (MNPs) can be used to locally target therapies and offer the benefit of using an AC magnetic field to combine hyperthermia treatment with the triggered release of therapeutic agents. Here, we investigate localization of MNPs in a simulated environment to understand the relationship between magnetic field intensity and bulk fluid dynamics to determine MNP retention in a simulated blood vessel. As MNPs travel through blood vessels, they can be slowed or trapped in a specific area by applying a magnetic field. Magnetic cobalt ferrite nanoparticles were synthesized and labeled with a fluorescent rhodamine tag to visualize patterns in a flow cell, as monitored by a fluorescence microscope. Particle retention was determined as a function of flow rate, concentration, and magnetic field strength. Understanding the relationship between magnetic field intensity, flow behavior and nanoparticle characteristics will aid in the development of therapeutic systems specifically targeted to diseased tissue.

  3. Carotid Body Tumor Presenting as Parotid Swelling Misdiagnosed ...

    African Journals Online (AJOL)

    the tumor with the surrounding tissues. DSA cannot only provide ... for embolization of blood vessels, resulting in decrease in intraoperative blood loss by .... serial measurements of brain natriuretic peptide in heart failure. Int J Cardiol 2004 ...

  4. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...... that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution....

  5. DLC coating of textile blood vessels using PLD

    Czech Academy of Sciences Publication Activity Database

    Kocourek, Tomáš; Jelínek, Miroslav; Vorlíček, Vladimír; Zemek, Josef; Janča, T.; Žížková, V.; Podlaha, J.; Popov, C.

    2008-01-01

    Roč. 93, č. 3 (2008), s. 627-632 ISSN 0947-8396 R&D Projects: GA MPO FI-IM2/068; GA ČR GA202/06/0216 Institutional research plan: CEZ:AV0Z10100522 Keywords : blood vessels * PLD * DLC * sp2 * sp3 Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.884, year: 2008

  6. 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.

  7. The evaluation of cerebral hemodynamics in patients with intracranial tumors by stable xenon CT; The effect of glycerol administration on regional cerebral blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Shimoda, Masami; Kawamata, Fumio; Yamamoto, Masahiro; Ohsuga, Hitoshi; Hidaka, Mitsuru; Oda, Shinri; Shibuya, Naoki; Yamamoto, Isao; Sato, Osamu (Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine)

    1989-04-01

    In evaluating cerebral regional blood flow (rCBF), stable xenon-enhanced tomography (XeCT) study associated with simultaneous blood sampling was applied in 15 cases of intracranial neoplasms. The effect of intravenous glycerol infusion on rCBF was also investigated. The results indicated that intratumoral rCBF values were not only variable and unrelated to their histological types and grades, but also were not correlated with the vascularity of the lesion as demonstrated by angiography. When a tumor mass was enhanced after the injection of iodinated contrast media, it proved to be useful in distinguishing tumor mass and its associated edema that the rCBF of the peritumoral edematous region was predominantly low (10{plus minus}5 ml/100 g/min). The regional cerebral blood flow in remote areas, both ipsilateral and contralateral to the lesion, was low in value, and there was no statistical significance between affected and sound sides. Following glycerol administration, rCBF was increased in the whole intracranial region, but not inside of the neoplasm, particularly when the intracranial pressure (ICP) was increased. It was assumed that the elevated rCBF after glycerol administration was due to the increase in the cerebral perfusion pressure resulting from the ICP reduction, the hemodilution effect, cerebral vessel dilatation after metabolic acidosis, and/or mechanically rectified microcirculation after edema reduction. (author).

  8. Thymidine analogues to assess microperfusion in human tumors

    International Nuclear Information System (INIS)

    Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C.

    2005-01-01

    Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation

  9. Cone-Beam CT Angiography for Determination of Tumor-Feeding Vessels During Chemoembolization of Liver Tumors: Comparison of Conventional and Dedicated-Software Analysis.

    Science.gov (United States)

    Ronot, Maxime; Abdel-Rehim, Mohamed; Hakimé, Antoine; Kuoch, Viseth; Roux, Marion; Chiaradia, Mélanie; Vilgrain, Valérie; de Baere, Thierry; Deschamps, Frédéric

    2016-01-01

    To compare the ability of dedicated software and conventional cone-beam computed tomography (CT) analysis to identify tumor-feeding vessels in hypervascular liver tumors treated with chemoembolization. Between January 2012 and January 2013, 45 patients (32 men, mean age of 61 y; range, 27-85 y) were enrolled, and 66 tumors were treated (mean, 32 mm ± 18; range, 10-81 mm) with conventional chemoembolization with arterial cone-beam CT. Data were independently analyzed by six interventional radiologists with standard postprocessing software, a computer-aided analysis with FlightPlan for liver (FPFL; ie, "raw FPFL"), and a review of this computer-aided FPFL analysis ("reviewed FPFL"). Analyses were compared with a reference reading established by two study supervisors in consensus who had access to all imaging data. Sensitivities, positive predictive values (PPVs), and false-positive (FP) ratios were compared by McNemar, χ(2), and Fisher exact tests. Analysis durations were compared by Mann-Whitney test, and interreader agreement was assessed. Reference reading identified 179 feeder vessels. The sensitivity of raw FPFL was significantly higher than those of reviewed FPFL and conventional analyses (90.9% vs 83.2% and 82.1%; P software enabled a fast, accurate, and sensitive detection of tumor feeder vessels. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  10. Establishment of an animal model of mice with radiation- injured soft tissue blood vessels

    International Nuclear Information System (INIS)

    Wang Daiyou; Yu Dahai; Wu Jiaxiao; Wei Shanliang; Wen Yuming

    2004-01-01

    Objective: The aim of this study was to establish an animal model of mice with radiation-injured soft tissue blood vessels. Methods: Forty male mice were irradiated with 30 Gy on the right leg. After the irradiation was finished each of the 40 male mice was tested with angiography, and its muscle tissues on the bilateral legs were examined with vessel staining assay and electron microscopy. Results: The results showed that the number of vessels on the right leg was less than that on the left leg, the microvessel density, average diameter and average sectional area of the right leg were all lower than those of the left, and the configuration and ultra-structure of vessels were also different between both sides of legs. Conclusion: In the study authors successfully established an animal model of mice with radiation-injured soft tissue blood vessels

  11. Quantification of tumor vessels in glioblastoma patients using time-of-flight angiography at 7 Tesla: a feasibility study.

    Directory of Open Access Journals (Sweden)

    Alexander Radbruch

    Full Text Available PURPOSE: To analyze if tumor vessels can be visualized, segmented and quantified in glioblastoma patients with time of flight (ToF angiography at 7 Tesla and multiscale vessel enhancement filtering. MATERIALS AND METHODS: Twelve patients with newly diagnosed glioblastoma were examined with ToF angiography (TR = 15 ms, TE = 4.8 ms, flip angle = 15°, FOV = 160 × 210 mm(2, voxel size: 0.31 × 0.31 × 0.40 mm(3 on a whole-body 7 T MR system. A volume of interest (VOI was placed within the border of the contrast enhancing part on T1-weighted images of the glioblastoma and a reference VOI was placed in the non-affected contralateral white matter. Automated segmentation and quantification of vessels within the two VOIs was achieved using multiscale vessel enhancement filtering in ImageJ. RESULTS: Tumor vessels were clearly visible in all patients. When comparing tumor and the reference VOI, total vessel surface (45.3 ± 13.9 mm(2 vs. 29.0 ± 21.0 mm(2 (p<0.035 and number of branches (3.5 ± 1.8 vs. 1.0 ± 0.6 (p<0.001 per cubic centimeter were significantly higher, while mean vessel branch length was significantly lower (3.8 ± 1.5 mm vs 7.2 ± 2.8 mm (p<0.001 in the tumor. DISCUSSION: ToF angiography at 7-Tesla MRI enables characterization and quantification of the internal vascular morphology of glioblastoma and may be used for the evaluation of therapy response within future studies.

  12. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  13. Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha.

    Directory of Open Access Journals (Sweden)

    Sara Leschner

    Full Text Available BACKGROUND: Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS: We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION: Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria.

  14. Numerical modelling of the influence of stromal cells on tumor growth and angiogenesis

    Science.gov (United States)

    Sakiyama, Nobuyuki; Nagayama, Katsuya

    2018-01-01

    According to the statistics provided by the Ministry of Health, Labor and Welfare the death of one in 3.5 Japanese people is attributed to tumor highlighting the need for active research on malignant tumors. Early detection can be cited as a countermeasure against malignant tumors, but it is often difficult to observe the growth process, and thorough understanding of the phenomena will aid in more efficient detection of such tumors. A malnourished benign tumor may create new blood vessels from existing ones and proliferate abnormally by absorbing nutrients from these newly created blood vessels to become malignant. Different factors influence the shape of tumors and shape is an important factor in evaluating their malignancy. Because interstitial cells greatly influence tumor growth, investigating the influence of stromal cells on tumor growth will help in developing a better understanding of the phenomenon.

  15. The efficiency of laser radiation absorption by hemoglobin and oxyhemoglobin in the skin blood vessels

    International Nuclear Information System (INIS)

    Asimov, M.; Asimov, R.; Gisbrecht, A.

    1999-01-01

    The results of the investigation of the efficiency of light absorption by oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) in cutaneous blood vessels in dependence on the radiation wavelength and the optical properties of the tissue is presented. Using the Kubelka - Munk optical model of the tissue the spectral dependence of the efficiency of laser interaction both on HbO 2 and Hb of blood vessels at different depths of the tissue layer are calculated. The obtained results show that for blood vessels located in tissue up to a depth of 2500 μm the efficiency of laser radiation absorption follows the shape of the Q -absorption bands of HbO 2 and Hb

  16. Gliomas and the vascular fragility of the blood brain barrier

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo eDubois

    2014-12-01

    Full Text Available Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB. By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM, characterized by a highly heterogeneous cell population (including tumor stem cells, extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the blood brain barrier and the concerns that arise when this barrier is affected.

  17. Simulative study on dose distribution of 103Pd stent in blood-vessel

    International Nuclear Information System (INIS)

    Yuan Shuyu; Dai Guangfu; Xu Zhiyong; Sun Fuyin; Xu Shuhe; Ma Fengwu

    2003-01-01

    Objective: To evaluate the dose distribution of 103 Pd stent in the blood-vessel. Methods: Simulative study on dose distribution of endovascular 103 Pd stent was conducted with thermoluminescence dosimeter. The vessel wall was substituted by muscle equivalent material in this simulative study. Results: When radioactivity of the study 103 Pd stent was 9.8 MBq the absorbed dose from the stent surface by muscle equivalent material was 9.8 Gy at 17 d (the half-life period of 103 Pd). The radioactivity of 103 Pd stent surface rapidly attenuated over the radial distance. 80% of the radioactivity at the area that was radially 0.4 mm apart from the stent surface was absorbed by the simulative blood-vessel wall. Conclusion: Endovascular 103 Pd stent does not exert significant injury on the surrounding organs or tissues

  18. 3-D segmentation of retinal blood vessels in spectral-domain OCT volumes of the optic nerve head

    Science.gov (United States)

    Lee, Kyungmoo; Abràmoff, Michael D.; Niemeijer, Meindert; Garvin, Mona K.; Sonka, Milan

    2010-03-01

    Segmentation of retinal blood vessels can provide important information for detecting and tracking retinal vascular diseases including diabetic retinopathy, arterial hypertension, arteriosclerosis and retinopathy of prematurity (ROP). Many studies on 2-D segmentation of retinal blood vessels from a variety of medical images have been performed. However, 3-D segmentation of retinal blood vessels from spectral-domain optical coherence tomography (OCT) volumes, which is capable of providing geometrically accurate vessel models, to the best of our knowledge, has not been previously studied. The purpose of this study is to develop and evaluate a method that can automatically detect 3-D retinal blood vessels from spectral-domain OCT scans centered on the optic nerve head (ONH). The proposed method utilized a fast multiscale 3-D graph search to segment retinal surfaces as well as a triangular mesh-based 3-D graph search to detect retinal blood vessels. An experiment on 30 ONH-centered OCT scans (15 right eye scans and 15 left eye scans) from 15 subjects was performed, and the mean unsigned error in 3-D of the computer segmentations compared with the independent standard obtained from a retinal specialist was 3.4 +/- 2.5 voxels (0.10 +/- 0.07 mm).

  19. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

    Science.gov (United States)

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-12-22

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

  20. "Sausage-string" appearance of arteries and arterioles can be caused by an instability of the blood vessel wall

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Beierholm, Ulrik; Mikkelsen, Rene

    2002-01-01

    Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage. A rela...... phenomenon. Experimental data suggest that the structural changes induced by the instability may cause secondary damage to the wall of small arteries and arterioles in the form of endothelial hyperpermeability followed by local fibrinoid necrosis of the vascular wall.......Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage....... A related vascular pattern has been observed in larger vessels from several organs during angiography. In the larger vessels the occurrence of the pattern does not appear to be related to acute hypertension. A unifying feature between the phenomenon in large and small vessels seems to be an increase...

  1. MACROMICROSCOPIC AND ULTRAMICROSCOPIC CHARACTERISTICS OF THE HART AND ITS BLOOD VESSELS IN MICE EHRLICHIOSIS INFECTION

    Directory of Open Access Journals (Sweden)

    Pokhil S. I.

    2013-12-01

    Full Text Available The macromicroscopic, ultramicroscopic studying change’s in the hart and its blood vessels in unlinear immunocomprometive laboratory male and female mice with the experimental ehrlichiosis is presented in this article. The cardiac destructive and degenerative changes,cardiomyopathy, cardiosclerosis had been established inexperimental animal group’s. The blood vessels endothelial lieyr disorganization, stasis, thrombosis has been noted.

  2. An experimental system for the study of ultrasound exposure of isolated blood vessels

    NARCIS (Netherlands)

    Tokarczyk, Anna; Rivens, Ian; van Bavel, E.; Symonds-Tayler, Richard; ter Haar, Gail

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and

  3. Modification method to reduce the impact of blood vessel on noncontact discrimination of human blood based on ;M+N; theory

    Science.gov (United States)

    Zhang, Linna; Ding, Hongyan; Lin, Ling; Wang, Yimin; Guo, Xin

    2018-01-01

    Noncontact discriminating human blood is significantly crucial for import-export ports and inspection and quarantine departments. We had already demonstrated that visible diffuse reflectance spectroscopy combining PLS-DA method can successfully realize noncontact human blood discrimination. However, the circulated blood vessels may be produced with different materials. The use of various kinds of blood tubes may have a negative effect on the discrimination, based on ;M+N; theory (Li et al., 2016). In this research, we explored the impact of different material of blood vessels, such as glass tube and plastic tube, on the prediction ability of the discrimination model. Furthermore, we searched for the modification method to reduce the influence from the blood tubes. Our work indicated that generalized diffuse reflectance method can greatly improve the discrimination accuracy. This research can greatly facilitate the application of noncontact discrimination method based on visible and near-infrared diffuse reflectance spectroscopy.

  4. Quantification of Tumor Vessels in Glioblastoma Patients Using Time-of-Flight Angiography at 7 Tesla: A Feasibility Study

    Science.gov (United States)

    Radbruch, Alexander; Eidel, Oliver; Wiestler, Benedikt; Paech, Daniel; Burth, Sina; Kickingereder, Philipp; Nowosielski, Martha; Bäumer, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Bendszus, Martin; Ladd, Mark; Nagel, Armin Michael; Heiland, Sabine

    2014-01-01

    Purpose To analyze if tumor vessels can be visualized, segmented and quantified in glioblastoma patients with time of flight (ToF) angiography at 7 Tesla and multiscale vessel enhancement filtering. Materials and Methods Twelve patients with newly diagnosed glioblastoma were examined with ToF angiography (TR = 15 ms, TE = 4.8 ms, flip angle = 15°, FOV = 160×210 mm2, voxel size: 0.31×0.31×0.40 mm3) on a whole-body 7 T MR system. A volume of interest (VOI) was placed within the border of the contrast enhancing part on T1-weighted images of the glioblastoma and a reference VOI was placed in the non-affected contralateral white matter. Automated segmentation and quantification of vessels within the two VOIs was achieved using multiscale vessel enhancement filtering in ImageJ. Results Tumor vessels were clearly visible in all patients. When comparing tumor and the reference VOI, total vessel surface (45.3±13.9 mm2 vs. 29.0±21.0 mm2 (pTesla MRI enables characterization and quantification of the internal vascular morphology of glioblastoma and may be used for the evaluation of therapy response within future studies. PMID:25415327

  5. Effect of x irradiation on the vascularization of experimental animal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, Y; Ogawa, F; Nishiguchi, H; Tanaka, N; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan)

    1975-03-01

    The authors studied the effect of ionizing radiation on blood vessels and tumor growth in two animal tumor systems: a third generation isoplants of a mammary cancer and a spontaneously arising squamous cell carcinoma. Single cell suspensions were transplanted into a C3H and a C3Hf mouse respectively. They were irradiated once with 2000 rad when the tumors reached about 8 mm in diameter. Microangiography was performed at a constant temperature and pressure, and a contrast medium containing lead-oxide and gelatin was flushed the vena cava for 10 min. at 120 mmHg. Tumor shrinkage was followed by continuous regrowth. The basic vasculature of the mammary carcinoma consisted of abundant large and fine blood vessels corkscrewed or stretched from the periphery of the tumor to its center in complex reticular networks. One day after irradiation there were small scattered avascular areas which, by the third day formed a large central necrosis. Supervascularization was also observed, indicating that some hypoxic tumor cells could be reoxygenized. In 5 days vascularization was similar to that of a nonirradiated tumor. Conversely, The squamous cell carcinoma showed peripheral and central vascularization with abundant vascular and avascular areas and extravasion in the large avascular area. Two days after irradiation the vessels were dilated. At 3 days peripheral fine vessels were damaged but the central vasculature remained intact. Unlike the mammary carcinoma, supervascularization was not the typical finding. At 5 days, vascularization was similar to that of a nonirradiated tumor.

  6. Segmentation of retinal blood vessels using artificial neural networks for early detection of diabetic retinopathy

    Science.gov (United States)

    Mann, Kulwinder S.; Kaur, Sukhpreet

    2017-06-01

    There are various eye diseases in the patients suffering from the diabetes which includes Diabetic Retinopathy, Glaucoma, Hypertension etc. These all are the most common sight threatening eye diseases due to the changes in the blood vessel structure. The proposed method using supervised methods concluded that the segmentation of the retinal blood vessels can be performed accurately using neural networks training. It uses features which include Gray level features; Moment Invariant based features, Gabor filtering, Intensity feature, Vesselness feature for feature vector computation. Then the feature vector is calculated using only the prominent features.

  7. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

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

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  9. A three-temperature model of selective photothermolysis for laser treatment of port wine stain containing large malformed blood vessels

    International Nuclear Information System (INIS)

    Li, D.; Wang, G.X.; He, Y.L.; Wu, W.J.; Chen, B.

    2014-01-01

    As congenital vascular malformations, port wine stain (PWS) is composed of ectatic venular capillary blood vessels buried within healthy dermis. In clinic, pulsed dye laser (PDL) in visible band (e.g. 585 nm) together with cryogen spray cooling (CSC) have become the golden standard for treatment of PWS. However, due to the limited energy deposition of the PDL in blood, large blood vessels are likely to survive from the laser irradiation. As a result, complete clearance of the lesions is rarely achieved. Assuming the local thermal non-equilibrium in skin tissue during the laser surgery, a three-temperature model is proposed to treat the PWS tissue as a porous media composed of a non-absorbing dermal matrix buried with the blood as well as the large malformed blood vessels. Three energy equations are constructed and solved coupling for the temperature of the blood in average-sized PWS vessels, non-absorbing dermal tissues and large malformed blood vessels, respectively. Subsequently, the thermal responses of human skin to visible (585 nm) and near-infrared (1064 nm) laser irradiations with various pulse durations in conjunction with cryogen spray cooling are investigated by the new model, and Arrhenius integral is used to analyze the thermal damage. The simulations show that the short pulse duration of 1.5 ms results in a higher selective heating of blood over epidermis, which will lead to a desired clinic outcome than the longer pulse duration. Due to a much deeper light penetration depth, laser irradiation with 1064 nm in wavelength is superior to that with 585 nm in treating patients with cutaneous hyper-vascular malformation. Complete coagulations are predicted in large-sized and deeply extending blood vessels by 1064 nm laser. - Highlights: •A three-temperature model is proposed for the laser treatment of port wine stain (PWS). •Average sized and large malformed blood vessels in porous medium (tissue) are considered. •Thermal responses of PWS to

  10. Rapid sealing of porcine renal blood vessels, ex vivo, using a high power, 1470-nm laser, and laparoscopic prototype

    Science.gov (United States)

    Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

    2017-05-01

    Energy-based, radiofrequency (RF) and ultrasonic (US) devices currently provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternate energy modality for vessel sealing, capable of generating less collateral thermal damage. Previous studies demonstrated feasibility of sealing vessels in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for testing in open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices currently in surgical use was developed, and performance tests were conducted on porcine renal blood vessels, ex vivo. The 5-mm outer-diameter laparoscopic prototype featured a traditional Maryland jaw configuration that enables tissue manipulation and blunt dissection. Laser energy was delivered through a 550-μm-core-diameter optical fiber with side-delivery from the lower jaw and beam dimensions of 18-mm length×1.2-mm width. The 1470-nm diode laser delivered 68 W with 3-s activation time, consistent with vessel seal times associated with RF and US-based devices. A total of 69 fresh porcine renal vessels with mean diameter of 3.3±1.7 mm were tested, ex vivo. Vessels smaller than 5-mm diameter were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038±474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174±221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7±0.8, 3.4±0.7, and 1.0±0.4 mm, respectively. Results demonstrated that the 5-mm optical laparoscopic prototype consistently sealed vessels less than 5-mm diameter with low thermal spread. Further in vivo studies are planned to test the performance across a variety of vessels and tissues.

  11. Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yu, De-cai; Chen, Jun; Sun, Xi-tai; Zhuang, Lin-yuan; Jiang, Chun-ping; Ding, Yi-tao

    2010-01-01

    We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p < 0.05), but no significant difference was found in the expression levels of COX-2 and NOS-2 between AT and TT. The expression of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, endostatin, COX-2, and NOS-2 in normal liver tissue was weaker than that in AT or TT. In cirrhotic mice, the number of circulating endothelial progenitor cells gradually increased, before decreasing again. In this mouse model, increased numbers of EPCs were recruited and homed specifically to the cirrhotic liver. Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs

  12. Tumor blood flow and systemic shunting in patients receiving intraarterial chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Wheeler, R.H.; Ziessman, H.A.; Medvec, B.R.; Juni, J.E.; Thrall, J.H.; Keyes, J.W.; Pitt, S.R.; Baker, S.R.

    1986-01-01

    Radionuclide techniques have been used to estimate the systemic shunt and to quantitate blood flow to the tumor and a reference normal tissue in nine patients undergoing intraarterial chemotherapy for head and neck cancer. The systemic shunt was calculated as the percentage of pulmonary trapping of intraarterially injected /sup 99m/Tc-labeled macroaggregated albumin. The mean systemic shunt in the 12 separate arteries studied was 23 +/- 13% (SE) (range 8-43%). Quantitative blood flow was determined from the slope of the washout curve of intraarterially injected 133 Xe. The mean tumor blood flow was 13.6 +/- 6.7 ml/100 g/min, while the mean blood flow to the scalp was 4.2 +/- 2.1 ml/100 g/min providing a mean tumor/normal tissue ratio of 3.9 +/- 2.7. An estimate of blood flow distribution was obtained by calculating the ratio of counts/pixel in the tumor mass versus the remainder of the head as determined by single photon emission computed tomography following an intraarterial injection of /sup 99m/Tc-labeled macroaggregated albumin. The mean ratio of tumor to normal tissue perfusion by this technique was 5.6 +/- 3.7. These techniques have allowed noninvasive determination of the blood flow parameters associated with intraarterial chemotherapy. At least part of the therapeutic advantage of regional chemotherapy in patients with head and neck cancer is due to a tumor/normal tissue blood flow ratio that favors drug delivery to the tumor contained within the infused volume

  13. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

    Science.gov (United States)

    Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

    2010-04-01

    Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

  14. Tumor blood flow modifying effects of electrochemotherapy. A potential vascular targeted mechanism

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Miklavcic, D.

    2003-01-01

    Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut down of the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that, in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumor blood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapy. (author)

  15. Improved magnetic resonance molecular imaging of tumor angiogenesis by avidin-induced clearance of nonbound bimodal liposomes

    NARCIS (Netherlands)

    Tilborg, van G.A.F.; Mulder, W.J.M.; Schaft, van der D.W.J.; Reutelingsperger, C.; Griffioen, A.W.; Strijkers, G.J.; Nicolay, K.

    2008-01-01

    Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the avß3 integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp

  16. Retinal blood vessel extraction using tunable bandpass filter and fuzzy conditional entropy.

    Science.gov (United States)

    Sil Kar, Sudeshna; Maity, Santi P

    2016-09-01

    Extraction of blood vessels on retinal images plays a significant role for screening of different opthalmologic diseases. However, accurate extraction of the entire and individual type of vessel silhouette from the noisy images with poorly illuminated background is a complicated task. To this aim, an integrated system design platform is suggested in this work for vessel extraction using a sequential bandpass filter followed by fuzzy conditional entropy maximization on matched filter response. At first noise is eliminated from the image under consideration through curvelet based denoising. To include the fine details and the relatively less thick vessel structures, the image is passed through a bank of sequential bandpass filter structure optimized for contrast enhancement. Fuzzy conditional entropy on matched filter response is then maximized to find the set of multiple optimal thresholds to extract the different types of vessel silhouettes from the background. Differential Evolution algorithm is used to determine the optimal gain in bandpass filter and the combination of the fuzzy parameters. Using the multiple thresholds, retinal image is classified as the thick, the medium and the thin vessels including neovascularization. Performance evaluated on different publicly available retinal image databases shows that the proposed method is very efficient in identifying the diverse types of vessels. Proposed method is also efficient in extracting the abnormal and the thin blood vessels in pathological retinal images. The average values of true positive rate, false positive rate and accuracy offered by the method is 76.32%, 1.99% and 96.28%, respectively for the DRIVE database and 72.82%, 2.6% and 96.16%, respectively for the STARE database. Simulation results demonstrate that the proposed method outperforms the existing methods in detecting the various types of vessels and the neovascularization structures. The combination of curvelet transform and tunable bandpass

  17. Optically measured microvascular blood flow contrast of malignant breast tumors.

    Directory of Open Access Journals (Sweden)

    Regine Choe

    Full Text Available Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS, a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63; tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66, and using normal tissue in the contralateral breast was 2.27 (1.90-2.70. Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography.

  18. Fine structural alterations of the blood vessels in the delayed radionecrosis of the human brain and its pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, H [Nagasaki Univ. (Japan). School of Medicine

    1981-05-01

    The blood vessels in the delayed radionecrosis of the human brain were studied under light and electron microscopes. Microscopically, the blood vessels demonstrated characteristic findings such as fibrinoid necrosis, hyalinized thickened vessels, perivascular fibrosis and thrombosed vessels. Electron microscopy revealed the formation of fenestrae, separation of endothelial cells, increased pinocytotic vesicles as well as the initial thrombus formation. Our results strongly verified that vascular alterations are primary in the pathogenesis of radionecrosis whereas the parenchymal changes are secondary.

  19. On a computational study for investigating acoustic streaming and heating during focused ultrasound ablation of liver tumor

    International Nuclear Information System (INIS)

    Solovchuk, Maxim A.; Sheu, Tony W.H.; Thiriet, Marc; Lin, Win-Li

    2013-01-01

    The influences of blood vessels and focused location on temperature distribution during high-intensity focused ultrasound (HIFU) ablation of liver tumors are studied numerically. A three-dimensional acoustics-thermal-fluid coupling model is employed to compute the temperature field in the hepatic cancerous region. The model construction is based on the linear Westervelt and bioheat equations as well as the nonlinear Navier–Stokes equations for the liver parenchyma and blood vessels. The effect of acoustic streaming is also taken into account in the present HIFU simulation study. Different blood vessel diameters and focal point locations were investigated. We found from this three-dimensional numerical study that in large blood vessels both the convective cooling and acoustic streaming can considerably change the temperature field and the thermal lesion near blood vessels. If the blood vessel is located within the beam width, both acoustic streaming and blood flow cooling effects should be addressed. The temperature rise on the blood vessel wall generated by a 1.0 MHz focused ultrasound transducer with the focal intensity 327 W/cm 2 was 54% lower when acoustic streaming effect was taken into account. Subject to the applied acoustic power the streaming velocity in a 3 mm blood vessel is 12 cm/s. Thirty percent of the necrosed volume can be reduced, when taking into account the acoustic streaming effect. -- Highlights: • 3D three-field coupling physical model for focused ultrasound tumor ablation is presented. • Acoustic streaming and blood flow cooling effects on ultrasound heating are investigated. • Acoustic streaming can considerably affect the temperature distribution. • The lesion can be reduced by 30% due to the acoustic streaming effect. • Temperature on the blood vessel wall is reduced by 54% due to the acoustic streaming effect

  20. Improved magnetic resonance molecular imaging of tumor angiogenesis by avidin-induced clearance of nonbound bimodal liposomes

    NARCIS (Netherlands)

    van Tilborg, Geralda A. F.; Mulder, Willem J. M.; van der Schaft, Daisy W. J.; Reutelingsperger, Chris P. M.; Griffioen, Arjan W.; Strijkers, Gustav J.; Nicolay, Klaas

    2008-01-01

    Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the alpha(v)beta(3) integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp

  1. Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

    International Nuclear Information System (INIS)

    Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

    1982-01-01

    Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

  2. Relations between radiobiological hypoxia and nuclear magnetic resonance-imaged blood microcirculation in experimental tumors

    International Nuclear Information System (INIS)

    Koike, Sachiko; Ando, Koichi; Ikehira, Hiroo.

    1993-01-01

    Characteristics of hypoxic cells subjected to radiation were investigated and compared with those of microcirculation for two murine fibrosarcomas growing in C3H mice. Small NFSa tumors, growing in air-breathing mice, developed a radioresistant tail on the survival curve. The tail was indistinguishably parallel to a survival curve for an artificially hypoxic tumor. As the NFSa tumors increased in size, the hypoxic tail moved upward with no change of Do, resulting in increase of hypoxic fraction from 3.9% to 40%. The R1137 tumors had no radioresistant tail nor hypoxic fraction regardless of tumor size. However, large-sized R1137 tumors developed a significant number of radioresistant, hypoxic cells with an intermediate Do, and were effectively sensitized by administrating misonidazole before irradiation. Thus, the NFSa tumors were fractionally hypoxic, and the large R1137 tumors had intermediate hypoxia. Measurement of tumor microcirculation by gadolinium-enhanced nuclear magnetic resonance indicated that both blood flow and blood volume decreased significantly when the NFSa tumor grew large. Similar reduction in these microcirculation parameters was also observed for the R1137 tumor. The small-sized NFSa tumor had relatively larger blood volume and faster blood flow than the small-sized R1137 tumor. When large-sized tumors were compared to each other, the NFSa again had better blood flow than the R1137. However, the blood volume in the large-sized tumors was significantly (p<0.05) smaller for the NFSa tumor than for the R1137 tumor. It was concluded that blood flow could not be a single determinant for tumor hypoxia, and the difference between fractional hypoxia and intermediate hypoxia would be reflected in the ratio of blood flow to blood volume. (author)

  3. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  4. Dependence of light scattering profile in tissue on blood vessel diameter and distribution: a computer simulation study.

    Science.gov (United States)

    Duadi, Hamootal; Fixler, Dror; Popovtzer, Rachela

    2013-11-01

    Most methods for measuring light-tissue interactions focus on the volume reflectance while very few measure the transmission. We investigate both diffusion reflection and diffuse transmission at all exit angles to receive the full scattering profile. We also investigate the influence of blood vessel diameter on the scattering profile of a circular tissue. The photon propagation path at a wavelength of 850 nm is calculated from the absorption and scattering constants via Monte Carlo simulation. Several simulations are performed where a different vessel diameter and location were chosen but the blood volume was kept constant. The fraction of photons exiting the tissue at several central angles is presented for each vessel diameter. The main result is that there is a central angle that below which the photon transmission decreased for lower vessel diameters while above this angle the opposite occurred. We find this central angle to be 135 deg for a two-dimensional 10-mm diameter circular tissue cross-section containing blood vessels. These findings can be useful for monitoring blood perfusion and oxygen delivery in the ear lobe and pinched tissues. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

  5. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  6. Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

    Science.gov (United States)

    Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

    2016-11-01

    The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

  7. Ultrasonographic Examination of Some Vessels in Dogs and the Characteristics of Blood Flow in These Vessels

    Directory of Open Access Journals (Sweden)

    Figurová M.

    2017-12-01

    Full Text Available The examination by Doppler ultrasonography provides haemodynamic information about blood flow velocity in a respective vessel. It specifies high- and lowresistance flow patterns. The aim of our study was to record the flow in a. carotis communis, a. femoralis and aa. renales in 16 adult clinically healthy dogs of small and medium size; characterize the types of vessels and also determine the pulsatility index (PI and the resistive index (RI of these vessels. The a. femoralis is a high-resistance vessel with a pronounced three-peak waveform. The aa. renales gives a typical picture of a low-resistance flow pattern. The characteristics of a. carotis communis involves different images of its branches a. carotis interna and a. carotis externa. In the investigated groups we observed a medium degree of pulsatility (atypical highresistance flow pattern with an absence of reverse flow. The mean measured values of indices for a. carotis communis were: left side PI 1.824 and RI 0.742; right side PI 1.891 and RI 0.746, and for aa. renales: PI 1.366 ± 0.04 and RI 0.684 ± 0.05.

  8. Vascular patterns in the heads of crocodilians: blood vessels and sites of thermal exchange.

    Science.gov (United States)

    Porter, William Ruger; Sedlmayr, Jayc C; Witmer, Lawrence M

    2016-12-01

    Extant crocodilians are a highly apomorphic archosaur clade that is ectothermic, yet often achieve large body sizes that can be subject to higher heat loads. Therefore, the anatomical and physiological roles that blood vessels play in crocodilian thermoregulation need further investigation to better understand how crocodilians establish and maintain cephalic temperatures and regulate neurosensory tissue temperatures during basking and normal activities. The cephalic vascular anatomy of extant crocodilians, particularly American alligator (Alligator mississippiensis) was investigated using a differential-contrast, dual-vascular injection technique and high resolution X-ray micro-computed tomography (μCT). Blood vessels were digitally isolated to create representations of vascular pathways. The specimens were then dissected to confirm CT results. Sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in evaporative cooling and cephalic thermoregulation in other diapsids. Blood vessels to and from sites of thermal exchange were studied to detect conserved vascular patterns and to assess their ability to deliver cooled blood to neurosensory tissues. Within the orbital region, both the arteries and veins demonstrated consistent branching patterns, with the supraorbital, infraorbital, and ophthalmotemporal vessels supplying and draining the orbit. The venous drainage of the orbital region showed connections to the dural sinuses via the orbital veins and cavernous sinus. The palatal region demonstrated a vast plexus that comprised both arteries and veins. The most direct route of venous drainage of the palatal plexus was through the palatomaxillary veins, essentially bypassing neurosensory tissues. Anastomotic connections with the nasal region, however, may provide an alternative route for palatal venous blood to reach neurosensory tissues. The nasal region in crocodilians is probably the most

  9. Hybrid PIV-PTV technique for measuring blood flow in rat mesenteric vessels.

    Science.gov (United States)

    Ha, Hojin; Nam, Kweon-Ho; Lee, Sang Joon

    2012-11-01

    The micro-particle tracking velocimetry (μ-PTV) technique is used to obtain the velocity fields of blood flow in the microvasculature under in vivo conditions because it can provide the blood velocity distribution in microvessels with high spatial resolution. The in vivo μ-PTV technique usually requires a few to tens of seconds to obtain a whole velocity profile across the vessel diameter because of the limited number density of tracer particles under in vivo conditions. Thus, the μ-PTV technique alone is limited in measuring unsteady blood flows that fluctuate irregularly due to the heart beating and muscle movement in surrounding tissues. In this study, a new hybrid PIV-PTV technique was established by combining PTV and particle image velocimetry (PIV) techniques to resolve the drawbacks of the μ-PTV method in measuring blood flow in microvessels under in vivo conditions. Images of red blood cells (RBCs) and fluorescent particles in rat mesenteric vessels were obtained simultaneously. Temporal variations of the centerline blood velocity were monitored using a fast Fourier transform-based cross-correlation PIV method. The fluorescence particle images were analyzed using the μ-PTV technique to extract the spatial distribution of the velocity vectors. Data from the μ-PTV and PIV methods were combined to obtain a better estimate of the velocity profile in actual blood flow. This technique will be useful in investigating hemodynamics in microcirculation by measuring unsteady irregular blood flows more accurately. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Feasibility evaluation of 3D photoacoustic imaging of blood vessel structure using multiple wavelengths with a handheld probe

    Science.gov (United States)

    Uchimoto, Yo; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2018-02-01

    Photoacoustic imaging is anticipated for use in portraying blood vessel structures (e.g. neovascularization in inflamed regions). To reduce invasiveness and enhance ease handling, we developed a handheld photoacoustic imaging system using multiple wavelengths. The usefulness of the proposed system was investigated in phantom experiments and in vivo measurements. A silicon tube was embedded into chicken breast meat to simulate the blood vessel. The tube was filled with ovine blood. Then laser light was guided to the phantom surface by an optical fiber bundle close to the linear ultrasound probe. Photoacoustic images were obtained at 750-950 nm wavelengths. Strong photoacoustic signals from the boundary between blood and silicon tube are observed in these images. The shape of photoacoustic spectrum at the boundary resembles that of the HbO2 absorption spectrum at 750-920 nm. In photoacoustic images, similarity between photoacoustic spectrum and HbO2 absorption spectrum was evaluated by calculating the normalized correlation coefficient. Results show high correlation in regions of strong photoacoustic signals in photoacoustic images. These analyses demonstrate the feasibility of portraying blood vessel structures under practical conditions. To evaluate the feasibility of three-dimensional vascular imaging, in vivo experiments were conducted using three wavelengths. A right hand and ultrasound probe were set in degassed water. By scanning a probe, cross-sectional ultrasound and photoacoustic images were obtained at each location. Then, all ultrasound or photoacoustic images were piled up respectively. Then three-dimensional images were constructed. Resultant images portrayed blood vessel-like structures three-dimensionally. Furthermore, to distinguish blood vessels from other tissues (e.g. skin), distinguishing images of them were constructed by comparing photoacoustic signal intensity among three wavelengths. The resultant image portrayed blood vessels as

  11. Analysis of trends and prospects regarding stents for human blood vessels.

    Science.gov (United States)

    Lee, Jeong Hee; Kim, Eung Do; Jun, Eun Jung; Yoo, Hyoung Sun; Lee, Joon Woo

    2018-01-01

    The purpose of this paper is to provide technology trends and information regarding market and prospects in stents used for human blood vessels in Korea and the world.A stent is a medical device in the form of a cylindrical metal net used to normalize flow when blood or other bodily fluids such as biliary fluids are obstructed in blood vessels, gastrointestinal tracts, etc. by inserting the stent into a narrowed or clogged area. Stents are classified into vascular and non-vascular stents. The coronary artery stent is avascular stent that is used for coronary atherosclerosis.The demand is increasing for stents to treat diseases such as those affecting the heart and blood vessels of elderly and middle-aged patients. Due to the current shift in the demographic structure caused by an aging society, the prospect for stents seems to be very bright.The use of a stent designed to prevent acute vascular occlusion and restenosis, which is a side effect of conventional balloon angioplasty, has rapidly become popular because it can prevent acute complications and improve clinical outcomes. Since the initial release of this stent, there have been significant developments in its design, the most notable of which has been the introduction of drug-eluting stents (DES). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, a true anatomical and functional "vascular restoration" instead of an artificial stiff tube encased by a persistent metallic foreign body. Data for this research were gathered from primary and secondary sources as well as the databases of the Korea Institute of Science Technology Information (KISTI) located in Seoul, Korea like KISTI Market Report. The sources used for primary research included the databases available from the Korea Institute of Science Technology Information, past industry research services/studies, economic and demographic data, and trade and industry journals. Secondary research was used

  12. Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

    Directory of Open Access Journals (Sweden)

    Ming Yuan

    2016-01-01

    Full Text Available Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4+ and CD8+ T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth.

  13. Role of blood flow and blood flow modifiers in clinical hyperthermia therapy

    International Nuclear Information System (INIS)

    Olch, A.J.

    1986-01-01

    A quantitative assessment of the effect of localized magnetic-loop hyperthermia on blood flow was performed on 12 patients (19 tumor studies) using the Xenon-133 clearance method. After it was discovered that blood flow in most of the tumors increased in response to needle injection, a physiologically based, one compartment model was developed that included both a hyperemic (transient) and a steady state component. In the tumors of six patients, increases in blood flow induced by heat were also observed. The same model was used to describe the measured clearance data for both types of hyperemic response. The ability of tumor vessels to respond dynamically to stress and the degree of response may be predictive of tumor heating efficiency and subsequent therapeutic response. Many tumors treated by hyperthermia, therefore, do not reach therapeutic temperatures (42 0 C). One explanation for this may be that some tumors react to thermal stress in a manner similar to normal tissues; i.e., they increase blood flow during hyperthermia in order to dissipate heat. Higher temperatures might be achieved in these heat-resistant tumors by administering vasoconstrictive agents in an effort to reduce blood flow. In the second part of this research study, the extent to which pharmacologic inhibition of local blood flow might allow higher temperatures to develop in normal muscles exposed to localized radiofrequency hyperthermia was determined. It was found that the local muscle temperature rise could be increased by at least 90% in dogs and rabbits with the use of a local vasoconstrictive drug

  14. Targeting Therapy Resistant Tumor Vessels

    Science.gov (United States)

    2008-08-01

    Morris LS. Hysterectomy vs. resectoscopic endometrial ablation for the control of abnormal uterine bleeding . A cost-comparative study. J Reprod Med 1994;39...after the antibody treatment contain a pericyte coat, vessel architecture is normal, the diameter of the vessels is smaller (dilated, abnormal vessels...involvement of proteases from inflammatory mast cells and functionally abnormal (Carmeliet and Jain, 2000; Pasqualini (Coussens et al., 1999) and other bone

  15. Effect of hyperthermia on blood flow in VX2 tumor transplanted in rabbit

    International Nuclear Information System (INIS)

    Arita, Takeshi

    1994-01-01

    Effect of hyperthermia on blood flow was evaluated using VX 2 rabbit carcinoma in both legs. Microwave energy at 2450 MHz was used to heat tumors for 40 minutes. An outer canula of 18 G Erasta was implanted in the depth of 2 cm in tumor to measure the temperature and to maintain at 43.0degC-44.0degC. The blood flow in tumors was evaluated by color doppler flow imaging and dynamic MRI. Disturbance of blood flow in the depth of surface 0 cm to 2 cm in tumors was showed at 10 minutes starting 43.0degC heating and at almost all sites disappearance of blood flow was showed at 40 minutes using color doppler flow imaging. But the blood flow beyond the depth of 2 cm was not so disturbed at 40 minutes, relatively. After hyperthermia T1WI and T2WI in heated tumor were no difference comparing with those in control tumor, but heated tumor showed no enhancement using dynamic MRI with TURBO-FLASH technique and post-enhanced T1WI. Histologically, there was extensive tumor necrosis and thrombus formation in heated tumor after 3 days and 1 week. Therefore color doppler flow imaging and dynamic MRI were considered to be useful for evaluation of blood flow in tumor after and during hyperthermia. (author)

  16. CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.

    Science.gov (United States)

    Dondossola, Eleonora; Rangel, Roberto; Guzman-Rojas, Liliana; Barbu, Elena M; Hosoya, Hitomi; St John, Lisa S; Molldrem, Jeffrey J; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2013-12-17

    Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.

  17. An experimental system for the study of ultrasound exposure of isolated blood vessels

    International Nuclear Information System (INIS)

    Tokarczyk, Anna; Rivens, Ian; Symonds-Tayler, Richard; Ter Haar, Gail; Van Bavel, E

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels. (paper)

  18. Why are tumour blood vessels abnormal and why is it important to know?

    Science.gov (United States)

    Nagy, J A; Chang, S-H; Dvorak, A M; Dvorak, H F

    2009-01-01

    Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are likely unresponsive to anti-VEGF-A therapies. PMID:19240721

  19. Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

    Science.gov (United States)

    Côté, Jérôme; Bovenzi, Veronica; Savard, Martin; Dubuc, Céléna; Fortier, Audrey; Neugebauer, Witold; Tremblay, Luc; Müller-Esterl, Werner; Tsanaclis, Ana-Maria; Lepage, Martin; Fortin, David; Gobeil, Fernand

    2012-01-01

    Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9)BK (LDBK) and SarLys[dPhe(8)]desArg(9)BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T(1)-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites.

  20. Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-05-01

    Full Text Available Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

  1. Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

    Directory of Open Access Journals (Sweden)

    Christian T Farrar

    Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

  2. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

    Science.gov (United States)

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

    2007-02-19

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

  3. Development in NMR spiral imaging and application to the assessment of the permeability of the blood-brain barrier on 2 models of brain tumors

    International Nuclear Information System (INIS)

    Beaumont, M.

    2007-12-01

    The results presented in this work were obtained as part of methodological developments in magnetic resonance imaging. First of all, the setting of the rapid imaging technique using a k-space sampling scheme along a variable density spiral is described. Numerical simulations were used to optimize the acquisitions parameters and to compare different reconstruction techniques. An original approach to calibrate the k-space trajectory was proposed. Then, spiral imaging was used to implement a method to measure the blood brain barrier permeability to Gd-DOTA. This protocol was combined to blood volume and vessel size index measurements using Sinerem. The results obtained highlighted differences between the microvascular parameters measured on C6 and RG2 tumor models. The presence of Sinerem induces a mean decrease of the transfer constant across the vascular wall (Ktrans), in the tumor, of 24 per cent. This study also showed extravasation of the Sinerem, during the first two hours after the product injection, only in the RG2 tumors. (author)

  4. The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Delia Nelson

    2014-01-01

    Full Text Available Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.

  5. Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels

    International Nuclear Information System (INIS)

    Gao, Feng; Li, Ming; Ge, Xiaojun; Ren, Qingguo; Hua, Yanqing; Zheng, Xiangpeng; Chen, Yan; Lv, Fangzhen

    2013-01-01

    To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. Of 108 GGNs, 10 were benign, 24 preinvasive nodules and 74 adenocarcinomas that were pathologically proven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant. (orig.)

  6. The tumor vasculature is a target for genetic radiotherapy

    International Nuclear Information System (INIS)

    Mauceri, Helena J.; Heimann, Ruth; Seetharam, Saraswathy; Beckett, Michael A.; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Tumor progression and metastasis require the growth of new capillaries from existing blood vessels. Tumor cells produce both activators and inhibitors of endothelial cell proliferation and migration. Changes in the balance between these regulators appear to govern an angiogenic switch which is activated during tumor development. Tumor necrosis factor-α (TNF-α) has a biphasic role in angiogenesis. It has been demonstrated that relatively low concentrations of TNF induce angiogenesis while high doses inhibit growth of blood vessels. In our previous studies, using the SQ-20B xenograft model system, we demonstrated increased tumor control when a virus containing the radiation-inducible promoter Egr-1 ligated to a cDNa for TNF-α was combined with radiation. The dominant histopathological feature of tumors receiving combined treatment with Ad.Egr-TNF and radiation was intratumoral vascular thrombosis. The present studies examine the role of TNF in tumor progression by investigating the effects of TNF on VEGF (vascular endothelial growth factor) production in vitro and on tumor vessel count in vivo. Methods: SQ-20B tumor cells in serum-free medium were exposed to hrTNF (10 ng/ml) 4 hours prior to a single dose of x-irradiation (10 Gy). 24 hrs. after treatment, the conditioned medium was harvested, centrifuged, diluted 1:10, and assayed for VEGF using a Quantikine TNF ELISA kit. For studies in vivo, female nude mice were injected sc in the right thigh with 10 6 SQ-20B cells. Xenografts were irradiated with four 5 Gy fractions (20 Gy) and injected twice with either Ad.Egr-TNF or Ad.null. Control tumors were injected with buffer. To highlight vessels, sections from paraffin embedded tissue were stained with anti-CD31 antibody using standard immunohistochemical techniques. Areas of high vascular density were identified and five high power fields (400X) were counted. Data are shown as the mean ± S.E.M. for each treatment group. Significance was evaluated using one

  7. Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects.

    Science.gov (United States)

    Berman, Seth D; West, Julie C; Danielian, Paul S; Caron, Alicia M; Stone, James R; Lees, Jacqueline A

    2009-09-01

    The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues.

  8. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

    OpenAIRE

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-01-01

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute...

  9. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

    1999-01-01

    Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

  10. In vivo measurement of hemodynamic information in stenosed rat blood vessels using X-ray PIV.

    Science.gov (United States)

    Park, Hanwook; Park, Jun Hong; Lee, Sang Joon

    2016-11-28

    Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

  11. Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

    Science.gov (United States)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

    2016-11-01

    The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

  12. Cancer intravasation-on-a-chip : a LEGO house for tumors!

    NARCIS (Netherlands)

    Eslami Amirabadi, H.; Sahebali, Sh.; Miggiels, A.L.W.; Frimat, J.Ph.; Luttge, R.; den Toonder, J.

    2015-01-01

    The process where cancer cells leave the primary tumor and invade to the blood vessel. As shown in figure 1, intravasation is highly regulated by the micro-environment of the tumor. An important component of the micro-environment is the extracellular matrix (ECM) which can be seen as the building

  13. Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

    Directory of Open Access Journals (Sweden)

    William Ruger Porter

    Full Text Available Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange. Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana was investigated using a differential-contrast, dual-vascular injection (DCDVI technique and high-resolution X-ray microcomputed tomography (μCT. Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory

  14. Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

    Science.gov (United States)

    Porter, William Ruger; Witmer, Lawrence M

    2015-01-01

    Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body) as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange). Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana) was investigated using a differential-contrast, dual-vascular injection (DCDVI) technique and high-resolution X-ray microcomputed tomography (μCT). Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory tissue temperature

  15. Dietary rice bran component γ-oryzanol inhibits tumor growth in tumor-bearing mice.

    Science.gov (United States)

    Kim, Sung Phil; Kang, Mi Young; Nam, Seok Hyun; Friedman, Mendel

    2012-06-01

    We investigated the effects of rice bran and components on tumor growth in mice. Mice fed standard diets supplemented with rice bran, γ-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet for two additional weeks. Tumor mass was significantly lower in the γ-oryzanol and less so in the phytic acid group. Tumor inhibition was associated with the following biomarkers: increases in cytolytic activity of splenic natural killer (NK) cells; partial restoration of nitric oxide production and phagocytosis in peritoneal macrophages increases in released the pro-inflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6 from macrophages; and reductions in the number of blood vessels inside the tumor. Pro-angiogenic biomarkers vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and 5-lipoxygenase-5 (5-LOX) were also significantly reduced in mRNA and protein expression by tumor genes. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX up to 30%. Reduced COX-2 and 5-LOX expression downregulated VEGF and inhibited neoangiogenesis inside the tumors. Induction of NK activity, activation of macrophages, and inhibition of angiogenesis seem to contribute to the inhibitory mechanism of tumor regression by γ-oryzanol. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Adaptable three-dimensional Monte Carlo modeling of imaged blood vessels in skin

    Science.gov (United States)

    Pfefer, T. Joshua; Barton, Jennifer K.; Chan, Eric K.; Ducros, Mathieu G.; Sorg, Brian S.; Milner, Thomas E.; Nelson, J. Stuart; Welch, Ashley J.

    1997-06-01

    In order to reach a higher level of accuracy in simulation of port wine stain treatment, we propose to discard the typical layered geometry and cylindrical blood vessel assumptions made in optical models and use imaging techniques to define actual tissue geometry. Two main additions to the typical 3D, weighted photon, variable step size Monte Carlo routine were necessary to achieve this goal. First, optical low coherence reflectometry (OLCR) images of rat skin were used to specify a 3D material array, with each entry assigned a label to represent the type of tissue in that particular voxel. Second, the Monte Carlo algorithm was altered so that when a photon crosses into a new voxel, the remaining path length is recalculated using the new optical properties, as specified by the material array. The model has shown good agreement with data from the literature. Monte Carlo simulations using OLCR images of asymmetrically curved blood vessels show various effects such as shading, scattering-induced peaks at vessel surfaces, and directionality-induced gradients in energy deposition. In conclusion, this augmentation of the Monte Carlo method can accurately simulate light transport for a wide variety of nonhomogeneous tissue geometries.

  17. A patient with Moyamoya-like vessels after radiation therapy for a tumor in the basal ganglia

    International Nuclear Information System (INIS)

    Ishiyama, Koichi; Tomura, Noriaki; Kato, Koki; Takahashi, Satoshi; Watarai, Jiro; Sasajima, Toshio; Mizoi, Kazuo

    2001-01-01

    A patient with Moyamoya-like vessels after radiation therapy for treatment of a tumor in the basal ganglia is reported. He was diagnosed as Down syndrome at birth. He had a tumor in the left basal ganglionic region at 12 years of the age. The tumor increased in size at age 14. He underwent cerebral angiography, which did not show a stenosis nor occlusion of the internal carotid artery, anterior cerebral artery, nor the middle cerebral artery. He received radiation therapy with a total dose of 56 Gy. He presented a dressing apraxia at age 19. MRI showed cerebral infarction in the left temporo-occipital region. Right internal carotid angiography revealed a severe stenosis of the internal carotid artery and anterior cerebral artery as well as a severe stenosis of the middle cerebral artery on the right side. Moyamoya-like vessels were seen in the basal ganglionic region. Left internal carotid angiography also showed a stenosis of the internal carotid artery and anterior cerebral artery as well as a severe stenosis of the middle cerebral artery on the left side. Moyamoya-like vessels were seen in the basal ganglionic region. Leptomeningeal anastomose and transdural anastomose were bilaterally seen. These arterial occlusion and stenotic phenomenon corresponded to a previous radiation field. These Moyamoya-like vessels with arterial stenosis and occlusion were thought to be due to radiation-induced vasculopathy, because a previous cerebral angiography showed a normal caliber of cerebral arteries. This patient showed that patients with radiation therapy in their early childhood should be carefully observed considering the possibility of the phenomenon. (author)

  18. Magnetic navigation system for the precise helical and translational motions of a microrobot in human blood vessels

    Science.gov (United States)

    Jeon, S. M.; Jang, G. H.; Choi, H. C.; Park, S. H.; Park, J. O.

    2012-04-01

    Different magnetic navigation systems (MNSs) have been investigated for the wireless manipulation of microrobots in human blood vessels. Here we propose a MNS and methodology for generation of both the precise helical and translational motions of a microrobot to improve its maneuverability in complex human blood vessel. We then present experiments demonstrating the helical and translational motions of a spiral-type microrobot to verify the proposed MNS.

  19. Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines

    NARCIS (Netherlands)

    Kunjachan, Sijumon; Pola, Robert; Gremse, Felix; Theek, Benjamin; Ehling, Josef; Moeckel, Diana; Hermanns-Sachweh, Benita; Pechar, Michal; Ulbrich, Karel; Hennink, Wim E.; Storm, Gert; Lederle, Wiltrud; Kiessling, Fabian; Lammers, Twan

    2014-01-01

    Enhanced permeability and retention (EPR) and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received considerable attention

  20. Selective drug-induced reduction of blood flow in tumor transplants

    International Nuclear Information System (INIS)

    Knapp, W.H.; Debatin, J.; Layer, K.; Helus, F.; Altmann, A.; Sinn, H.J.; Ostertag, H.

    1985-01-01

    The effect of a calcium antagonist and a physiological amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine and 5-hydroxy tryptamine (5-HT) were administered ip in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 in the Walker carcinoma and an increase in the muscle of the hind leg. 5-HT caused a drop in the Walker carcinoma and only a slight fall of the washout rate in muscle. Tumor-to-muscle uptake ratios of 11 C-butanol fell. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects

  1. The usefulness of US with contrast agent on breast tumors

    International Nuclear Information System (INIS)

    Jung, Hye An; Jung, Jung Im; Kim, Hak Hee; Son, Sang Bum; Byun, Jae Young; Lee, Jae Mun; Hahn, Sung Tae; Kim, Choon Yul

    2000-01-01

    To evaluate the usefulness of US with contrast agent breast tumors. Fifteen breast tumors in fourteen patients underwent color Doppler US before and after intravenous injection of a microbubble contrast agent (Levovist, Schering AG, Berlin, Germany). Benign lesions were 8 and malignant lesions were 7 among these. Real-time power Doppler ultrasonographic images were recorded on a videotape and representative images were color-printed. Tumor vascularity was analyzed on real-time images in regard to its presence or absence, and changes in diameter and number of vessels, presence or absence of blush around the vessels. Two observers reached a consensus. Results of malignant tumors were compared with those of benign tumors. Color Doppler signal intensity increased in 12 of 15 cases (80%). Number of vessel increased in 9 of 15 cases (60%) and diameter of vessel increased in 12 of 15 cases (80%). Vascular blush around the enhanced vessel was present in 5 of 15 patients (53%). Color Doppler signal increased in 5 of 8 benign lesions (63%) and 7 of 7 malignant lesions (100%). Number of vessel increased in 4 of 8 benign lesion (50%) and 5 of 7 malignant lesions (71%). Diameter of vessel increased in 5 of 8 benign lesions (63%) and 7 of 7 malignant lesions (100%). Blush around the enhanced vessel was present in one of 8 benign lesions (13%) and 4 of 7 malignant lesions (57%). The time to peak enhancement was shorter in malignant cases (mean=45 sec) than benign cases (mean=82 sec). US with contrast agent on breast tumors is effective to detect blood flow within the mass and may be helpful to differentiate malignant from benign lesions.

  2. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    Directory of Open Access Journals (Sweden)

    Zhao Yan

    2009-01-01

    various malignant tumors compared to those in patients with chronic inflammation and benign tumors. This was consistent with immunohistochemical results. Additionally, PADI4 and cAT levels were significantly associated with higher levels of known tumor markers. Conclusion Our results suggest that PADI4 expression is increased in the blood and tissues of many malignant tumors, a finding useful for further understanding of tumorigenesis.

  3. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    International Nuclear Information System (INIS)

    Chang, Xiaotian; Han, Jinxiang; Pang, Li; Zhao, Yan; Yang, Yi; Shen, Zhonglin

    2009-01-01

    with chronic inflammation and benign tumors. This was consistent with immunohistochemical results. Additionally, PADI4 and cAT levels were significantly associated with higher levels of known tumor markers. Our results suggest that PADI4 expression is increased in the blood and tissues of many malignant tumors, a finding useful for further understanding of tumorigenesis

  4. Induction of cancer cell death by proton beam in tumor hypoxic region

    International Nuclear Information System (INIS)

    Lee, Y. M.; Heo, T. R.; Lee, K. B.; Jang, K. H.; Kim, H. N.; Lee, S. H.; Jeong, M. H.

    2008-04-01

    Proton beam has been applied to treat various tumor patients in clinical studies. However, it is still undefined whether proton radiation can inhibit the blood vessel formation and induce the cell death in vascular endothelial cells in growing organs. The aim of this study are first, to develop an optimal animal model for the observation of blood vessel development with low dose of proton beam and second, to investigate the effect of low dose proton beam on the inhibition of blood vessel formation induced by hypoxic conditions. In this study, flk1-GFP transgenic zebrafish embryos were used to directly visualize and determine the inhibition of blood vessels by low dose (1, 2, 5 Gy) of proton beam with spread out Bragg peak (SOBP). And we observed cell death by acridine orange staining at 96 hours post fertilization (hpf) stage of embryos after proton irradiation. We also compared the effects of proton beam with those of gamma-ray. An antioxidant, N-acetyl cystein (NAC) was used to investigate whether reactive oxygen species (ROS) were involved in the cell deaths induced by proton irradiation. Irradiated flk-1-GFP transgenic embryos with proton beam irradiation (35 MeV, spread out Bragg peak, SOBP) demonstrated a marked inhibition of embryonic growth and an altered fluorescent blood vessel development in the trunk region. When the cells with DNA damage in the irradiated zebrafish were stained with acridine orange, green fluorescent cell death spots were increased in trunk regions compared to non-irradiated control embryos. Proton beam also significantly increased the cell death rate in human umbilical vein endothelial cells (HUVEC), but pretreatment of N-acetyl cystein (NAC), an antioxidant, recovered the proton-induced cell death rate (p<0.01). Moreover, pretreatment of NAC abrogated the effect of proton beam on the inhibition of trunk vessel development and malformation of trunk truncation. From this study, we found that proton radiation therapy can inhibit the

  5. The effect of transluminal stent-graft placement on blood flow of abdominal branch vessels in type B aortic dissection

    International Nuclear Information System (INIS)

    Huang Lianjun; Yang Jian; Yu Feicheng; Sun Lizhong; Zhu Junming; Zhang Yan; Jiang Shiliang

    2005-01-01

    Objective: To evaluate the effect of TSGP on blood flow of abdominal branch vessels of Type B dissection. Methods: Thirty-five patients with type B aortic dissection underwent TSGP. The blood flow of abdominal branch vessels was analyzed via EBCT, MRI, and DSA before and after procedure. Results: A total of 140 important vessels from abdominal aorta in 35 patients, including celiac artery, SMA, right and left renal arteries were analyzed via EBCT, MRI, and DSA. 58 branches were affected by dissection, of which 14 (10% ) were dynamic impairment; and 44 (31.4%) were static impairment. After TSGP, the blood flow of impaired branches all showed improvement at different degrees, no post-operative ischemic complications occurred. Conclusion: TSGP could improve the blood flow immediately not only the dynamic but also the static ischemia of abdominal aorta branch vessels caused by type B aortic dissection. Further study is still need to observe the mid-term and long-term effect of TSGP. (authors)

  6. [Conjunct changes in the resistance and engorgement of the cerebral vessels in shifts in the blood gas composition].

    Science.gov (United States)

    Krasil'nikov, V G; Artem'eva, A I

    1982-08-01

    In anesthetized cats, under perfusion and with constant volume of the hemodynamically isolated brain, hypercapnia and hypoxia led to a decrease of cerebral vessels resistance and to a reduction of the brain blood flow, whereas a decrease in the PCO2 and an increase in the PO2 in the blood exerted on opposite effect. The different responses of the vessels had some similar features in respect to threshold changes of the PCO2 and PO2, to potentiation of effects of both parts of the brain vascular system on increased shifts of the blood gas tension, to greater sensitivity of both parts to PCO2 changes, to effect of the blood gas tension on reactivity of both parts to noradrenaline. The authors suggest a possibility of alterations of the filter-absorption interrelationships in the brain due to different responses of arterial and venous vessels to changes of the blood gas tension.

  7. Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

    International Nuclear Information System (INIS)

    Fenton, Bruce M.

    1997-01-01

    Background and purpose: Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships. Materials and methods: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO 2 saturation profiles were determined cryospectrophotometrically. Results: HbO 2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO 2 levels remained unchanged. Following 2.5 Gy, HbO 2 changes were minimal. At 24 h following 10 Gy, HbO 2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO 2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls. Conclusions: Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO 2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor

  8. Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

    International Nuclear Information System (INIS)

    Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

    2001-01-01

    We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

  9. Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels*

    Science.gov (United States)

    Jacobo, Sarah Melissa P.; Kazlauskas, Andrius

    2015-01-01

    Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. Furthermore, stabilization was associated with prolonged Erk activity. In the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which is dependent on Erk activity and associated with prolonged activation. PMID:25564613

  10. Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

    2012-02-01

    At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

  11. Warthin's tumor: an unknown pathogenesis: a neoplasm or a reactive hyperplasia?

    Science.gov (United States)

    Rabia, Arpaci Bozdogan; Ebru, Linke Serınsoz; Tuba, Kara; Didar, Gursoy; Gulhan, Orekici; Cengiz, Ozcan

    2015-01-01

    To examine the probable role of angiogenesis and lymphangiogenesis in the pathogenesis of Warthin's tumor. Sixty-one patients with Warthin's tumor (n = 40), branchial cysts (n = 6), thymic cysts (n = 3), or tonsillar lymphoepithelial cysts (n = 12) were included. Forty Warthin's tumors were used as the lesion group, and 21 lymphoepithelial cysts were used as a control group. 29 lymph nodes around the Warthin's tumor, four of which showed salivary duct inclusions, were also evaluated. Blood vessel density was defined as an indicator of angiogenesis by examining CD31 and FVIII Ag expression, and lymphatic vascular density was defined as an indicator of lymphangiogenesis by evaluating LYVE-1 and podoplanin expression by immunohistochemical analysis. Data are expressed with descriptive statistics. Comparative analysis was performed using Shapiro-Wilks, Mann-Whitney U, and Kruskal-Wallis tests. A P < 0.005 was considered to indicate statistical significance. Statistical analysis was performed using the MedCalc ® v.10.3.0 software. The lesion group had higher mean values of age (58 vs. 11 years, P = 0.001), smoking rate (92.3% vs. 19%, P < 0.001), stromal degeneration (100% vs. 42.9%, P < 0.001), lymph node involvement around the lesion (87.9% vs. 12.1%, P < 0.001), salivary duct inclusion (25% vs. 0%, P = 0.0001), than those of lymphoepithelial cysts. Blood vessel density (51.92 ± 25.64 vs. 8 ± 5.35, number/5 high power fields (HPF), P < 0.001) and lymphatic vascular density (68.95 ± 21.32 vs. 21.10 ± 4.05 number/5 HPF, P < 0.001) were higher in Warthin's tumors than lymphoepithelial cysts. Warthin's tumors, and lymph nodes with inclusions had similar levels of blood and lymphatic vascular density, which was higher than those of lymph nodes (P < 0.0001). Warthin's tumor is a true neoplastic epithelial proliferation associated with increased angiogenesis and lymphangiogenesis and induces reactive lymph node hyperplasia.

  12. [Do double gloves protect against contamination during cannulation of blood vessels? A prospective randomized study].

    Science.gov (United States)

    Szarpak, Łukasz; Kurowski, Andrzej

    2014-01-01

    Undamaged medical gloves protect medical personnel from contact with physiological fluids of the patient. Thus they protect the assistance provider from hand skin contamination with potentially infectious biological materials. The aim of the study was to evaluate the occurrence of pierce, perforations or damage of medical gloves during cannulation of blood vessels. In the prospective randomized study 303 pairs of gloves, used during cannulation of blood vessels under simulated resuscitation, were analyzed. Gloves were tested by the water leak test. The water test revealed 44 cases of damage to the gloves used during cannulation of blood vessels. Significant differences were noted in the frequency of damage to both the outer and single pairs of gloves and the inner pair of gloves. The study showed that the use of double gloves provides a higher level of security for a paramedic than the use of a single pair of gloves, however, double gloves reduce the manual dexterity of a paramedic. A large number of damages to gloves are not noticed by medical personnel during surgery.

  13. [Stem and progenitor cells in biostructure of blood vessel walls].

    Science.gov (United States)

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  14. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  15. The Behaviors of Ferro-Magnetic Nano-Particles In and Around Blood Vessels under Applied Magnetic Fields

    Science.gov (United States)

    Nacev, A.; Beni, C.; Bruno, O.; Shapiro, B.

    2010-01-01

    In magnetic drug delivery, therapeutic magnetizable particles are typically injected into the blood stream and magnets are then used to concentrate them to disease locations. The behavior of such particles in-vivo is complex and is governed by blood convection, diffusion (in blood and in tissue), extravasation, and the applied magnetic fields. Using physical first-principles and a sophisticated vessel-membrane-tissue (VMT) numerical solver, we comprehensively analyze in detail the behavior of magnetic particles in blood vessels and surrounding tissue. For any blood vessel (of any size, depth, and blood velocity) and tissue properties, particle size and applied magnetic fields, we consider a Krogh tissue cylinder geometry and solve for the resulting spatial distribution of particles. We find that there are three prototypical behaviors (blood velocity dominated, magnetic force dominated, and boundary-layer formation) and that the type of behavior observed is uniquely determined by three non-dimensional numbers (the magnetic-Richardson number, mass Péclet number, and Renkin reduced diffusion coefficient). Plots and equations are provided to easily read out which behavior is found under which circumstances (Figures 5, 6, 7, and 8). We compare our results to previously published in-vitro and in-vivo magnetic drug delivery experiments. Not only do we find excellent agreement between our predictions and prior experimental observations, but we are also able to qualitatively and quantitatively explain behavior that was previously not understood. PMID:21278859

  16. A Morphological Hessian Based Approach for Retinal Blood Vessels Segmentation and Denoising Using Region Based Otsu Thresholding.

    Directory of Open Access Journals (Sweden)

    Khan BahadarKhan

    Full Text Available Diabetic Retinopathy (DR harm retinal blood vessels in the eye causing visual deficiency. The appearance and structure of blood vessels in retinal images play an essential part in the diagnoses of an eye sicknesses. We proposed a less computational unsupervised automated technique with promising results for detection of retinal vasculature by using morphological hessian based approach and region based Otsu thresholding. Contrast Limited Adaptive Histogram Equalization (CLAHE and morphological filters have been used for enhancement and to remove low frequency noise or geometrical objects, respectively. The hessian matrix and eigenvalues approach used has been in a modified form at two different scales to extract wide and thin vessel enhanced images separately. Otsu thresholding has been further applied in a novel way to classify vessel and non-vessel pixels from both enhanced images. Finally, postprocessing steps has been used to eliminate the unwanted region/segment, non-vessel pixels, disease abnormalities and noise, to obtain a final segmented image. The proposed technique has been analyzed on the openly accessible DRIVE (Digital Retinal Images for Vessel Extraction and STARE (STructured Analysis of the REtina databases along with the ground truth data that has been precisely marked by the experts.

  17. Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation.

    Science.gov (United States)

    Ahirwar, Dinesh K; Nasser, Mohd W; Ouseph, Madhu M; Elbaz, Mohamad; Cuitiño, Maria C; Kladney, Raleigh D; Varikuti, Sanjay; Kaul, Kirti; Satoskar, Abhay R; Ramaswamy, Bhuvaneswari; Zhang, Xiaoli; Ostrowski, Michael C; Leone, Gustavo; Ganju, Ramesh K

    2018-05-03

    The chemokine CXCL12 has been shown to regulate breast tumor growth, however, its mechanism in initiating distant metastasis is not well understood. Here, we generated a novel conditional allele of Cxcl12 in mice and used a fibroblast-specific Cre transgene along with various mammary tumor models to evaluate CXCL12 function in the breast cancer metastasis. Ablation of CXCL12 in stromal fibroblasts of mice significantly delayed the time to tumor onset and inhibited distant metastasis in different mouse models. Elucidation of mechanisms using in vitro and in vivo model systems revealed that CXCL12 enhances tumor cell intravasation by increasing vascular permeability and expansion of a leaky tumor vasculature. Furthermore, our studies revealed CXCL12 enhances permeability by recruiting endothelial precursor cells and decreasing endothelial tight junction and adherence junction proteins. High expression of stromal CXCL12 in large cohort of breast cancer patients was directly correlated to blood vessel density and inversely correlated to recurrence and overall patient survival. In addition, our analysis revealed that stromal CXCL12 levels in combination with number of CD31+ blood vessels confers poorer patient survival compared to individual protein level. However, no correlation was observed between epithelial CXCL12 and patient survival or blood vessel density. Our findings describe the novel interactions between fibroblasts-derived CXCL12 and endothelial cells in facilitating tumor cell intrvasation, leading to distant metastasis. Overall, our studies indicate that cross-talk between fibroblast-derived CXCL12 and endothelial cells could be used as novel biomarker and strategy for developing tumor microenvironment based therapies against aggressive and metastatic breast cancer.

  18. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  19. Functional response of tumor vasculature in rats' glioma to hypercarbia evaluated by MR perfusion weighted imaging

    International Nuclear Information System (INIS)

    Zhang Qingbo; Feng Xiaoyuan; Liang Zonghui; Chen Shuan

    2008-01-01

    Objective: To evaluate the feasibility of MR PWI in judging maturity and variability of tumor vasculature in gliomas in rats. Methods: Twenty male SD rats were randomly assigned to tumor group and control group. Four weeks after implantation of C6 glioma cells in the brains of tumor group and injection of saline in the brains of control group, all rats were examined using MR PWI before and after inhalation of a mixture of 10% CO2 and 90% air. PaCO 2 and blood pH values of rats were monitored. Relative cerebral blood volume (rCBV) and relative cerebral blood flow(rCBF) values of tumors and normal brain tissue were measured. Brain sample were examined histologically using HE and immunohistochemical staining for smooth muscle actin(SMA). The histological features of gliomas were observed and SMA positively stained vessels of each tumor were counted manually using a light microscope. Perfusion data and pathological findings were analyzed statistically with SPSS for Windows. Results: PaCO 2 increased significantly [from(4.69±0.62)kPa to (7.62±0.81) kPa in tumor group and from (4.67±0.51) kPa to (7.63±0.78) kPa in control group, P 0.05), while changing rate of rCBV, rCBF in normal brain tissue correlated well with number of positive SMA labeled vessels (r=0.721 and 0.525, P 2 increase in the normal brain and in the tumor. It may be a useful technique to measure maturity of tumor vessels. (authors)

  20. Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

    Science.gov (United States)

    Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2017-01-01

    The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

  1. Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

    Science.gov (United States)

    BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

    1998-01-01

    Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

  2. Efficacy of thermoradiotherapy combined with hyperglycemia in tumors of various sizes and blood supply

    International Nuclear Information System (INIS)

    Kozin, S.V.; Zajtsev, A.V.

    1992-01-01

    The mean and individual values of three parameters, tumor size and blood supply level, as well as duration of the tumor growth delay were compared in mice with Erlich's carcinomas of various sizes after irradiation and that followed by artificial hyperthermia and local hyperthermia. Blood supply to the tumors and the antitumor effect of irradiation reduced with the tumor growth. Analysis of individual values of the considered parameters has shown the principle role of tumor blood flow depression in enhancement of the antitumor effect of irradiation by means of postradiation induced hyperglycemia and local hyperthermia, as well as in the relationship between this antitumor effect and the tumor size

  3. Treatment-independent miRNA signature in blood of wilms tumor patients

    Directory of Open Access Journals (Sweden)

    Schmitt Jana

    2012-08-01

    Full Text Available Abstract Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.

  4. Enhancement of 67Ga tumor-to-blood ratios by chelating agent

    International Nuclear Information System (INIS)

    Saji, Hideo; Yokoyama, Akira; Hata, Naotaka; Misaki, Atsushi; Tanaka, Hisashi.

    1980-01-01

    Chelating agent, such as, CaEDTA, CaDTPA, D-penicillamine, DMSA, desferoxamine, NTA, cysteine ethyl ester, BAL, α-MPG, phthalein complexone, were tested as a possible contrast enhancing agent for tumor imaging with 67 Ga-citrate. The intravenous administration of a chelating agent to Ehrlich's tumor bearing mice, one hour after the injection of 67 Ga-citrate, accelerated the blood clearance with only a very slight change of activity in the target, increasing the tumor-to-blood ratio, and consequently achieving a better visualization. Among the tested chelating agents, D-penicillamine showed the highest target-to-nontarget ratio at a shorter time: a good tumor-to-blood ratio, performed after 24 hr with non-treated animals, was achieved in only 1-3 hr with post-treated animals. Thus, D-penicillamine hold a considerable promise as a contrast enhancing agent for future clinical use. (author)

  5. Warthin′s tumor: An unknown pathogenesis: A neoplasm or a reactive hyperplasia?

    Directory of Open Access Journals (Sweden)

    Arpaci Bozdogan Rabia

    2015-01-01

    Full Text Available Background and Aims: To examine the probable role of angiogenesis and lymphangiogenesis in the pathogenesis of Warthin′s tumor. Materials and Methods: Sixty-one patients with Warthin′s tumor (n = 40, branchial cysts (n = 6, thymic cysts (n = 3, or tonsillar lymphoepithelial cysts (n = 12 were included. Forty Warthin′s tumors were used as the lesion group, and 21 lymphoepithelial cysts were used as a control group. 29 lymph nodes around the Warthin′s tumor, four of which showed salivary duct inclusions, were also evaluated. Blood vessel density was defined as an indicator of angiogenesis by examining CD31 and FVIII Ag expression, and lymphatic vascular density was defined as an indicator of lymphangiogenesis by evaluating LYVE-1 and podoplanin expression by immunohistochemical analysis. Statistical Analysis Used: Data are expressed with descriptive statistics. Comparative analysis was performed using Shapiro-Wilks, Mann-Whitney U, and Kruskal-Wallis tests. A P < 0.005 was considered to indicate statistical significance. Statistical analysis was performed using the MedCalc ® v.10.3.0 software. Results: The lesion group had higher mean values of age (58 vs. 11 years, P = 0.001, smoking rate (92.3% vs. 19%, P < 0.001, stromal degeneration (100% vs. 42.9%, P < 0.001, lymph node involvement around the lesion (87.9% vs. 12.1%, P < 0.001, salivary duct inclusion (25% vs. 0%, P = 0.0001, than those of lymphoepithelial cysts. Blood vessel density (51.92 ± 25.64 vs. 8 ± 5.35, number/5 high power fields (HPF, P < 0.001 and lymphatic vascular density (68.95 ± 21.32 vs. 21.10 ± 4.05 number/5 HPF, P < 0.001 were higher in Warthin′s tumors than lymphoepithelial cysts. Warthin′s tumors, and lymph nodes with inclusions had similar levels of blood and lymphatic vascular density, which was higher than those of lymph nodes (P < 0.0001. Conclusions: Warthin′s tumor is a true neoplastic epithelial proliferation associated with increased angiogenesis

  6. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light

    International Nuclear Information System (INIS)

    Selman, S.H.; Kreimer-Birnbaum, M.; Klaunig, J.E.; Goldblatt, P.J.; Keck, R.W.; Britton, S.L.

    1984-01-01

    Following hematoporphyrin derivative (HPD) photochemotherapy, blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thia-zolyl] formamide-induced urothelial tumors was determined by a radioactive microsphere technique using either 103 Ru or 141 Ce. Two tumors were implanted s.c. on the abdominal wall of Fischer 344 weanling rats. HPD (10 mg/kg body weight) was administered 24 hr prior to phototherapy (red light, greater than 590 nm; 360 J/sq cm). One of the two tumors was shielded from light exposure and served as an internal control. Blood flows were determined in control animals that received no treatment (Group 1), HPD only (Group 2), or light only (Group 3). In Groups 4 and 5, animals received the combination of HPD and light but differed in the time interval between treatment and blood flow determinations (10 min and 24 hr, respectively). Only blood flow to tumors treated with HPD and light showed a significant decrease (p less than 0.05) when compared with their internal controls both at 10 min (Group 4) and 24 hr (Group 5) after completion of phototherapy. These studies suggest that disruption of tumor blood flow may be an important mechanism of action of this method of cancer therapy

  7. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer.

    Science.gov (United States)

    Venneri, Mary Anna; De Palma, Michele; Ponzoni, Maurilio; Pucci, Ferdinando; Scielzo, Cristina; Zonari, Erika; Mazzieri, Roberta; Doglioni, Claudio; Naldini, Luigi

    2007-06-15

    Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), have been implicated in tumor progression. We recently described a lineage of mouse monocytes characterized by expression of the Tie2 angiopoietin receptor and required for the vascularization and growth of several tumor models. Here, we report that TIE2 expression in human blood identifies a subset of monocytes distinct from classical inflammatory monocytes and comprised within the less abundant "resident" population. These TIE2-expressing monocytes (TEMs) accounted for 2% to 7% of blood mononuclear cells in healthy donors and were distinct from rare circulating endothelial cells and progenitors. In human cancer patients, TEMs were observed in the blood and, intriguingly, within the tumors, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in nonneoplastic tissues. In vitro, TEMs migrated toward angiopoietin-2, a TIE2 ligand released by activated endothelial cells and angiogenic vessels, suggesting a homing mechanism for TEMs to tumors. Purified human TEMs, but not TEM-depleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumors, suggesting a potentially critical role of TEMs in human cancer progression. Human TEMs may provide a novel, biologically relevant marker of angiogenesis and represent a previously unrecognized target of cancer therapy.

  8. Intracerebral hemorrhage in brain tumors

    International Nuclear Information System (INIS)

    Fujita, Katsuzo; Matsumoto, Satoshi

    1980-01-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief. (author)

  9. Intracerebral hemorrhage in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, K; Matsumoto, S [Kobe Univ. (Japan). School of Medicine

    1980-10-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief.

  10. Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

    International Nuclear Information System (INIS)

    Suga, Kazuyoshi

    1986-01-01

    Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

  11. Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

    International Nuclear Information System (INIS)

    Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

    1991-01-01

    Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

  12. Colon cancer: association of histopathological parameters and patients' survival with clinical presentation.

    Science.gov (United States)

    Alexiusdottir, Kristin K; Snaebjornsson, Petur; Tryggvadottir, Laufey; Jonasson, Larus; Olafsdottir, Elinborg J; Björnsson, Einar Stefan; Möller, Pall Helgi; Jonasson, Jon G

    2013-10-01

    Available data correlating symptoms of colon cancer patients with the severity of the disease are very limited. In a population-based setting, we correlated information on symptoms of colon cancer patients with several pathological tumor parameters and survival. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 for this retrospective, population-based study was obtained from the Icelandic Cancer Registry. Information on symptoms of patients and blood hemoglobin was collected from patients' files. Pathological parameters were obtained from a previously performed standardized tumor review. A total of 768 patients entered this study; the median age was 73 years. Tumors in patients presenting at diagnosis with visible blood in stools were significantly more likely to be of lower grade, having pushing border, conspicuous peritumoral lymphocytic infiltration, and lower frequency of vessel invasion. Patients with abdominal pain and anemia were significantly more likely to have vessel invasion. Logistic regression showed that visible blood in stools was significantly associated with protecting pathological factors (OR range 0.38-0.83, p characteristics and adverse outcome for patients. © 2013 APMIS Published by Blackwell Publishing Ltd.

  13. Mathematical Modeling of Bingham Plastic Model of Blood Flow Through Stenotic Vessel

    OpenAIRE

    S.R. Verma

    2014-01-01

    The aim of the present paper is to study the axially symmetric, laminar, steady, one-dimensional flow of blood through narrow stenotic vessel. Blood is considered as Bingham plastic fluid. The analytical results such as pressure drop, resistance to flow and wall shear stress have been obtained. Effect of yield stress and shape of stenosis on resistance to flow and wall shear stress have been discussed through tables and graphically. It has been shown that resistance to flow and th...

  14. Segmentation of retinal blood vessels for detection of diabetic retinopathy: A review

    Directory of Open Access Journals (Sweden)

    Rezty Amalia Aras

    2016-05-01

    Full Text Available Diabetic detinopathy (DR is effect of diabetes mellitus to the human vision that is the major cause of blindness. Early diagnosis of DR is an important requirement in diabetes treatment. Retinal fundus image is commonly used to observe the diabetic retinopathy symptoms. It can present retinal features such as blood vessel and also capture the pathologies which may lead to DR. Blood vessel is one of retinal features which can show the retina pathologies. It can be extracted from retinal image by image processing with following stages: pre-processing, segmentation, and post-processing. This paper contains a review of public retinal image dataset and several methods from various conducted researches. All discussed methods are applicable to each researcher cases. There is no further analysis to conclude the best method which can be used for general cases. However, we suggest morphological and multiscale method that gives the best accuracy in segmentation.

  15. Differential peripheral blood gene expression profile based on Her2 expression on primary tumors of breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Oana Tudoran

    Full Text Available Breast cancer prognosis and treatment is highly dependent on the molecular features of the primary tumors. These tumors release specific molecules into the environment that trigger characteristic responses into the circulatory cells. In this study we investigated the expression pattern of 84 genes known to be involved in breast cancer signaling in the peripheral blood of breast cancer patients with ER-, PR- primary tumors. The patients were grouped according to Her2 expression on the primary tumors in Her2+ and Her2- cohorts. Transcriptional analysis revealed 15 genes to be differentially expressed between the two groups highlighting that Her2 signaling in primary tumors could be associated with specific blood gene expression. We found CCNA1 to be up-regulated, while ERBB2, RASSF1, CDH1, MKI67, GATA3, GLI1, SFN, PTGS2, JUN, NOTCH1, CTNNB1, KRT8, SRC, and HIC1 genes were down-regulated in the blood of triple negative breast cancer patients compared to Her2+ cohort. IPA network analysis predicts that the identified genes are interconnected and regulate each other. These genes code for cell cycle regulators, cell adhesion molecules, transcription factors or signal transducers that modulate immune signaling, several genes being also associated with cancer progression and treatment response. These results indicate an altered immune signaling in the peripheral blood of triple negative breast cancer patients. The involvement of the immune system is necessary in favorable treatment response, therefore these results could explain the low response rates observed for triple negative breast cancer patients.

  16. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

    International Nuclear Information System (INIS)

    Liguori, Manuela; Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola

    2011-01-01

    Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression

  17. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Manuela; Solinas, Graziella; Germano, Giovanni [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Mantovani, Alberto [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Department of Translational Medicine, University of Milano, Milano 20089 (Italy); Allavena, Paola, E-mail: paola.allavena@humanitasresearch.it [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy)

    2011-09-28

    Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

  18. Reduced blood flow increases the in vivo ammonium ion concentration in the RIF-1 tumor

    International Nuclear Information System (INIS)

    Constantinidis, Ioannis; Gamcsik, Michael P.

    1995-01-01

    Purpose: Previous studies from our laboratory have suggested that pooling of ammonium in tumor tissues may be caused by its inefficient removal due to the poor vasculature commonly found in tumors. The purpose of these experiments was to validate the relationship between tumor ammonium ion concentration and tumor blood flow, and to determine whether large concentrations of ammonium ion detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced within the tumor or simply imported into the tumor through the blood stream. Methods and Materials: To test this hypothesis, we reduced blood flow in subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by creating partial ischemia with a bolus injection of hydralazine or by occlusion with surgical sutures. 14 N and 31 P NMR spectroscopy were used to detect the presence of ammonium, and to assess the bioenergetic status of the tumors, respectively. Results: A correlation between ammonium ion concentration and (PCr(P i )) ratio was established for untreated tumors. An increase in the in vivo tumor ammonium ion concentration was observed for every tumor that experienced a reduction in blood flow caused by either hydralazine injection or suture ligation. Changes in ammonium ion concentration paralleled changes in the bioenergetics of hydralazine-treated tumors. Conclusion: Our results support the hypothesis that a reduction in tumor blood flow is responsible for the accumulation of ammonium in tumors, and that detected ammonium originated from within the tumor

  19. Automated artery-venous classification of retinal blood vessels based on structural mapping method

    Science.gov (United States)

    Joshi, Vinayak S.; Garvin, Mona K.; Reinhardt, Joseph M.; Abramoff, Michael D.

    2012-03-01

    Retinal blood vessels show morphologic modifications in response to various retinopathies. However, the specific responses exhibited by arteries and veins may provide a precise diagnostic information, i.e., a diabetic retinopathy may be detected more accurately with the venous dilatation instead of average vessel dilatation. In order to analyze the vessel type specific morphologic modifications, the classification of a vessel network into arteries and veins is required. We previously described a method for identification and separation of retinal vessel trees; i.e. structural mapping. Therefore, we propose the artery-venous classification based on structural mapping and identification of color properties prominent to the vessel types. The mean and standard deviation of each of green channel intensity and hue channel intensity are analyzed in a region of interest around each centerline pixel of a vessel. Using the vector of color properties extracted from each centerline pixel, it is classified into one of the two clusters (artery and vein), obtained by the fuzzy-C-means clustering. According to the proportion of clustered centerline pixels in a particular vessel, and utilizing the artery-venous crossing property of retinal vessels, each vessel is assigned a label of an artery or a vein. The classification results are compared with the manually annotated ground truth (gold standard). We applied the proposed method to a dataset of 15 retinal color fundus images resulting in an accuracy of 88.28% correctly classified vessel pixels. The automated classification results match well with the gold standard suggesting its potential in artery-venous classification and the respective morphology analysis.

  20. 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.

  1. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies

    Science.gov (United States)

    Kohandel, M.; Kardar, M.; Milosevic, M.; Sivaloganathan, S.

    2007-07-01

    Tumors cannot grow beyond a certain size (about 1-2 mm in diameter) through simple diffusion of oxygen and other essential nutrients into the tumor. Angiogenesis, the formation of blood vessels from pre-existing vessels, is a crucial and observed step, through which a tumor obtains its own blood supply. Thus, strategies that interfere with the development of this tumor vasculature, known as anti-angiogenic therapy, represent a novel approach to controlling tumor growth. Several pre-clinical studies have suggested that currently available angiogenesis inhibitors are unlikely to yield significant sustained improvements in tumor control on their own, but rather will need to be used in combination with conventional treatments to achieve maximal benefit. Optimal sequencing of anti-angiogenic treatment and radiotherapy or chemotherapy is essential to the success of these combined treatment strategies. Hence, a major challenge to mathematical modeling and computer simulations is to find appropriate dosages, schedules and sequencing of combination therapies to control or eliminate tumor growth. Here, we present a mathematical model that incorporates tumor cells and the vascular network, as well as their interplay. We can then include the effects of two different treatments, conventional cytotoxic therapy and anti-angiogenic therapy. The results are compared with available experimental and clinical data.

  2. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

    Directory of Open Access Journals (Sweden)

    Daniel Y Joh

    Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

  3. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

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

  4. Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Zheng-Yu, E-mail: linsinlan@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Chen, Jin, E-mail: snow8968851@163.com [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Deng, Xiu-Fen, E-mail: dxf197286@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China)

    2012-11-15

    Objective: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with iodine-125 (I-125) radioactive seed implantation. Methods: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35 {+-} 1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels ({>=}3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. Results: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1 {+-} 6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. Conclusion: The 1.5T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology.

  5. Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

    Directory of Open Access Journals (Sweden)

    Jérôme Côté

    Full Text Available Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB. B1 receptors (B1R, inducible prototypical G-protein coupled receptors (GPCR can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9BK (LDBK and SarLys[dPhe(8]desArg(9BK (NG29, in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer at tumoral sites (T(1-weighted imaging. These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry. We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peritumoral sites.

  6. Detection of Blood Vessels in Color Fundus Images using a Local Radon Transform

    Directory of Open Access Journals (Sweden)

    Reza Pourreza

    2010-09-01

    Full Text Available Introduction: This paper addresses a method for automatic detection of blood vessels in color fundus images which utilizes two main tools: image partitioning and local Radon transform. Material and Methods: The input images are firstly divided into overlapping windows and then the Radon transform is applied to each. The maximum of the Radon transform in each window corresponds to the probable available sub-vessel. To verify the detected sub-vessel, the maximum is compared with a predefined threshold. The verified sub-vessels are reconstructed using the Radon transform information. All detected and reconstructed sub-vessels are finally combined to make the final vessel tree. Results: The algorithm’s performance was evaluated numerically by applying it to 40 images of DRIVE database, a standard retinal image database. The vessels were extracted manually by two physicians. This database was used to test and compare the available and proposed algorithms for vessel detection in color fundus images. By comparing the output of the algorithm with the manual results, the two parameters TPR and FPR were calculated for each image and the average of TPRs and FPRs were used to plot the ROC curve. Discussion and Conclusion: Comparison of the ROC curve of this algorithm with other algorithms demonstrated the high achieved accuracy. Beside the high accuracy, the Radon transform which is integral-based makes the algorithm robust against noise.

  7. Blood Vessel Extraction in Color Retinal Fundus Images with Enhancement Filtering and Unsupervised Classification

    Directory of Open Access Journals (Sweden)

    Zafer Yavuz

    2017-01-01

    Full Text Available Retinal blood vessels have a significant role in the diagnosis and treatment of various retinal diseases such as diabetic retinopathy, glaucoma, arteriosclerosis, and hypertension. For this reason, retinal vasculature extraction is important in order to help specialists for the diagnosis and treatment of systematic diseases. In this paper, a novel approach is developed to extract retinal blood vessel network. Our method comprises four stages: (1 preprocessing stage in order to prepare dataset for segmentation; (2 an enhancement procedure including Gabor, Frangi, and Gauss filters obtained separately before a top-hat transform; (3 a hard and soft clustering stage which includes K-means and Fuzzy C-means (FCM in order to get binary vessel map; and (4 a postprocessing step which removes falsely segmented isolated regions. The method is tested on color retinal images obtained from STARE and DRIVE databases which are available online. As a result, Gabor filter followed by K-means clustering method achieves 95.94% and 95.71% of accuracy for STARE and DRIVE databases, respectively, which are acceptable for diagnosis systems.

  8. Vascular thermal adaptation in tumors and normal tissue in rats

    International Nuclear Information System (INIS)

    Nah, Byung Sik; Choi, Ihl-Bohng; Oh, Won Young; Osborn, James L.; Song, Chang W.

    1996-01-01

    Purpose: The vascular thermal adaptation in the R3230 adenocarcinoma, skin and muscle in the legs of Fischer rats was studied. Methods and Materials: The legs of Fischer rats bearing the R3230 AC adenocarcinoma (subcutaneously) were heated once or twice with a water bath, and the blood flow in the tumor, skin and muscle of the legs was measured with the radioactive microsphere method. Results: The blood flow in control R3230 AC tumors was 23.9 ml/100 g/min. The tumor blood flow increased about 1.5 times in 30 min and then markedly decreased upon heating at 44.5 deg. C for 90 min. In the tumors preheated 16 h earlier at 42.5 deg. C for 60 min, reheating at 44.5 deg. C increased the tumor blood flow by 2.5-fold in 30 min. Contrary to the decline in blood flow following an initial increase during the 44.5 deg. C heating without preheating, the tumor blood flow remained elevated throughout the 90 min reheating at 44.5 deg. C. These results indicated that thermal adaptation or thermotolerance developed in the tumor vasculatures after the preheating at 42.5 deg. C for 60 min. The magnitude of vascular thermal adaptation in the tumors 24 h and 48 h after the preheating, as judged from the changes in blood flow, were smaller than that 16 h after the preheating. Heating at 42.5 deg. C for 60 min induced vascular thermal adaptation also in the skin and muscle, which peaked in 48 h and 24 h, respectively, after the heating. Conclusion: Heating at 42.5 deg. C for 1 h induced vascular thermal adaptation in the R3230 AC tumor, skin, and muscle of rats that peaked 16-48 h after the heating. When the tumor blood vessels were thermally adapted, the tumor blood flow increased upon heating at temperatures that would otherwise reduce the tumor blood flow. Such an increase in tumor blood flow may hinder raising the tumor temperature while it may increase tumor oxygenation.

  9. Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

    International Nuclear Information System (INIS)

    Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

    2015-01-01

    Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

  10. A computational study for investigating acoustic streaming and tissue heating during high intensity focused ultrasound through blood vessel with an obstacle

    Science.gov (United States)

    Parvin, Salma; Sultana, Aysha

    2017-06-01

    The influence of High Intensity Focused Ultrasound (HIFU) on the obstacle through blood vessel is studied numerically. A three-dimensional acoustics-thermal-fluid coupling model is employed to compute the temperature field around the obstacle through blood vessel. The model construction is based on the linear Westervelt and conjugate heat transfer equations for the obstacle through blood vessel. The system of equations is solved using Finite Element Method (FEM). We found from this three-dimensional numerical study that the rate of heat transfer is increasing from the obstacle and both the convective cooling and acoustic streaming can considerably change the temperature field.

  11. Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo

    Science.gov (United States)

    Fan, Jun-jun; Mu, Tian-wang; Qin, Jun-jun; Bi, Long; Pei, Guo-xian

    2014-01-01

    To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve. PMID:25101279

  12. Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

    International Nuclear Information System (INIS)

    Roberts, R.E.; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H.

    2013-01-01

    relaxations were associated with an inhibition of calcium entry. • Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. • Umbelliferone produced a rapid, transient nitric oxide-dependent relaxation

  13. Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

    Science.gov (United States)

    Dombrowski, S M; Deshpande, A; Dingwall, C; Leichliter, A; Leibson, Z; Luciano, M G

    2008-03-18

    Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (Pblood vessel expression was related to focal compression alone or in combination with global ischemia/hypoxia conditions as previously described. These findings suggest that VEGFR-2 may play an adaptive role in angiogenesis after CH

  14. Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R.E., E-mail: Richard.roberts@nottingham.ac.uk; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H., E-mail: steve.alexander@nottingham.ac.uk

    2013-11-01

    relaxations were associated with an inhibition of calcium entry. • Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. • Umbelliferone produced a rapid, transient nitric oxide-dependent relaxation.

  15. Histomorphometric comparative study of blood vessels and their pattern in follicular cyst, odontogenic keratocyst, and ameloblastoma.

    Science.gov (United States)

    Seifi, Safora; Feizi, Farideh; Khafri, Thoraya; Aram, Mehrdad

    2013-03-01

    The present study aimed at assessment and histomorphometric analysis of intratumoral and peritumoral (cystic) blood vessels in odontogenic lesions and their pattern on their clinical behavior by immunohistochemistry and morphometry. In a descriptive and analytical cross-sectional study, 45 paraffin blocks of ameloblastoma, odontogenic keratocyst, and follicular cyst were selected and stained immunohistochemically for CD34. In each slide, images of 3 microscopic fields with the highest microvessel density in intratumoral and peritumoral (cystic) areas were captured at 40× magnification with attached camera system. Inner vascular diameter (IVD) and outer vascular diameter (OVD), cross-sectional area (CSA), and the wall thickness (WT) of the vessels were measured with Motic Plus 2 software. The vascular pattern in odontogenic lesions was analyzed. Outer vascular diameter, IVD, and CSA of the vessels in peritumoral (cystic) areas were greater in ameloblastoma than keratocyst (P = 0.001) and follicular cyst (P keratocyst and follicular cyst. Morphometric specifications of blood vessels (IVD, OVD, CSA) and their pattern in peritumoral (cystic) areas may influence the aggressive clinical behavior of ameloblastoma in comparison with keratocyst and follicular cyst.

  16. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  17. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

    2016-01-15

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  18. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

    Directory of Open Access Journals (Sweden)

    Griffiths Gary L

    2009-06-01

    Full Text Available Abstract Background The existence of large pores in the blood-tumor barrier (BTB of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5 through generation 8 (G8 polyamidoamine dendrimers were labeled with gadolinium (Gd-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5 the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8

  19. Monstrous venous haemangioma tumor of the retroperitonial space - Diagnosis and diagnostic problems

    International Nuclear Information System (INIS)

    Leinung, S.; Wuerl, P.; Frey, A.; Schoenfelder, M.; Lotz, I.; Lochhaas, L.

    2000-01-01

    The preoperative diagnosis and its inherent problems are illustrated using a coincidentally diagnosed monstrous haemangioma tumor of the retroperitonial space in a twenty year old patient. With respect to our patient, X-ray, computer tomography and angiography all failed as diagnostic tools. Only the use of Doppler sonographic flow signals suggested the presence of a haemangioma. The morphology, prognosis and clinical significance of blood vessel tumors are multifaceted. The most important differential diagnoses to the venous haemangioma are the cavernous and the cappilliary haemangioma. The venous haemangioma distinguishes itself through the presence of blood vessel walls. Haemangiomas are common benign tumors. In the presence of highly developed muscular components, there exists a transition to angiomyomas and to leiomyomas. Venal haemangiomas are extremely rare in the demonstrated localisation of the retroperitoneal space. Here they can grow to monstrous preportions whilst remaining undetected. Thus the patient is under the potential danger of bleeding to death through trivial injuries. The therapy of choice reamins total surgical excision. (orig.) [de

  20. Effect of hepatic blood flow alteration on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit: an experimental study

    International Nuclear Information System (INIS)

    Guo Zhi; Ni Hong; Li Baoguo; Hu Yonghua; Xing Wenge; Liu Fang

    2008-01-01

    Objective: To investigate the effect of alteration of blood flow in the hepatic artery on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit model. Methods: Thirty rabbits with VX2 hepatic tumor were divided into three groups according to hepatic artery blood flow: complete occlusion of the hepatic artery(group A), partial occlusion of the hepatic artery (group B), and no occlusion of the hepatic artery (group C). With conventional CT scan and perfusion scan, the values of blood flow (BF) and blood volume(BV) of VX 2 tumor were computed and the differences among the three groups were analyzed. After cryoablation, the animals were euthanized and the livers were removed. The hepatic tissue from the cryoablation area and surrounding area underwent both methyl thiazolyl tetrazolium (MTY) diaphorase staining and triphenyl tetrazolium chloride (TTC) staining. The gross pathology and histopathological changes were observed. Results: (1)The BF and BV in the three groups were: (7.23 + 2. 15 ) ml·100 g -1 ·min -1 and (1.63±0.52) ml/100 g in group A; (32.65±6.12) ml·100 g -1 ·min -1 and (9.32±2.63) ml/100 g in group B; (61.34±12.15) ml·100 g -1 ·min -1 and (17.51± 3.14) ml/100 g in group C, respectively. There were significant differences among the three groups in the BF and BV (F value was 452.16 and 421.33 in the BF and BV, respectively, P <0.01); (2) The maximum diameter of cryoablation-induced necrosis was (2.3±0.3)cm in group A, (1.5±0.2) cm in group B, and (0.8±0.1) cm in group C, respectively. The difference was significant among the groups (F value was 315.32,P <0.01). (3) There were well-defined frozen areas, bordering areas and normal surrounding areas in MTT staining. In group C, positive staining around some blood vessels could be seen. Conclusion: Alteration of the blood flow in the hepatic artery can affect the cryoablation efficacy. With the decrease of hepatic artery blood flow, the efficacy of cryoablation on liver tumor

  1. Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

    Science.gov (United States)

    He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

    2018-06-01

    High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Blood vessel classification into arteries and veins in retinal images

    Science.gov (United States)

    Kondermann, Claudia; Kondermann, Daniel; Yan, Michelle

    2007-03-01

    The prevalence of diabetes is expected to increase dramatically in coming years; already today it accounts for a major proportion of the health care budget in many countries. Diabetic Retinopathy (DR), a micro vascular complication very often seen in diabetes patients, is the most common cause of visual loss in working age population of developed countries today. Since the possibility of slowing or even stopping the progress of this disease depends on the early detection of DR, an automatic analysis of fundus images would be of great help to the ophthalmologist due to the small size of the symptoms and the large number of patients. An important symptom for DR are abnormally wide veins leading to an unusually low ratio of the average diameter of arteries to veins (AVR). There are also other diseases like high blood pressure or diseases of the pancreas with one symptom being an abnormal AVR value. To determine it, a classification of vessels as arteries or veins is indispensable. As to our knowledge despite the importance there have only been two approaches to vessel classification yet. Therefore we propose an improved method. We compare two feature extraction methods and two classification methods based on support vector machines and neural networks. Given a hand-segmentation of vessels our approach achieves 95.32% correctly classified vessel pixels. This value decreases by 10% on average, if the result of a segmentation algorithm is used as basis for the classification.

  3. Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows association with the course of the disease: a pilot study.

    Directory of Open Access Journals (Sweden)

    Albertas Dauksa

    Full Text Available Pancreatic tumors are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. Toward this aim, we investigated in a pilot study the power of methylation changes in whole blood as predictive markers for the detection of pancreatic tumors. We investigated methylation levels at selected CpG sites in the CpG rich regions at the promoter regions of p16, RARbeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 in the blood of 30 pancreatic tumor patients and in the blood of 49 matching controls. In addition, we studied LINE-1 and Alu repeats using degenerate amplification approach as a surrogate marker for genome-wide methylation. The site-specific methylation measurements at selected CpG sites were done by the SIRPH method. Our results show that in the patient's blood, tumor suppressor genes were slightly but significantly higher methylated at several CpG sites, while repeats were slightly less methylated compared to control blood. This was found to be significantly associated with higher risk for pancreatic ductal adenocarcinoma. Additionally, high methylation levels at TNFRSCF10C were associated with positive perineural spread of tumor cells, while higher methylation levels of TNFRSF10C and ACIN1 were significantly associated with shorter survival. This pilot study shows that methylation changes in blood could provide a promising method for early detection of pancreatic tumors. However, larger studies must be carried out to explore the clinical usefulness of a whole blood methylation based test for non-invasive early detection of pancreatic tumors.

  4. Retinal hemodynamic oxygen reactivity assessed by perfusion velocity, blood oximetry and vessel diameter measurements

    DEFF Research Database (Denmark)

    Klefter, Oliver Niels; Lauritsen, Anne Øberg; Larsen, Michael

    2015-01-01

    PURPOSE: To test the oxygen reactivity of a fundus photographic method of measuring macular perfusion velocity and to integrate macular perfusion velocities with measurements of retinal vessel diameters and blood oxygen saturation. METHODS: Sixteen eyes in 16 healthy volunteers were studied at two...... is a valid method for assessing macular perfusion. Results were consistent with previous observations of hyperoxic blood flow reduction using blue field entoptic and laser Doppler velocimetry. Retinal perfusion seemed to be regulated around individual set points according to blood glucose levels. Multimodal...

  5. Activity of the hypoxia-activated pro-drug TH-302 in hypoxic and perivascular regions of solid tumors and its potential to enhance therapeutic effects of chemotherapy.

    Science.gov (United States)

    Saggar, Jasdeep K; Tannock, Ian F

    2014-06-01

    Many chemotherapy drugs have poor therapeutic activity in regions distant from tumor blood vessels because of poor tissue penetration and low cytotoxic activity against slowly-proliferating cells. The hypoxia-activated pro-drug TH-302 may have selective toxicity for hypoxic and neighboring cells in tumors. Here we characterize the spatial distribution and ability of TH-302 to selectively target hypoxic regions and complement the effect of doxorubicin and docetaxel by modifying biomarker distribution. Athymic nude mice bearing human breast MCF-7 or prostate PC-3 tumors were treated with doxorubicin or docetaxel respectively and TH-302 alone or in combination. Biomarkers of drug effect including γH2aX (a marker of DNA damage), cleaved caspase-3 or -6 (markers of apoptosis) and reduction in Ki-67 (a marker of cell proliferation) were quantified in tumor sections in relation to functional blood vessels (recognized by DiOC7) and hypoxia (recognized by EF5) using immunohistochemistry. γH2aX expression at 10 min and cleaved caspase-3 or -6 at 24 hr after doxorubicin or docetaxel decreased with increasing distance from tumor blood vessels, with minimal expression in hypoxic regions; maximum reduction in Ki67 levels was observed in regions closest to vasculature at 24 hr. TH-302 induced maximal cell damage in hypoxic and neighboring regions, but was also active in tumor regions closer to blood vessels. TH-302 given 4 hr before doxorubicin or docetaxel increased DNA damage and apoptosis throughout the tumor compared to chemotherapy alone. When given with doxorubicin or docetaxel, TH-302 complements and enhances anticancer effects in both perivascular and hypoxic regions but also increases toxicity. © 2013 UICC.

  6. Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

    Directory of Open Access Journals (Sweden)

    Haque Inamul

    2010-08-01

    Full Text Available Abstract Background New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs to pericytes and their recruitment in the tumor angiogenesis process. Results We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1 in mesenchymal stem cells. Conclusion These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.

  7. 1H-NMR of human blood lipids in cases of malignant and benign tumors

    International Nuclear Information System (INIS)

    Yushmanov, V.E.; Kotrikadze, N.G.; Pershin, A.D.; Dzhishkariani, O.S.; Tsartsidze, M.A.; Lomsadze, B.A.; Sibel'dina, L.A.

    1989-01-01

    High resolution 1 H-NMR (360MH z ) combined with thin-layer chromatography was used to study profile and molecular structure changes of inverted micelles of human blood developing in patients with malignant and benign tumors of the breast and uterus. Alterations were demonstrated in relative intensities of some lipid NMR peaks in tumor, as compared to normal blood. Changes in blood - lipid levels, e.g. cholesterol, in tumor affect lipid structural and dynamical status thus elucidating NMR-regularities obtained

  8. BPA and BSH accumulation in experimental tumors

    International Nuclear Information System (INIS)

    Patel, H.; Sedgwick, E.M.

    2000-01-01

    The accumulation of boronated compounds into tumors is a critical component to the success of BNCT. To date, great variability has been demonstrated in the tumor:blood ratio achieved in samples both from different patients and within samples taken from the same patient. The factors that probably influence the level of uptake include the vascular perfusion within the tumor, the permeability of these vessels and the viability of the tumor cells themselves. These experiments were designed to measure these various factors in different experimental tumor models and to relate these measurements to the uptake of both BPA (Boronophenylalanine) and BSH (Sodiumborocaptate). They demonstrate that within different tumors there can be wide variations in the vascular parameters. In addition, the viability of the tumor cells may also be an important determinant of tumor uptake. (author)

  9. [Topography of the blood vessels in the hilum of the kidney of Myrmecophaga tridactyla].

    Science.gov (United States)

    Souza, W M; Miglino, M A; Arantes, I G; Nascimento, A A

    1991-01-01

    The study was undertaken in 10 formol-imbibed kidneys of great anteater (Myrmecophaga tridactyla). After the dissection the following characteristics were showed: kidney blood vessels are distributed in 2 different sites, namely hilar and extrahilar, amounting 3 to 6 in the right side 3 to 7 in the left side. Arterial branches in extrahilar region range from 1 to 2 in both sides and in hilar region they present from 1 to 4 in the right and 1 to 2 in the left. Venous roots occur in 1 to 2 vessels in the right and 1 to 3 vessels in the left, occupying only the hilar region, except one case where it was present in the right side.

  10. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

    Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

  11. Imaging transient blood vessel fusion events in zebrafish by correlative volume electron microscopy.

    Directory of Open Access Journals (Sweden)

    Hannah E J Armer

    Full Text Available The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM and Serial Block Face/Scanning Electron Microscopy (SBF/SEM. The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism.

  12. Concordance of genotype for polymorphisms in DNA isolated from peripheral blood and colorectal cancer tumor samples

    NARCIS (Netherlands)

    van Huis-Tanja, Lieke; Kweekel, Dinemarie; Gelderblom, Hans; Koopman, Miriam; Punt, Kees; Guchelaar, Henk-Jan; van der Straaten, Tahar

    2013-01-01

    Background & aim: Results from different pharmacogenetic association studies in colorectal cancer are often conflicting. Both peripheral blood and formalin-fixed, paraffin-embedded (FFPE) tissue are routinely used as DNA source. This could cause bias due to somatic alterations in tumor tissue, such

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

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

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

  14. A Strategy for Rapid Construction of Blood Vessel-Like Structures with Complex Cell Alignments.

    Science.gov (United States)

    Wang, Nuoxin; Peng, Yunhu; Zheng, Wenfu; Tang, Lixue; Cheng, Shiyu; Yang, Junchuan; Liu, Shaoqin; Zhang, Wei; Jiang, Xingyu

    2018-04-17

    A method is developed that can rapidly produce blood vessel-like structures by bonding cell-laden electrospinning (ES) films layer by layer using fibrin glue within 90 min. This strategy allows control of cell type, cell orientation, and material composition in separate layers. Furthermore, ES films with thicker fibers (polylactic-co-glycolic acid, fiber diameter: ≈3.7 µm) are used as cell-seeding layers to facilitate the cell in-growth; those with thinner fibers (polylactic acid, fiber diameter: ≈1.8 µm) are used as outer reinforcing layers to improve the mechanical strength and reduce the liquid leakage of the scaffold. Cells grow, proliferate, and migrate well in the multilayered structure. This design aims at a new type of blood vessel substitute with flexible control of parameters and implementation of functions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Tumor blood flow, pO2, and radioresponse are improved by mild temperature hyperthermia

    International Nuclear Information System (INIS)

    Shakil, Abdus; Griffin, Robert J.; Song, Chang W.

    1997-01-01

    Purpose/Objective: The purpose of this study was to elucidate the changes in tumor blood flow, tumor pO 2 and the radiation response of the tumors caused by mild temperature hyperthermia (MTH). Materials And Methods: Experiments were carried out using the R3230 Adenocarcinoma (R3230 AC tumor), grown subcutaneously in the right hind limbs of male Fischer rats. Tumors were heated once at 40.5 deg.to 43.5 deg.C for 30 or 60 min, or twice at a 24 hr interval. Tumor blood flow and tumor pO 2 were measured immediately after the hyperthermic treatments or after 24 hr using a radioactive microsphere method and by an Eppendorf pO 2 Histograph, respectively. The influence of MTH on the effect of X-irradiation (250 kVp) on this tumor was investigated with tumor growth delay and the in vivo/in vitro excision assay for surviving tumor cell fraction. Results: Tumor blood flow and pO 2 increased upon heating for 30 min at 40.5 deg.C to 43.5 deg.C, but following 60 min heating, the pO 2 was similar to that in control tumors. The tumor blood flow increased about 1.4-fold and the tumor pO 2 increased more than 3 times after 30 min heating at 42.5 deg.C. Therefore, the in vivo/in vitro assay and the growth delay were carried out following treatment with 42.5 deg.C for 30 min. As shown in Table 1, the reduction in surviving fraction by MTH before radiation was markedly greater than that by MTH after radiation. Table 1 also shows that MTH alone caused no growth delay compared to control and while heat after radiation increased the growth delay by 2 days, MTH before radiation increased the growth delay by 5 days compared to radiation alone. Conclusion: The results indicate that MTH is effective in increasing tumor blood flow and oxygenation and that MTH for 30 min at 42.5 deg.C, applied before radiation, significantly improves the radiation response of R3230 AC tumors

  16. Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    Purpose of reviews This review focuses on recent advance in the diagnosis pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Recent findings Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and

  17. Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

    Science.gov (United States)

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

    2017-01-01

    ABSTRACT We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression. PMID:27715464

  18. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

    2008-01-01

    Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...

  19. 3D discrete angiogenesis dynamic model and stochastic simulation for the assessment of blood perfusion coefficient and impact on heat transfer between nanoparticles and malignant tumors.

    Science.gov (United States)

    Yifat, Jonathan; Gannot, Israel

    2015-03-01

    Early detection of malignant tumors plays a crucial role in the survivability chances of the patient. Therefore, new and innovative tumor detection methods are constantly searched for. Tumor-specific magnetic-core nano-particles can be used with an alternating magnetic field to detect and treat tumors by hyperthermia. For the analysis of the method effectiveness, the bio-heat transfer between the nanoparticles and the tissue must be carefully studied. Heat diffusion in biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where blood perfusion plays an important role. Malignant tumors are known to initiate an angiogenesis process, where endothelial cell migration from neighboring vasculature eventually leads to the formation of a thick blood capillary network around them. This process allows the tumor to receive its extensive nutrition demands and evolve into a more progressive and potentially fatal tumor. In order to assess the effect of angiogenesis on the bio-heat transfer problem, we have developed a discrete stochastic 3D model & simulation of tumor-induced angiogenesis. The model elaborates other angiogenesis models by providing high resolution 3D stochastic simulation, capturing of fine angiogenesis morphological features, effects of dynamic sprout thickness functions, and stochastic parent vessel generator. We show that the angiogenesis realizations produced are well suited for numerical bio-heat transfer analysis. Statistical study on the angiogenesis characteristics was derived using Monte Carlo simulations. According to the statistical analysis, we provide analytical expression for the blood perfusion coefficient in the Pennes equation, as a function of several parameters. This updated form of the Pennes equation could be used for numerical and analytical analyses of the proposed detection and treatment method. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Julie A Wallace

    Full Text Available Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies.

  1. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

    Directory of Open Access Journals (Sweden)

    Luissint Anny-Claude

    2012-11-01

    Full Text Available Abstract The Blood–brain barrier (BBB, present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit. The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.

  2. Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

    Science.gov (United States)

    Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

    2014-01-01

    Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

  3. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  4. Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Luukkainen, A; Seppälä, M; Renkonen, J; Renkonen, R; Hagstrő M, J; Huhtala, H; Rautiainen, M; Myller, J; Paavonen, T; Ranta, A; Torkkeli, T; Toppila-Salmi, S

    2017-06-01

    Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

  5. Vessel abnormalization: another hallmark of cancer? Molecular mechanisms and therapeutic implications.

    Science.gov (United States)

    De Bock, Katrien; Cauwenberghs, Sandra; Carmeliet, Peter

    2011-02-01

    As a result of excessive production of angiogenic molecules, tumor vessels become abnormal in structure and function. By impairing oxygen delivery, abnormal vessels fuel a vicious cycle of non-productive angiogenesis, which creates a hostile microenvironment from where tumor cells escape through leaky vessels and which renders tumors less responsive to chemoradiation. While anti-angiogenic strategies focused on inhibiting new vessel growth and destroying pre-existing vessels, clinical studies showed modest anti-tumor effects. For many solid tumors, anti-VEGF treatment offers greater clinical benefit when combined with chemotherapy. This is partly due to a normalization of the tumor vasculature, which improves cytotoxic drug delivery and efficacy and offers unprecedented opportunities for anti-cancer treatment. Here, we overview key novel molecular players that induce vessel normalization. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels

    International Nuclear Information System (INIS)

    Sivaramakrishnan, Mathangi; Maslov, Konstantin; Zhang, Hao F; Stoica, George; Wang, Lihong V

    2007-01-01

    We investigate the feasibility of obtaining accurate quantitative information, such as local blood oxygenation level (sO 2 ), with a spatial resolution of about 50 μm from spectral photoacoustic (PA) measurements. The optical wavelength dependence of the peak values of the PA signals is utilized to obtain the local blood oxygenation level. In our in vitro experimental models, the PA signal amplitude is found to be linearly proportional to the blood optical absorption coefficient when using ultrasonic transducers with central frequencies high enough such that the ultrasonic wavelengths are shorter than the light penetration depth into the blood vessels. For an optical wavelength in the 578-596 nm region, with a transducer central frequency that is above 25 MHz, the sensitivity and accuracy of sO 2 inversion is shown to be better than 4%. The effect of the transducer focal position on the accuracy of quantifying blood oxygenation is found to be negligible. In vivo oxygenation measurements of rat skin microvasculature yield results consistent with those from in vitro studies, although factors specific to in vivo measurements, such as the spectral dependence of tissue optical attenuation, dramatically affect the accuracy of sO 2 quantification in vivo

  7. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S

    2015-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  8. Modulation of the tumor vasculature and oxygenation to improve therapy

    DEFF Research Database (Denmark)

    Siemann, Dietmar W; Horsman, Michael R

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient...... important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers...

  9. Chronic kidney disease, 24-h blood pressure and small vessel diseases are independently associated with cognitive impairment in lacunar infarct patients

    International Nuclear Information System (INIS)

    Yamamoto, Yasumasa; Ohara, Tomoyuki; Nagakane, Yoshinari; Tanaka, Eijiro; Morii, Fukiko; Koizumi, Takashi; Akiguchi, Ichiro

    2011-01-01

    Although the relationships between chronic kidney disease (CKD) and cognitive impairment (CI) have been highlighted, the etiology of CI in CKD remains uncertain. Subjects comprised 224 consecutive patients with symptomatic lacunar infarction who underwent magnetic resonance imaging and ambulatory blood pressure monitoring (ABPM). Diurnal blood pressure (BP) patterns were categorized into three groups: dippers, non-dippers and risers. Lacunar infarcts (LIs), including both symptomatic and silent and diffuse white matter lesions (WMLs), were graded into three grades according to their degree. The results of kidney function were evaluated using estimated glomerular filtration rate (eGFR), categorized into three groups: stage 1, >60; stage 2, 30-60; and stage 3, -1 per 1.73 m 2 . There were 44 patients with CI. Confluent WMLs, including WML 2 and WML 3, were found in 36 patients (81.8%), and multiple lacunae including LI 2 and LI 3 were found in 30 patients (68.1%) with CI. Age >75 years (odds ratio (OR), 5.5; P -1 per 1.73 m 2 (OR, 2.9; P -1 per 1.73 m 2 (OR, 23.8; P 75 years (OR, 4.1; P -1 per 1.73 m 2 (OR, 3.7; P -1 per 1.73 m 2 (OR, 8.7; P<0.05) were independently associated with WML grade 3. Extensive small vessel diseases, CKD and non-dipping status were independently associated with CI. CKD appears to mainly contribute to vascular CI, whereas possibilities of overlapping with other mechanisms such as degenerative CI cannot be excluded. Strict night time BP control and renoprotective treatment may be warranted to prevent CI. (author)

  10. [Intracranial collision tumor--A case report (author's transl)].

    Science.gov (United States)

    Fukaya, T; Yoshida, J; Banno, T; Kageyama, N; Ito, M

    1976-06-01

    A 21-year-old man with nasopharyngeal tumor was first admitted to the Nagoya University Hospital on April 15, 1972. He had difficulty in speaking and swallowing, and developed double vision prior to admission. A soft and yellow tumor was found in the nasopharynx and revealed typical features of chordoma. The patient underwent Co60 irradiation after the operation. On January 25, 1973, the patient developed double vision of severe degree. Microscopic examination of the specimen which was obtained at the time of the second operation in February 9, 1973, disclosed a coexistence (collision) of chordoma and hemangioblastoma. The two different tumors were situated in juxtaposition on histological examination. Co60 irradiation was added during his second hospitalization. Three months after the second operation, he developed symptoms of meningitis and was hospitalized for the third time on June 3, 1973, at which time the tumor tissue extended through the right frontal and middle fossa. The third operation was done with frontal craniotomy and tumor was partially removed. The histological diagnosis was hemangioblastoma. Postoperatively the patient went downhill and died on September 19, 1973. The report of a collision tumor of intracranial chordoma and hemangioblastoma is not found in the previous literature. There have been many theories as to the origin of collision tumor. Some investigators have proposed that the existence of hyperplastic blood vessels within the glioblastoma is responsible for the collision tumor of sarcoma and glioblastoma. Since the advent of radiotherapy, several examples of sarcoma have been discovered at postmortem examination in patient irradiated for treatment of cerebral neoplasm, both gliogeneous and nongliogenous, suggesting a possible relationship between the tumor and the radiation therapy. In our case, the chordoma showed neither hyperplastic blood vessels nor malignant pattern on histological examination. It was suspected that post

  11. Quantitative assessment of postoperative blood collection in brain tumor surgery under valproate medication.

    Science.gov (United States)

    Psaras, T; Will, B E; Schoeber, W; Rona, S; Mittelbronn, M; Honegger, J B

    2008-11-01

    The aim of the study was to evaluate whether valproate (VPA) increases the risk of bleeding complications in patients undergoing brain tumor surgery. A retrospective chart review of 85 patients operated on between January and December 2005 was performed. 19 patients received VPA, 22 patients were given other anti-epileptic drugs (AEDs), 44 patients received no AEDs. Data analyzed included intraoperative blood loss, transfusion, important comorbidity factors and concomitant diseases. Preoperative and postoperative laboratory data included hemoglobin, hematocrit, fibrinogen, platelet count, INR, prothrombin time, partial thromboplastin time and RBC count. The tumor volume was evaluated by preoperative MRI and CT scans of the brain. All 85 patients underwent a native CT scan of the brain on the first day after the operation. The volume of the resection cavity and the volume of blood were documented. We could show that the volume of the tumor had a significant effect on the amount of blood in the tumor cavity, whereas VPA medication had no effect. In our dataset, we found that tumor size had a significant effect on postoperative blood volume. In contrast, no serious bleeding complications occurred in the patients receiving VPA. Therefore, the present study does not provide any evidence for the need to discontinue VPA medication prior to and during surgery.

  12. Comparison of the number of gingival blood vessels between type 2 diabetes mellitus and chronic periodontitis patients: An immunohistological study

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    Gautami Subhadra Penmetsa

    2015-01-01

    Full Text Available Background: The relationship between diabetes and periodontitis has been studied for more than 50 years and is generally agreed that the periodontal disease is more prevalent in diabetic patients compared to nondiabetics. Vascular changes like increased thickness of basement membrane in small vessels has been reported in diabetic patients, but the quantity of blood vessels in gingiva of diabetic patients has not been discussed much. The aim of this study was to compare the number of blood vessels in gingiva between chronic periodontitis (CP patients, CP with diabetes (type 2, and normal healthy gingiva. Materials and Methods: The study included 75 patients, divided into three groups of 25 patients each-Group I with healthy periodontium (HP, Group II with CP, and Group III with CP with diabetes mellitus (CPDM.Gingival biopsies were obtained from the subjects undergoing crown lengthening procedure for Group I, and in patients with CP and in CPDM biopsies were collected from teeth undergoing extraction. Sections were prepared for immune histochemical staining with CD34. Results: Difference was observed in the average number of blood vessels when compared between HP, CP, and CPDM groups. Statistical significant difference was observed when the HP and CP groups and HP and CPDM groups were compared. Conclusion: The results of the study indicated that the number of blood vessels in gingival connective tissue is significantly higher in CP and CPDM patients.

  13. The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis

    International Nuclear Information System (INIS)

    Milosevic, Michael F.; Fyles, Anthony W.; Hill, Richard P.

    1999-01-01

    Purpose: To examine the hypothesis that elevated interstitial fluid pressure (IFP) is a cause of reduced blood flow in tumors. Materials and Methods: A physiologic model of tumor blood flow was developed based on a semipermeable, compliant capillary in the center of a spherical tumor. The model incorporates the interaction between the tumor vasculature and the interstitium, as mediated by IFP. It also incorporates the dynamic behavior of the capillary wall in response to changes in transmural pressure, and the effect of viscosity on blood flow. Results: The model predicted elevated tumor IFP in the range of 0 to 56 mmHg. The capillary diameter in the setting of elevated IFP was greatest at the arterial end, and constricted to between 3.2 and 4.4 μm at the venous end. This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of the capillary. The IFP exceeded the intravascular pressure distally in the capillary, but vascular collapse did not occur. Capillary diameter constriction resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow relative to a state of near-zero IFP. Conclusion: The results suggest that steady-state vascular constriction occurs in the setting of elevated IFP, and leads to reduced tumor blood flow. This may in turn contribute to the development of hypoxia, which is an important cause of radiation treatment failure in many tumors

  14. X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study.

    Science.gov (United States)

    Park, Hanwook; Yeom, Eunseop; Lee, Sang Joon

    2016-01-18

    X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.

  15. Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection

    Science.gov (United States)

    Norcic, Gregor; Jelenc, Franc; Cerkovnik, Petra; Stegel, Vida; Novakovic, Srdjan

    2016-01-01

    In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients. In all these patients, the specimen of normal bowel resected with the tumor was also tested for the presence of the same mutations in order to exclude the germ-line mutations. Only patients who tested positive for the specific mutation in the primary tumor were included in further analysis for the presence of tumor-specific mutation in the peripheral blood. No statistically significant differences were found between the detection rates of tumor mutations in the blood and different tumor stages (P=0.491). However, statistically significant differences in the proportions of patients with detected tumor-specific DNA mutations in the peripheral blood were found when comparing the groups of patients with R0 and R2 resections (P=0.038). Tumor-specific DNA mutations in the peripheral blood were more frequently detected in the patients with an incomplete surgical clearance of the tumor due to macroscopic residual disease (R2 resections). Therefore, the study concludes that the follow-up of somatic KRAS- and BRAF-mutated DNA in the peripheral blood of CRC patients may be useful in assessing the surgical clearance of the disease. PMID:27900004

  16. Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

    Science.gov (United States)

    Armstrong, R A; Cairns, N J; Lantos, P L

    1998-12-01

    The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (upper cortical laminae.

  17. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images.

    Science.gov (United States)

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-08-07

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots.

  18. Clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in the resection of sacral tumors

    International Nuclear Information System (INIS)

    Chen Wenhua; Wang Qi; He Zhongming; Zhou Jian; Wang Yimin; Wang Jie

    2012-01-01

    Objective: To investigate the clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in performing the surgical resection of sacral tumors. Methods: Conventional surgical excision of sacral tumors was employed in 24 patients with sacral tumors (control group), while preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta was carried out in 32 patients with sacral tumors (study group). The operation time, blood loss during the surgery and the one-year recurrence rate of both groups were documented, and the results were statistically analyzed. Results: Angiography showed that in the study group the sacral tumors were supplied by several vessels, and these feeding arteries were occluded separately. The tumors were successfully removed in all patients with the help of intraoperative balloon occlusion of the abdominal aorta. During the surgery, the surgical area was clearly exposed and the blood loss wa remarkably reduced. After the surgery, no ectopic vascular embolization, renal ischemia, limb ischemia or other complications occurred. Statistically significant difference in the operation time, blood loss during the surgery and the one-year recurrence rate existed between the two groups (P<0.05). Conclusion: Preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta can effectively shorten the operation time, reduce the blood loss during the surgery and provide a clear surgical field, and thus the surgical safety can be significantly ensured. (authors)

  19. N-glycan signatures identified in tumor interstitial fluid and serum of breast cancer patients - association with tumor biology and clinical outcome.

    Science.gov (United States)

    Terkelsen, Thilde; Haakensen, Vilde D; Saldova, Radka; Gromov, Pavel; Hansen, Merete Kjaer; Stöckmann, Henning; Lingjaerde, Ole Christian; Børresen-Dale, Anne-Lise; Papaleo, Elena; Helland, Åslaug; Rudd, Pauline M; Gromova, Irina

    2018-04-26

    Particular N-glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N-glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N-glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N-glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids (TIF, n=85), paired normal interstitial fluids (NIF, n=54) and serum samples (n=28) followed by independent evaluation, with the ultimate goal of identifying tumor-related N-glycan patterns in blood of breast cancer patients. The segregation of N-linked oligosaccharides revealed 33 compositions, which exhibited differential abundances between TIF and NIF. TIFs were depleted of bisecting N-glycans, which are known to play essential roles in tumor suppression. An increased level of simple high mannose N-glycans in TIF strongly correlated with the presence of tumor infiltrating lymphocytes within tumor. At the same time, a low level of highly complex N-glycans in TIF inversely correlated with the presence of infiltrating lymphocytes within tumor. Survival analysis showed that patients exhibiting increased TIF abundance of GP24 had better outcomes, whereas low levels of GP10, GP23, GP38, and coreF were associated with poor prognosis. Levels of GP1, GP8, GP9, GP14, GP23, GP28, GP37, GP38, and coreF were significantly correlated between TIF and paired serum samples. Cross-validation analysis using an independent serum dataset supported the observed correlation between TIF and serum, for five out of nine N-glycan groups: GP8, GP9, GP14, GP23, and coreF. Collectively, our results imply that profiling of N-glycans from proximal breast tumor fluids is a promising strategy for determining tumor-derived glyco-signature(s) in the blood. N-glycans structures

  20. Numerical modeling of the pulse wave propagation in large blood vessels based on liquid and wall interaction

    International Nuclear Information System (INIS)

    Rup, K; Dróżdż, A

    2014-01-01

    The purpose of this article is to develop a non-linear, one-dimensional model of pulse wave propagation in the arterial cardiovascular system. The model includes partial differential equations resulting from the balance of mass and momentum for the fluid-filled area and the balance equation for the area of the wall and vessels. The considered mathematical model of pulse wave propagation in the thoracic aorta section takes into account the viscous dissipation of fluid energy, realistic values of parameters describing the physicochemical properties of blood and vessel wall. Boundary and initial conditions contain the appropriate information obtained from in vivo measurements. As a result of the numerical solution of the mass and momentum balance equations for the blood and the equilibrium equation for the arterial wall area, time- dependent deformation, respective velocity profiles and blood pressure were determined.

  1. 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.

  2. An Automatic Cognitive Graph-Based Segmentation for Detection of Blood Vessels in Retinal Images

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    Rasha Al Shehhi

    2016-01-01

    Full Text Available This paper presents a hierarchical graph-based segmentation for blood vessel detection in digital retinal images. This segmentation employs some of perceptual Gestalt principles: similarity, closure, continuity, and proximity to merge segments into coherent connected vessel-like patterns. The integration of Gestalt principles is based on object-based features (e.g., color and black top-hat (BTH morphology and context and graph-analysis algorithms (e.g., Dijkstra path. The segmentation framework consists of two main steps: preprocessing and multiscale graph-based segmentation. Preprocessing is to enhance lighting condition, due to low illumination contrast, and to construct necessary features to enhance vessel structure due to sensitivity of vessel patterns to multiscale/multiorientation structure. Graph-based segmentation is to decrease computational processing required for region of interest into most semantic objects. The segmentation was evaluated on three publicly available datasets. Experimental results show that preprocessing stage achieves better results compared to state-of-the-art enhancement methods. The performance of the proposed graph-based segmentation is found to be consistent and comparable to other existing methods, with improved capability of detecting small/thin vessels.

  3. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.

    Science.gov (United States)

    Carlson, David J; Keall, Paul J; Loo, Billy W; Chen, Zhe J; Brown, J Martin

    2011-03-15

    Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Vessel calibre and haemoglobin effects on pulse oximetry

    International Nuclear Information System (INIS)

    McEwen, M P; Reynolds, K J; Bull, G P

    2009-01-01

    Despite its success as a clinical monitoring tool, pulse oximetry may be improved with respect to the need for empirical calibration and the reports of biases in readings associated with peripheral vasoconstriction and haemoglobin concentration. To effect this improvement, this work aims to improve the understanding of the photoplethysmography signal—as used by pulse oximeters—and investigates the effect of vessel calibre and haemoglobin concentration on pulse oximetry. The digital temperature and the transmission of a wide spectrum of light through the fingers of 57 people with known haemoglobin concentrations were measured and simulations of the transmission of that spectrum of light through finger models were performed. Ratios of pulsatile attenuations of light as used in pulse oximetry were dependent upon peripheral temperature and on blood haemoglobin concentration. In addition, both the simulation and in vivo results showed that the pulsatile attenuation of light through fingers was approximately proportional to the absorption coefficients of blood, only when the absorption coefficients were small. These findings were explained in terms of discrete blood vessels acting as barriers to light transmission through tissue. Due to the influence of discrete blood vessels on light transmission, pulse oximeter outputs tend to be dependent upon haemoglobin concentration and on the calibre of pulsing blood vessels—which are affected by vasoconstriction/vasodilation. The effects of discrete blood vessels may account for part of the difference between the Beer–Lambert pulse oximetry model and empirical calibration

  5. Cerebral amyloid angiopathy, blood-brain barrier disruption and amyloid accumulation in SAMP8 mice.

    Science.gov (United States)

    del Valle, Jaume; Duran-Vilaregut, Joaquim; Manich, Gemma; Pallàs, Mercè; Camins, Antoni; Vilaplana, Jordi; Pelegrí, Carme

    2011-01-01

    Cerebrovascular dysfunction and β-amyloid peptide deposition on the walls of cerebral blood vessels might be an early event in the development of Alzheimer's disease. Here we studied the time course of amyloid deposition in blood vessels and blood-brain barrier (BBB) disruption in the CA1 subzone of the hippocampus of SAMP8 mice and the association between these two variables. We also studied the association between the amyloid deposition in blood vessels and the recently described amyloid clusters in the parenchyma, as well as the association of these clusters with vessels in which the BBB is disrupted. SAMP8 mice showed greater amyloid deposition in blood vessels than age-matched ICR-CD1 control mice. Moreover, at 12 months of age the number of vessels with a disrupted BBB had increased in both strains, especially SAMP8 animals. At this age, all the vessels with amyloid deposition showed BBB disruption, but several capillaries with an altered BBB showed no amyloid on their walls. Moreover, amyloid clusters showed no spatial association with vessels with amyloid deposition, nor with vessels in which the BBB had been disrupted. Finally, we can conclude that vascular amyloid deposition seems to induce BBB alterations, but BBB disruption may also be due to other factors. Copyright © 2011 S. Karger AG, Basel.

  6. A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts

    Directory of Open Access Journals (Sweden)

    Liang Y

    2018-03-01

    Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Cynthia Besch-Williford,2 Salman M Hyder1 1Deparment of Biomedical Sciences and Dalton Cardiovascular Research Center, Columbia, MO, USA; 2IDEXX BioResearch, Columbia, MO, USA Background: Between 30 and 40% of human breast cancers express a defective tumor suppressor p53 gene. Wild-type p53 tumor suppressor protein promotes cell-cycle arrest and apoptosis and inhibits vascular endothelial growth factor–dependent angiogenesis, whereas mutant p53 protein (mtp53 lacks these functions, resulting in tumor cell survival and metastasis. Restoration of p53 function is therefore a promising drug-targeted strategy for combating mtp53-expressing breast cancer. Methods: In this study, we sought to determine whether administration of APR-246, a small-molecule drug that restores p53 function, in combination with 2aG4, an antibody that targets phosphatidylserine residues on tumor blood vessels and disrupts tumor vasculature, effectively inhibits advanced hormone-dependent breast cancer tumor growth. Results: APR-246 reduced cell viability in mtp53-expressing BT-474 and T47-D human breast cancer cells in vitro, and significantly induced apoptosis in a dose-dependent manner. However, APR-246 did not reduce cell viability in MCF-7 breast cancer cells, which express wild-type p53. We next examined APR-246’s anti-tumor effects in vivo using BT-474 and T47-D tumor xenografts established in female nude mice. Tumor-bearing mice were treated with APR-246 and/or 2aG4 and tumor volume followed over time. Tumor growth was more effectively suppressed by combination treatment than by either agent alone, and combination therapy completely eradicated some tumors. Immunohistochemistry analysis of tumor tissue sections demonstrated that combination therapy more effectively induced apoptosis and reduced cell proliferation in tumor xenografts than either agent alone. Importantly, combination therapy dramatically reduced the density of blood

  7. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

    Directory of Open Access Journals (Sweden)

    Giulia Ottaviani

    2016-09-01

    Full Text Available Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

  8. Perioperative blood transfusion: does it influence survival and cancer progression in metastatic spine tumor surgery?

    Science.gov (United States)

    Zaw, Aye Sandar; Kantharajanna, Shashidhar B; Maharajan, Karthikeyan; Tan, Barry; Vellayappan, Balamurugan; Kumar, Naresh

    2017-02-01

    Despite advances in surgical techniques for spinal metastases, there is often substantial blood loss, resulting in patients requiring blood transfusion during the perioperative period. Allogeneic blood transfusion (ABT) has been the main replenishment method for lost blood. However, the impact of ABT on cancer-related outcomes has been controversial in various studies. We aimed to evaluate the influence of perioperative ABT on disease progression and survival in patients undergoing metastatic spinal tumor surgery (MSTS). We conducted a retrospective study that included 247 patients who underwent MSTS at a single tertiary institution between 2005 and 2014. The impact of using perioperative ABT (either exposure to or quantities of transfusion) on disease progression and survival was assessed using Cox regression analyses while adjusting for potential confounding variables. Of 247 patients, 133 (54%) received ABT. The overall median number of blood units transfused was 2 (range, 0-10 units). Neither blood transfusion exposure nor quantities of transfusion were associated with overall survival (hazard ratio [HR], 1.15 [p = 0.35] and 1.10 [p = 0.11], respectively) and progression-free survival (HR, 0.87 [p = 0.18] and 0.98 [p = 0.11], respectively). The factors that influenced overall survival were primary tumor type and preoperative Eastern Cooperative Oncology Group performance status, whereas primary tumor type was the only factor that had an impact on progression-free survival. This is the first study providing evidence that disease progression and survival in patients who undergo MSTS are less likely to be influenced by perioperative ABT. The worst oncologic outcomes are more likely to be caused by the clinical circumstances necessitating blood transfusion, but not transfusion itself. However, because ABT can have a propensity toward developing postoperative infections, including surgical site infection, the use of patient blood management

  9. A SURVEY OF RETINA BASED DISEASE IDENTIFICATION USING BLOOD VESSEL SEGMENTATION

    Directory of Open Access Journals (Sweden)

    P Kuppusamy

    2016-11-01

    Full Text Available The colour retinal photography is one of the most essential features to identify the confirmation of various eye diseases. The iris is primary attribute to authenticate the human. This research work presents the survey and comparison of various blood vessel related feature identification, segmentation, extraction and enhancement methods. Additionally, this study is observed the various databases performance for storing the images and testing in minimal time. This paper is also provides the better performance techniques based on the survey.

  10. Variability in blood flow and pO2 in tumors in response to carbogen breathing

    International Nuclear Information System (INIS)

    Lanzen, Jennifer L.; Braun, Rod D.; Ong, Aqui L.; Dewhirst, Mark W.

    1998-01-01

    Purpose: There is speculation that the CO 2 in carbogen (95% O 2 , 5% CO 2 ) can block the vasoconstrictive effects of oxygen. However, it has recently been shown that blood flow in human tumors is variable while patients breathe carbogen. Furthermore, we have shown a consistent decrease in tumor blood flow (TBF) with carbogen breathing in the rat window chamber model. Also, we have previously shown that there is no significant difference in tumor growth time after radiation with air vs. carbogen breathing. This study was designed to investigate the effects of carbogen breathing on blood flow and oxygen levels in a solid tumor. Methods: Measurements were made in Fischer-344 rats with 8-10 mm diameter R3230Ac tumors transplanted either within the quadriceps muscle (n = 16) or subcutis (n = 14). Nontumor-bearing quadriceps muscle was studied in six other rats. After a 20-minute air-breathing baseline, rats breathed carbogen for an additional 40 minutes. Partial pressure of oxygen (pO 2 ) was continuously monitored at one position for 60 minutes using 9-12 μm diameter oxygen microelectrodes. Blood flow was simultaneously monitored in all animals using laser Doppler flowmetry (1-2 probes/tumor). Results: Blood flow changes during carbogen breathing were variable in all tissues and intratumoral heterogeneity was observed. Despite variability in blood flow, pO 2 consistently increased in normal muscle but varied in both tumor sites. During carbogen breathing, the percent pO 2 measurements greater than the baseline average were 99.5% ± 0.4% (mean ± SEM), 42.7% ± 13.8%, and 79.8% ± 11.0% in normal muscle, subcutaneous tumor, and muscle tumor, respectively. To show the magnitude of change, average pO 2 values during air and carbogen breathing were calculated for each site. Normal muscle increased from 14.9 ± 2.3 to 39.0 ± 6.4 mm Hg (paired t-test; p = 0.009). Muscle tumors showed a rise from 14.6 ± 3.2 to 34.5 ± 8.2 mm Hg (p = 0.019). However, pO 2 in subcutaneous

  11. Lymphatic Vessel Density as Prognostic Factor in Breast Carcinoma: Relation to Clinico pathologic Parameters

    International Nuclear Information System (INIS)

    El-Gendi, S.; Abdel-Hadi, M.

    2009-01-01

    Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic micro vessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immuno stained for D2-40, CD31 and VEGF. Median lymphatic and blood micro vessel densities, as well as VEGF expression, were related to each other and to clinico pathologic parameters including lymph node (Ln) status. The efficacy of haematoxylin and eosin (H and E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H and E. VEGF was expressed in 85% of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H and E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis

  12. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Christina Rose Kyrtsos

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ deposition and the presence of neurofibrillary tangles (NFTs within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  13. CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

    Science.gov (United States)

    Hakimé, Antoine; Peddi, Himaja; Hines-Peralta, Andrew U; Wilcox, Carol J; Kruskal, Jonathan; Lin, Shezhang; de Baere, Thierry; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2007-06-01

    To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). Multisection CT perfusion techniques may provide an accurate and more reproducible

  14. Semiautomated segmentation of blood vessels using ellipse-overlap criteria: Method and comparison to manual editing

    International Nuclear Information System (INIS)

    Shiffman, Smadar; Rubin, Geoffrey D.; Schraedley-Desmond, Pamela; Napel, Sandy

    2003-01-01

    Two-dimensional intensity-based methods for the segmentation of blood vessels from computed-tomography-angiography data often result in spurious segments that originate from other objects whose intensity distributions overlap with those of the vessels. When segmented images include spurious segments, additional methods are required to select segments that belong to the target vessels. We describe a method that allows experts to select vessel segments from sequences of segmented images with little effort. Our method uses ellipse-overlap criteria to differentiate between segments that belong to different objects and are separated in plane but are connected in the through-plane direction. To validate our method, we used it to extract vessel regions from volumes that were segmented via analysis of isolabel-contour maps, and showed that the difference between the results of our method and manually-edited results was within inter-expert variability. Although the total editing duration for our method, which included user-interaction and computer processing, exceeded that of manual editing, the extent of user interaction required for our method was about a fifth of that required for manual editing

  15. Magnetic resonance imaging of nasopharyngeal malignant tumors

    International Nuclear Information System (INIS)

    Sakakihara, Junji; Kanoh, Naoyuki; Hayakawa, Katsumi.

    1988-01-01

    Magnetic Resonance Imaging (MRI) was used in the examination of three patients with nasopharyngeal malignant tumor and cranial nerve symptoms. Coronal and saggital sections were very useful for determining skull base invasion. Its high contrast resolution enabled us to visualize several cranial nerves directly. Differentiation between tumor and effusion in the paranasal sinuses was easy especially in T2 weighted images. Bone destruction could also be detected as bone marrow replacement by tumor or as interruption of the black line of compact bone. Local relationships of tumor and large blood vessels were visualized by MRI without invasive contrast enhancing methods. Despite such advantages, in one patient whose symptoms were highly suggestive of cranial invasion, no cranial invasion was detected by CT or MRI. (author)

  16. Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism.

    Science.gov (United States)

    Halder, Sebok K; Kant, Ravi; Milner, Richard

    2018-05-01

    Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O 2 for up to 7 days) affects blood vessel remodeling in the spinal cord. We found that CMH promoted the following: (1) endothelial proliferation and increased vascularity as a result of angiogenesis and arteriogenesis, (2) increased vascular expression of the angiogenic extracellular matrix protein fibronectin as well as concomitant increases in endothelial expression of the fibronectin receptor α5β1 integrin, (3) strongly upregulated endothelial expression of the tight junction proteins claudin-5, ZO-1 and occludin and (4) astrocyte activation. Of note, the vascular remodeling changes induced by CMH were more extensive in white matter. Interestingly, hypoxic-induced vascular remodeling in spinal cord blood vessels was markedly attenuated in mice lacking endothelial α5 integrin expression (α5-EC-KO mice). Taken together, these studies demonstrate the considerable remodeling potential of spinal cord blood vessels and highlight an important angiogenic role for the α5β1 integrin in promoting endothelial proliferation. They also imply that stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

  17. High-resolution ultrasound imaging and noninvasive optoacoustic monitoring of blood variables in peripheral blood vessels

    Science.gov (United States)

    Petrov, Irene Y.; Petrov, Yuriy; Prough, Donald S.; Esenaliev, Rinat O.

    2011-03-01

    Ultrasound imaging is being widely used in clinics to obtain diagnostic information non-invasively and in real time. A high-resolution ultrasound imaging platform, Vevo (VisualSonics, Inc.) provides in vivo, real-time images with exceptional resolution (up to 30 microns) using high-frequency transducers (up to 80 MHz). Recently, we built optoacoustic systems for probing radial artery and peripheral veins that can be used for noninvasive monitoring of total hemoglobin concentration, oxyhemoglobin saturation, and concentration of important endogenous and exogenous chromophores (such as ICG). In this work we used the high-resolution ultrasound imaging system Vevo 770 for visualization of the radial artery and peripheral veins and acquired corresponding optoacoustic signals from them using the optoacoustic systems. Analysis of the optoacoustic data with a specially developed algorithm allowed for measurement of blood oxygenation in the blood vessels as well as for continuous, real-time monitoring of arterial and venous blood oxygenation. Our results indicate that: 1) the optoacoustic technique (unlike pure optical approaches and other noninvasive techniques) is capable of accurate peripheral venous oxygenation measurement; and 2) peripheral venous oxygenation is dependent on skin temperature and local hemodynamics. Moreover, we performed for the first time (to the best of our knowledge) a comparative study of optoacoustic arterial oximetry and a standard pulse oximeter in humans and demonstrated superior performance of the optoacoustic arterial oximeter, in particular at low blood flow.

  18. Oxygen distribution in tumors: A qualitative analysis and modeling study providing a novel Monte Carlo approach

    International Nuclear Information System (INIS)

    Lagerlöf, Jakob H.; Kindblom, Jon; Bernhardt, Peter

    2014-01-01

    Purpose: To construct a Monte Carlo (MC)-based simulation model for analyzing the dependence of tumor oxygen distribution on different variables related to tumor vasculature [blood velocity, vessel-to-vessel proximity (vessel proximity), and inflowing oxygen partial pressure (pO 2 )]. Methods: A voxel-based tissue model containing parallel capillaries with square cross-sections (sides of 10 μm) was constructed. Green's function was used for diffusion calculations and Michaelis-Menten's kinetics to manage oxygen consumption. The model was tuned to approximately reproduce the oxygenational status of a renal carcinoma; the depth oxygenation curves (DOC) were fitted with an analytical expression to facilitate rapid MC simulations of tumor oxygen distribution. DOCs were simulated with three variables at three settings each (blood velocity, vessel proximity, and inflowing pO 2 ), which resulted in 27 combinations of conditions. To create a model that simulated variable oxygen distributions, the oxygen tension at a specific point was randomly sampled with trilinear interpolation in the dataset from the first simulation. Six correlations between blood velocity, vessel proximity, and inflowing pO 2 were hypothesized. Variable models with correlated parameters were compared to each other and to a nonvariable, DOC-based model to evaluate the differences in simulated oxygen distributions and tumor radiosensitivities for different tumor sizes. Results: For tumors with radii ranging from 5 to 30 mm, the nonvariable DOC model tended to generate normal or log-normal oxygen distributions, with a cut-off at zero. The pO 2 distributions simulated with the six-variable DOC models were quite different from the distributions generated with the nonvariable DOC model; in the former case the variable models simulated oxygen distributions that were more similar to in vivo results found in the literature. For larger tumors, the oxygen distributions became truncated in the lower

  19. Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture

    NARCIS (Netherlands)

    Kolkman, R.G.M.; Hondebrink, Erwin; Steenbergen, Wiendelt; van Leeuwen, Ton; de Mul, F.F.M.

    2004-01-01

    A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two

  20. Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

    DEFF Research Database (Denmark)

    Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie

    2017-01-01

    with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. RESULTS: Using structured qualitative analysis of tumor blood flow...... using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.......BACKGROUND: Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being...

  1. Multispectral Imaging Analysis of Circulating Tumor Cells in Negatively Enriched Peripheral Blood Samples.

    Science.gov (United States)

    Miller, Brandon; Lustberg, Maryam; Summers, Thomas A; Chalmers, Jeffrey J

    2017-01-01

    A variety of biomarkers are present on cells in peripheral blood of patients with a variety of disorders, including solid tumor malignancies. While rare, characterization of these cells for specific protein levels with the advanced technology proposed, will lead to future validation studies of blood samples as "liquid biopsies" for the evaluation of disease status and therapeutic response. While circulating tumor cells (CTCs) have been isolated in the blood samples of patients with solid tumors, the exact role of CTCs as clinically useful predictive markers is still debated. Current commercial technology has significant bias in that a positive selection technology is used that preassumes specific cell surface markers (such as EpCAM) are present on CTCs. However, CTCs with low EpCAM expression have been experimentally demonstrated to be more likely to be missed by this method. In contrast, this application uses a previously developed, technology that performs a purely negative enrichment methodology on peripheral blood, yielding highly enriched blood samples that contain CTCs as well as other, undefined cell types. The focus of this contribution is the use of multispectral imaging of epifluorescent, microscopic images of these enriched cells in order to help develop clinically relevant liquid biopsies from peripheral blood samples.

  2. Modelling Nanoparticle Diffusion into Cancer Tumors

    Science.gov (United States)

    Podduturi, Vishwa Priya; Derosa, Pedro

    2011-03-01

    Cancer is one of the major, potentially deadly diseases and has been for years. Non-specific delivery of the drug can damage healthy tissue seriously affecting in many cases the patient's living condition. Nanoparticles are being used for a targeted drug delivery thereby reducing the dose. In addition, metallic nanoparticles are being used in thermal treatment of cancer cells where nanoparticles help concentrate heat in the tumor and away from living tissue. We proposed a model that combines random walk with diffusion principles. The particle drift velocity is taken from the Hagen-Poiseuille equation and the velocity profile of the particle at the pores in the capillary wall is obtained using the Coventorware software. Pressure gradient and concentration gradient through the capillary wall are considered. Simulations are performed in Matlab using the Monte Carlo technique. Number of particles leaving the blood vessel through a pore is obtained as a function of blood pressure, the osmotic pressure, temperature, particle concentration, blood vessel radius, and pore size, and the relative effect of each of the parameters is discussed.

  3. Diagnostic of flow rate of the tumors of the boobs at increment of the blood pressure

    International Nuclear Information System (INIS)

    Pohlodek, K.; Sohn, Ch.

    1998-01-01

    54 patients with ultrasonography evident tumors of the mammary glands were examined by angiography on flow rate of the blood in the tumor (14 patients with benign tumor and 40 patients with carcinoma at increment of the blood pressure. At evaluating of the findings 4 characteristic curves were obtained: first type was typical for malignant tumors; second type was characteristic for benign findings and third and fourth types were non-specific. (authors)

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

    Science.gov (United States)

    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. CT perfusion of the liver during selective hepatic arteriography. Pure arterial blood perfusion of liver tumor and parenchyma

    International Nuclear Information System (INIS)

    Komemushi, Atsushi; Tanigawa, Noboru; Kojima, Hiroyuki; Kariya, Shuji; Sawada, Satoshi

    2003-01-01

    The purpose of this study was to quantify pure arterial blood perfusion of liver tumor and parenchyma by using CT perfusion during selective hepatic arteriography. A total of 44 patients underwent liver CT perfusion study by injection of contrast medium via the hepatic artery. CT-perfusion parameters including arterial blood flow, arterial blood volume, and arterial mean transit time in the liver parenchyma and liver tumor were calculated using the deconvolution method. The CT-perfusion parameters and vascularity of the tumor were compared. A complete analysis could be performed in 36 of the 44 patients. For liver tumor and liver parenchyma, respectively, arterial blood flow was 184.6±132.7 and 41.0±27.0 ml/min/100 g, arterial blood volume was 19.4±14.6 and 4.8±4.2 ml/100 g, and arterial mean transit time was 8.9±4.2 and 10.2±5.3 sec. Arterial blood flow and arterial blood volume correlated significantly with the vascularity of the tumor; however no correlation was detected between arterial mean transit time and the vascularity of the tumor. This technique could be used to quantify pure hepatic arterial blood perfusion. (author)

  6. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses

    Science.gov (United States)

    Sundaresan, Tilak K.; Sequist, Lecia V.; Heymach, John V.; Riely, Gregory J.; Jänne, Pasi A.; Koch, Walter H.; Sullivan, James P.; Fox, Douglas B.; Maher, Robert; Muzikansky, Alona; Webb, Andrew; Tran, Hai T.; Giri, Uma; Fleisher, Martin; Yu, Helena A.; Wei, Wen; Johnson, Bruce E.; Barber, Thomas A.; Walsh, John R.; Engelman, Jeffrey A.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Toner, Mehmet

    2015-01-01

    Purpose The T790M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKIs). As third generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management. Experimental Design As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Results T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47–50% of patients using each of the genotyping assays, with concordance among them ranging from 57–74%. While CTC- and ctDNA-based genotyping were each unsuccessful in 20–30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate. Conclusion Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient’s cancer, which should be validated in predicting response to T790M-targeted inhibitors. PMID:26446944

  7. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

    Directory of Open Access Journals (Sweden)

    Łukasz Pietrzyk

    2016-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

  8. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates.

    Science.gov (United States)

    Pietrzyk, Łukasz

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

  9. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.

    Science.gov (United States)

    Toh, Huishi; Cao, Mingju; Daniels, Eugene; Bateman, Andrew

    2013-01-01

    Progranulin is a secreted glycoprotein that regulates cell proliferation, migration and survival. It has roles in development, tumorigenesis, wound healing, neurodegeneration and inflammation. Endothelia in tumors, wounds and placenta express elevated levels of progranulin. In culture, progranulin activates endothelial proliferation and migration. This suggested that progranulin might regulate angiogenesis. It was, however, unclear how elevated endothelial progranulin levels influence vascular growth in vivo. To address this issue, we generated mice with progranulin expression targeted specifically to developing endothelial cells using a Tie2-promoter/enhancer construct. Three Tie2-Grn mouse lines were generated with varying Tie2-Grn copy number, and were called GrnLo, GrnMid, and GrnHi. All three lines showed increased mortality that correlates with Tie2-Grn copy number, with greatest mortality and lowest germline transmission in the GrnHi line. Death of the transgenic animals occurred around birth, and continued for three days after birth. Those that survived beyond day 3 survived into adulthood. Transgenic neonates that died showed vascular abnormalities of varying severity. Some exhibited bleeding into body cavities such as the pericardial space. Smaller localized hemorrhages were seen in many organs. Blood vessels were often dilated and thin-walled. To establish the development of these abnormalities, we examined mice at early (E10.5-14.5) and later (E15.5-17.5) developmental phases. Early events during vasculogenesis appear unaffected by Tie2-Grn as apparently normal primary vasculature had been established at E10.5. The earliest onset of vascular abnormality was at E15.5, with focal cerebral hemorrhage and enlarged vessels in various organs. Aberrant Tie2-Grn positive vessels showed thinning of the basement membrane and reduced investiture with mural cells. We conclude that progranulin promotes exaggerated vessel growth in vivo, with subsequent effects in

  10. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.

    Directory of Open Access Journals (Sweden)

    Huishi Toh

    Full Text Available Progranulin is a secreted glycoprotein that regulates cell proliferation, migration and survival. It has roles in development, tumorigenesis, wound healing, neurodegeneration and inflammation. Endothelia in tumors, wounds and placenta express elevated levels of progranulin. In culture, progranulin activates endothelial proliferation and migration. This suggested that progranulin might regulate angiogenesis. It was, however, unclear how elevated endothelial progranulin levels influence vascular growth in vivo. To address this issue, we generated mice with progranulin expression targeted specifically to developing endothelial cells using a Tie2-promoter/enhancer construct. Three Tie2-Grn mouse lines were generated with varying Tie2-Grn copy number, and were called GrnLo, GrnMid, and GrnHi. All three lines showed increased mortality that correlates with Tie2-Grn copy number, with greatest mortality and lowest germline transmission in the GrnHi line. Death of the transgenic animals occurred around birth, and continued for three days after birth. Those that survived beyond day 3 survived into adulthood. Transgenic neonates that died showed vascular abnormalities of varying severity. Some exhibited bleeding into body cavities such as the pericardial space. Smaller localized hemorrhages were seen in many organs. Blood vessels were often dilated and thin-walled. To establish the development of these abnormalities, we examined mice at early (E10.5-14.5 and later (E15.5-17.5 developmental phases. Early events during vasculogenesis appear unaffected by Tie2-Grn as apparently normal primary vasculature had been established at E10.5. The earliest onset of vascular abnormality was at E15.5, with focal cerebral hemorrhage and enlarged vessels in various organs. Aberrant Tie2-Grn positive vessels showed thinning of the basement membrane and reduced investiture with mural cells. We conclude that progranulin promotes exaggerated vessel growth in vivo, with

  11. 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

  12. A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering.

    Science.gov (United States)

    Badhe, Ravindra V; Bijukumar, Divya; Chejara, Dharmesh R; Mabrouk, Mostafa; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

    2017-02-10

    A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A DTI Study to Probe Tumor Microstructure And Its Connection With Hypoxia

    OpenAIRE

    Majumdar, Shreyan; Kotecha, Mrignayani; Triplett, William; Epel, Boris; Halpern, Howard

    2014-01-01

    Solid tumors have chaotic organization of blood vessels, disruptive nerve paths and muscle fibers that result in a hostile and heterogeneous microenvironment. These tumor regions are often hypoxic and resistant to radiation therapy. The knowledge of partial pressure of oxygen concentration (pO2), in conjunction with the information about tissue organization, can predict tissue health and may eventually be used in combination with intensity-modulated radiation therapy (IMRT) for targeted destr...

  14. Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

    2017-12-01

    The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

  15. Early Prediction of Outcome in Advanced Head-and-Neck Cancer Based on Tumor Blood Volume Alterations During Therapy: A Prospective Study

    International Nuclear Information System (INIS)

    Cao Yue; Popovtzer, Aron; Li, Diana; Chepeha, Douglas B.; Moyer, Jeffrey S.; Prince, Mark E.; Worden, Francis; Teknos, Theodoros; Bradford, Carol; Mukherji, Suresh K.; Eisbruch, Avraham

    2008-01-01

    Purpose: To assess whether alterations in tumor blood volume (BV) and blood flow (BF) during the early course of chemo-radiotherapy (chemo-RT) for head-and-neck cancer (HNC) predict treatment outcome. Methods and Materials: Fourteen patients receiving concomitant chemo-RT for nonresectable, locally advanced HNC underwent dynamic contrast-enhanced (DCE) MRI scans before therapy and 2 weeks after initiation of chemo-RT. The BV and BF were quantified from DCE MRI. Preradiotherapy BV and BF, as well as their changes during RT, were evaluated separately in the primary gross tumor volume (GTV) and nodal GTV for association with outcomes. Results: At a median follow-up of 10 months (range, 5-27 months), 9 patients had local-regional controlled disease. One patient had regional failure, 3 had local failures, and 1 had local-regional failure. Reduction in tumor volume after 2 weeks of chemo-RT did not predict for local control. In contrast, the BV in the primary GTV after 2 weeks of chemo-RT was increased significantly in the local control patients compared with the local failure patients (p < 0.03). Conclusions: Our data suggest that an increase in available primary tumor blood for oxygen extraction during the early course of RT is associated with local control, thus yielding a predictor with potential to modify treatment. These findings require validation in larger studies

  16. Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

    Science.gov (United States)

    He, Wei; Kularatne, Sumith A; Kalli, Kimberly R; Prendergast, Franklyn G; Amato, Robert J; Klee, George G; Hartmann, Lynn C; Low, Philip S

    2008-10-15

    Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.

  17. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.

    Science.gov (United States)

    Best, Myron G; Sol, Nik; Kooi, Irsan; Tannous, Jihane; Westerman, Bart A; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Koster, Jan; Ylstra, Bauke; Ameziane, Najim; Dorsman, Josephine; Smit, Egbert F; Verheul, Henk M; Noske, David P; Reijneveld, Jaap C; Nilsson, R Jonas A; Tannous, Bakhos A; Wesseling, Pieter; Wurdinger, Thomas

    2015-11-09

    Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies". Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  19. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S.

    2015-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain. PMID:26448331

  20. Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

    Energy Technology Data Exchange (ETDEWEB)

    Umetani, Keiji [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)], E-mail: umetani@spring8.or.jp; Uesugi, Kentaro [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki [Kawasaki Medical School, Matsushima, Kurashiki-shi, Okayama 701-0192 (Japan)

    2009-10-01

    Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 {mu}m has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results

  1. Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

    International Nuclear Information System (INIS)

    Umetani, Keiji; Uesugi, Kentaro; Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki

    2009-01-01

    Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 μm has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results

  2. Perfusion MRI as a neurosurgical tool for improved targeting in stereotactic tumor biopsies.

    Science.gov (United States)

    Lefranc, M; Monet, P; Desenclos, C; Peltier, J; Fichten, A; Toussaint, P; Sevestre, H; Deramond, H; Le Gars, D

    2012-01-01

    Stereotactic biopsies are subject to sampling errors (essentially due to target selection). The presence of contrast enhancement is not a reliable marker of malignancy. The goal of the present study was to determine whether perfusion-weighted imaging can improve target selection in stereotactic biopsies. We studied 21 consecutive stereotactic biopsies between June 2009 and March 2010. Perfusion-weighted magnetic resonance imaging (MRI) was integrated into our neuronavigator. Perfusion-weighted imaging was used as an adjunct to conventional MRI data for target determination. Conventional MRI alone was used to determine the trajectory. We found a linear correlation between regional cerebral blood volume (rCBV) and vessel density (number of vessels per mm(2); R = 0.64; p < 0.001). Perfusion-weighted imaging facilitated target determination in 11 cases (52.4%), all of which were histopathologically diagnosed as glial tumors. For glial tumors, which presented with contrast enhancement, perfusion-weighted imaging identified a more precisely delimited target in 9 cases, a different target in 1 case, and exactly the same target in 1 other case. In all cases, perfusion-selected sampling provided information on cellular features and tumor grading. rCBV was significantly associated with grading (p < 0.01), endothelial proliferation (p < 0.01), and vessel density (p < 0.01). For lesions with rCBV values ≤1, perfusion-weighted MRI did not help to determine the target but was useful for surgical management. For stereotactic biopsies, targeting based on perfusion-weighted imaging is a feasible method for reducing the sampling error and improving target selection in the histopathological diagnosis of tumors with high rCBVs. Copyright © 2012 S. Karger AG, Basel.

  3. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    Saban, Marcia R; Wu, Xue-Ru; Saban, Ricardo; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie

    2007-01-01

    The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF

  4. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.

    Science.gov (United States)

    Vasselli, James R; Shih, Joanna H; Iyengar, Shuba R; Maranchie, Jodi; Riss, Joseph; Worrell, Robert; Torres-Cabala, Carlos; Tabios, Ray; Mariotti, Andra; Stearman, Robert; Merino, Maria; Walther, McClellan M; Simon, Richard; Klausner, Richard D; Linehan, W Marston

    2003-06-10

    To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.

  5. Automatic blood vessel based-liver segmentation using the portal phase abdominal CT

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Shimada, Mitsuo; Iinuma, Gen

    2018-02-01

    Liver segmentation is the basis for computer-based planning of hepatic surgical interventions. In diagnosis and analysis of hepatic diseases and surgery planning, automatic segmentation of liver has high importance. Blood vessel (BV) has showed high performance at liver segmentation. In our previous work, we developed a semi-automatic method that segments the liver through the portal phase abdominal CT images in two stages. First stage was interactive segmentation of abdominal blood vessels (ABVs) and subsequent classification into hepatic (HBVs) and non-hepatic (non-HBVs). This stage had 5 interactions that include selective threshold for bone segmentation, selecting two seed points for kidneys segmentation, selection of inferior vena cava (IVC) entrance for starting ABVs segmentation, identification of the portal vein (PV) entrance to the liver and the IVC-exit for classifying HBVs from other ABVs (non-HBVs). Second stage is automatic segmentation of the liver based on segmented ABVs as described in [4]. For full automation of our method we developed a method [5] that segments ABVs automatically tackling the first three interactions. In this paper, we propose full automation of classifying ABVs into HBVs and non- HBVs and consequently full automation of liver segmentation that we proposed in [4]. Results illustrate that the method is effective at segmentation of the liver through the portal abdominal CT images.

  6. Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

    Science.gov (United States)

    Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie; Rasmussen, Torben Riis; Thygesen, Jesper; Hager, Henrik; Andersen, Niels Trolle; Rasmussen, Finn

    2017-05-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being studied, allowing for quick identification of the areas with the highest or lowest blood flow and blood volume. To examine whether DCE-CT could be used to distinguish between malignant and benign lung tumors in patients with suspected lung cancer. Fifty-nine patients with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. Using structured qualitative analysis of tumor blood flow patterns, it was possible to distinguish between malignant and benign lung tumors (Fisher-Freeman-Halton exact test, P  = 0.022). The inter-reader agreement of this method of analysis was slight to moderate (kappa = 0.30; 95% confidence interval [CI] = 0.13-0.46). DCE-CT in suspected lung cancer using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.

  7. Antibody deposition in tumor in relation to blood clearance using a nephrectomized mouse model

    International Nuclear Information System (INIS)

    Nelp, W.B.; Eary, J.F.; Beaumier, P.; Krohn, K.A.; Hellstrom, K.E.; Hellstrom, I.

    1985-01-01

    The purpose of this experiment was to study tumor deposition of monoclonal anti-p97 melanoma antibody (Fab) as a function of its blood concentration over time. I-131-anti-p97 Fab and I-125 non-specific Fab were injected I.V. into 28 control athymic (nude) mice (CM) bearing human xenografted malignant melanoma containing p-97 antigen. Fab (M.W. 50,000) is rapidly excreted by kidney and >90% excretion occurred in 24 hr. To create maximum sustained high blood concentrations of Fab 10 similar mice were likewise injected 1 hr after acute nephrectomy (NM). In this case 24 hr. body excretion was <1%. Blood clearance in CM was biexponential with initial T-1/2 0.4 hr. (80%) a second T-1/2 of 4.4 hr. In NM clearance was monoexponential with a T-1/2 of 29.6 hr. Blood concentrations at 4 hrs. were 2 vs. 19% dose/gm (CM vs NM) and 0.15 vs 12 at 24 hrs. This tumor binding resembled a 2nd order phenomenon. Such information may be useful in predicting the effect of dosage manipulations (multiple bolus or sustained infusions) designed to increase Fab blood levels and enhance tumor labeling with Fab. The NM model should be useful to study the kinetics of antibody tumor deposition with various antibodies

  8. Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro

    International Nuclear Information System (INIS)

    Vigl, Benjamin; Zgraggen, Claudia; Rehman, Nadia; Banziger-Tobler, Nadia E.; Detmar, Michael; Halin, Cornelia

    2009-01-01

    Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity

  9. Glucose metabolism in diabetic blood vessels

    International Nuclear Information System (INIS)

    Brown, B.J.; Crass, M.F. III

    1986-01-01

    Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

  10. High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

    2016-04-01

    Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

  11. Rapid sealing and cutting of porcine blood vessels, ex vivo, using a high-power, 1470-nm diode laser.

    Science.gov (United States)

    Giglio, Nicholas C; Hutchens, Thomas C; Perkins, William C; Latimer, Cassandra; Ward, Arlen; Nau, William H; Fried, Nathaniel M

    2014-03-01

    Suture ligation with subsequent cutting of blood vessels to maintain hemostasis during surgery is time consuming and skill intensive. Energy-based electrosurgical and ultrasonic devices are often used to replace sutures and mechanical clips to provide rapid hemostasis and decrease surgery time. Some of these devices may create undesirably large collateral zones of thermal damage and tissue necrosis, or require separate mechanical blades for cutting. Infrared lasers are currently being explored as alternative energy sources for vessel sealing applications. In a previous study, a 1470-nm laser was used to seal vessels 1 to 6 mm in diameter in 5 s, yielding burst pressures of ∼500  mmHg. The purpose of this study was to provide vessel sealing times comparable with current energy-based devices, incorporate transection of sealed vessels, and demonstrate high vessel burst pressures to provide a safety margin for future clinical use. A 110-W, 1470-nm laser beam was transmitted through a fiber and beam shaping optics, producing a 90-W linear beam 3.0 by 9.5 mm for sealing (400  W/cm2), and 1.1 by 9.6 mm for cutting (1080  W/cm2). A two-step process sealed and then transected ex vivo porcine renal vessels (1.5 to 8.5 mm diameter) in a bench top setup. Seal and cut times were 1.0 s each. A burst pressure system measured seal strength, and histologic measurements of lateral thermal spread were also recorded. All blood vessels tested (n=55 seal samples) were sealed and cut, with total irradiation times of 2.0 s and mean burst pressures of 1305±783  mmHg. Additional unburst vessels were processed for histological analysis, showing a lateral thermal spread of 0.94±0.48  mm (n=14 seal samples). This study demonstrated that an optical-based system is capable of precisely sealing and cutting a wide range of porcine renal vessel sizes and, with further development, may provide an alternative to radiofrequency- and ultrasonic-based vessel sealing devices.

  12. Comparison between PVHIS on the MRI and the permeability of brain blood vessels in elderly patients

    International Nuclear Information System (INIS)

    Yamaguchi, Katsuhiko; Tanaka, Yuriko; Kubo, Hideki; Takagi, Yasushi; Tachikawa, Shinzo; Katsunuma, Hideyo.

    1989-01-01

    The degree of PVHIS (periventricular high intensity signal) on the MRI was composed with the permeability of brain blood vessels using the cerebrospinal fluid (CSF)/serum ratio for albumin, and the CSF/serum ratio for IgG in elderly patients. The 47 elderly patients (mean age=79.9) were divided into three groups: (1) Mild group (20 cases, M:6, F:14, mean age=75.8), (2) Moderate group (18 cases, M:7, F:11, mean age=82.6), (3) Severe group (9 cases, M:2, F:7, mean age=82.9), in accordance with the degree of PVHIS on the MRI. The MRI was operated at a field strength of 0.22 tesla. The pulse sequence (used on all patients) had a repetition times (TR) of 2,000 msec and a time to echo (TE) of 40 msec. The levels of albumin and IgG in the serum and CSF were measured. The CSF/serum ratio for albumin was used of analyze the permeability of the brain blood vessels in each group. There was no significant difference in the level of the serum albumin, the CSF albumin, the serum IgG, the CSF IgG and the CSF/serum ratio for IgG among the three groups. The same was found to be true for the IgG index which indicates the synthesis of immunoglobulin in the central nervous system. However, there was a statistically significant difference (p<0.05) in the CSF/serum ratio for albumin between groups (1) and (3). The increased CSF/serum ratio for albumin in the severe group indicated there were confluent lesions involving the entire extent of the periventriular white matter on the MRI. This suggested an increased permeability of brain blood vessels which revealed the dysfunction of the blood brain barrier due to affected cerebral endothelial cells in capillaries. (author)

  13. The Physics of Coronary Blood Flow

    CERN Document Server

    Zamir, M

    2005-01-01

    Coronary blood flow is blood flow to the heart for its own metabolic needs. In the most common form of heart disease there is a disruption in this flow because of obstructive disease in the vessels that carry the flow. The subject of coronary blood flow is therefore associated mostly with the pathophysiology of this disease, rarely with dynamics or physics. Yet, the system responsible for coronary blood flow, namely the "coronary circulation," is a highly sophisticated dynamical system in which the dynamics and physics of the flow are as important as the integrity of the conducting vessels. While an obstruction in the conducting vessels is a fairly obvious and clearly visible cause of disruption in coronary blood flow, any discord in the complex dynamics of the system can cause an equally grave, though less conspicuous, disruption in the flow. This book is devoted specifically to the dynamics and physics of coronary blood flow. While relevance to the clinical and pathophysiological issues is clearly maintaine...

  14. Hemodynamics in stenotic vessels of small diameter under steady state conditions: Effect of viscoelasticity and migration of red blood cells.

    Science.gov (United States)

    Dimakopoulos, Yannis; Kelesidis, George; Tsouka, Sophia; Georgiou, Georgios C; Tsamopoulos, John

    2015-01-01

    In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood. In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model's accuracy is evaluated. A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed. The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases. Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.

  15. In vivo MR monitoring of pH and blood flow during hyperglycemia in a brain tumor model

    International Nuclear Information System (INIS)

    Mitchell, S.L.; Ross, B.D.; Merkle, H.; Garwood, M.

    1988-01-01

    Previous investigations have shown that tumors exhibit an acidotic pH shift following hyperglycemia, which may aid in hyperthermic treatments. P-31 and H-1 magnetic resonance spectroscopy were used to monitor hyperglycemia-induced pH and blood flow changes, respectively, in subcutaneous and intracerebral C6 gliomas in rats. Subcutaneous tumors had a 78.2% +- 8.03% (standard error of the mean) decrease in blood flow and a concomitant pH decrease of 0.76 units +- 0.08. However, intracerebral tumors displayed an average blood flow reduction of only 20.9% +- 6.1%, with no significant pH change following hyperglycemia. These results indicate that the tissue harboring the tumor may have an important role in the overall tumor response to hyperglycemia

  16. The effects of Anadara granosa shell-Stichopus hermanni on bFGF expressions and blood vessel counts in the bone defect healing process of Wistar rats

    Directory of Open Access Journals (Sweden)

    Rima Parwati Sari

    2017-12-01

    Full Text Available Background: Bone damage can be caused by various factors with treatment usually involving graft materials being applied to the defective area. Moreover, in the bone defect healing process, blood vessels are also considered to be an important energy source for cell proliferation. One of the angiogenic factors playing an important role in blood vessel formation is basic fibroblast growth factor (bFGF. Furthermore, synthesized hydroxyapatite derived from Anadara granosa (AG shells constitutes one of the potential materials for use in bone graft. The gold sea cucumber genus Stichopus hermanni (SH possesses the ability to stimulate endothelial progenitor cells inducing bFGF. Purpose: This study aims to investigate the effects of AG shells and SH on bFGF expressions and blood vessel counts within the bone healing process. Methods: Twenty four male Wistar rats were divided into three groups, namely: a control group (C, a treatment group was administered with blood cockle shell (AG, and a treatment group with blood cockle shell and golden sea cucumber (AG+SH. Defects were made on their femurs measuring half the diameter of a circular, no. 018. bur These rats were subsequently sacrificed on day 7 after surgery. The expressions of bFGF were measured by means of IHC technique, while the number of blood vessels was quantified using HE technique. The resulting data was subjected to statistical analysis using an Anova test followed by an LSD test (p < 0.05. Results: The one-way Anova test results combined with those of an LSD test showed there to be significant differences in bFGF expressions and blood vessel counts between the control group (K and the treatment group (AG as well as between the treatment group (AG and the treatment group (AG+SH. Conclusions: A combination of Anadara granosa shell and Stichopus hermanni can increase the expression of bFGF and the number of blood vessels on day 7 during the bone healing process in Wistar rats.

  17. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

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    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  18. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy.

    Science.gov (United States)

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

    2014-08-20

    The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  19. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  20. Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

    Science.gov (United States)

    Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

    2017-06-01

    We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

  1. The correlation between the rise of the tumor temperature during the hyperthermia treatment and the tumor blood flow measured by dynamic CT and 15O gas-positron emission tomography

    International Nuclear Information System (INIS)

    Hattori, Hideyuki

    1993-01-01

    This study was designed to determine the correlation between the rise of tumor temperature during hyperthermia treatment and the blood flow of the tumors measured by dynamic CT (DCT) and 15 O gas-positron emission tomography. In this report, we observed 20 patients with malignant tumors which underwent hyperthermia treatment. In each case, the temperature of the tumor was monitored with a photofiber sensor. DCT's and 15 O gas-positron emission tomographies were applied before the hyperthermia treatment. During the DCT, the tumor blood flow of each tumor was estimated by analyzing the time-dependent activity curve after a bolus injection. During the 15 O gas-positron emission tomography, the tumor blood flow was estimated by the C 15 O 2 -steady-state method. The value of the tumor blood flow estimated by DCT were proportional to those calculated by the 15 O gas-positron emission tomography. These values were inversely proportional to the rise of the temperature of the tumors during hyperthermia treatment. Our results imply that DCT as well as the 15 O gas-positron emission tomography can be used for the prediction of the tumor temperature rise during the hyperthermia treatment. (author)

  2. Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

    Science.gov (United States)

    Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

    2015-12-01

    Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

  3. White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

    Science.gov (United States)

    Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

    2010-01-01

    The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

  4. The Pleiotropic Role of L1CAM in Tumor Vasculature

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    Francesca Angiolini

    2017-01-01

    Full Text Available Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM, a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

  5. Intraoperative evaluation of renal blood flow during laparoscopic partial nephrectomy with a novel Doppler system.

    Science.gov (United States)

    Mues, Adam C; Okhunov, Zhamshid; Badani, Ketan; Gupta, Mantu; Landman, Jaime

    2010-12-01

    Hemostasis remains a major challenge associated with laparoscopic renal surgery. We evaluated a cost-effective novel Doppler probe (DP) for assessment of vascular control during laparoscopic partial nephrectomy (LPN). We prospectively collected data during LPN procedures. We documented tumor location and size as well as subjective quality of the hilar dissection. The DP was compared with our standard intraoperative ultrasound system (SUS) for the ability to detect blood flow during hilar dissection and to determine parenchymal ischemia around the tumor after clamping of the renal vessels. Twenty patients underwent LPN by a single surgeon. The mean tumor size was 3.0 cm (range: 1.2-6.3 cm). The times to assess the kidney using the SUS and DP were 68.6 seconds (range: 20-155) and 44.5 seconds (range: 15-180), respectively. Evaluation prior to renal hilar clamping demonstrated the presence of blood flow in all 20 patients (100%) using the SUS and in 17 of 20 (85%) using the DP. Similarly, cessation of blood flow with clamping was documented in 100% of cases with SUS and 85% with DP. Persistent flow was detected by both SUS and DP in two patients requiring further dissection and reclamping. Then, both systems detected the absence of flow before tumor resection. With blood flow interruption confirmation, no patient had significant bleeding at the time of renal parenchymal transection. Intraoperative Doppler ultrasound technologies minimize the risk of significant bleeding during LPN. The DP is a small, simple, effective probe that can be used to assess blood flow interruption to the kidney during laparoscopic renal surgery.

  6. Endocrine Tumors Causing Arterial Hypertension: Pathophysiological Mechanisms and Clinical Implications.

    Science.gov (United States)

    Buonacera, Agata; Stancanelli, Benedetta; Malatino, Lorenzo

    2017-09-01

    Some tumors are a relatively rare and amendable cause of hypertension, often associated with a higher cardiovascular morbidity and mortality, as compared with that of both general population and patients with essential hypertension. This worse prognosis is not entirely related to blood pressure increase, because the release of substances from the tumor can directly influence blood pressure behavior. Diagnostic approach is challenging and needs a deep knowledge of the different neuro-hormonal and genetic mechanisms determining blood pressure increase. Surgical tumor removal can, but not always, cause blood pressure normalization, depending on how early was tumor detection, since a long-standing history of hypertension is often associated with a much weaker effect on blood pressure. Moreover, target organ damage can be affected by the substances themselves released by the tumors as well as by tumor removal. In this review we consider the phenotype and genetic features of patients with tumor-induced hypertension and focus on their diagnostic work-up.

  7. Spatial relationship between tumor perfusion and endogeneous glucose distribution

    International Nuclear Information System (INIS)

    Schroeder, T.; Larrier, N.; Viglianti, B.; Rabbani, Z.N.; Peltz, C.; Vujascovic, Z.; Dewhirst, M.W.

    2003-01-01

    Earlier studies detecting glucose in tissue and solid tumors by bioluminescence imaging suggested, that glucose distribution patterns may be spatially related to functional vascularity. The purpose of this study was to evaluate this relationship by comparing glucose distribution patterns as determined by bioluminescence imaging to perfusion patterns of endogeneous Hoechst 33342 in rats bearing mammary carcinomas. R 3230 mammary carcinoma cells have been implanted subcutaneously into 7 female Fischer 344 rats. Two months post implantation, after injection of Hoechst 33342 the tumors were removed and snap frozen to conserve metabolite levels. Concomitantly, blood was sampled from the animals for analysis of glucose concentrations using a micodialysis analyzer. Cryosections of the tumors have been prepared, and every slice has been analyzed for both, Hoechst binding by fluorescence microscopy, and for glucose distribution patterns using bioluminescence imaging. In many cases vascular structures could be retrieved by the spatial pattern of glucose distribution. In some cases however, higher glucose concentrations could be found independent from Hoechst signal. On the other hand, regions of high Hoechst signal are not necessarily correlated with high glucose concentrations. When comparing blood and tissue glucose levels, tissue glucose content as measured with bioluminescence imaging (1.9-3.5 mM) is considerably lower than blood glucose (5.6-8.0 mM), demonstrating the expected gradient from blood to tissue. This study demonstrates the feasibility of monitoring glucose gradients in relation to functional vasculature throughout the body, from blood down to tissue or tumor and further, throughout the microenvironment of the solid tumor. Glucose distribution patterns may be an important tool in perfusion studies, e. g. in detecting the direction of blood flow in ex-vivo samples or in estimating glucose consumption rates of tumor cells adjacent to or in between perfused

  8. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

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    Sharma Kamal

    2008-12-01

    Full Text Available Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

  9. 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.

  10. Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth.

    Science.gov (United States)

    Asano, Ryoko; Asai-Sato, Mikiko; Miyagi, Yohei; Mizushima, Taichi; Koyama-Sato, Makiko; Nagashima, Yoji; Taguri, Masataka; Sakakibara, Hideya; Hirahara, Fumiki; Miyagi, Etsuko

    2015-08-01

    Myomatous erythrocytosis syndrome is a rare complication of uterine leiomyoma caused by erythropoietin (EPO) that is produced by tumor cells. We assessed the EPO expression in leiomyomas and investigated the effects of EPO on the tumor growth. Tissue samples were collected from 114 patients with uterine leiomyomas who underwent myomectomy or hysterectomy in Yokohama City University Hospital. From 17 patients, the corresponding normal myometrium was also collected. All samples were analyzed for EPO messenger RNA (mRNA) expression by real-time reverse transcription-polymerase chain reaction. EPO protein expression was determined by an enzyme-linked immunosorbent assay. The relationships between EPO expression and clinicopathological features were retrospectively analyzed using the patients' charts. Blood vessel density and maturity were assessed using hematoxylin-eosin staining and CD34 immunohistochemistry. EPO mRNA expression was detected in 108 of 114, or 95%, of the leiomyomas. The mean EPO mRNA expression in the leiomyoma was higher than the corresponding normal myometrium (3836 ± 4122 vs 1455 ± 2141; P = .025 by Wilcoxon rank test). The EPO mRNA expression in the leiomyomas varied extensively among samples, ranging from undetectable levels to 18-fold above the mean EPO mRNA of normal myometrium. EPO protein production was observed concomitant with mRNA expression. A positive correlation of leiomyoma size and EPO mRNA expression was shown by Spearman rank correlation coefficient (ρ = 0.294; P = .001), suggesting the involvement of EPO in leiomyoma growth. The blood vessel maturity was also significantly increased in EPO-producing leiomyomas (high vessel maturity in high vs low EPO group: 67% vs 20%; P = .013 by Fisher exact test). This report demonstrates that EPO is produced in most of conventional leiomyomas and supports a model in which EPO accelerates tumor growth, possibly by inducing vessel maturity. Our study suggests one possible mechanism by which

  11. C - reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Sonja Predrag Cekic

    2014-08-01

    Full Text Available The aim of the study was to investegate the correlation between the levels of CRP and YKL-40 in blood samples with morphometric parameters of retinal blood vessels in patients with diabetic retinopathy.Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA.Morphmetric analysis was performed with ImageJ software (http://rsbweb.nih.gov/ij/ for digital retinal photography. We measured the number, diameter of retinal blood vessels in five different parts concentric to the optic disc. Differences between the morphometric parameters and the blood test analysis results were evaluated using the Student’s t – test. One Way ANOVA was used to establish the significance of differences.CRP and YKL-40 levels were moderately higher in the group of patients with severe diabetic retinopathy. Levels of YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy.Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  12. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  13. Effect of heat transfer on unsteady MHD flow of blood in a permeable vessel in the presence of non-uniform heat source

    OpenAIRE

    A. Sinha; J.C. Misra; G.C. Shit

    2016-01-01

    This paper presents a theoretical analysis of blood flow and heat transfer in a permeable vessel in the presence of an external magnetic field. The unsteadiness in the coupled flow and temperature fields is considered to be caused due to the time-dependent stretching velocity and the surface temperature of the vessel. The non-uniform heat source/sink effect on blood flow and heat transfer is taken into account. This study is of potential value in the clinical treatment of cardiovascular disor...

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

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    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.

  15. Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

    Science.gov (United States)

    Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

    2016-10-01

    Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. An HRE-Binding Py-Im Polyamide Impairs Hypoxic Signaling in Tumors.

    Science.gov (United States)

    Szablowski, Jerzy O; Raskatov, Jevgenij A; Dervan, Peter B

    2016-04-01

    Hypoxic gene expression contributes to the pathogenesis of many diseases, including organ fibrosis, age-related macular degeneration, and cancer. Hypoxia-inducible factor-1 (HIF1), a transcription factor central to the hypoxic gene expression, mediates multiple processes including neovascularization, cancer metastasis, and cell survival. Pyrrole-imidazole polyamide 1: has been shown to inhibit HIF1-mediated gene expression in cell culture but its activity in vivo was unknown. This study reports activity of polyamide 1: in subcutaneous tumors capable of mounting a hypoxic response and showing neovascularization. We show that 1: distributes into subcutaneous tumor xenografts and normal tissues, reduces the expression of proangiogenic and prometastatic factors, inhibits the formation of new tumor blood vessels, and suppresses tumor growth. Tumors treated with 1: show no increase in HIF1α and have reduced ability to adapt to the hypoxic conditions, as evidenced by increased apoptosis in HIF1α-positive regions and the increased proximity of necrotic regions to vasculature. Overall, these results show that a molecule designed to block the transcriptional activity of HIF1 has potent antitumor activity in vivo, consistent with partial inhibition of the tumor hypoxic response. Mol Cancer Ther; 15(4); 608-17. ©2015 AACR. ©2015 American Association for Cancer Research.

  17. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kun Shang

    Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

  18. Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

    Science.gov (United States)

    Wang, Chen; Wang, Zhen; Gu, Hong-Yu; Du, Xiang; Zhou, Xiao-Yan; Zheng, Chun-Lei; Chi, Ya-Yun; Mukaida, Naofumi; Li, Ying-Yi

    2012-01-01

    Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. PMID:23272179

  19. Flow cytometric analysis of peripheral blood and tumor-infiltrating regulatory T cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Tominaga, Makiko; Horiuchi, Yutaka; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Kadosawa, Tsuyoshi

    2010-05-01

    It is well known that tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) from patients with advanced-stage cancer have a poor immune response. Regulatory T cells (Tregs), characterized by the expression of a cluster of differentiation 4 and intracellular FoxP3 markers, can inhibit antitumor immunoresponse. In the present study, the prevalence of Tregs in peripheral blood and tumor tissue from dogs with oral malignant melanoma was evaluated by triple-color flow cytometry. The percentage of Tregs in the peripheral blood of the dogs with malignancy was significantly increased compared with healthy control dogs, and the percentage of Tregs within tumors was significantly increased compared with Tregs in peripheral blood of dogs with oral malignant melanoma. This finding suggests that the presence of tumor cells induced either local proliferation or selective migration of Tregs to tumor-infiltrated sites. A better understanding of the underlying mechanisms of Treg regulation in patients with cancer may lead to an effective anticancer immunotherapy against canine malignant melanoma and possibly other tumors.

  20. Rapid analysis of vessel elements (RAVE: a tool for studying physiologic, pathologic and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Marc E Seaman

    Full Text Available Quantification of microvascular network structure is important in a myriad of emerging research fields including microvessel remodeling in response to ischemia and drug therapy, tumor angiogenesis, and retinopathy. To mitigate analyst-specific variation in measurements and to ensure that measurements represent actual changes in vessel network structure and morphology, a reliable and automatic tool for quantifying microvascular network architecture is needed. Moreover, an analysis tool capable of acquiring and processing large data sets will facilitate advanced computational analysis and simulation of microvascular growth and remodeling processes and enable more high throughput discovery. To this end, we have produced an automatic and rapid vessel detection and quantification system using a MATLAB graphical user interface (GUI that vastly reduces time spent on analysis and greatly increases repeatability. Analysis yields numerical measures of vessel volume fraction, vessel length density, fractal dimension (a measure of tortuosity, and radii of murine vascular networks. Because our GUI is open sourced to all, it can be easily modified to measure parameters such as percent coverage of non-endothelial cells, number of loops in a vascular bed, amount of perfusion and two-dimensional branch angle. Importantly, the GUI is compatible with standard fluorescent staining and imaging protocols, but also has utility analyzing brightfield vascular images, obtained, for example, in dorsal skinfold chambers. A manually measured image can be typically completed in 20 minutes to 1 hour. In stark comparison, using our GUI, image analysis time is reduced to around 1 minute. This drastic reduction in analysis time coupled with increased repeatability makes this tool valuable for all vessel research especially those requiring rapid and reproducible results, such as anti-angiogenic drug screening.

  1. An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel.

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    Antonia E Curtin

    Full Text Available PURPOSE: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. METHODS: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. RESULTS: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. CONCLUSION: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on

  2. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression.

    Science.gov (United States)

    Wang, Feng-Wei; Cai, Mu-Yan; Mai, Shi-Juan; Chen, Jie-Wei; Bai, Hai-Yan; Li, Yan; Liao, Yi-Ji; Li, Chang-Peng; Tian, Xiao-Peng; Kung, Hsiang-Fu; Guan, Xin-Yuan; Xie, Dan

    2014-08-30

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.

  3. Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

    Science.gov (United States)

    Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

    2008-08-01

    Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

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

    Science.gov (United States)

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

    2016-04-01

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

  5. Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

    Energy Technology Data Exchange (ETDEWEB)

    Gladysz, J [Akademia Medyczna, Poznan (Poland)

    1974-01-01

    Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

  6. Blood Vessel Enhancement and Segmentation for Screening of Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Ibaa Jamal

    2012-06-01

    Full Text Available Diabetic retinopathy is an eye disease caused by the increase of insulin in blood and it is one of the main cuases of blindness in idusterlized countries. It is a progressive disease and needs an early detection and treatment. Vascular pattern of human retina helps the ophthalmologists in automated screening and diagnosis of diabetic retinopathy. In this article, we present a method for vascular pattern ehnacement and segmentation. We present an automated system which uses wavelets to enhance the vascular pattern and then it applies a piecewise threshold probing and adaptive thresholding for vessel localization and segmentation respectively. The method is evaluated and tested using publicly available retinal databases and we further compare our method with already proposed techniques.

  7. Blood vessels segmentation of hatching eggs based on fully convolutional networks

    Science.gov (United States)

    Geng, Lei; Qiu, Ling; Wu, Jun; Xiao, Zhitao

    2018-04-01

    FCN, trained end-to-end, pixels-to-pixels, predict result of each pixel. It has been widely used for semantic segmentation. In order to realize the blood vessels segmentation of hatching eggs, a method based on FCN is proposed in this paper. The training datasets are composed of patches extracted from very few images to augment data. The network combines with lower layer and deconvolution to enables precise segmentation. The proposed method frees from the problem that training deep networks need large scale samples. Experimental results on hatching eggs demonstrate that this method can yield more accurate segmentation outputs than previous researches. It provides a convenient reference for fertility detection subsequently.

  8. Efficacy and biological effects of techniques used to induce hypoxia in tumors

    International Nuclear Information System (INIS)

    Rockwell, S.; Moulder, J.E.; Martin, D.F.

    1985-01-01

    The authors tested several aspects of the assumptions using BA1112 rat rhabdomyosacromas and EMT6 mouse mammary tumors. Both techniques were effective in producing hypoxia: survival curves for tumors made hypoxic by the 2 techniques were the same, and were indistinguishable from survival curves for hypoxic tumor cells in vitro. Induction of hypoxia for the 30-60 min necessary for irradiation did not alter the yield or clonogenicity of cells suspended from the tumors. Longer clamping was cytotoxic. Clamping did not alter tumor growth unless a major blood vessel was injured. However, clamping BA1112 tumors for 30 min and removing the clamp just before irradiation altered the tumor cell survival curve and TCD/sub 50/. Anesthesia or restrain, often used during clamping, can have major effects

  9. Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia

    International Nuclear Information System (INIS)

    Ogose, A.; Hotta, Tetsuo; Hatano, Hiroshi; Endo, Naoto; Emura, Iwao; Umezu, Hajime; Inoue, Yoshiya

    2001-01-01

    Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or rickets. The tumor typically follows a benign clinical course. Even in the rare malignant cases, local recurrence and distant metastasis are uncommon. We report on an example of a malignant phosphaturic mesenchymal tumor which recurred several times over 16 years concurrently causing hypophosphatemia, bone pain, and osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The patient died of disease 17 years after the first surgery. Histologically, the initial tumor was composed of small spindle cells with clusters of giant cells, prominent blood vessels, poorly formed cartilaginous areas, and crystalline material. Cytological atypia was minimal. Following multiple recurrences, the tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism, numerous mitotic figures, and p53 overexpression. This case illustrates the potential lethality of incompletely removed phosphaturic mesenchymal tumors. (orig.)

  10. Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Ogose, A.; Hotta, Tetsuo; Hatano, Hiroshi; Endo, Naoto [Dept. of Orthopedic Surgery, Niigata University School of Medicine, Asahimachi, Niigata (Japan); Emura, Iwao; Umezu, Hajime [Dept. of Pathology, Niigata University School of Medicine, Niigata (Japan); Inoue, Yoshiya [Dept. of Orthopedic Surgery, Seirei Hamamatsu General Hospital, Hamamatsu (Japan)

    2001-02-01

    Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or rickets. The tumor typically follows a benign clinical course. Even in the rare malignant cases, local recurrence and distant metastasis are uncommon. We report on an example of a malignant phosphaturic mesenchymal tumor which recurred several times over 16 years concurrently causing hypophosphatemia, bone pain, and osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The patient died of disease 17 years after the first surgery. Histologically, the initial tumor was composed of small spindle cells with clusters of giant cells, prominent blood vessels, poorly formed cartilaginous areas, and crystalline material. Cytological atypia was minimal. Following multiple recurrences, the tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism, numerous mitotic figures, and p53 overexpression. This case illustrates the potential lethality of incompletely removed phosphaturic mesenchymal tumors. (orig.)

  11. An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section

    Directory of Open Access Journals (Sweden)

    Nga Tran Kim

    2003-01-01

    Full Text Available Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.

  12. Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, A.; Sako, K.; Diksic, M.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using YF-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of YF. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

  13. Subarachnoid hemorrhage in pituitary tumor

    Directory of Open Access Journals (Sweden)

    Ashis Patnaik

    2013-01-01

    Full Text Available Subarachnoid hemorrhage (SAH is the bleeding into the subarachnoid space containing cerebrospinal fluid. The most common cause of SAH is trauma. Rupture of aneurysms, vascular anomalies, tumor bleeds and hypertension are other important etiologies. SAH in the setting of pituitary tumor can result from various causes. It can be due to intrinsic tumor related pathology, injury to surrounding the vessel during the operative procedure or due to an associated aneurysm. We discuss the pathological mechanisms and review relevant literature related to this interesting phenomenon. Early and accurate diagnosis of the cause of the SAH in pituitary tumors is important, as this influences the management.

  14. In 6- to 8-year-old children, hair cortisol is associated with body mass index and somatic complaints, but not with stress, health-related quality of life, blood pressure, retinal vessel diameters, and cardiorespiratory fitness.

    Science.gov (United States)

    Gerber, Markus; Endes, Katharina; Brand, Serge; Herrmann, Christian; Colledge, Flora; Donath, Lars; Faude, Oliver; Pühse, Uwe; Hanssen, Henner; Zahner, Lukas

    2017-02-01

    Hair cortisol measurement has become an increasingly accepted approach in endocrinology and biopsychology. However, while in adult research hair cortisol has been proposed as a relevant biomarker for chronic stress (and its adverse consequences), studies with children are scarce. Therefore, the goal of the present exploratory study was to examine the associations between hair cortisol concentrations (HCCs), stress, and a series of health-related outcomes in a sample of Swiss first grade schoolchildren. The sample consisted of 318 children (53% girls, M age =7.26, SD=0.35). Hair strands were taken near the scalp from a posterior vertex position, and HCCs were tested for the first 3-cm hair segment. Parents provided information about their children's age, gender, parental education, children's stress (recent critical life events, daily hassles), health-related quality of life, and psychosomatic complaints. Body composition, blood pressure, retinal vessel diameters, and cardiorespiratory fitness were measured with established methods. In multiple regression analyses, higher HCCs were weakly associated with increased BMI in girls (β=0.22, pstress, health-related quality of life, blood pressure, retinal vessel diameters, and cardiorespiratory fitness. Although small significant relationships were found between HCCs, BMI and somatic complaints, the findings of this exploratory study challenge the view that HCCs can be used as a reliable biomarker of recent critical life events, daily hassles, health-related quality of life, and cardiovascular health indicators in non-clinical young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  16. Morphological evaluation of the cerebral blood vessels in the late gestation fetal sheep following hypoxia in utero.

    Science.gov (United States)

    Baburamani, Ana A; Lo, Camden; Castillo-Melendez, Margie; Walker, David W

    2013-01-01

    Hypoxia can significantly contribute to the development of permanent brain injury in the term neonate; however the response of cerebral blood vessels is not well understood. This study aimed to quantitatively measure vascular density and morphology using laminin immunohistochemistry as a marker of blood vessels, and determine the effects of a single, severe bout of hypoxia (umbilical cord occlusion, UCO) late in gestation on the developing cerebrovasculature in fetal sheep. At 124-126 days gestation singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. A 10 min UCO or sham UCO (n=5) occurred at 132 days gestation. Fetal brains were collected at 24 h (n=5) or 48 h (n=4) after UCO for vascular density and morphology analysis of laminin immunohistochemistry. 48 h following a single, brief bout of severe hypoxia late in gestation decreased vascular density was seen in the caudate nucleus and no changes in vascular morphology occurred. However closer analysis revealed a significant shift in the frequency of smaller (≤10 μm) to larger (≤100 μm) perimeter blood vessels in periventricular and subcortical white matter. Close examination of the frequency distribution of vascular perimeter highlights that alterations in vascular morphology persist in the near term fetal brain for up to 48 h following a brief (10 min) hypoxia in white but not gray matter. These findings suggest that the near term brain may still be vulnerable to white matter injury following in utero hypoxia. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Present rank of angiography within complex tumor diagnosis

    International Nuclear Information System (INIS)

    Waigand, J.

    1990-01-01

    The development of noninvasive imaging methods with high diagnostic accuracy in the last decade has led to a new determination of the role of angiographic techniques in oncologic diagnosis. The disadvantages of angiography are discussed and the major indications in tumor diagnosis are delineated: preoperative vascular mapping, vascular involvement of the great vessels, CT and ultrasound equivocal, selective blood sampling and interventional procedures. The increasing importance of interventional radiology in oncology is emphasized. (author)

  18. Metastatic spine tumor surgery: does perioperative blood transfusion influence postoperative complications?

    Science.gov (United States)

    Zaw, Aye Sandar; Kantharajanna, Shashidhar B; Maharajan, Karthikeyan; Tan, Barry; Saparamadu, Amarasinghe A; Kumar, Naresh

    2017-11-01

    The question of independent association between allogeneic blood transfusion (ABT) and postoperative complications in cancer surgeries has been controversial and remains so. In metastatic spine tumor surgery (MSTS), previous studies investigated the influence of ABT on survival, but not on postoperative complications. We aimed to evaluate the influence of perioperative ABT on postoperative complications and infections in patients undergoing MSTS. This retrospective study included 247 patients who underwent MSTS at a single tertiary institution between 2005 and 2014. The outcome measures were postoperative complications and infections within 30 days after MSTS. Multivariate logistic regression analyses were performed to assess influence of blood transfusion on the outcomes after adjusting for potential confounders. Of 247 patients, 133 (54%) received ABT with overall median (range) of 2 (0-10) units. The adjusted odds of developing any postoperative complication was 2.27 times higher in patients with transfusion (95% confidence interval [CI], 1.17-4.38; p = 0.01) and 1.24 times higher odds per every unit increase in blood transfusion (95% CI, 1.05-1.46; p blood transfusion also increased the odds of having overall postoperative infections (odds ratio, 3.58; 95% CI, 1.15-11.11; p = 0.02) and there were 1.24 times higher odds per every unit increase in transfusion (95% CI, 1.01-1.54; p = 0.04). This study adds evidence to the literature implicating ABT to be influential on postoperative complications and infections in patients undergoing MSTS. Appropriate blood management measures should, therefore, be given a crucial place in the care of these patients so as to reduce any putative effect of blood transfusion. © 2017 AABB.

  19. Study of blood flow inside the stenosis vessel under the effect of solenoid magnetic field using ferrohydrodynamics principles

    Science.gov (United States)

    Badfar, Homayoun; Motlagh, Saber Yekani; Sharifi, Abbas

    2017-10-01

    In this paper, biomagnetic blood flow in the stenosis vessel under the effect of the solenoid magnetic field is studied using the ferrohydrodynamics (FHD) model. The parabolic profile is considered at an inlet of the axisymmetric stenosis vessel. Blood is modeled as electrically non-conducting, Newtonian and homogeneous fluid. Finite volume and the SIMPLE (Semi-Implicit Method for Pressure Linked Equations) algorithm are utilized to discretize governing equations. The investigation is studied at different magnetic numbers ( MnF=164, 328, 1640 and 3280) and the number of the coil loops (three, five and nine loops). Results indicate an increase in heat transfer, wall shear stress and energy loss (pressure drop) with an increment in the magnetic number (ratio of Kelvin force to dynamic pressure force), arising from the FHD, and the number of solenoid loops. Furthermore, the flow pattern is affected by the magnetic field, and the temperature of blood can be decreased up to 1.48 {}°C under the effect of the solenoid magnetic field with nine loops and reference magnetic field ( B0) of 2 tesla.

  20. Sensing of Vascular Permeability in Inflamed Vessel of Live Animal

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    Sang A Park

    2018-01-01

    Full Text Available Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP. Measurement of the concentration of intravenously (i.v. injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

  1. Evidence of Flicker-Induced Functional Hyperaemia in the Smallest Vessels of the Human Retinal Blood Supply.

    Directory of Open Access Journals (Sweden)

    Angelina Duan

    Full Text Available Regional changes in blood flow are initiated within neural tissue to help fuel local differences in neural activity. Classically, this response was thought to arise only in larger arterioles and venules. However, recently, it has been proposed that a the smallest vessels of the circulation make a comparable contribution, and b the response should be localised intermittently along such vessels, due to the known distribution of contractile mural cells. To assess these hypotheses in human neural tissue in vivo, we imaged the retinal microvasculature (diameters 3-28 μm non-invasively, using adaptive optics, before and after delivery of focal (360 μm patches of flickering visible light. Our results demonstrated a definite average response in 35% of all vessel segments analysed. In these responding vessels, the magnitude of proportional dilation (mean ± SEM for pre-capillary arterioles 13 ± 5%, capillaries 31 ± 8%, and post-capillary venules 10 ± 3% is generally far greater than the magnitudes we and others have measured in the larger retinal vessels, supporting proposition a above. The dilations observed in venules were unexpected based on previous animal work, and may be attributed either to differences in stimulus or species. Response heterogeneity across the network was high; responses were also heterogeneous along individual vessels (45% of vessel segments showed demonstrable locality in their response. These observations support proposition b above. We also observed a definite average constriction across 7% of vessel segments (mean ± SEM constriction for capillaries -16 ± 3.2%, and post-capillary venules -18 ± 12%, which paints a picture of dynamic redistribution of flow throughout the smallest vessel networks in the retina in response to local, stimulus-driven metabolic demand.

  2. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  3. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Science.gov (United States)

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  4. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

    Science.gov (United States)

    Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

    2016-07-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

  5. Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging.

    Science.gov (United States)

    Kiyuna, Tasuku; Tome, Yasunori; Uehara, Fuminari; Murakami, Takashi; Zhang, Yong; Zhao, Ming; Kanaya, Fuminori; Hoffman, Robert M

    2018-01-01

    We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam® color-coded imaging assay. Gelfoam® was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam®, control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small-animal imaging system and confocal fluorescence microscopy. Nascent blood vessels expressing ND-GFP extended into the Gelfoam® over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28. The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. 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

  7. An automated vessel segmentation of retinal images using multiscale vesselness

    International Nuclear Information System (INIS)

    Ben Abdallah, M.; Malek, J.; Tourki, R.; Krissian, K.

    2011-01-01

    The ocular fundus image can provide information on pathological changes caused by local ocular diseases and early signs of certain systemic diseases, such as diabetes and hypertension. Automated analysis and interpretation of fundus images has become a necessary and important diagnostic procedure in ophthalmology. The extraction of blood vessels from retinal images is an important and challenging task in medical analysis and diagnosis. In this paper, we introduce an implementation of the anisotropic diffusion which allows reducing the noise and better preserving small structures like vessels in 2D images. A vessel detection filter, based on a multi-scale vesselness function, is then applied to enhance vascular structures.

  8. Blood Brain Barrier: A Challenge for Effectual Therapy of Brain Tumors

    OpenAIRE

    Bhowmik, Arijit; Khan, Rajni; Ghosh, Mrinal Kanti

    2015-01-01

    Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and n...

  9. Changes in peripapillary blood vessel density in Graves' orbitopathy after orbital decompression surgery as measured by optical coherence tomography angiography.

    Science.gov (United States)

    Lewis, Kyle T; Bullock, John R; Drumright, Ryan T; Olsen, Matthew J; Penman, Alan D

    2018-03-08

    The purpose is to evaluate the utility of optical coherence tomography (OCT) angiography in the evaluation of Graves' orbitopathy (GO) and response to orbital decompression in patients with and without dysthyroid optic neuropathy (DON). This was a single-center, prospective case series in a cohort of 12 patients (24 orbits) with GO and ±DON, (6 orbits) who underwent bilateral orbital decompression. All patients underwent pre- and postoperative OCT angiography of the peripapillary area. Vessel density indices were calculated in a 4.5 mm × 4.5 mm ellipsoid centered on the optic disk using split-spectrum amplitude decorrelation angiography algorithm, producing the vessel density measurements. Mean change in vessel density indices was compared between pre- and postoperative sessions and between patients with and without DON. Patient 1, a 34-year-old male with GO and unilateral DON OD, showed a significant reduction in blood vessel density indices oculus dexter (OD) (DON eye) after decompression while a more modest reduction was found oculus sinister (OS) with the greatest change noted intrapapillary. Patient 2, a 50-year-old male with DON OU, showed worsening neuropathy following decompression OD that was confirmed by angiographic density indices. Patient 3, a 55-year-female with DON, showed a reduction in blood vessel density OD and increased density OS. Patients without DON showed overall less impressive changes in indices as compared to those with DON. Using OCT angiography, response to surgical treatment in GO orbits, more so in orbits with DON, can be demonstrated and quantified using vessel density indices with reproducibility.

  10. Tumor angiogenesis in advanced stage ovarian carcinoma.

    Science.gov (United States)

    Hollingsworth, H C; Kohn, E C; Steinberg, S M; Rothenberg, M L; Merino, M J

    1995-07-01

    Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

  11. Fast magnetic reconstruction of the portal vein with allogeneic blood vessels in canines.

    Science.gov (United States)

    Wang, Shan-Pei; Yan, Xiao-Peng; Xue, Fei; Dong, Ding-Hui; Zhang, Xu-Feng; Ma, Feng; Wang, Hao-Hua; Lv, Yi

    2015-06-01

    The resection and reconstruction of large vessels, including the portal vein, are frequently needed in tumor resection. Warm ischemia before reconstruction might have deleterious effects on the function of some vital organs and therefore, how to reconstruct the vessels quickly after resection is extremely important. The present study was to introduce a new type of magnetic compression anastomosis (MCA) device to establish a quick non-suture anastomosis of the portal vein after resection in canines. The new MCA device consists of a pair of titanium alloy and neodymium-ferrum-boron magnet (Ti-NdFeB) composite rings. The NdFeB magnetic ring as a core of the device was hermetically sealed inside the biomedical titanium alloy case. Twelve canines were divided into two groups: a MCA group in which the end-to-end anastomoses was made with a new device after resection in the portal vein and a traditional manual suture (TMS) group consisted of 6 canines. The anastomosis time, anastomotic patency and quality were investigated at week 24 postoperatively. The portal vein was reconstructed successfully in all of the animals and they all survived. The duration of portal vein anastomosis was significantly shorter in the MCA group than in the TMS group (8.16+/-1.25 vs 36.24+/-2.17 min, PNdFeB composite MCA device was applicable in reconstruction of large vessels after resection. This device was easy to use and the anastomosis was functionally better than the traditional sutured anastomosis.

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

    International Nuclear Information System (INIS)

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

    1975-01-01

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

  13. [Changes of renal blood flow during organ-associated foot reflexology measured by color Doppler sonography].

    Science.gov (United States)

    Sudmeier, I; Bodner, G; Egger, I; Mur, E; Ulmer, H; Herold, M

    1999-06-01

    Using colour Doppler sonography blood flow changes of the right kidney during foot reflexology were determined in a placebo-controlled, double-blind, randomised study. 32 healthy young adults (17 women, 15 men) were randomly assigned to the verum or placebo group. The verum group received foot reflexology at zones corresponding to the right kidney, the placebo group was treated on other foot zones. Before, during and after foot reflexology the blood flow of three vessels of the right kidney was measured using colour Doppler sonography. Systolic peak velocity and end diastolic peak velocity were measured in cm/s, and the resistive index, a parameter of the vascular resistance, was calculated. The resistive index in the verum group showed a highly significant decrease (p foot reflexology. There was no difference between men and women and no difference between smokers and non-smokers. Verum and placebo group significantly differed concerning alterations of the resistive index both between the measuring points before versus during foot reflexology (p = 0.002) and those during versus after foot reflexology (p = 0.031). The significant decrease of the resistive index during foot reflexology in the verum group indicates a decrease of flow resistance in renal vessels and an increase of renal blood flow. These findings support the hypothesis that organ-associated foot reflexology is effective in changing renal blood flow during therapy.

  14. Small vessel vasculitis History, classification, etiology, histopathology, clinic, diagnosis and treatment

    International Nuclear Information System (INIS)

    Iglesias Gamarra, Antonio; Matteson, Eric L; Restrepo, Jose Felix

    2007-01-01

    Small-vessel vasculitis is a convenient descriptor for a wide range of diseases characterized by vascular inflammation of the venules, capillaries, and/or arterioles with pleomorphic clinical manifestations. The classical clinical phenotype is leucocytoclastic vasculitis with palpable purpura, but manifestations vary widely depending upon the organs involved. Histopathologic examination in leucocytoclastic vasculitis reveals angiocentric segmental inflammation, fibrinoid necrosis, and a neutrophilic infiltrate around the blood vessel walls with erythrocyte extravasation. The etiology of small-vessel vasculitis is unknown in many cases, but in others, drugs, post viral syndromes, malignancy, primary vasculitis such as microscopic polyarteritis, and connective tissue disorders are associated, The diagnosis of small- vessel vasculitis relies on a thorough history and physical examination, as well as relevant antibody testing including antinuclear antibody and anti neutrophil cytoplasmic antibody, hepatitis B and C serologies, assessment of complement, immunoglobulins, blood count, serum creatinine liver function tests, urinalysis, radiographic imaging and biopsy. The treatment is based primarily on corticosteroid and immunosuppressive agents

  15. Ultrastructural analysis of small blood vessels in skin biopsies in CADASIL

    Directory of Open Access Journals (Sweden)

    Lačković Vesna

    2008-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an inherited small- and medium-artery disease of the brain caused by mutation of the Notch3 gene. Very often, this disease is misdiagnosed. We examined skin biopsies in two members of the first discovered Serbian family affected by CADASIL. Electron microscopy showed that skin blood vessels of both patients contain numerous deposits of granular osmiophilic material (GOM around vascular smooth muscle cells (VSMCs. We observed degeneration of VSMCs, reorganization of their cytoskeleton and dense bodies, disruption of myoendothelial contacts, and apoptosis. Our results suggest that the presence of GOM in small skin arteries represents a specific marker in diagnosis of CADASIL.

  16. Human BCAS3 expression in embryonic stem cells and vascular precursors suggests a role in human embryogenesis and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Kavitha Siva

    Full Text Available Cancer is often associated with multiple and progressive genetic alterations in genes that are important for normal development. BCAS3 (Breast Cancer Amplified Sequence 3 is a gene of unknown function on human chromosome 17q23, a region associated with breakpoints of several neoplasms. The normal expression pattern of BCAS3 has not been studied, though it is implicated in breast cancer progression. Rudhira, a murine WD40 domain protein that is 98% identical to BCAS3 is expressed in embryonic stem (ES cells, erythropoiesis and angiogenesis. This suggests that BCAS3 expression also may not be restricted to mammary tissue and may have important roles in other normal as well as malignant tissues. We show that BCAS3 is also expressed in human ES cells and during their differentiation into blood vascular precursors. We find that BCAS3 is aberrantly expressed in malignant human brain lesions. In glioblastoma, hemangiopericytoma and brain abscess we note high levels of BCAS3 expression in tumor cells and some blood vessels. BCAS3 may be associated with multiple cancerous and rapidly proliferating cells and hence the expression, function and regulation of this gene merits further investigation. We suggest that BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker.

  17. Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery

    Science.gov (United States)

    Dong, Lixin; Kudrimoti, Mahesh; Cheng, Ran; Shang, Yu; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2012-01-01

    This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements. PMID:22312579

  18. Experimental assessment of the role of the blood flow inhibition in hyperglycemia-enhanced radiation injury to tumor

    International Nuclear Information System (INIS)

    Kozin, S.V.; Sevast'yanov, A.I.; Yarmonenko, S.P.

    1986-01-01

    Experimental assessment of the role of the blood flow inhibition in enhancement of radiation injury to tumors using short-term hyperglycemia was provided. Experiments on mice with Ehrlich solid carcinoma showed the dependence of a rise of the antitumor effect of preceding radiation induced by glucose and glucose combined with mexamin on a degree of the blood flow inhibition under the influence of these modifying agents. It was established that a considerable enhancement of radiation injury occured but in such tumors where short-term hyperglycemia and mexamin decreased the blood flow level not less than 5-10 fold as estimated by 133 Xe clearance. The results of the above experiments showed that the noticeable inhibition of the blood flow in tumors was a necessary tough, probably, not the only condition for a high efficacy of short-term hyperglycemia used an ajuvant to radiotherapy

  19. Mind the GAP: A Novel Tumor-Promoting Mechanism | Center for Cancer Research

    Science.gov (United States)

    RAS proteins, like light switches, toggle between an “on” conformation where they promote cell growth, survival, and/or the formation of blood vessels (known as angiogenesis) and an “off” conformation in which they are unable to stimulate their target effector proteins. Nearly one-third of human tumors express a mutated RAS gene, which encodes a protein locked permanently in

  20. Associations between tumor types in irradiated BALB/c female mice

    International Nuclear Information System (INIS)

    Storer, J.B.

    1982-01-01

    Associations between pairs of 12 different tumor types were estimated for a population of over 3800 irradiated BALB/c female mice. The associations were adjusted for age and radiation dose. Of the 66 pairs of tumor types, 21 showed significant positive or negative associations. Of these, 8 were considered to be spurious, principally because one or both of the tumors was rapidly lethal, leading to an apparent negative association. Six of the remaining 13 significant associations involed tumors of endocrine organs or tumors known to be endocrine related. Six others involved associations between lung, vascular tissue, or reticular tissue tumors, and tumors of endocrine organs. The remaining and highly negative association was between reticulum cell sarcomas and other lymphomas and leukemias. It was concluded that in irradiated female mice of this strain, at least, tumors are not independent and that alterations in host factors (principally endocrine) lead to animals developing both tumors (positive associations) or to one tumor but not the other (negative associations)