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Sample records for prevent tumor formation

  1. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  2. 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model

    Directory of Open Access Journals (Sweden)

    Babak Esmaeelian

    2013-12-01

    Full Text Available Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g was found to significantly enhance the apoptotic index (p ≤ 0.001 and reduced cell proliferation (p ≤ 0.01 in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.

  3. Mesenchymal stem cells promote formation of colorectal tumors in mice.

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    Tsai, Kuo-Shu; Yang, Shung-Haur; Lei, Yen-Ping; Tsai, Chih-Chien; Chen, Hsin-Wei; Hsu, Chih-Yuan; Chen, Ling-Lan; Wang, Hsei-Wei; Miller, Stephanie A; Chiou, Shih-Hwa; Hung, Mien-Chie; Hung, Shih-Chieh

    2011-09-01

    Tumor-initiating cells are a subset of tumor cells with the ability to form new tumors; however, they account for less than 0.001% of the cells in colorectal or other types of tumors. Mesenchymal stem cells (MSCs) integrate into the colorectal tumor stroma; we investigated their involvement in tumor initiation. Human colorectal cancer cells, MSCs, and a mixture of both cell types were injected subcutaneously into immunodeficient mice. We compared the ability of each injection to form tumors and investigated the signaling pathway involved in tumor initiation. A small number (≤ 10) of unsorted, CD133⁻, CD166⁻, epithelial cell adhesion molecule⁻(EpCAM⁻), or CD133⁻/CD166⁻/EpCAM⁻ colorectal cancer cells, when mixed with otherwise nontumorigenic MSCs, formed tumors in mice. Secretion of interleukin (IL)-6 by MSCs increased the expression of CD133 and activation of Janus kinase 2-signal transducer and activator of transcription 3 (STAT3) in the cancer cells, and promoted sphere and tumor formation. An antibody against IL-6 or lentiviral-mediated transduction of an interfering RNA against IL-6 in MSCs or STAT3 in cancer cells prevented the ability of MSCs to promote sphere formation and tumor initiation. IL-6, secreted by MSCs, signals through STAT3 to increase the numbers of colorectal tumor-initiating cells and promote tumor formation. Reagents developed to disrupt this process might be developed to treat patients with colorectal cancer. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation

    DEFF Research Database (Denmark)

    Eichenlaub, Teresa; Cohen, Stephen M; Herranz, Héctor

    2016-01-01

    Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechan......Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging....... The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells...... of the Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms...

  5. Understanding Tumor Dormancy as a Means of Secondary Prevention

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-12-1-0300 TITLE: Understanding Tumor Dormancy as a Means of Secondary Prevention PRINCIPAL INVESTIGATOR: Gregory...CONTRACT NUMBER Understanding Tumor Dormancy as a Means of Secondary Prevention 5b. GRANT NUMBER BW81XWH-12-1-0300 5c. PROGRAM ELEMENT NUMBER 6...was stably in remission. Once our understanding of this is more complete, it is hoped that we can devise strategies for secondary prevention . This

  6. Crack formation and prevention in colloidal drops

    Science.gov (United States)

    Kim, Jin Young; Cho, Kun; Ryu, Seul-A.; Kim, So Youn; Weon, Byung Mook

    2015-08-01

    Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticles.

  7. The MC160 Protein Expressed by the Dermatotropic Poxvirus Molluscum Contagiosum Virus Prevents Tumor Necrosis Factor Alpha-Induced NF-κB Activation via Inhibition of I Kappa Kinase Complex Formation

    Science.gov (United States)

    Nichols, Daniel Brian; Shisler, Joanna L.

    2006-01-01

    The pluripotent cytokine tumor necrosis factor alpha (TNF-α) binds to its cognate TNF receptor I (TNF-RI) to stimulate inflammation via activation of the NF-κB transcription factor. To prevent the detrimental effects of TNF-α in keratinocytes infected with the molluscum contagiosum virus (MCV), this poxvirus is expected to produce proteins that block at least one step of the TNF-RI signal transduction pathway. One such product, the MC160 protein, is predicted to interfere with this cellular response because of its homology to other proteins that regulate TNF-RI-mediated signaling. We report here that expression of MC160 molecules did significantly reduce TNF-α-mediated NF-κB activation in 293T cells, as measured by gene reporter and gel mobility shift assays. Since we observed that MC160 decreased other NF-κB activation pathways, namely those activated by receptor-interacting protein, TNF receptor-associated factor 2, NF-κB-inducing kinase, or MyD88, we hypothesized that the MC160 product interfered with I kappa kinase (IKK) activation, an event common to multiple signal transduction pathways. Indeed, MC160 protein expression was associated with a reduction in in vitro IKK kinase activity and IKK subunit phosphorylation. Further, IKK1-IKK2 interactions were not detected in MC160-expressing cells, under conditions demonstrated to induce IKK complex formation, but interactions between the MC160 protein and the major IKK subunits were undetectable. Surprisingly, MC160 expression correlated with a decrease in IKK1, but not IKK2 levels, suggesting a mechanism for MC160 disruption of IKK1-IKK2 interactions. MCV has probably retained its MC160 gene to inhibit NF-κB activation by interfering with signaling via multiple biological mediators. In the context of an MCV infection in vivo, MC160 protein expression may dampen the cellular production of proinflammatory molecules and enhance persistent infections in host keratinocytes. PMID:16378960

  8. Tumor thrombus formation in two dogs with insulinomas.

    Science.gov (United States)

    Hambrook, Lydia E; Kudnig, Simon T

    2012-10-15

    A 9-year-old sexually intact male Staffordshire Bull Terrier and a 9-year-old neutered male Boxer were evaluated for intermittent neurologic signs including muscle tremors, ataxia, episodic collapse, disorientation, and seizures. Both dogs had low blood glucose and high serum insulin concentrations. Results of abdominal ultrasonography were unremarkable for both dogs. Exploratory laparotomy revealed a mass that extended from the body of the pancreas into the pancreaticoduodenal vein in each dog. Marginal resection of pancreatic masses was performed, and tumor thrombi were removed via venotomy in both dogs. Histologic evaluation indicated the masses were pancreatic islet cell tumors with tumor thrombi. Clinical signs resolved following surgical resection of tumors and tumor thrombi, and the dogs were euglycemic during the follow-up period (17 and 45 months after surgery). Although gross tumor thrombus formation has been identified in humans with insulinomas, tumor thrombi have not been previously reported for dogs with insulinomas. Surgical removal of tumor thrombi via venotomy seemed to be well tolerated by the dogs. Tumor thrombus formation did not seem to adversely affect prognosis for the 2 dogs of this report.

  9. Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

    International Nuclear Information System (INIS)

    Korbelik, M.; Sun, J.

    2003-01-01

    Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

  10. Revisiting the TCA cycle: signaling to tumor formation.

    Science.gov (United States)

    Raimundo, Nuno; Baysal, Bora E; Shadel, Gerald S

    2011-11-01

    A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathway likely promotes the growth of these neoplasias into tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Combination cisplatin and sulforaphane treatment reduces proliferation, invasion, and tumor formation in epidermal squamous cell carcinoma.

    Science.gov (United States)

    Kerr, Candace; Adhikary, Gautam; Grun, Daniel; George, Nicholas; Eckert, Richard L

    2018-01-01

    Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet-derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma. Both agents suppress cell proliferation, growth of cancer stem cell spheroids, matrigel invasion and migration of SCC-13 and HaCaT cells, and combination treatment is more efficient. In addition, SCC-13 cell derived cancer stem cells are more responsive to these agents than non-stem cancer cells. Both agents suppress tumor formation, but enhanced suppression is observed with combined treatment. Moreover, both agents reduce the number of tumor-resident cancer stem cells. SFN treatment of cultured cells or tumors increases apoptosis and p21 Cip1 level, and both agents increase tumor apoptosis. We suggest that combined therapy with sulforaphane and cisplatin is efficient in suppressing tumor formation and may be a treatment option for advanced epidermal squamous cell carcinoma. © 2017 Wiley Periodicals, Inc.

  12. Prevention of organic iodide formation in BWR's

    International Nuclear Information System (INIS)

    Karjunen, T.; Laitinen, T.; Piippo, J.; Sirkiae, P.

    1996-01-01

    During an accident, many different forms of iodine may emerge. Organic iodides, such as methyl iodide and ethyl iodide, are relatively volatile, and thus their appearance leads to increased concentration of gaseous iodine. Since organic iodides are also relatively immune to most accident mitigation measures, such as sprays and filters, they can affect the accident source term significantly even when only a small portion of iodine is in organic form. Formation of organic iodides may not be limited by the amount of organic substances available. Excessive amounts of methane can be produced, for example, during oxidation of boron carbide, which is used in BWR's as a neutron absorber material. Another important source is cable insulation. In a BWR, a large quantity of cables is placed below the pressure vessel. Thus a large quantity of pyrolyse gases will be produced, should the vessel fail. Organic iodides can be formed as a result of many different reactions, but at least in certain conditions the main reaction takes place between an organic radical produced by radiolysis and elemental iodine. A necessary requirement for prevention of organic iodide production is therefore that the pH in the containment water pools is kept high enough to eliminate formation of elemental iodine. In a typical BWR the suppression pool water is usually unbuffered. As a result, the pH may be dominated by chemicals introduced during an accident. If no system for adding basic chemicals is operable, the main factor affecting pool water pH may be hydrochloric acid released during cable degradation. Should this occur, the conditions could be very favorable for production of elemental iodine and, consequently, formation of organic iodides. Although high pH is necessary for iodine retention, it could have also adverse effects. High pH may, for example, accelerate corrosion of containment materials and alter the characteristics of the solid corrosion products. (author) 6 figs., 1 tab., 13 refs

  13. Surface coating for prevention of crust formation

    Energy Technology Data Exchange (ETDEWEB)

    Kronberg, J.W.

    1994-05-24

    A flexible surface coating which promotes the removal of deposits as they reach the surface by preventing adhesion and crust formation is disclosed. Flexible layers are attached to each side of a flexible mesh substrate comprising of a plurality of zones composed of one or more neighboring cells, each zone having a different compressibility than its adjacent zones. The substrate is composed of a mesh made of strands and open cells. The cells may be filled with foam. Studs or bearings may also be positioned in the cells to increase the variation in compressibility and thus the degree of flexing of the coating. Surface loading produces varying amounts of compression from point to point causing the coating to flex as deposits reach it, breaking up any hardening deposits before a continuous crust forms. Preferably one or more additional layers are also used, such as an outer layer of a non-stick material such as TEFLON, which may be pigmented, and an inner, adhesive layer to facilitate applying the coating to a surface. 5 figs.

  14. Dedifferentiation of neurons precedes tumor formation in Lola mutants.

    Science.gov (United States)

    Southall, Tony D; Davidson, Catherine M; Miller, Claire; Carr, Adrian; Brand, Andrea H

    2014-03-31

    The ability to reprogram differentiated cells into a pluripotent state has revealed that the differentiated state is plastic and reversible. It is evident, therefore, that mechanisms must be in place to maintain cells in a differentiated state. Transcription factors that specify neuronal characteristics have been well studied, but less is known about the mechanisms that prevent neurons from dedifferentiating to a multipotent, stem cell-like state. Here, we identify Lola as a transcription factor that is required to maintain neurons in a differentiated state. We show that Lola represses neural stem cell genes and cell-cycle genes in postmitotic neurons. In lola mutants, neurons dedifferentiate, turn on neural stem cell genes, and begin to divide, forming tumors. Thus, neurons rather than stem cells or intermediate progenitors are the tumor-initiating cells in lola mutants. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. [Evaluation of knowledge about colon cancer prevention versus other tumors].

    Science.gov (United States)

    Sanguinetti, José María; Henry, Nicolás; Ocaña, Domingo; Polesel, Julio Lotero

    2015-06-01

    In Argentina almost 7% of deaths are due to different cancers with screening strategies. Evaluate knowledge about cancer prevention compared with other tumors. Materials. A descriptive and comparative study. A survey between April and June 2013 in Salta City, province of Salta, Argentina. Correct answers were considered. Statistical analysis: Descriptive (mean and percentage), comparative Chi square Test (significance level Pmama and cervix. 20% (CI 0,13-0,28) knew that colon cancer has a genetic predisposition and 58% (CI 0,48-0,67) about mama. 73% (CI 0,63-0,8) received information about cancer prevention. The main source of information was the physician. 46% (CI 0,36-0,55) received medical care in private institutions. Those who had social security, higher educational levels and medical care in private institutions had better knowledge about cancer prevention except in colon cancer. The global results showed levels below 70% in general but extremely low in colon cancer. Not having social security, receiving medical care in public institutions and having a low educational level are related with poor knowledge about cancer prevention except for colon and prostate cancer.

  16. PRIMARY PREVENTION OF MALIGNANT SKIN TUMORS – PHOTOPROTECTION

    Directory of Open Access Journals (Sweden)

    Ana Benedičič - Pilih

    2001-12-01

    Full Text Available Background. The incidence of skin cancer is increasing in the world as well as in our country. Decades of research have increased the understanding of the ethiopathogenetic influences and risk factors for development of malignant skin tumors and stimulated efforts to promote their prevention. There are successes of prevention programs in some places in the world expressing with the reduction of mortality because of the cutaneous malignant melanoma. A primary prevention of a skin cancer attempts to change population knowledge, attitudes and beliefs about sunlight, leading to reduce of sunlight exposure.Conclusions. In this article we are discussing guidelines for photoprevention. The best approach to it is a reduction in the overall exposure to sunlight. The natural protection with the use of shade, clothing and hats is promoted as the best protection. Sunscreens are assumed as an important component of adjuvant photoprotection based on their convenience of use and also on their widespread promotion. While it has been argued that all tanning is a manifestation of skin injury, avoiding of artificial tanning devices is proposed also.

  17. Inhibition of proliferation by PERK regulates mammary acinar morphogenesis and tumor formation.

    Directory of Open Access Journals (Sweden)

    Sharon J Sequeira

    Full Text Available Endoplasmic reticulum (ER stress signaling can be mediated by the ER kinase PERK, which phosphorylates its substrate eIF2alpha. This in turn, results in translational repression and the activation of downstream programs that can limit cell growth through cell cycle arrest and/or apoptosis. These responses can also be initiated by perturbations in cell adhesion. Thus, we hypothesized that adhesion-dependent regulation of PERK signaling might determine cell fate. We tested this hypothesis in a model of mammary acini development, a morphogenetic process regulated in part by adhesion signaling. Here we report a novel role for PERK in limiting MCF10A mammary epithelial cell proliferation during acinar morphogenesis in 3D Matrigel culture as well as in preventing mammary tumor formation in vivo. We show that loss of adhesion to a suitable substratum induces PERK-dependent phosphorylation of eIF2alpha and selective upregulation of ATF4 and GADD153. Further, inhibition of endogenous PERK signaling during acinar morphogenesis, using two dominant-negative PERK mutants (PERK-DeltaC or PERK-K618A, does not affect apoptosis but results instead in hyper-proliferative and enlarged lumen-filled acini, devoid of proper architecture. This phenotype correlated with an adhesion-dependent increase in translation initiation, Ki67 staining and upregulation of Laminin-5, ErbB1 and ErbB2 expression. More importantly, the MCF10A cells expressing PERKDeltaC, but not a vector control, were tumorigenic in vivo upon orthotopic implantation in denuded mouse mammary fat pads. Our results reveal that the PERK pathway is responsive to adhesion-regulated signals and that it is essential for proper acinar morphogenesis and in preventing mammary tumor formation. The possibility that deficiencies in PERK signaling could lead to hyperproliferation of the mammary epithelium and increase the likelihood of tumor formation, is of significance to the understanding of breast cancer.

  18. Photoacoustic monitoring of clot formation during surgery and tumor surgery

    Science.gov (United States)

    Juratli, Mazen A.; Galanzha, Ekaterina I.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Suen, James Y.; Zharov, Vladimir P.

    2013-03-01

    When a blood vessel is injured, the normal physiological response of the body is to form a clot (thrombus) to prevent blood loss. Alternatively, even without injury to the blood vessel, the pathological condition called thromboembolism may lead to the formation of circulating blood clots (CBCs), also called emboli, which can clog blood vessels throughout the body. Veins of the extremities (venous thromboembolism), lungs (pulmonary embolism ), brain (embolic stroke), heart (myocardial infarction), kidneys, and gastrointestinal tract are often affected. Emboli are also common complications of infection, inflammation, cancer, surgery, radiation and coronary artery bypass grafts. Despite the clear medical significance of CBCs, however, little progress has been made in the development of methods for real-time detection and identification of CBCs. To overcome these limitations, we developed a new modification of in vivo photoacoustic (PA) flow cytometry (PAFC) for real-time detection of white, red, and mixed clots through a transient decrease, increase or fluctuation of PA signal amplitude, respectively. In this work, using PAFC and mouse models, we present for the first time direct evidence that some medical procedures, such as conventional or cancer surgery may initiate the formation of CBCs. In conclusion, the PA diagnostic platform can be used in real-time to define risk factors for cardiovascular diseases, assist in the prognosis and potential prevention of stroke by using a well-timed therapy or as a clot count as a marker of therapy efficacy.

  19. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

    OpenAIRE

    Kentaro Nakamura; Hidekazu Tonouchi; Akina Sasayama; Kinya Ashida

    2018-01-01

    Low-carbohydrate, high-fat diets (ketogenic diets) might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF) is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR), tumor-bearing (TB), and ketogenic fo...

  20. Pathophysiological Basis for the Formation of the Tumor Microenvironment

    DEFF Research Database (Denmark)

    Horsman, Michael R; Vaupel, Peter

    2016-01-01

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

  1. Tumor formation in hybrids between Solanum lycopersicum and S ...

    African Journals Online (AJOL)

    Genetic tumors are neoplastic growths that arise spontaneously in particular genotypes in plants. In the present study, we observed the occurrence of tumors in interspecific hybrids between Solanum lycopersicum L. and Solanum habrochaites S. Knapp and D. M. Spooner. The hybridity of these plants was confirmed based ...

  2. Industasis, a promotion of tumor formation by nontumorigenic stray cells

    Czech Academy of Sciences Publication Activity Database

    Pajer, Petr; Karafiát, Vít; Pečenka, Vladimír; Průková, Dana; Dudlová, J.; Plachý, Jiří; Kašparová, P.; Dvořák, Michal

    2009-01-01

    Roč. 69, č. 11 (2009), s. 4605-4612 ISSN 0008-5472 R&D Projects: GA ČR GA204/06/1728; GA MŠk(CZ) LC06061; GA AV ČR IAA500520608 Institutional research plan: CEZ:AV0Z50520514 Keywords : tumor promotion * lung tumors * Fyn-related kinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.543, year: 2009

  3. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation.

    Science.gov (United States)

    Takano, Shingo

    2012-04-01

    Glioblastomas are highly vascular tumors. Recent preclinical and clinical investigations have revealed that agents targeting angiogenesis may have efficacy against this type of tumor. Antibodies to vascular endothelial growth factor are being studied in this patient population. Unfortunately, treatment inevitably fails. This review provides an update on recent research on the mechanisms by which tumor cells acquire resistance, and discusses recent preclinical and experimental development of novel new-generation anti-angiogenic agents that overcome this problem, especially those based on the molecular mechanisms of tumor vessel formation. The tumor vasculature not only nourishes glioblastomas, but also provides a specialized microenvironment for tumor stem-like cells and for the brain tumor. The factors, pathways, and interactions described in this review provide information about the cell biology of glioblastomas which may ultimately result in new modes of treatment.

  4. Wine protein haze: mechanisms of formation and advances in prevention.

    Science.gov (United States)

    Van Sluyter, Steven C; McRae, Jacqui M; Falconer, Robert J; Smith, Paul A; Bacic, Antony; Waters, Elizabeth J; Marangon, Matteo

    2015-04-29

    Protein haze is an aesthetic problem in white wines that can be prevented by removing the grape proteins that have survived the winemaking process. The haze-forming proteins are grape pathogenesis-related proteins that are highly stable during winemaking, but some of them precipitate over time and with elevated temperatures. Protein removal is currently achieved by bentonite addition, an inefficient process that can lead to higher costs and quality losses in winemaking. The development of more efficient processes for protein removal and haze prevention requires understanding the mechanisms such as the main drivers of protein instability and the impacts of various wine matrix components on haze formation. This review covers recent developments in wine protein instability and removal and proposes a revised mechanism of protein haze formation.

  5. Invasion Precedes Tumor Mass Formation in a Malignant Brain Tumor Model of Genetically Modified Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Oltea Sampetrean

    2011-09-01

    Full Text Available Invasiveness, cellular atypia, and proliferation are hallmarks of malignant gliomas. To effectively target each of these characteristics, it is important to understand their sequence during tumorigenesis. However, because most gliomas are diagnosed at an advanced stage, the chronology of gliomagenesis milestones is not well understood. The aim of the present study was to determine the onset of these characteristics during tumor development. Brain tumor-initiating cells (BTICs were established by overexpressing H-RasV12 in normal neural stem/progenitor cells isolated from the subventricular zone of adult mice harboring a homozygous deletion of the Ink4a/Arf locus. High-grade malignant brain tumors were then created by orthotopic implantation of 105 BTICs into the forebrain of 6-week-old wild-type mice. Micewere killed every week for 5 weeks, and tumors were assessed for cellular atypia, proliferation, hemorrhage, necrosis, and invasion. All mice developed highly invasive, hypervascular glioblastoma-like tumors. A 100% penetrance rate and a 4-week median survival were achieved. Tumor cell migration along fiber tracts started within days after implantation and was followed by perivascular infiltration of tumor cells with marked recruitment of reactive host cells. Next, cellular atypia became prominent. Finally, mass proliferation and necrosis were observed in the last stage of the disease. Video monitoring of BTICs in live brain slices confirmed the early onset of migration, as well as the main cell migration patterns. Our results showed that perivascular and intraparenchymal tumor cell migration precede tumor mass formation in the adult brain, suggesting the need for an early and sustained anti-invasion therapy.

  6. Alerting the immune system via stromal cells is central to the prevention of tumor growth

    DEFF Research Database (Denmark)

    Navikas, Shohreh

    2013-01-01

    Anticancer immunotherapies are highly desired. Conversely, unwanted inflammatory or immune responses contribute to oncogenesis, tumor progression, and cancer-related death. For non-immunogenic therapies to inhibit tumor growth, they must promote, not prevent, the activation of anticancer immune...... responses. Here, the central immunoregulatory role of brain-specific stromal cells and neurons as well as their ability to maintain an immunological balance and prevent the development of glioblastoma is discussed....

  7. Dominant negative retinoic acid receptor initiates tumor formation in mice

    Directory of Open Access Journals (Sweden)

    Farias Eduardo F

    2006-03-01

    Full Text Available Abstract Background Retinoic acid suppresses cell growth and promotes cell differentiation, and pharmacological retinoic acid receptor (RAR activation is anti-tumorigenic. This begs the question of whether chronic physiological RAR activation by endogenous retinoids is likewise anti-tumorigenic. Results To address this question, we generated transgenic mice in which expression of a ligand binding defective dominant negative RARα (RARαG303E was under the control of the mouse mammary tumor virus (MMTV promoter. The transgene was expressed in the lymphoid compartment and in the mammary epithelium. Observation of aging mice revealed that transgenic mice, unlike their wild type littermates, developed B cell lymphomas at high penetrance, with a median latency of 40 weeks. MMTV-RARαG303E lymphomas were high grade Pax-5+, surface H+L Ig negative, CD69+ and BCL6- and cytologically and phenotypically resembled human adult high grade (Burkitt's or lymphoblastic lymphomas. We postulated that mammary tumors might arise after a long latency period as seen in other transgenic models of breast cancer. We tested this idea by transplanting transgenic epithelium into the cleared fat pads of wild type hosts, thus bypassing lymphomagenesis. At 17 months post-transplantation, a metastatic mammary adenocarcinoma developed in one of four transplanted glands whereas no tumors developed in sixteen of sixteen endogenous glands with wild type epithelium. Conclusion These findings suggest that physiological RAR activity may normally suppress B lymphocyte and mammary epithelial cell growth and that global RAR inactivation is sufficient to initiate a stochastic process of tumor development requiring multiple transforming events. Our work makes available to the research community a new animal resource that should prove useful as an experimental model of aggressive sporadic lymphoma in immunologically uncompromised hosts. We anticipate that it may also prove useful as a

  8. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

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

  9. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

    Science.gov (United States)

    Nakamura, Kentaro; Tonouchi, Hidekazu; Sasayama, Akina; Ashida, Kinya

    2018-02-14

    Low-carbohydrate, high-fat diets (ketogenic diets) might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF) is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR), tumor-bearing (TB), and ketogenic formula (KF) groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum . KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  10. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Kentaro Nakamura

    2018-02-01

    Full Text Available Low-carbohydrate, high-fat diets (ketogenic diets might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR, tumor-bearing (TB, and ketogenic formula (KF groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  11. Tumor Angiogenesis as a Target for Dietary Cancer Prevention

    Directory of Open Access Journals (Sweden)

    William W. Li

    2012-01-01

    Full Text Available Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome, cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.

  12. Integrated imaging (ultrasound, computed tomography, intravenous urography) in diagnosing renal tumors and tumor-like formations

    International Nuclear Information System (INIS)

    Drudi, F.M.; Capanna, G.; Poggi, R.; Occhiato, R.; Iannicelli, E.; Nardo, R.; di Passariello, R.

    1994-01-01

    This is an assessment of semiologic imaging criteria based on computerised tomography, ultrasound diagnosis and intravenous urography in renal tumors. The purpose is to obtain differential diagnostic data capable to modify the treatment approach. Over the last three years, a total of 570 cases of kidney tumors are observed. In 490 of them (86%) the imaging patterns obtained by either of the three techniques leads to correct diagnosis. In 62 of the remaining 80 patients, the integration of two techniques allows to unveil the neoplastic nature of the disease (27 cases), or the presence of a benign process (35 cases). In 15 of the remaining 18 cases only integration of the three techniques results in diagnosing renal tumors or tumor-like conditions (3 adeno-carcinomas, 5 abscesses, 3 cases of tuberculosis, 2 - pyeloxanthogranulomatosis, 2 dysmorphisms). In the last three cases definite diagnosis is made on the basis of needle biopsy. The radiological diagnosis is confirmed intraoperatively or during clinical follow-up study. The obtained data underscore the clinical relevance of imaging integration in evaluating renal lesions. This is particularly valid whenever the clinical data are nonspecific or misleading. 15 refs., 3 figs., 5 tabs. (orig.)

  13. Composite implants coated with biodegradable polymers prevent stimulating tumor progression

    Energy Technology Data Exchange (ETDEWEB)

    Litviakov, N. V., E-mail: nvlitv72@yandex.ru; Tsyganov, M. M., E-mail: TsyganovMM@yandex.ru; Cherdyntseva, N. V., E-mail: nvch@oncology.tomsk.ru [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation); Tverdokhlebov, S. I., E-mail: tverd@tpu.ru; Bolbasov, E. N., E-mail: ebolbasov@gmail.com [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Perelmuter, V. M., E-mail: pvm@ngs.ru; Kulbakin, D. E., E-mail: kulbakin2012@gmail.com [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Zheravin, A. A., E-mail: zheravin2010@yandex.ru [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Academician E.N. Meshalkin Novosibirsk State Research Institute of Circulation Pathology, Novosibirsk (Russian Federation); Svetlichnyi, V. A., E-mail: v-svetlichnyi@bk.ru [National Research Tomsk State University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    In this experiment we studied oncologic safety of model implants created using the solution blow spinning method with the use of the PURASORB PL-38 polylactic acid polymer and organic mineral filler which was obtained via laser ablation of a solid target made of dibasic calcium phosphate dihydrate. For this purpose the implant was introduced into the area of Wistar rats’ iliums, and on day 17 after the surgery the Walker sarcoma was transplanted into the area of the implant. We evaluated the implant’s influence on the primary tumor growth, hematogenous and lymphogenous metastasis of the Walker sarcoma. In comparison with sham operated animals the implant group demonstrated significant inhibition of hematogenous metastasis on day 34 after the surgery. The metastasis inhibition index (MII) equaled 94% and the metastases growth inhibition index (MGII) equaled 83%. The metastasis frequency of the Walker sarcoma in para aortic lymph nodes in the implant group was not statistically different from the control frequency; there was also no influence of the implant on the primary tumor growth noted. In case of the Walker sarcoma transplantation into the calf and the palmar pad of the ipsilateral limb to the one with the implant in the ilium, we could not note any attraction of tumor cells to the implant area, i.e. stimulation of the Walker sarcoma relapse by the implant. Thus, the research concluded that the studied implant meets the requirements of oncologic safety.

  14. Tumor Angiogenesis as a Target for Dietary Cancer Prevention

    OpenAIRE

    Li, William W.; Li, Vincent W.; Hutnik, Michelle; Chiou, Albert S.

    2011-01-01

    Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic d...

  15. Enzymatic treatment for preventing biofilm formation in the paper industry.

    Science.gov (United States)

    Torres, Claudia Esperanza; Lenon, Giles; Craperi, Delphine; Wilting, Reinhard; Blanco, Angeles

    2011-10-01

    Microbiological control programmes at industrial level should aim at reducing both the detrimental effects of microorganisms on the process and the environmental impact associated to the use of biocides as microbiological control products. To achieve this target, new efficient and environmentally friendly products are required. In this paper, 17 non-specific, commercial enzymatic mixtures were tested to assess their efficacy for biofilm prevention and control at laboratory and pilot plant scale. Pectin methylesterase, an enzyme found in the formulation of two of the mixtures tested, was identified as an active compound able to reduce biofilm formation by 71% compared to control tests.

  16. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena

    1995-06-01

    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  17. Dietary supplement use and colorectal tumors : from prevention to diagnosis

    NARCIS (Netherlands)

    Bröring, R.C.

    2015-01-01

    Background: Expert guidelines formulated by the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) advised no use of dietary supplements for cancer prevention. However, it is unclear whether those recommendations also apply to populations at high

  18. Truncated Hormone Inhibits Breast Tumor Blood Vessel Formation, Not Tumor Growth | Center for Cancer Research

    Science.gov (United States)

    The hormone prolactin (PRL) plays a critical role in normal breast development by stimulating the proliferation of mammary cells, the production of milk proteins, and the formation of new mammary blood vessels. Unfortunately, the same cell and vessel growth pathways controlled by PRL in normal cells also operate in breast cancer cells, and elevated plasma PRL is a risk factor for breast cancer, especially in post-menopausal women.

  19. Novel thermosensitive hydrogel for preventing formation of abdominal adhesions

    Directory of Open Access Journals (Sweden)

    Gao X

    2013-07-01

    Full Text Available Xiang Gao,1,2 Xiaohui Deng,3 Xiawei Wei,2 Huashan Shi,2 Fengtian Wang,2 Tinghong Ye,2 Bin Shao,2 Wen Nie,2 Yuli Li,2 Min Luo,2 Changyang Gong,2 Ning Huang1 1Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 3Department of Human Anatomy, Xinxiang Medical University, Xinxiang, People’s Republic of China Abstract: Adhesions can form after almost any type of abdominal surgery. Postoperative adhesions can be prevented by improved surgical techniques, such as reducing surgical trauma, preventing ischemia, and avoiding exposure of the peritoneal cavity to foreign materials. Although improved surgical techniques can potentially reduce formation of adhesions, they cannot be eliminated completely. Therefore, finding more effective methods to prevent postoperative adhesions is imperative. Recently, we found that a novel thermosensitive hydrogel, ie, poly(ε-caprolactone-poly(ethylene glycol-poly(ε-caprolactone (PCEC had the potential to prevent postoperative adhesions. Using the ring-opening polymerization method, we prepared a PCEC copolymer which could be dissolved and assembled at 55°C into PCEC micelles with mean size of 25 nm. At body temperature, a solution containing PCEC micelles could convert into a hydrogel. The PCEC copolymer was biodegradable and had low toxicity in vitro and in vivo. We found that most animals in a hydrogel-treated group (n = 10 did not develop adhesions. In contrast, 10 untreated animals developed adhesions that could only be separated by sharp dissection (P < 0.001. The hydrogel could adhere to peritoneal wounds and degraded gradually over 7–9 days, transforming into a viscous fluid that was completely absorbed within 12 days. The injured parietal and visceral peritoneum remesothelialized over about seven and nine days

  20. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  1. Collaborative Falls Prevention: Interprofessional Team Formation, Implementation, and Evaluation.

    Science.gov (United States)

    Lasater, Kathie; Cotrell, Victoria; McKenzie, Glenise; Simonson, William; Morgove, Megan W; Long, Emily E; Eckstrom, Elizabeth

    2016-12-01

    As health care rapidly evolves to promote person-centered care, evidence-based practice, and team-structured environments, nurses must lead interprofessional (IP) teams to collaborate for optimal health of the populations and more cost-effective health care. Four professions-nursing, medicine, social work, and pharmacy-formed a teaching team to address fall prevention among older adults in Oregon using an IP approach. The teaching team developed training sessions that included interactive, evidence-based sessions, followed by individualized team coaching. This article describes how the IP teaching team came together to use a unique cross-training approach to teach each other. They then taught and coached IP teams from a variety of community practice settings to foster their integration of team-based falls-prevention strategies into practice. After coaching 25 teams for a year each, the authors present the lessons learned from the teaching team's formation and experiences, as well as feedback from practice team participants that can provide direction for other IP teams. J Contin Educ Nurs. 2016;47(12):545-550. Copyright 2016, SLACK Incorporated.

  2. Reciprocal Interactions between Multiple Myeloma Cells and Osteoprogenitor Cells Affect Bone Formation and Tumor Growth

    Science.gov (United States)

    2014-10-01

    SUBJECT TERMS Multiple Myeloma, Blood Cancer , Hematological Malignancy , Bone Metastasis, 3D Model, In vitro, silk scaffolds, osteogenic microRNAs...platform to study cancer -bone interactions. Keywords Multiple Myeloma, Blood Cancer , Hematological Malignancy , Bone Metastasis, 3D Model, In vitro...Affect Bone Formation and Tumor Growth” PRINCIPAL INVESTIGATOR: Michaela Reagan CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute, Inc

  3. USP10 Antagonizes c-Myc Transcriptional Activation through SIRT6 Stabilization to Suppress Tumor Formation

    Directory of Open Access Journals (Sweden)

    Zhenghong Lin

    2013-12-01

    Full Text Available The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

  4. Prevention of organic iodide formation in BWR`s

    Energy Technology Data Exchange (ETDEWEB)

    Karjunen, T. [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland); Laitinen, T.; Piippo, J.; Sirkiae, P. [VTT Manufacturing Technology (Finland)

    1996-12-01

    During an accident, many different forms of iodine may emerge. Organic iodides, such as methyl iodide and ethyl iodide, are relatively volatile, and thus their appearance leads to increased concentration of gaseous iodine. Since organic iodides are also relatively immune to most accident mitigation measures, such as sprays and filters, they can affect the accident source term significantly even when only a small portion of iodine is in organic form. Formation of organic iodides may not be limited by the amount of organic substances available. Excessive amounts of methane can be produced, for example, during oxidation of boron carbide, which is used in BWR`s as a neutron absorber material. Another important source is cable insulation. In a BWR, a large quantity of cables is placed below the pressure vessel. Thus a large quantity of pyrolyse gases will be produced, should the vessel fail. Organic iodides can be formed as a result of many different reactions, but at least in certain conditions the main reaction takes place between an organic radical produced by radiolysis and elemental iodine. A necessary requirement for prevention of organic iodide production is therefore that the pH in the containment water pools is kept high enough to eliminate formation of elemental iodine. In a typical BWR the suppression pool water is usually unbuffered. As a result, the pH may be dominated by chemicals introduced during an accident. If no system for adding basic chemicals is operable, the main factor affecting pool water pH may be hydrochloric acid released during cable degradation. Should this occur, the conditions could be very favorable for production of elemental iodine and, consequently, formation of organic iodides. Although high pH is necessary for iodine retention, it could have also adverse effects. High pH may, for example, accelerate corrosion of containment materials and alter the characteristics of the solid corrosion products. (author) 6 figs., 1 tab., 13 refs.

  5. HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation

    Directory of Open Access Journals (Sweden)

    Anna Spina

    2015-01-01

    Full Text Available Tumor metastases are responsible for approximately 90% of all cancer-related deaths. Metastasis formation is a multistep process that requires acquisition by tumor cells of a malignant phenotype that allows them to escape from the primary tumor site and invade other organs. Each step of this mechanism involves a deep crosstalk between tumor cells and their microenvironment where the host cells play a key role in influencing metastatic behavior through the release of many secreted factors. Among these signaling molecules, Hepatocyte Growth Factor (HGF is released by many cell types of the tumor microenvironment to target its receptor c-MET within the cells of the primary tumor. Many studies reveal that HGF/c-MET axis is implicated in various human cancers, and genetic and epigenetic gain of functions of this signaling contributes to cancer development through a variety of mechanisms. In this review, we describe the specific types of cells in the tumor microenvironment that release HGF in order to promote the metastatic outgrowth through the activation of extracellular matrix remodeling, inflammation, migration, angiogenesis, and invasion. We dissect the potential use of new molecules that interfere with the HGF/c-MET axis as therapeutic targets for future clinical trials in cancer disease.

  6. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    for chemically induced hepatocarcinogenesis, the resistant hepatocyte model. Selenite in supra-nutritional but subtoxic doses (1 and 5 p.p.m.) was administrated to the animals through the drinking water. Such supplementation during the initiation phase did not have a tumor preventive effect. However, selenite...

  7. [Role of tumor microenvironment in the formation and progression of skin melanoma].

    Science.gov (United States)

    Olbryt, Magdalena

    2013-05-14

    Melanoma develops from melanocytes localized mainly in skin, to a lesser extent in uvea and mucosal tissue. It is one of the most aggressive tumors, resistant to standard therapies. It is caused mainly by UV radiation. Approximately 10% of melanomas have a familial background. Transformation of melanocytes is driven mainly by mutations in genes coding for proteins regulating proliferation, cell growth, cell cycle, and death. Although genetic changes are indisputable causes of melanoma formation, the key role of the skin microenvironment is becoming more and more acknowledged. Normal cells of the skin, such as keratinocytes, fibroblasts, endothelial, and immune cells, alongside melanocytes constitute a special microenvironment in which disturbed homeostasis may facilitate melanoma development. The process of transformation is initiated by aberrant interaction of keratinocytes and melanocytes. Proliferation and invasive growth of the developing neoplasm may be further facilitated by myofibroblasts as well as macrophages residing within the tumor. They are able to stimulate angiogenesis and suppress the immune response. Macrophages may, additionally, create aggressive hybrid cells through fusion with melanoma cells. Indispensable in the process of metastasis are endothelial cells which co-form blood vessels, the main routes of tumor cells' seeding. All of the aforementioned processes take place in a tumor growth-promoting atmosphere of low oxygen tension in the skin, further decreasing during tumor growth. Probably the tumor growth-promoting microenvironment is one of the main factors responsible for melanoma aggressiveness.

  8. Effect of Resveratrol on the Prevention of Intra-Abdominal Adhesion Formation in a Rat Model

    Directory of Open Access Journals (Sweden)

    Guangbing Wei

    2016-06-01

    Full Text Available Background: Intra-abdominal adhesions are a very common complication following abdominal surgery. Our previous studies have demonstrated that the inhibition of inflammation at the sites of peritoneal injury can prevent the formation of intra-abdominal adhesions. Resveratrol is a natural extract with a broad range of anti-inflammatory effects. Therefore, we propose that resveratrol can reduce the formation of intra-abdominal adhesions after surgery. The aim of this study was to investigate the effect of resveratrol on intra-abdominal adhesion prevention in a rat model with surgery-induced peritoneal adhesions. Materials and Methods: The cecum wall and its opposite parietal peritoneum were abraded following laparotomy to induce intra-abdominal adhesion formation. Varying doses of resveratrol were administered to the animals. On the eighth day after surgery, the adhesion score was assessed using a visual scoring system. Picrosirius red staining and a hydroxyproline assay were used to assess the amount of collagen deposition in the adhesion tissues. The levels of serum interleukin-6 (IL-6, tumor necrosis factor (TNF-α, and transforming growth factor beta-1 (TGF-β1 were determined by an enzyme-linked immunosorbent assay (ELISA. Western blotting was performed to determine the protein expression of TGF-β1, fibrinogen, and α-smooth muscle actin (α-SMA in rat peritoneal adhesion tissue. Real-time RT-PCR was performed to quantify the mRNA expression of TGF-β1, fibrinogen, and α-SMA. Results: Resveratrol significantly reduced intra-abdominal adhesion formation and fibrin deposition in the rat model. Furthermore, resveratrol significantly reduced the serum levels of IL-6, TNF-α, and TGF-β1. The protein and mRNA expression of TGF-β1, fibrinogen, and α-SMA in the rat peritoneum and adhesion tissues were also down-regulated due to resveratrol intervention. Conclusion: Resveratrol can effectively prevent the formation of postoperative intra

  9. Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase

    Directory of Open Access Journals (Sweden)

    Alakel N

    2017-02-01

    Full Text Available Nael Alakel,1 Jan Moritz Middeke,1 Johannes Schetelig,1,2 Martin Bornhäuser1 1Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden, 2German Bone Marrow Donor Center DKMS, Tübigen, Germany Abstract: Tumor lysis syndrome (TLS is a potentially life-threatening condition that occurs in oncologic and hematologic patients with large tumor burden, either due to cytotoxic therapy or, less commonly, spontaneously because of massive tumor cell lysis. TLS is clinically characterized by acute renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While limited options are available for treating TLS, identifying patients at high risk for developing TLS and prevention in high-risk patients remain an important aspect in the treatment of cancer patients. In general, treatment of TLS consists of intensive hydration, stimulation of diuresis, and, more specifically, in the use of allopurinol and rasburicase. Rasburicase, a recombinant urate oxidase, rapidly and effectively reduces hyperuricemia, which subsequently significantly decreases the risk of acute renal failure and other clinical manifestations of TLS. For this review, a comprehensive literature search using the term “tumor lysis syndrome” and/or “rasburicase” was performed considering articles listed in MEDLINE. Incidence, prevention, and therapy of TLS with a special focus on the role of rasburicase are discussed. We evaluated 120 relevant articles including 35 case reports, 32 clinical trials, and 14 meta-analyses. Keywords: rasburicase, tumor lysis syndrome, hyperuricemia, acute kidney injury

  10. Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection

    DEFF Research Database (Denmark)

    Qvamme, G; Axelsson, C. K.; Lanng, C

    2015-01-01

    BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS: This was a do...

  11. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    Directory of Open Access Journals (Sweden)

    R. Tyler Hillman

    2015-05-01

    Full Text Available Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%. Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13. A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%. Six patients sought insurance approval for a targeted therapy and two were declined (33%. One patient (4% received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.

  12. Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells

    Directory of Open Access Journals (Sweden)

    Florian Kopp

    2014-12-01

    Full Text Available Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC–specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition.

  13. Role of tumor microenvironment in the formation and progression of skin melanoma

    Directory of Open Access Journals (Sweden)

    Magdalena Olbryt

    2013-05-01

    Full Text Available Melanoma develops from melanocytes localized mainly in skin, to a lesser extent in uvea and mucosal tissue. It is one of the most aggressive tumors, resistant to standard therapies. It is caused mainly by UV radiation. Approximately 10�0of melanomas have a familial background. Transformation of melanocytes is driven mainly by mutations in genes coding for proteins regulating proliferation, cell growth, cell cycle, and death. Although genetic changes are indisputable causes of melanoma formation, the key role of the skin microenvironment is becoming more and more acknowledged. Normal cells of the skin, such as keratinocytes, fibroblasts, endothelial, and immune cells, alongside melanocytes constitute a special microenvironment in which disturbed homeostasis may facilitate melanoma development. The process of transformation is initiated by aberrant interaction of keratinocytes and melanocytes. Proliferation and invasive growth of the developing neoplasm may be further facilitated by myofibroblasts as well as macrophages residing within the tumor. They are able to stimulate angiogenesis and suppress the immune response. Macrophages may, additionally, create aggressive hybrid cells through fusion with melanoma cells. Indispensable in the process of metastasis are endothelial cells which co-form blood vessels, the main routes of tumor cells’ seeding. All of the aforementioned processes take place in a tumor growth-promoting atmosphere of low oxygen tension in the skin, further decreasing during tumor growth. Probably the tumor growth-promoting microenvironment is one of the main factors responsible for melanoma aggressiveness.

  14. Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer

    NARCIS (Netherlands)

    Binnemars-Postma, Karin; Bansal, Ruchi; Storm, Gert; Prakash, Jai

    2017-01-01

    Tumor-associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. These protumoral macrophages display an M2 phenotype induced by IL-4 and IL-13 cytokines. In this

  15. Spontaneous Formation of Tumorigenic Hybrids between Breast Cancer and Multipotent Stromal Cells Is a Source of Tumor Heterogeneity

    OpenAIRE

    Rappa, Germana; Mercapide, Javier; Lorico, Aurelio

    2012-01-01

    Breast cancer progression involves cancer cell heterogeneity, with generation of invasive/metastatic breast cancer cells within populations of nonmetastatic cells of the primary tumor. Sequential genetic mutations, epithelial-to-mesenchymal transition, interaction with local stroma, and formation of hybrids between cancer cells and normal bone marrow–derived cells have been advocated as tumor progression mechanisms. We report herein the spontaneous in vitro formation of heterotypic hybrids be...

  16. [Secondary prevention after urological tumor diseases. Focusing on the kidneys, testes, and bladder].

    Science.gov (United States)

    Mathers, M J; Lazica, D A; Klotz, T; Sommer, F; Roth, S

    2007-06-01

    It is generally agreed upon that patients require a caring as well as careful medical follow-up after cancer treatment. The goal of secondary prevention is to recognize a recurrence at an early stage and to use the curative chance while the tumor mass is still small. There is evidence of a medically effective and successful follow-up for tumors of the testicle and the bladder. For quality reasons, these follow-up regimes should be adhered to for quality reasons. In other diseases, e.g., renal cell carcinoma, prospective randomized studies are missing which demonstrate the effectiveness of follow-ups. In these cases asymptomatic patients should be stratified to individualized follow-up care.

  17. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.

  18. Treatment and prevention of tumor lysis syndrome in children. Experience of Associazione Italiana Ematologia Oncologia Pediatrica.

    Science.gov (United States)

    Pession, Andrea; Barbieri, Eveline

    2005-01-01

    Hyperuricemia and tumor lysis syndrome (TLS) are complications that can arise from treatment of rapidly proliferating and drug-sensitive neoplasms. Clinical trials have shown rasburicase, a recombinant urate oxidase to be more effective than allopurinol for the prevention and treatment of malignancy-associated hyperuricemia. We investigated the safety and efficacy of rasburicase in the AIEOP centers' experience. We reviewed the data of 26 children with malignancy at risk for TLS, submitted to treatment (group 1) or prophylaxis (group 2) of acute hyperuricemia with rasburicase (0.20 mg/kg intravenously daily) for a median period of 4 days. Rasburicase produced a significant decrease in uric acid concentrations in all the patients. The control of uric acid levels was obtained in both the groups within 24 h of the first dose with a response rate of 100% (group 1) and 93% (group 2). Normalization of creatinine and phosphorus levels was obtained in 5 and 4 days respectively. Tolerance was excellent without toxicity. These data confirm that rasburicase is a safe, highly and rapidly effective agent in the treatment and prevention of malignancy-associated acute hyperuricemia and could be considered the treatment of choice to prevent tumor lysis syndrome in children at high risk for this metabolic complication.

  19. Does vitamin E-blended UHMWPE prevent biofilm formation?

    Science.gov (United States)

    Williams, Dustin L; Vinciguerra, John; Lerdahl, Julia M; Bloebaum, Roy D

    2015-03-01

    Biofilm-related periprosthetic infections are catastrophic to patients and clinicians. Data suggest the addition of vitamin E to UHMWPE may have the ability to reduce biofilm formation on the surface of UHMWPE; however, previous studies were performed using stagnant broth solutions that may not have simulated a physiologic environment. In addition, the observed differences in levels of bacterial attachment, though statistically significant, may not be clinically significant. We blended vitamin E with UHMWPE material and tested it for the ability to resist biofilm formation using a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). Three additional materials were tested for comparison: highly crosslinked UHMWPE, compression-molded UHMWPE, and polyetheretherketone. We also determined whether the surface roughness of these materials facilitated biofilm formation. Using a flow cell system, samples of each material type were placed into separate chambers. A 10% solution of brain-heart infusion broth containing 10(5) colony-forming units (CFUs)/mL was flowed through the flow cell over 48 hours. The number of bacteria that adhered to the surface was quantified and biofilm formation was observed qualitatively using scanning electron microscopy. Optical profilometry was used to determine the surface roughness of each material type. Vitamin E-blended UHMWPE did not reduce biofilm formation of a clinically relevant strain of MRSA compared to materials that did not have vitamin E. More specifically, vitamin E-blended materials had similar amounts of biofilm formation (~ 8 log10 CFUs/cm(2)) compared to materials not containing vitamin E (~ 8.1 log10 CFUs/cm(2)) (p > 0.4). The roughness of vitamin E-blended material surfaces (mean ± SD: 1.85 ± 0.46 µm) compared to that of materials without vitamin E (2.06 ± 1.24 µm) did not appear to influence biofilm formation. Under physiologically relevant conditions, vitamin E-blended UHMWPE did not have the ability

  20. Causes and preventive management of scale formation in oilfield ...

    African Journals Online (AJOL)

    ... removal of at least one scaling component from the system, pH reduction, choosing a surface that resists scale adhesion, application of physical fields example magnetic or electrostatic, the use of scale inhibitors and proactive application of scale prediction models or soft wares. Keywords: Scale formation, oilfield systems ...

  1. Prevention of biofilm formation in dialysis water treatment systems.

    Science.gov (United States)

    Smeets, Ed; Kooman, Jeroen; van der Sande, Frank; Stobberingh, Ellen; Frederik, Peter; Claessens, Piet; Grave, Willem; Schot, Arend; Leunissen, Karel

    2003-04-01

    Biofilm formations in dialysis systems may be relevant because they continuously release bacterial compounds and are resistant against disinfection. The aim of the study was to compare the development of biofilm between a water treatment system based on a single reverse osmosis unit producing purified dialysate water [bacterial count, 350 colony-forming unit (CFU)/L] (center A) and a water treatment system based on double reverse osmosis and electric deionization, which is continuously disinfected with ultraviolet light and treated with ozone once a week (bacterial count, 1 CFU/L) (center B). During a period of 12 weeks, biofilm formation was studied in the tubing segment between the water piping and the dialysis module, using four dialysis monitors in each center. On a weekly basis, tubing samples of 5 cm length (N = 96) were taken under aseptic conditions and investigated for microbiologic contamination [cystine lactose electrolyte-deficient (CLED) Agar], endotoxin levels [limulus amoeben lysate (LAL) gel test, cutoff value, 0.0125 EU/mL], and biofilm formation [electron scanning microscopy (SEM)]. In center A, tube cultures were positive (>100 CFU/mL) in 16% of samples at 22 degrees C and 37 degrees C, compared to 3% of samples of center B (P tubing samples of center A and negative in all of the samples of center B (P < 0.05). Biofilm was present in 91.7% of the samples of center A (Fig. 1), and only present in one sample (taken after 9 weeks) of center B (P < 0.05) (Fig. 2). In center A, biofilm formation was already observed after 1 week. In contrast to a standard water treatment system producing purified water, the use of a system producing highly purified water, which is also treated with regular disinfection procedures, leads to a significant reduction in biofilm formation, bacterial growth, and endotoxin levels in a highly vulnerable part of a water treatment system.

  2. Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xi, E-mail: xizheng@rci.rutgers.edu [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Cui, Xiao-Xing [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Khor, Tin Oo; Huang, Ying [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); DiPaola, Robert S; Goodin, Susan [Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Lee, Mao-Jung [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Yang, Chung S [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Kong, Ah-Ng [Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); Allan H, Conney [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States)

    2011-09-28

    In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that γ-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of γ-TmT increased the levels of α-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that γ-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of γ-TmT for prostate cancer in humans.

  3. Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice

    International Nuclear Information System (INIS)

    Zheng, Xi; Cui, Xiao-Xing; Khor, Tin Oo; Huang, Ying; DiPaola, Robert S; Goodin, Susan; Lee, Mao-Jung; Yang, Chung S; Kong, Ah-Ng; Allan H, Conney

    2011-01-01

    In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that γ-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of γ-TmT increased the levels of α-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that γ-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of γ-TmT for prostate cancer in humans

  4. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  5. Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Pimenta, Erica M. [Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States); Barnes, Betsy J., E-mail: barnesbe@njms.rutgers.edu [Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States)

    2014-04-23

    Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin{sup ®}) and rituximab (Rituxan{sup ®})) and the first approved cancer vaccine, Provenge{sup ®} (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.

  6. Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    International Nuclear Information System (INIS)

    Pimenta, Erica M.; Barnes, Betsy J.

    2014-01-01

    Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin ® ) and rituximab (Rituxan ® )) and the first approved cancer vaccine, Provenge ® (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response

  7. Role of Tertiary Lymphoid Structures (TLS in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Directory of Open Access Journals (Sweden)

    Erica M. Pimenta

    2014-04-01

    Full Text Available Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin® and rituximab (Rituxan® and the first approved cancer vaccine, Provenge® (sipuleucel-T, investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS within the tumor microenvironment may be used to enhance immunotherapy response.

  8. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity

    DEFF Research Database (Denmark)

    Danovi, Davide; Meulmeester, Erik; Pasini, Diego

    2004-01-01

    Human tumors are believed to harbor a disabled p53 tumor suppressor pathway, either through direct mutation of the p53 gene or through aberrant expression of proteins acting in the p53 pathway, such as p14(ARF) or Mdm2. A role for Mdmx (or Mdm4) as a key negative regulator of p53 function in vivo...

  9. A simple and effective approach for treatment of situs tumor and metastasis:to promote intratumor pus formation

    Directory of Open Access Journals (Sweden)

    Hong Li

    2015-12-01

    Full Text Available Purpose: The recent emergence of the tumor microenvironment as the critical determinant in cancer outcome opens a new routes to fight cancer, however, the clinical results of targeting microenvironment for treating human cancer have not met expectations. Our purpose is to investigate how to target microenvironment for treatment of situs tumor and metastasis.Methods : We suppose that tumor is a robber from times of anarchy and disorder and can be eradicated in flourishing age. We also suppose that carcinogenesis is largely attributed to physically weak that cann’t get rid of ulcer by pus formation. In vivo,the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of Astragalus mongholicus(huangqi and Spina Gleditsiae (zaojiaoci by intragastric administration b.i.d for ten weeks, and the influences of Astragalus mongholicus and Spina Gleditsiae  on tumor progression were evaluated by body temperature,blood oxygen saturation,red cell ATPase,blood  rheology,intratumor hypoxia,capillary permeability, matrix metalloproteinase (MMPs and intratumor pus formation.  Results:We found that both of Astragalus mongholicus and Spina Gleditsiae could keep body temperature,blood oxygen saturation,red cell ATPase and blood rheology,and improve intratumor hypoxia,capillary permeability and MMPs in tumor bearing mice,which led to slower tumor growth and less metastasis. Astragalus mongholicus could remove body poison and stimulate immune responses, and Spina Gleditsiae  could  promote pus formation and proteolytic enzymes. The combination of  Astragalus mongholicus and Spina Gleditsiae favored the restoration of tumor immune responses and proteolytic activity at the tumor site, which not only result to an increase in aseptic pus formation, but also to a decrease in necrotic tissue accumulation, and finally caused a complete intratumor pus

  10. The manner in which calories are restricted impacts mammary tumor cancer prevention

    Directory of Open Access Journals (Sweden)

    Margot P Cleary

    2011-01-01

    Full Text Available Although treatments for breast cancer have improved and long-term survival after diagnosis is now common, prevention of the disease is the ultimate goal. Weight loss or weight maintenance is one approach that has been recommended to reduce the risk of breast cancer, particularly for peri/postmenopausal women. This approach is supported by decades of data indicating that calorie restriction prevents spontaneous and chemically induced mammary tumor development in rodents. In most cases, calorie restriction was implemented by a consistent daily reduction of calories, i.e. chronic calorie restriction (CCR. There have also been several studies where periods of reduced caloric intake were followed by periods of refeeding, i.e. intermittent calorie restriction (ICR, resulting in the prevention of spontaneous mammary tumorigenesis. In most of the early studies, there were no direct comparisons of CCR to ICR. One study using moderate calorie restriction in a chemically induced breast cancer rat model found a slight increase in mammary tumor incidence compared with ad libitum fed and CCR rats. However, recently, it has been demonstrated in several transgenic mouse models of breast cancer that ICR consistently provided a greater degree of protection than CCR. This review will provide a detailed comparison of ICR and CCR for breast cancer prevention. It will also examine potential mechanisms of action that may include periods of reduced IGF-I and leptin as well as an increase in the adiponectin:leptin ratio. Application of this approach to at-risk women may provide an approach to lower the risk of breast cancer in overweight/obese women.

  11. Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth.

    Science.gov (United States)

    Xia, Siyuan; Lin, Ruiting; Jin, Lingtao; Zhao, Liang; Kang, Hee-Bum; Pan, Yaozhu; Liu, Shuangping; Qian, Guoqing; Qian, Zhiyu; Konstantakou, Evmorfia; Zhang, Baotong; Dong, Jin-Tang; Chung, Young Rock; Abdel-Wahab, Omar; Merghoub, Taha; Zhou, Lu; Kudchadkar, Ragini R; Lawson, David H; Khoury, Hanna J; Khuri, Fadlo R; Boise, Lawrence H; Lonial, Sagar; Lee, Benjamin H; Pollack, Brian P; Arbiser, Jack L; Fan, Jun; Lei, Qun-Ying; Chen, Jing

    2017-02-07

    Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice. Treatment with hypolipidemic agents to lower circulating acetoacetate levels or an inhibitory homolog of acetoacetate, dehydroacetic acid, to antagonize acetoacetate-BRAF V600E binding attenuated BRAF V600E tumor growth. These findings reveal a signaling basis underlying a pathogenic role of dietary fat in BRAF V600E-expressing melanoma, providing insights into the design of conceptualized "precision diets" that may prevent or delay tumor progression based on an individual's specific oncogenic mutation profile. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. [Innovations on technology, management and concept are indispensible for scientific research, prevention and treatment of malignant tumor in China].

    Science.gov (United States)

    Cao, G W

    2017-01-10

    Malignant tumor has become the top cause of deaths before the average life expectancy in Chinese population. From the variations in the morbidity rate and mortality rate of malignant tumor in the mainland of China between 2000 and 2011, the primary prevention targeting the risk factors/etiological agents significantly reduced the morbidity rates of gastric cancer, esophageal cancer, and primary liver cancer, therefore reduced the mortality rates of these cancers. However, the contribution of clinical treatments to the mortality reduction was not obviously improved during this period. Importantly, it is necessary to conduct research to identify precancerous lesions and early tumors which are prone to progress to aggressive diseases for the active secondary prevention to avoid over-diagnosis and over-treatment. Multi-center, prospective randomized controlled clinical trials and prognosis evaluation independently carried out by third parts are needed to evaluate the longterm effectiveness of some clinical treatment efficiency for cancers with different histological types. On the basis of a series of population-based studies in China, the prevention and clinical treatments for malignant tumor need innovations on technology, management, and even concept; the mechanisms of "forward placement of strategic pass" for the prevention and control of malignant tumor should be established and improved to reduce the increasing disease burden due to malignant tumor in China.

  13. Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.

    Directory of Open Access Journals (Sweden)

    Maoyong Fu

    Full Text Available Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2, a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

  14. State of cellular and humoral immune system in women of reproductive age with tumor-like ovary formations

    Directory of Open Access Journals (Sweden)

    O. S. Shapoval

    2014-12-01

    Full Text Available Aim. Violations occurring in the immune system in women with ovary tumor-like formations are one of the most important factors in the pathogenesis and development of the disease. In order to study features of immune disorders in 105 women of reproductive age with tumor-like ovary formations determination of cellular and humoral immunity indices was carried out. Methods and results. Variants of immunological reactivity in women with tumor-like ovary formations with different possibilities of reproductive function implementing were established. Conclusion. This indicates that the identification of one of the variants of immunological reactivity disorder in the precurative stage is one of the components of the effective prescribed therapy necessary to select the appropriate tactics of medical correction of homeostasis.

  15. Prevention of human papillomavirus (HPV)-related tumors in people living with human immunodeficiency virus (HIV).

    Science.gov (United States)

    Poljak, Mario; Šterbenc, Anja; Lunar, Maja M

    2017-11-01

    In comparison to their HIV-negative counterparts, people living with HIV (PLWH) have a higher prevalence of human papillomavirus (HPV) infection in various anatomical sites coupled with increased HPV persistence, higher risk of HPV-related tumors, and faster disease progression. Areas covered: Gender-neutral prevention strategies for HPV-related cancers in PLWH discussed: ABC approach, HPV vaccination, antiretroviral treatment (ART), anal cancer screening, and smoking cessation. Gender specific strategies: cervical cancer screening reduces the incidence and mortality of cervical cancer and circumcision might reduce the risk of HPV infections in men. Expert commentary: HPV-related cancer incidence has not declined (e.g. cervical cancer) and has even increased (e.g. anal cancer) in the ART era, demanding an effective HPV prevention strategy. HPV vaccination should be introduced into national prevention programs worldwide immediately because current prophylactic vaccines are safe, tolerable, and immunogenic in PLWH. HPV vaccine efficacy trials in PLWH are essential to determine the most appropriate immunization schedule. The population most at risk of anal cancer is HIV-positive men who have sex with men, who are not protected by herd immunity if only the female population is vaccinated. Unvaccinated PLWH need enhanced surveillance for early detection of HPV-related cancers and their precursors.

  16. Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells.

    Science.gov (United States)

    Guillem-Llobat, Paloma; Dovizio, Melania; Bruno, Annalisa; Ricciotti, Emanuela; Cufino, Valerio; Sacco, Angela; Grande, Rosalia; Alberti, Sara; Arena, Vincenzo; Cirillo, Mariangela; Patrono, Carlo; FitzGerald, Garret A; Steinhilber, Dieter; Sgambato, Alessandro; Patrignani, Paola

    2016-05-31

    We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and a proaggregatory action on platelets. These changes were prevented by different antiplatelet agents, aspirin[an inhibitor of cyclooxygenase(COX)-1], DG-041[an antagonist of prostaglandin(PG)E2 EP3 receptor] and ticagrelor (a P2Y12 receptor antagonist). The injection of HT29 cells, exposed to platelets in vitro, into the tail vein of humanized immunodeficient mice led to higher incidence of lung metastasis compared to the injection of untreated HT29 cells. This effect was associated with enhanced systemic biosynthesis of thromboxane(TX)A2 and PGE2in vivo. Platelet COX-1 inhibition by aspirin administration to mice prevented the increased rate of metastasis as well as the enhanced production of TXA2 and PGE2 induced by the in vitro priming of HT29 cells by platelets. In conclusion, targeting platelet COX-1 with low-dose aspirin exerts an antimetastatic action by averting the stem cell mimicry of cancer cells associated with enhanced proaggregatory effects induced by platelet-tumor cell interactions. These effects may be shared by other antiplatelet drugs.

  17. Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells

    NARCIS (Netherlands)

    Perdicchio, Maurizio; Cornelissen, Lenneke A. M.; Streng-Ouwehand, Ingeborg; Engels, Steef; Verstege, Marleen I.; Boon, Louis; Geerts, Dirk; van Kooyk, Yvette; Unger, Wendy W. J.

    2016-01-01

    The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector

  18. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

    DEFF Research Database (Denmark)

    Seminatore, Christine; Polentes, Jerome; Ellman, Ditte

    2010-01-01

    Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors....

  19. Suprarenal inferior vena cava filter placement prior to transcatheter arterial embolization (TAE) of a renal cell carcinoma with large renal vein tumor thrombus: Prevention of pulmonary tumor emboli after TAE

    International Nuclear Information System (INIS)

    Hirota, Shozo; Matsumoto, Shinnichi; Ichikawa, Satoshi; Tomita, Masaru; Koshino, Tukasa; Sako, Masao; Kono, Michio

    1997-01-01

    To prevent embolization of necrotic renal vein tumor after transcatheter embolization of a left renal cell carcinoma, we placed a suprarenal Bird's nest inferior vena cava filter. The patient tolerated the procedure well and had extensive tumor infarction including the tumor thrombus on 6-month follow-up computed tomography

  20. Nicorandil prevents sirolimus-induced production of reactive oxygen species, endothelial dysfunction, and thrombus formation

    Directory of Open Access Journals (Sweden)

    Ken Aizawa

    2015-03-01

    Full Text Available Sirolimus (SRL is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS play a critical role in endothelial dysfunction and thrombus formation. The present study investigated the protective effect of nicorandil (NIC, an anti-angina agent, on SRL-associated thrombosis. In human coronary artery endothelial cells (HCAECs, SRL stimulated ROS production, which was prevented by co-treatment with NIC. The preventive effect of NIC on ROS was abolished by 5-hydroxydecanoate but not by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. NIC also inhibited SRL-induced up-regulation of NADPH oxidase subunit p22phox mRNA. Co-treatment with NIC and SRL significantly up-regulated superoxide dismutase 2. NIC treatment significantly improved SRL-induced decrease in viability of HCAECs. The functional relevance of the preventive effects of NIC on SRL-induced ROS production and impairment of endothelial viability was investigated in a mouse model of thrombosis. Pretreatment with NIC inhibited the SRL-induced acceleration of FeCl3-initiated thrombus formation and ROS production in the testicular arteries of mice. In conclusion, NIC prevented SRL-induced thrombus formation, presumably due to the reduction of ROS and to endothelial protection. The therapeutic efficacy of NIC could represent an additional option in the prevention of SRL-related thrombosis.

  1. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

    Science.gov (United States)

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, José; Anderson, Kathryn V

    2016-01-01

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

  2. Cytochrome b5 reductase 2 suppresses tumor formation in nasopharyngeal carcinoma by attenuating angiogenesis.

    Science.gov (United States)

    Ming, Huixin; Lan, Ying; He, Feng; Xiao, Xue; Zhou, Xiaoying; Zhang, Zhe; Li, Ping; Huang, Guangwu

    2015-08-15

    Cytochrome b5 reductase 2 (CYB5R2) is a potential tumor suppressor that inhibits cell proliferation and motility in nasopharyngeal carcinoma (NPC). Inactivation of CYB5R2 is associated with lymph node metastasis in NPC. This study aimed to explore the mechanisms contributing to the anti-neoplastic effects of CYB5R2. Polymerase chain reaction (PCR) assays were used to analyze the transcription of 84 genes known to be involved in representative cancer pathways in the NPC cell line HONE1. NPC cell lines CNE2 and HONE1 were transiently transfected with CYB5R2, and data was validated by real-time PCR. A chick chorioallantoic membrane (CAM) embryo model was implanted with CYB5R2-expressing CNE2 and HONE1 cells to evaluate the effect of CYB5R2 on angiogenesis. An immunohistochemical assay of the CAM model was used to analyze the protein expression of vascular endothelial growth factor (VEGF). In CYB5R2-transfected NPC cells, PCR assays revealed up-regulated mRNA levels of Fas cell surface death receptor (FAS), FBJ murine osteosarcoma viral oncogene homolog (FOS), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), integrin beta 3 (ITGB3), metastasis suppressor 1 (MTSS1), interferon beta 1 (IFNB1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) and down-regulated levels of integrin beta 5 (ITGB5), insulin-like growth factor 1 (IGF1), TEK tyrosine kinase (TEK), transforming growth factor beta receptor 1 (TGFBR1), and VEGF. The angiogenesis in the CAM model implanted with CYB5R2-transfected NPC cells was inhibited. Down-regulation of VEGF by CYB5R2 in NPC cells was confirmed by immunohistochemical staining in the CAM model. CYB5R2 up-regulates the expression of genes that negatively modulate angiogenesis in NPC cells and down-regulates the expression of VEGF to reduce angiogenesis, thereby suppressing tumor formation.

  3. Does salivary duct repositioning prevent complications after tumor resection or salivary gland surgery?

    Science.gov (United States)

    Sakakibara, Akiko; Minamikawa, Tsutomu; Hashikawa, Kazunobu; Sakakibara, Shunsuke; Hasegawa, Takumi; Akashi, Masaya; Furudoi, Shungo; Komori, Takahide

    2015-05-01

    Tissue that is resected for the treatment of oral tumors often includes salivary gland ducts. At their institution, the authors conserve and transfer as much of the salivary duct as possible during these procedures to avoid obstructive complications. Differentiating these obstructive complications from a metastatic node can be challenging and can confound subsequent oncologic management. This study compared and examined the effectiveness of salivary duct repositioning in decreasing the incidence of obstructive complications. Cases of oromandibular disease treated with salivary duct resection at Kobe University Graduate School of Medicine from 2008 to 2013 were retrospectively analyzed. Thirty-two cases (25 patients) of Wharton duct resection and 31 cases (31 patients) of Stensen duct resection were included. The incidence of complications after salivary duct repositioning, duct ligation, and retention of the sublingual gland around the Wharton duct was compared. Wharton ducts were repositioned in 30 cases and ligated in 2 cases. Complications, including oral swelling at the Wharton duct, were observed in 5 cases of repositioning and 2 cases of ligation. Stensen ducts were repositioned in 9 cases and ligated in 22 cases. The only complication reported was a single case of salivary fistula after ligation. Salivary duct repositioning is performed to prevent blockage of physiologic salivary discharge. Complications were more frequently associated with Wharton ducts than with Stensen ducts because of the unique physiologic and anatomic characteristics of the Wharton duct. Repositioning of the salivary duct is a suitable method for preventing complications associated with the Wharton duct. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

    Directory of Open Access Journals (Sweden)

    Fabio Penna

    Full Text Available BACKGROUND: The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

  5. Regulation of Mammary Tumor Formation and Lipid Biosynthesis by Spot14

    Science.gov (United States)

    2014-06-01

    Months 6-9) The preserved tumor samples collected from the recipient mice will be analyzed using qPCR, western blot, MRS, and immunohistochemistry...diameter. The tumor and other tissues will be harvested and preserved . We anticipate completing this aim in the second quarter of the second year...significantly elevated genes in Neu/S14 tumors was Elf5, a transcription factor that regulates alveolar differentiation during pregnancy in the mouse mammary

  6. The use of theory based semistructured elicitation questionnaires: formative research for CDC's Prevention Marketing Initiative.

    Science.gov (United States)

    Middlestadt, S E; Bhattacharyya, K; Rosenbaum, J; Fishbein, M; Shepherd, M

    1996-01-01

    Through one of its many HIV prevention programs, the Prevention Marketing Initiative, the Centers for Disease Control and Prevention promotes a multifaceted strategy for preventing the sexual transmission of HIV/AIDS among people less than 25 years of age. The Prevention Marketing Initiative is an application of marketing and consumer-oriented technologies that rely heavily on behavioral research and behavior change theories to bring the behavioral and social sciences to bear on practical program planning decisions. One objective of the Prevention Marketing Initiative is to encourage consistent and correct condom use among sexually active young adults. Qualitative formative research is being conducted in several segments of the population of heterosexually active, unmarried young adults between 18 and 25 using a semistructured elicitation procedure to identify and understand underlying behavioral determinants of consistent condom use. The purpose of this paper is to illustrate the use of this type of qualitative research methodology in designing effective theory-based behavior change interventions. Issues of research design and data collection and analysis are discussed. To illustrate the methodology, results of content analyses of selected responses to open-ended questions on consistent condom use are presented by gender (male, female), ethnic group (white, African American), and consistency of condom use (always, sometimes). This type of formative research can be applied immediately to designing programs and is invaluable for valid and relevant larger-scale quantitative research.

  7. Formative research in a school-based obesity prevention program for Native American school children (Pathways)

    Science.gov (United States)

    Gittelsohn, Joel; Evans, Marguerite; Helitzer, Deborah; Anliker, Jean; Story, Mary; Metcalfe, Lauve; Davis, Sally; Cloud, Patty Iron

    2016-01-01

    This paper describes how formative research was developed and implemented to produce obesity prevention interventions among school children in six different Native American nations that are part of the Pathways study. The formative assessment work presented here was unique in several ways: (1) it represents the first time formative research methods have been applied across multiple Native American tribes; (2) it is holistic, including data collection from parents, children, teachers, administrators and community leaders; and (3) it was developed by a multi-disciplinary group, including substantial input from Native American collaborators. The paper describes the process of developing the different units of the protocol, how data collection was implemented and how analyses were structured around the identification of risk behaviors. An emphasis is placed on describing which units of the formative assessment protocol were most effective and which were less effective. PMID:10181023

  8. Interaction of Munc18c and syntaxin4 facilitates invadopodium formation and extracellular matrix invasion of tumor cells.

    Science.gov (United States)

    Brasher, Megan I; Martynowicz, David M; Grafinger, Olivia R; Hucik, Andrea; Shanks-Skinner, Emma; Uniacke, James; Coppolino, Marc G

    2017-09-29

    Tumor cell invasion involves targeted localization of proteins required for interactions with the extracellular matrix and for proteolysis. The localization of many proteins during these cell-extracellular matrix interactions relies on membrane trafficking mediated in part by SNAREs. The SNARE protein syntaxin4 (Stx4) is involved in the formation of invasive structures called invadopodia; however, it is unclear how Stx4 function is regulated during tumor cell invasion. Munc18c is known to regulate Stx4 activity, and here we show that Munc18c is required for Stx4-mediated invadopodium formation and cell invasion. Biochemical and microscopic analyses revealed a physical association between Munc18c and Stx4, which was enhanced during invadopodium formation, and that a reduction in Munc18c expression decreases invadopodium formation. We also found that an N-terminal Stx4-derived peptide associates with Munc18c and inhibits endogenous interactions of Stx4 with synaptosome-associated protein 23 (SNAP23) and vesicle-associated membrane protein 2 (VAMP2). Furthermore, expression of the Stx4 N-terminal peptide decreased invadopodium formation and cell invasion in vitro Of note, cells expressing the Stx4 N-terminal peptide exhibited impaired trafficking of membrane type 1 matrix metalloproteinase (MT1-MMP) and EGF receptor (EGFR) to the cell surface during invadopodium formation. Our findings implicate Munc18c as a regulator of Stx4-mediated trafficking of MT1-MMP and EGFR, advancing our understanding of the role of SNARE function in the localization of proteins that drive tumor cell invasion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

    Directory of Open Access Journals (Sweden)

    Roberta Lotti

    2016-01-01

    Full Text Available Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC originate from alterations in keratinocyte stem cells (KSC gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD and non-RAD (NRAD cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin, while it increases the level of differentiation markers (K10, involucrin. Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

  10. Over-expression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor null mice

    OpenAIRE

    Teichert, Arnaud; Elalieh, Hashem; Elias, Peter; Welsh, JoEllen; Bikle, Daniel D.

    2011-01-01

    The vitamin D receptor (VDR) ligand, 1,25(OH)2D3, reduces proliferation and enhances differentiation and thus has been investigated for a role in preventing or treating cancer. Mice deficient for the VDR display a hyperproliferative response in the hair follicle and epidermis and decreased epidermal differentiation. Unlike their wild type littermates, when treated with 7,12 dimethylbenzanthracene (DMBA) or UVB, they develop skin tumors, including some characteristic of over-expression of the ...

  11. Control and prevention of ice formation and accretion on heat exchangers for ventilation systems

    DEFF Research Database (Denmark)

    Rahimi, Maral; Afshari, Alireza

    2015-01-01

    In cold climates, the application of mechanical ventilation systems with heat recovery like are airto-air exchangers is used for reducing energy consumption for heating buildings by transferring heat exhausted air to supply air. However, increase efficiency of heat exchanger results in lower...... exhaust air temperatures and Ice formation on heat exchanger fins, which can cause problem and is not favourable. Therefore, prevention and control of ice formation on heat exchangers is necessary. The existing methods are divided into two different methods: active and passive ice control methods...

  12. Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.

    Science.gov (United States)

    Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

    2006-05-01

    Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (Phibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (Phibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the

  13. The educative prevention of the early stage of educationist’s formation.

    OpenAIRE

    Marta Alfonso Nazco; Evaristo Reinoso Porra; Ana Consuelo Figueroa Carbonell

    2010-01-01

    The article introduces a characterization of the educative prevention stage at the early professional formation process of educacionist in Sancti Spìritus province. The study is done by the indication analysis of assistant, learning, permanence and behavior at youths who course pedagogical carrers, and haven’t expressed a desire stage yet. The main shown results dealt with the assumption of the searching variables and its indicators, the construction of instruments and the definition of aspec...

  14. Formative research to inform intervention development for diabetes prevention in the Republic of the Marshall Islands.

    Science.gov (United States)

    Cortes, L M; Gittelsohn, J; Alfred, J; Palafox, N A

    2001-12-01

    Formative research was conducted in the Republic of the Marshall Islands to help develop a diabetes prevention intervention. Methods included in-depth interviews, semistructured interviews, and direct observation of household behaviors in urban and remote settings. Foods were classified into two main conceptual spheres: foods from the islands/Marshallese foods and imported/American foods. Diabetes (nanimij in tonal) is a highly salient illness and is believed to be caused by foods high in fat and sugar, consumption of imported/American foods, family background, and the atomic bomb testing. Physical activity and eating a traditional diet were viewed as important for preventing diabetes. The traditional belief system links a large body with health, and a thin body with illness; however, perceptions are changing with increased acculturation and education about the health risks of obesity. These findings were used to develop a diabetes prevention home visit intervention currently being implemented and evaluated in Marshallese households.

  15. Prevention of spontaneous and radiation-induced tumors in rats by reduction of food intake

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.

    1990-01-01

    In our previous studies carried out on inbred Sprague-Dawley rats, we reported a striking increase in the incidence of tumors following total-body gamma-irradiation [150 rads (1.5 Gy) five times at weekly intervals]. Subsequently, we observed that two or three irradiations, and to a lesser extent even a single irradiation, were sufficient to induce an impressive increase in the incidence of tumors, particularly in females. A significant reduction of the incidence of radiation-induced tumors resulted when the rats were placed on calorically restricted diet. In experiments reported here, we increased slightly the amount of food given to animals on restricted diet. In the new study, among 102 irradiated females on full diet, 91 (89%) developed tumors, as compared with 29 out of 128 female rats (23%) also irradiated but maintained on restricted diet and 43 out of 89 (48%) untreated control females. None of 77 nonirradiated females on restricted diet developed tumors. Among 65 irradiated male rats, 29 (45%) developed tumors, as compared with 5 out of 74 (7%) rats also irradiated but maintained on restricted diet. Of the 49 males in the nonirradiated groups, 2 (4%) developed tumors. There was a significant weight reduction in both females and males maintained on restricted diet; animals on restricted diet lived longer than those on full diet

  16. Formation of Gold Nanostar-Coated Hollow Mesoporous Silica for Tumor Multimodality Imaging and Photothermal Therapy.

    Science.gov (United States)

    Li, Xin; Xing, Lingxi; Zheng, Kailiang; Wei, Ping; Du, Lianfang; Shen, Mingwu; Shi, Xiangyang

    2017-02-22

    Development of multifunctional nanoplatforms for tumor multimode imaging and therapy is of great necessity. Herein, we report a new type of Au nanostar (NS)-coated, perfluorohexane (PFH)-encapsulated hollow mesoporous silica nanocapsule (HMS) modified with poly(ethylene glycol) (PEG) for tumor multimode ultrasonic (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, and photothermal therapy (PTT). HMSs were first synthesized, silanized to have thiol surface groups, and coated with gold nanoparticles via a Au-S bond. Followed by growth of Au NSs on the surface of the HMSs, encapsulation of PFH in the interior of the HMSs, and surface conjugation of thiolated PEG, multifunctional HMSs@Au-PFH-mPEG NSs (for short, HAPP) were formed and well-characterized. We show that the HAPP are stable in a colloidal manner and noncytotoxic in the studied range of concentrations, possess multimode US/CT/PA/thermal imaging ability, and can be applied for multimode US/CT/PA/thermal imaging of tumors in vivo after intravenous or intratumoral injection. Additionally, the near-infrared absorption property of the HAPP enables the use of the HAPP for photothermal ablation of cancer cells in vitro and a tumor model in vivo after intratumoral injection. The developed multifunctional HAPP may be used as a novel multifunctional theranostic nanoplatform for tumor multimode imaging and PTT.

  17. Expression of stabilized β-catenin in differentiated neurons of transgenic mice does not result in tumor formation

    International Nuclear Information System (INIS)

    Kratz, John E; Stearns, Duncan; Huso, David L; Slunt, Hilda H; Price, Donald L; Borchelt, David R; Eberhart, Charles G

    2002-01-01

    Medulloblastomas, embryonal tumors arising in the cerebellum, commonly contain mutations that activate Wnt signaling. To determine whether increased Wnt signaling in the adult CNS is sufficient to induce tumor formation, we created transgenic mice expressing either wild-type or activated β-catenin in the brain. Wild-type and mutant human β-catenin transgenes were expressed under the control of a murine PrP promoter fragment that drives high level postnatal expression in the CNS. Mutant β-catenin was stabilized by a serine to phenylalanine alteration in codon 37. Expression of the mutant transgene resulted in an approximately two-fold increase in β-catenin protein levels in the cortex and cerebellum of adult animals. Immunohistochemical analysis revealed nuclear β-catenin in hippocampal, cortical and cerebellar neurons of transgenic animals but not in non-transgenic controls. Tail kinking was observed in some transgenic animals, but no CNS malformations or tumors were detected. No tumors or morphologic alterations were detected in the brains of transgenic mice expressing stabilized β-catenin, suggesting that postnatal Wnt signaling in differentiated neurons may not be sufficient to induce CNS tumorigenesis

  18. Expression of matrix metalloproteinase 9 in pancreatic ductal carcinoma is associated with tumor metastasis formation.

    Directory of Open Access Journals (Sweden)

    Andrzej Kemona

    2007-03-01

    Full Text Available The objective of the current study was to assess the expression of matrix metalloproteinase 9 (MMP-9 in pancreatic ductal carcinoma and to examine its correlation with chosen clinico-anatomical parameters. The study group consisted of 36 patients with pancreatic ductal carcinoma. Tumors were stained using immunohistochemical method (NCL -MMP-9, Novocastra. No correlation was found between tumor MMP-9 expression and age, gender or grade of histological malignancy. However, statistical analysis revealed a relationship between tumor MMP-9 expression and histological type (adenocarcinoma mucinosum of pancreatic carcinoma. The expression was strongly correlated with lymph node involvement and occurrence of distant metastases (p<0.00001. The results indicate a correlation between the expression of MMP-9 in pancreatic ductal carcinoma and worse prognosis (shown by lymph node involvement and distant metastases.

  19. Formative research in clinical trial development: attitudes of patients with arthritis in enhancing prevention trials

    Science.gov (United States)

    Taylor, Holly A; Sugarman, Jeremy; Pisetsky, David S; Bathon, Joan

    2007-01-01

    In preparation for randomised controlled trials (RCTs) of disease‐modifying antirheumatic drugs in patients with early inflammatory arthritis (EIA), formative research was conducted to enhance the design of such trials. The objectives of this research were to (1) determine patients' educational needs as they relate to the necessary elements of informed consent; and (2) assess patients' interest in enrolling in a hypothetical prevention trial. In‐depth interviews were conducted with nine patients. Seven patients were women and all but one white. The mean age was 48 years. During the 4‐month enrolment period, only three patients with EIA were identified; six patients with longer duration of symptoms were also interviewed. Most patients were able to express the primary aim of a hypothetical prevention trial presented. Factors cited by patients favouring enrolment were potential for direct medical benefit and knowledge that they would be withdrawn from the trial if they developed symptoms. Factors cited by patients against enrolment were the inclusion of a placebo and general uncertainty regarding treatment required by the RCT design. Pending larger‐scale empirical projects to explore patients' attitudes about prevention trials, small‐scale formative research in advance of such trials ought to be conducted. PMID:16984939

  20. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo.

    Science.gov (United States)

    Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

    2014-06-01

    The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.

  1. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo *

    Science.gov (United States)

    Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

    2014-01-01

    The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. PMID:24903991

  2. Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity.

    Science.gov (United States)

    Rappa, Germana; Mercapide, Javier; Lorico, Aurelio

    2012-06-01

    Breast cancer progression involves cancer cell heterogeneity, with generation of invasive/metastatic breast cancer cells within populations of nonmetastatic cells of the primary tumor. Sequential genetic mutations, epithelial-to-mesenchymal transition, interaction with local stroma, and formation of hybrids between cancer cells and normal bone marrow-derived cells have been advocated as tumor progression mechanisms. We report herein the spontaneous in vitro formation of heterotypic hybrids between human bone marrow-derived multipotent stromal cells (MSCs) and two different breast carcinoma cell lines, MDA-MB-231 (MDA) and MA11. Hybrids showed predominantly mesenchymal morphological characteristics, mixed gene expression profiles, and increased DNA ploidy. Both MA11 and MDA hybrids were tumorigenic in immunodeficient mice, and some MDA hybrids had an increased metastatic capacity. Both in culture and as xenografts, hybrids underwent DNA ploidy reduction and morphological reversal to breast carcinoma-like morphological characteristics, while maintaining a mixed breast cancer-mesenchymal expression profile. Analysis of coding single-nucleotide polymorphisms by RNA sequencing revealed genetic contributions from both parental partners to hybrid tumors and metastasis. Because MSCs migrate and localize to breast carcinoma, our findings indicate that formation of MSC-breast cancer cell hybrids is a potential mechanism of the generation of invasive/metastatic breast cancer cells. Our findings reconcile the fusion theory of cancer progression with the common observation that breast cancer metastases are generally aneuploid, but not tetraploid, and are histopathologically similar to the primary neoplasm. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia

    DEFF Research Database (Denmark)

    Song, Shilin; Herranz, Héctor; Cohen, Stephen M.

    2017-01-01

    Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit...

  4. Application of chimeric glucanase comprising mutanase and dextranase for prevention of dental biofilm formation.

    Science.gov (United States)

    Otsuka, Ryoko; Imai, Susumu; Murata, Takatoshi; Nomura, Yoshiaki; Okamoto, Masaaki; Tsumori, Hideaki; Kakuta, Erika; Hanada, Nobuhiro; Momoi, Yasuko

    2015-01-01

    Water-insoluble glucan (WIG) produced by mutans streptococci, an important cariogenic pathogen, plays an important role in the formation of dental biofilm and adhesion of biofilm to tooth surfaces. Glucanohydrolases, such as mutanase (α-1,3-glucanase) and dextranase (α-1,6-glucanase), are able to hydrolyze WIG. The purposes of this study were to construct bi-functional chimeric glucanase, composed of mutanase and dextranase, and to examine the effects of this chimeric glucanase on the formation and decomposition of biofilm. The mutanase gene from Paenibacillus humicus NA1123 and the dextranase gene from Streptococcus mutans ATCC 25175 were cloned and ligated into a pE-SUMOstar Amp plasmid vector. The resultant his-tagged fusion chimeric glucanase was expressed in Escherichia coli BL21 (DE3) and partially purified. The effects of chimeric glucanase on the formation and decomposition of biofilm formed on a glass surface by Streptococcus sobrinus 6715 glucosyltransferases were then examined. This biofilm was fractionated into firmly adherent, loosely adherent, and non-adherent WIG fractions. Amounts of WIG in each fraction were determined by a phenol-sulfuric acid method, and reducing sugars were quantified by the Somogyi-Nelson method. Chimeric glucanase reduced the formation of the total amount of WIG in a dose-dependent manner, and significant reductions of WIG in the adherent fraction were observed. Moreover, the chimeric glucanase was able to decompose biofilm, being 4.1 times more effective at glucan inhibition of biofilm formation than a mixture of dextranase and mutanase. These results suggest that the chimeric glucanase is useful for prevention of dental biofilm formation. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  5. Chemoselective Methylation of Phenolic Hydroxyl Group Prevents Quinone Methide Formation and Repolymerization During Lignin Depolymerization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kwang Ho; Dutta, Tanmoy; Walter, Eric D.; Isern, Nancy G.; Cort, John R.; Simmons, Blake A.; Singh, Seema

    2017-03-30

    Chemoselective blocking of the phenolic hydroxyl (Ar-OH) group by methylation was found to suppress secondary repolymerization and charring during lignin depolymerization. Methylation of Ar-OH prevents formation of reactive quinone methide intermediates, which are partly responsible for undesirable secondary repolymerization reactions. Instead, this structurally modified lignin produces more relatively low molecular weight products from lignin depolymerization compared to unmodified lignin. This result demonstrates that structural modification of lignin is desirable for production of low molecular weight phenolic products. This approach could be directed toward alteration of natural lignification processes to produce biomass more amenable to chemical depolymerization.

  6. Investigating the role of macrophages in tumor formation using a MaFIA mouse model.

    Science.gov (United States)

    Clifford, A B; Elnaggar, A M; Robison, R A; O'Neill, K

    2013-08-01

    Tumor-associated macrophages (TAMs) interact with tumors in their development, growth and metastatic activities. Using a transgenic mouse model that allows for the selective depletion of macrophages we were able to access the macrophage's potential to facilitate metastasis. In the MaFIA (Macrophage Fas-Induced Apoptosis) mouse, transgene-expressing cells of the myeloid lineage undergo death by apoptosis in the presence of the drug AP20187. Enhanced green fluorescent protein (EGFP) was fused to the suicide gene to allow identification of transgene-expressing cells. Tumor induction was accomplished by subdermal and intravenous injections of B16-F10 melanoma cells. Metastasis in mice with depleted macrophages was compared to metastasis in normal control mice. The lungs and kidneys were examined for metastatic cells. The macrophage-depleted groups showed significantly less metastasis (P>0.001) compared to the control groups. We theorize that macrophages may aid the metastatic process by fusing with melanoma cells. Using appropriate cell markers and fluorescence-activated cell sorting, we were able to detect a small population of double-positive cells. We confirmed cell fusion by microscopic analysis, visualizing the cell's morphology by both immunohistochemistry and immunofluorescence. The presence of double-positive cells suggests macrophage/cancer cell fusion could be a possible mechanism for metastasis.

  7. Developing a diabetes prevention education programme for community health-care workers in Thailand: formative findings.

    Science.gov (United States)

    Sranacharoenpong, Kitti; Hanning, Rhona M

    2011-10-01

    The aim of this study was to investigate barriers to and supports for implementing a diabetes prevention education programme for community health-care workers (CHCWs) in Chiang Mai province, Thailand. The study also aimed to get preliminary input into the design of a tailored diabetes prevention education programme for CHCWs. Thailand has faced under-nutrition and yet, paradoxically, the prevalence of diseases of over-nutrition, such as obesity and diabetes, has escalated. As access to diabetes prevention programme is limited in Thailand, especially in rural and semi-urban areas, it becomes critical to develop a health information delivery system that is relevant, cost-effective, and sustainable. Health-care professionals (n = 12) selected from health centres within one district participated in in-depth interviews. In addition, screened people at risk for diabetes participated in interviews (n = 8) and focus groups (n = 4 groups, 23 participants). Coded transcripts from audio-taped interviews or focus groups were analysed by hand and using NVivo software. Concept mapping illustrated the findings. Health-care professionals identified potential barriers to programme success as a motivation for regular participation, and lack of health policy support for programme sustainability. Health-care professionals identified opportunities to integrate health promotion and disease prevention into CHCWs' duties. Health-care professionals recommended small-group workshops, hands-on learning activities, case studies, and video presentations that bring knowledge to practice within their cultural context. CHCWs should receive a credit for continuing study. People at risk for diabetes lacked knowledge of nutrition, diabetes risk factors, and resources to access health information. They desired two-way communication with CHCWs. Formative research supports the need for an effective, sustainable programme to support knowledge translation to CHCWs and at-risk populations in the

  8. Prevention of H-Aggregates Formation in Cy5 Labeled Macromolecules

    Directory of Open Access Journals (Sweden)

    Jing Kang

    2010-01-01

    Full Text Available H-aggregates of the cyanine dye Cy5 are formed during covalent linkage to the cationic macromolecule Poly(allylamine (PAH. The nonfluorescent H-aggregates strongly restrict the usage of the dye for analytical purposes and prevent a quantitative determination of the labeled macromolecules. The behavior of the H-aggregates has been studied by investigation of the absorption and fluorescence spectra of the dye polymer in dependence on solvent, label degree and additional sulfonate groups. H-aggregate formation is caused by an inhomogeneous distribution of the Cy5 molecules on the polymer chain. The H-aggregates can be destroyed by conformational changes of the PAH induced by interactions with polyanions or in organic solvents. It has been found that the polymer labeling process in high content of organic solvents can prevent the formation of H-aggregates. The results offer a better understanding and improvement of the use of the Cy5 dye for labeling purposes in fluorescence detection of macromolecules.

  9. Methylene blue 1% solution on the prevention of intraperitoneal adhesion formation in a dog model

    Directory of Open Access Journals (Sweden)

    Marco Augusto Machado Silva

    Full Text Available Intraperitoneal adhesions usually are formed after abdominal surgeries and may cause technical difficulties during surgical intervention, chronic abdominal pain and severe obstructions of the gastrointestinal tract. The current study aimed to evaluate the efficacy of methylene blue (MB 1% solution on the prevention of intraperitoneal postsurgical adhesion formation in a canine surgical trauma model. Twenty bitches were submitted to falciform ligament resection, omentectomy, ovariohysterectomy and scarification of a colonic segment. Prior to abdominal closure, 10 bitches received 1mg kg-1 MB intraperitoneally (MB group and 10 bitches received no treatment (control group, CT. On the 15th postoperative day the bitches were submitted to laparoscopy to assess adhesions. The mean adhesion scores were 13.9 (±5.6 for MB group and 20.5 (±6.4 for the CT group (P=0,043. In conclusion, the 1% MB solution was efficient on the prevention of intraperitoneal postoperative adhesion formation in bitches, especially those involving the colonic serosa.

  10. Can Dietary Polyphenols Prevent the Formation of Toxic Compounds from Maillard Reaction?

    Science.gov (United States)

    Del Turco, Serena; Basta, Giuseppina

    2016-01-01

    Polyphenols are functional compounds in edible vegetable and food such as tea, coffee and red wine and increasing evidence demonstrates a positive link between consumption of polyphenol-rich foods and disease prevention. In this review we have focused on the current knowledge of the potential anti-glycation effects of polyphenols, particularly in regard to their influence on Maillard reaction, a non-enzymatic reaction between amino acids and reducing sugars that contributes to the production of toxic compounds, mainly reactive carbonyl species, advanced glycation end-products (AGEs) and other toxicants. The Maillard reaction occurs in the human body during hyperglycemic condition, but it is well known as browning reaction in thermally processed foods and it is responsible for flavor and toxicant formation. Dietary polyphenols can have anti-glycation effects and actively participate in Maillard reaction, mitigating the AGE formation and the heat-induced production of toxic compounds. In a time in which the role of a healthy diet in the prevention of chronic diseases is welcome and the borderline between food and medicine is becoming very thin, an improved mechanistic knowledge of how polyphenols can function to reduce harmful and unhealthy substances is mandatory.

  11. Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition.

    Directory of Open Access Journals (Sweden)

    Esther Gies

    2010-12-01

    Full Text Available Protein aggregation is a hallmark of many neurodegenerative diseases and has been linked to the failure to degrade misfolded and damaged proteins. In the cell, aberrant proteins are degraded by the ubiquitin proteasome system that mainly targets short-lived proteins, or by the lysosomes that mostly clear long-lived and poorly soluble proteins. Both systems are interconnected and, in some instances, autophagy can redirect proteasome substrates to the lysosomes.To better understand the interplay between these two systems, we established a neuroblastoma cell population stably expressing the GFP-ubiquitin fusion protein. We show that inhibition of the proteasome leads to the formation of large ubiquitin-containing inclusions accompanied by lower solubility of the ubiquitin conjugates. Strikingly, the formation of the ubiquitin-containing aggregates does not require ectopic expression of disease-specific proteins. Moreover, formation of these focused inclusions caused by proteasome inhibition requires the lysine 63 (K63 of ubiquitin. We then assessed selected compounds that stimulate autophagy and found that the antihelmintic chemical niclosamide prevents large aggregate formation induced by proteasome inhibition, while the prototypical mTORC1 inhibitor rapamycin had no apparent effect. Niclosamide also precludes the accumulation of poly-ubiquitinated proteins and of p62 upon proteasome inhibition. Moreover, niclosamide induces a change in lysosome distribution in the cell that, in the absence of proteasome activity, may favor the uptake into lysosomes of ubiquitinated proteins before they form large aggregates.Our results indicate that proteasome inhibition provokes the formation of large ubiquitin containing aggregates in tissue culture cells, even in the absence of disease specific proteins. Furthermore our study suggests that the autophagy-inducing compound niclosamide may promote the selective clearance of ubiquitinated proteins in the absence

  12. Comparison of human papillomavirus type 16 L1 chimeric virus-like particles versus L1/L2 chimeric virus-like particles in tumor prevention.

    Science.gov (United States)

    Wakabayashi, Mark T; Da Silva, Diane M; Potkul, Ronald K; Kast, W Martin

    2002-01-01

    Chimeric human papillomavirus (HPV) virus-like particles (cVLPs) with the HPV16 E7 antigen fused to either the major capsid protein, L1, or the minor capsid protein, L2, have been used independently to protect against the formation of HPV-induced tumors in animal models. However, the advantages and disadvantages of both types of particles with respect to production and vaccine efficacy have never been analyzed. Therefore, in this study, we compared cVLPs with the HPV16 E7 antigen fused to L1 versus cVLPs with E7 fused to L2 with respect to their ability to protect mice from tumor challenge. The first 57 amino acids of E7 were used to overcome the size limitation and limited VLP production imposed by inserting polypeptides into L1 cVLPs. C57BL/6 mice were immunized with the above cVLPs at various doses. Tumor challenge was then performed with HPV16 E7-positive TC-1 cells. HPV16 L1-E7((1-57)) was superior to HPV16 L1/L2-E7((1-57)) in eliciting tumor protection at equivalent doses, although both types of particles were able to protect mice. Both cVLPs induced a specific cytotoxic T lymphocyte (CTL) response to the H2-D(b)-restricted E7 peptide (E7(49-57)) as determined by an ELISPOT assay and tetramer staining; however, immunization with the L1-E7((1-57)) cVLPs resulted in twofold higher CTL precursor frequencies. Our results demonstrate that cVLPs with the antigen fused to L1 are a more efficient vaccine with respect to tumor prevention than cVLPs with the antigen fused to L2. At the same time, however, L1 cVLPs are limited by the size of the antigen that can be incorporated and in the amount of cVLP that can be obtained from cultures when compared to L1/L2 cVLPs. This balances out their superior ability to induce protective immunity. Copyright 2002 S. Karger AG, Basel

  13. Acute intracranial hematoma formation following excision of a cervical subdural tumor: a report of two cases and literature review.

    Science.gov (United States)

    Ma, Xuexiao; Zhang, Yan; Wang, Ting; Li, Guizhi; Zhang, Guoqing; Khan, Hassan; Xiang, Hongfei; Chen, Bohua

    2014-01-01

    An intracranial hematoma is a rare, yet significant, complication following spinal surgery. The authors describe two cases with acute intracranial hematoma formation after excision of a cervical subdural schwannoma. One was a 14-year-old girl who developed bilateral intracranial extradural hematomas immediately following excision of the C4 subdural schwannoma. The other was a 59-year-old woman who had an acute cerebellar hematoma after removal of the C2-C5 subdural schwannoma. During the surgeries of both cases, spinal dura was partially removed together with the tumor and the dural sac could not be repaired, resulting in large amounts of intraoperative CSF loss and persistent postoperative CSF leakage. Both patients failed to regain consciousness from anesthesia after surgery, and a cranial CT scan identified large intracranial hematomas. Urgent hematoma evacuation was ultimately performed to save the patients. Based on the authors' experience and literature review, a conclusion was drawn that considerable CSF leakage and a sharp decrease of CSF pressure are common features during the excision of a spinal subdural tumor, which may lead to acute intracranial hematomas. Continual postoperative monitoring in patients with this condition should be of a very high priority. A CT or MRI should be immediately investigated to exclude intracranial hematomas for any patient with delayed emergence from anesthesia following spinal surgery. Hematoma evacuation is indispensable once an intracranial hematoma is identified in the patient who fails to regain consciousness from anesthesia post surgery. Furthermore, the possible pathophysiological mechanisms responsible for the formation of an intracranial hematoma after spinal procedures, particularly after manipulations of a cervical subdural tumor, are discussed.

  14. S6Ks isoforms contribute to viability, migration, docetaxel resistance and tumor formation of prostate cancer cells

    International Nuclear Information System (INIS)

    Amaral, Camila L.; Freitas, Lidia B.; Tamura, Rodrigo E.; Tavares, Mariana R.; Pavan, Isadora C. B.; Bajgelman, Marcio C.; Simabuco, Fernando M.

    2016-01-01

    The S6 Kinase (S6K) proteins are some of the main downstream effectors of the mammalian Target Of Rapamycin (mTOR) and act as key regulators of protein synthesis and cell growth. S6K is overexpressed in a variety of human tumors and is correlated to poor prognosis in prostate cancer. Due to the current urgency to identify factors involved in prostate cancer progression, we aimed to reveal the cellular functions of three S6K isoforms–p70-S6K1, p85-S6K1 and p54-S6K2–in prostate cancer, as well as their potential as therapeutic targets. In this study we performed S6K knockdown and overexpression and investigated its role in prostate cancer cell proliferation, colony formation, viability, migration and resistance to docetaxel treatment. In addition, we measured tumor growth in Nude mice injected with PC3 cells overexpressing S6K isoforms and tested the efficacy of a new available S6K1 inhibitor in vitro. S6Ks overexpression enhanced PC3-luc cell line viability, migration, resistance to docetaxel and tumor formation in Nude mice. Only S6K2 knockdown rendered prostate cancer cells more sensitive to docetaxel. S6K1 inhibitor PF-4708671 was particularly effective for reducing migration and proliferation of PC3 cell line. These findings demonstrate that S6Ks play an important role in prostate cancer progression, enhancing cell viability, migration and chemotherapy resistance, and place both S6K1 and S6K2 as a potential targets in advanced prostate cancer. We also provide evidence that S6K1 inhibitor PF-4708671 may be considered as a potential drug for prostate cancer treatment. The online version of this article (doi:10.1186/s12885-016-2629-y) contains supplementary material, which is available to authorized users

  15. Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Maura McGrail

    2011-04-01

    Full Text Available Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish lines that contain large concatemers of T2/OncZ were isolated by injection of linear DNA into the zebrafish embryo. The T2/OncZ transposons were mobilized throughout the zebrafish genome from the transgene array by injecting SB11 transposase RNA at the 1-cell stage. Alternatively, the T2/OncZ zebrafish were crossed to a transgenic line that constitutively expresses SB11 transposase. T2/OncZ transposon integration sites were cloned by ligation-mediated PCR and sequenced on a Genome Analyzer II. Between 700-6800 unique integration events in individual fish were mapped to the zebrafish genome. The data show that introduction of transposase by transgene expression or RNA injection results in an even distribution of transposon re-integration events across the zebrafish genome. SB11 mRNA injection resulted in neoplasms in 10% of adult fish at ∼10 months of age. T2/OncZ-induced zebrafish tumors contain many mutated genes in common with human and mouse cancer genes. These analyses validate our mutagenesis approach and provide additional support for the involvement of these genes in human cancers. The zebrafish T2/OncZ cancer model will be useful for identifying novel and conserved genetic drivers of human cancers.

  16. Prevention of Risky Sexual Behaviour through the Formation of Psychological Readiness to Parenthood

    Directory of Open Access Journals (Sweden)

    Krysko A.A.,

    2018-04-01

    Full Text Available In the world there are tendencies of early entering into sexual relations and simultaneous withdrawal of the age of marriage, an increase in the number of early pregnancies and abortions among minors. Existing programs for the prevention of risky sexual behavior are ineffective, since they are one-time, narrowly focused. The author presents the results of an experiment on the prevention of risky sexual behavior in adolescents based on the formation of their ideas of parenting and child-parent relations, and through the prism of this topic, allowing to build an image of reproductive behavior in the present and future. The program is designed taking into account the psychology of modern adolescents, in accordance with the principles of awareness and responsibility, is based on a restorative approach and resource approach to the formation of psychological readiness for parenthood M.E. Lantsburg. The program for the development of psychological preparedness for parenting in adolescents has two targets: the nearest: preventing adolescent pregnancy and reducing its negative consequences in the event of an early pregnancy, and strategic - preparing for the planning and birth of the coveted child in the future. The results prove that the adolescents' views about the family depend both on the experiences they experienced in their own childhood and on the trends in the social and political space discussed in this topic. The study showed that adolescents' views on sexual relations, family and parenthood can be purposefully influenced through a program based on the knowledge of age-related psychology, resource and recovery approaches and using interactive methods of teaching relevant to this age group.

  17. A failure of matrix metalloproteinase inhibition in the prevention of rat intracranial aneurysm formation

    International Nuclear Information System (INIS)

    Kaufmann, T.J.; Kallmes, D.F.; Marx, W.F.

    2006-01-01

    We tested the hypothesis that nonspecific matrix metalloproteinase (MMP) inhibition with doxycycline would decrease the incidence of intracranial aneurysm formation in a rat aneurysm model. We performed common carotid artery ligation on 96 Long-Evans rats. A treatment group of 48 animals was chosen at random to receive oral doxycycline (3 mg/kg) in addition to standard rat chow, and the control group of 48 animals received standard rat chow only. The major circle of Willis arteries was dissected at 1 year following carotid ligation, and the proportions of animals with aneurysms were compared between groups using Fisher's exact test. Four animals given oral doxycycline and ten control animals expired before 1 year. Of the examined animals, eight saccular intracranial aneurysms were found in 8 of 45 animals which had received doxycycline (17.8%) and seven saccular intracranial aneurysms were found in 7 of 37 control animals (18.9%). There was no significant difference in aneurysm formation between the doxycycline-treated and control groups (P=0.894). Nonspecific MMP inhibition with doxycycline is not effective in preventing intracranial aneurysm formation in a rat model. (orig.)

  18. The role of succinylcholine in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors

    International Nuclear Information System (INIS)

    Cesur, M.; Erdem, Ali F.; Alici, Haci A.; Yuksek, Mustafa S.; Yapanoglu, T.; Aksoy, Y.

    2008-01-01

    Objective was to present our 8 year experience in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors. This study was performed in Ataturk University Hospital between 1999 and 2007. We retrospectively reviewed the records of 89 patients with inferolateral bladder tumors, who underwent transurethral resection under epidural or general anesthesia and requested obturator nerve reflex inhibition. Epidural anesthesia was administered to 57 patients, while the remaining 32 patients underwent general anesthesia via mask; and succinylcholine was administered prior to resection. Of the 57 patients received epidural anesthesia, 18 were diagnosed as inferolateral bladder tumors during endoscopy and had to undergo general anesthesia. Obturator nerve block was attempted preoperatively in 39 patients. However, a nerve identification failure, hematoma and 4 obturator nerve reflex events, despite the block, were observed and these patients were subjected to general anesthesia with succinylcholine. Fifty-six patients (32 patients initially had general anesthesia and 24 converted from epidural to general anesthesia) were all given succinylcholine prior to resection. Due to its mechanisms of action, succinylcholine is completely effective and represents a simple alternative to obturator nerve block. No contraction was observed in any patient given succinylcholine. (author)

  19. Effect of Nigella sativa seed administration on prevention of febrile neutropenia during chemotherapy among children with brain tumors.

    Science.gov (United States)

    Mousa, HebatAlla Fathi Mohamed; Abd-El-Fatah, Nesrin Kamal; Darwish, Olfat Abdel-Hamid; Shehata, Shehata Farag; Fadel, Shady Hassan

    2017-05-01

    Seeds of Nigella sativa (NS) are used to combat various disease conditions through their antibacterial effects. To evaluate the seeds' potential, we studied their effect on the prevention of febrile neutropenia (FN) in children with brain tumors. A randomized pretest-post-test control group study including 80 children (2-18 years) with brain tumors undergoing chemotherapy were equally allocated into two groups. Intervention group received 5 g of NS seeds daily throughout treatment while controls received nothing. CBC with differentials, incidence of FN, and LOS were noted on each follow-up. The majority of children 38/40 (95%), of the intervention group, took the seeds for 3-9 consecutive months. Eight out of 372 (2.2%) FN episodes were experienced by children of intervention group compared to controls 63/327 (19.3%) (p = 0.001) and a shorter LOS (median = 2.5 days) vs 5 days in the control group (p = 0.006). Children in both groups belonged to almost same geographical area with similar socio-economic background. Weights of children were almost equal at diagnosis. NS seeds showed a decrease in incidence of FN in children with brain tumors with shortening of subsequent LOS which may improve their outcome and thereby quality of life. Larger scale studies are needed to further evaluate the seeds' potential.

  20. Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells

    Directory of Open Access Journals (Sweden)

    Li-Qiao Liu

    2018-02-01

    Full Text Available The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression.

  1. Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

    Science.gov (United States)

    2011-09-01

    steps of this work, and it is also appended to this document. In that manuscript we first demonstrate that E0771 breast cancer cells do not produce...this grant, and it is appended to this document: Burke R, Madden K, Perry S, Zettel M, Brown E. (2011) Tumor-associated macrophages and stromal...monocytic cell line, THP-1. J Biol Chem 1996, 271:27936-27941. 17. Dschietzig T, Bartsch C, Greinwald M, Baumann G, Stangl K: The pregnancy hormone

  2. Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

    Science.gov (United States)

    Berrahmoune, Saoussen; Bezdetnaya, Lina; de Witte, Peter; Leroux, Agnès; Dumas, Dominique; Guillemin, François; D'Hallewin, Marie Ange

    2009-06-01

    The prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T1 or poorly visible malignant or pre-malignant disease1. Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix, has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression ratesImplantation of viable tumor cells, dispersed during resection, is a third factor influencing bladder cancer recurrence. The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks.

  3. Shenlingbaishusan, a chines herbal medicine, in the prevention and treatment of colo-rectal radiation reactions during pelvic tumor radiotherapy

    International Nuclear Information System (INIS)

    Hu Yueran; Liu Yajie; Wu Chaoquan; Chen Chuping; Wang Yaobang; Li Xianming; Zhong Heli; Wu Dong

    2005-01-01

    Objective: To study the effect of traditional Chinese herbal medicine-Shenlingbaishusan in preventing and treating colon and rectum radiation reactions. Methods: Ninty-six patients with female pelvic tumor (cervical and endometrial cancer) were randomly divided into two groups: radiotherapy (RT) alone group (47 patients) and RT+ Shenlingbaishusan group(49 patients). RT in both groups, being similar, 1.8-2.0 Gy/per fraction, five fractions/per week, to a total dose of 48-50 Gy/5-6 weeks to the whole pelvis by external irradiation plus brachytherapy: to a total dose of 42-49 Gy/6-7 weeks for cervix carcinoma, and 10-15 Gy/1-2 weeks for endometrial cancer. Results: All patients have been were followed for more than one year after radiotherapy. The incidence of acute and late colon and rectum radiation reactions. was:15 patients in the RT + Shenlingbaishusan group: grade I10 patients, Grade II3 patients, grade III2 patients incontrast to the 47 patients in the RT group: grade I 24 patients, grade II 14 patients and grade III 9 patients (P<0.01). Conclusions: The traditional Chinese medicine-Shenlingbaishusan is effective in preventing and treating colon and rectum radiation reactions during pelvic tumor radiotherapy.(authors)

  4. Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

    Science.gov (United States)

    2017-04-01

    administration of agents that promote apoptosis and/or inhibit pro-survival autophagy will inhibit MPNST formation and progression in transgenic mouse models of...lysosomotropic agents to inhibit Schwann cell hyperproliferation, MPNST formation and progression in transgenic mouse models. 2. To determine the effects...were given in combination. Based on these in vitro findings, we are now testing these agents alone and in combination in our in vivo MPNST transgenic

  5. Development and formative evaluation of a family-centred adolescent HIV prevention programme in South Africa.

    Science.gov (United States)

    Visser, Maretha; Thurman, Tonya R; Spyrelis, Alexandra; Taylor, Tory M; Nice, Johanna K; Finestone, Michelle

    2018-03-06

    Preventing HIV among young people is critical to achieving and sustaining global epidemic control. Evidence from Western settings suggests that family-centred prevention interventions may be associated with greater reductions in risk behaviour than standard adolescent-only models. Despite this, family-centred models for adolescent HIV prevention are nearly non-existent in South Africa - home to more people living with HIV than any other country. This paper describes the development and formative evaluation of one such intervention: an evidence-informed, locally relevant, adolescent prevention intervention engaging caregivers as co-participants. The programme, originally consisting of 19 sessions for caregivers and 14 for adolescents, was piloted with 12 groups of caregiver-adolescent dyads by community-based organizations (CBOs) in KwaZulu-Natal and Gauteng provinces. Literature and expert reviews were employed in the development process, and evaluation methods included analysis of attendance records, session-level fidelity checklists and facilitator feedback forms collected during the programme pilot. Facilitator focus group discussions and an implementer programme workshop were also held. Results highlighted the need to enhance training content related to cognitive behavioural theory and group management techniques, as well as increase the cultural relevance of activities in the curriculum. Participant attendance challenges were also identified, leading to a shortened and simplified session set. Findings overall were used to finalize materials and guidance for a revised 14-week group programme consisting of individual and joint sessions for adolescents and their caregivers, which may be implemented by community-based facilitators in other settings. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. GSK-3β signaling determines autophagy activation in the breast tumor cell line MCF7 and inclusion formation in the non-tumor cell line MCF10A in response to proteasome inhibition.

    Science.gov (United States)

    Gavilán, E; Sánchez-Aguayo, I; Daza, P; Ruano, D

    2013-04-04

    The ubiquitin-proteasome system and the autophagy-lysosome pathway are the two main mechanisms for eukaryotic intracellular protein degradation. Proteasome inhibitors are used for the treatment of some types of cancer, whereas autophagy seems to have a dual role in tumor cell survival and death. However, the relationship between both pathways has not been extensively studied in tumor cells. We have investigated both proteolytic systems in the human epithelial breast non-tumor cell line MCF10A and in the human epithelial breast tumor cell line MCF7. In basal condition, tumor cells showed a lower proteasome function but a higher autophagy activity when compared with MCF10A cells. Importantly, proteasome inhibition (PI) leads to different responses in both cell types. Tumor cells showed a dose-dependent glycogen synthase kinase-3 (GSK-3)β inhibition, a huge increase in the expression of the transcription factor CHOP and an active processing of caspase-8. By contrast, MCF10A cells fully activated GSK-3β and showed a lower expression of both CHOP and processed caspase-8. These molecular differences were reflected in a dose-dependent autophagy activation and cell death in tumor cells, while non-tumor cells exhibited the formation of inclusion bodies and a decrease in the cell death rate. Importantly, the behavior of the MCF7 cells can be reproduced in MCF10A cells when GSK-3β and the proteasome were simultaneously inhibited. Under this situation, MCF10A cells strongly activated autophagy, showing minimal inclusion bodies, increased CHOP expression and cell death rate. These findings support GSK-3β signaling as a key mechanism in regulating autophagy activation or inclusion formation in human tumor or non-tumor breast cells, respectively, which may shed new light on breast cancer control.

  7. Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

    Science.gov (United States)

    Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

    2013-01-01

    Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

  8. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

    Science.gov (United States)

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

  9. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Science.gov (United States)

    Kim, Peter S; Lee, Peter P

    2012-01-01

    A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  10. The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infections and Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Kyung-Soo Hahm

    2011-09-01

    Full Text Available Over the last decade, decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. Furthermore, biofilms, which are microbial communities that cause serious chronic infections and dental plaque, form environments that enhance antimicrobial resistance. As a result, there is a continuous search to overcome or control such problems, which has resulted in antimicrobial peptides being considered as an alternative to conventional drugs. Antimicrobial peptides are ancient host defense effector molecules in living organisms. These peptides have been identified in diverse organisms and synthetically developed by using peptidomimic techniques. This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health. In addition, combinations of antimicrobial peptides and conventional drugs were considered due to their synergetic effects and low cost for therapeutic treatment.

  11. Steps in the design, development and formative evaluation of obesity prevention-related behavior change trials

    Directory of Open Access Journals (Sweden)

    Baranowski Janice

    2009-01-01

    Full Text Available Abstract Obesity prevention interventions through dietary and physical activity change have generally not been effective. Limitations on possible program effectiveness are herein identified at every step in the mediating variable model, a generic conceptual framework for understanding how interventions may promote behavior change. To minimize these problems, and thereby enhance likely intervention effectiveness, four sequential types of formative studies are proposed: targeted behavior validation, targeted mediator validation, intervention procedure validation, and pilot feasibility intervention. Implementing these studies would establish the relationships at each step in the mediating variable model, thereby maximizing the likelihood that an intervention would work and its effects would be detected. Building consensus among researchers, funding agencies, and journal editors on distinct intervention development studies should avoid identified limitations and move the field forward.

  12. Bryophyllum pinnatum leaf extracts prevent formation of renal calculi in lithiatic rats

    Directory of Open Access Journals (Sweden)

    Mahendra Yadav

    2016-01-01

    Full Text Available Background: Bryophyllum pinnatum, commonly known as Pattharcaṭṭa, is used traditionally in ethnomedicinal practices for the treatment of kidney stone and urinary insufficiency. Aim: The present study evaluated the effect of Bryophyllum pinnatum on ethylene glycol (EG-induced renal calculi in rats. Materials and Methods: Renal calculi were induced in rats by administration of 0.75% EG in drinking water and co-treated orally with standard drug, Cystone (750 mg/kg, or alcoholic and hydro-alcoholic extracts in doses of 100, 200 and 400 mg/kg for 28 days. Weekly body weights were recorded. On day 29, urolithiasis was confirmed by assessing the urinary parameters (urine volume, pH, uric acid, calcium, phosphorus, oxalate, magnesium and creatinine clearance, serum biochemical parameters (creatinine, uric acid, urea, calcium, phosphorus and magnesium, oxidative stress parameters and histology of kidney. Results: Treatment with extracts attenuated the EG-induced decrease in body weight and elevation in urinary parameters (uric acid, calcium, phosphorus and oxalate and serum biochemical parameters (creatinine, uric acid, urea, calcium, phosphorus and magnesium. Extract treatment also reversed EG-induced decrease in urine volume, pH, magnesium and creatinine clearance, oxidative and histological damages in kidneys. Results were comparable to standard drug, Cystone. Results indicated that EG administration caused renal calculi formation which is prevented by treatment with extracts. The observed antilithiatic effect may be attributed to the presence of high content of phenolics, flavonoids and saponins in the extracts. Conclusion: Bryophyllum pinnatum leaves showed preventive effect against renal calculi formation and validates its ethnomedicinal use in urinary disorders. It further supports its therapeutic potential for the treatment of urinary calculi.

  13. Overexpression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor-null mice.

    Science.gov (United States)

    Teichert, Arnaud E; Elalieh, Hashem; Elias, Peter M; Welsh, JoEllen; Bikle, Daniel D

    2011-11-01

    The vitamin D receptor (VDR) ligand, 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), reduces proliferation and enhances differentiation, and thus has been investigated for a role in preventing or treating cancer. Mice deficient for the VDR display a hyperproliferative response in the hair follicle and epidermis and decreased epidermal differentiation. Unlike their wild-type littermates, when treated with 7,12 dimethylbenzanthracene (DMBA) or UVB, they develop skin tumors, including some characteristic of overexpression of the hedgehog (Hh) pathway. Both the epidermis and utricles of the VDR-null animals overexpress elements of the Hh pathway (sonic hedgehog (Shh) 2.02-fold, patched1 1.58-fold, smoothened 3.54-fold, glioma-associated oncogene homolog (Gli)1 1.17-fold, and Gli2 1.66-fold). This overexpression occurs at an age (11 weeks) at which epidermal hyperproliferation is most visible and is spatially controlled in the epidermis. DMBA- or UVB-induced tumors in the VDR-null mice also overexpress elements of this pathway. Moreover, 1,25(OH)(2)D(3) downregulates the expression of some members of the Hh pathway in an epidermal explants culture system, suggesting a direct regulation by 1,25(OH)(2)D(3). Our results suggest that increased expression of Shh in the keratinocytes of the VDR-null animal activates the Hh pathway, predisposing the skin to the development of both malignant and benign epidermal neoplasms.

  14. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    Directory of Open Access Journals (Sweden)

    Diego Lobos-Urbina

    2017-03-01

    Full Text Available Resumen Los pacientes con tumores cerebrales, primarios o metastásicos, presentan riego de desarrollar convulsiones durante la evolución de su enfermedad, por lo que se ha propuesto el uso profiláctico de anticonvulsivantes. Sin embargo, el efecto de esta intervención no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 12 revisiones sistemáticas que en conjunto incluyen ochenta estudios primarios. Doce corresponden a estudios aleatorizados, pero sólo dos responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que la prevención primaria con anticonvulsivantes podría no disminuir el riesgo de convulsiones en tumores o metástasis cerebrales, y se asocia a efectos adversos frecuentes.

  15. Targeted disruption of Smad4 in mouse epidermis results in failure of hair follicle cycling and formation of skin tumors.

    Science.gov (United States)

    Yang, Leilei; Mao, Chunming; Teng, Yan; Li, Wenlong; Zhang, Jishuai; Cheng, Xuan; Li, Xiaobing; Han, Xinghai; Xia, Zhaofan; Deng, Hongkui; Yang, Xiao

    2005-10-01

    Smad4 is the common mediator of transforming growth factor-beta (TGF-beta) superfamily signaling, which functions in diverse developmental processes in mammals. To study the role of Smad4 in skin development, a keratinocyte-specific null mutant of Smad4 (Smad4(co/co);K5-Cre) was generated in mice using the Cre-loxP system. The Smad4-mutant mice exhibited progressive alopecia as a result of the mutant hair follicles failing to undergo programmed regression. Sonic hedgehog (Shh) was only detected in Smad4-mutant hair follicles at the catagen stage. Seventy percent of Smad4(co/co); K5-Cre mice developed spontaneous tumors within 12 months of birth. c-Myc and cyclin D1 were up-regulated whereas p21 and p27 expressions were decreased, which correlated with the epidermal hyperplasia in Smad4 mutants. Interestingly, coordinated deletion of the Smad4 and PTEN genes resulted in accelerated hair loss and skin tumor formation, suggesting that Smad4 and PTEN act synergistically to regulate epidermal proliferation and differentiation. All of our data indicate that Smad4 is essential for catagen induction and acts as a critical suppressor in skin tumorigenesis.

  16. Circular RNA alterations are involved in resistance to avian leukosis virus subgroup-J-induced tumor formation in chickens.

    Science.gov (United States)

    Zhang, Xinheng; Yan, Yiming; Lei, Xiaoya; Li, Aijun; Zhang, Huanmin; Dai, Zhenkai; Li, Xinjian; Chen, Weiguo; Lin, Wencheng; Chen, Feng; Ma, Jingyun; Xie, Qingmei

    2017-05-23

    Avian leukosis virus subgroup (ALV-J) is an oncogenic neoplasm-inducing retrovirus that causes significant economic losses in the poultry industry. Recent studies have demonstrated circular RNAs (circRNAs) are implicated in pathogenic processes; however, no research has indicated circRNAs are involved in resistance to disease. In this study, over 1800 circRNAs were detected by circRNA sequencing of liver tissues from ALV-J-resistant (n = 3) and ALV-J-susceptible chickens (n = 3). 32 differentially expressed circRNAs were selected for analyzing including 12 upregulated in ALV-J-resistant chickens and 20 upregulated in ALV-J-susceptible chickens, besides, the top five microRNAs (miRNAs) for 12 upregulated circRNAs in ALV-J-resistant chickens were analyzed. Gene ontology and KEGG pathway analyses were performed for miRNA target genes, the predicted genes were mainly involved in immune pathways. This study provides the first evidence that circRNA alterations are involved in resistance to ALV-J-induced tumor formation. We propose circRNAs may help to mediate tumor induction and development in chickens.

  17. MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.

    Science.gov (United States)

    Zhang, Yiting; Zhu, Xinyue; Zhu, Xiaomin; Wu, Yan; Liu, Yajun; Yao, Borui; Huang, Zhenping

    2017-03-01

    Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.

  18. Formative evaluation of the telecare fall prevention project for older veterans

    Directory of Open Access Journals (Sweden)

    Saliba Debra

    2011-05-01

    Full Text Available Abstract Background Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage patients to appropriate services. Here we report the formative evaluation of this project. Methods To evaluate the intervention we: 1 interviewed patient and employee stakeholders, 2 reviewed participating patients' electronic health record data and 3 abstracted information from meeting minutes. We describe the implementation process, including whether the project was implemented according to plan; identify barriers and facilitators to implementation; and assess the incremental benefit to the quality of health care for fall prevention received by patients in the project. We also estimate the cost of developing the pilot project. Results The project underwent multiple changes over its life span, including the addition of an option to mail patients educational materials about falls. During the project's lifespan, 113 patients were considered for inclusion and 35 participated. Patient and employee interviews suggested support for the project, but revealed that transportation to medical care was a major barrier in following up on fall risks identified by nurse telephone triage. Medical record review showed that the project enhanced usual medical care with respect to home safety counseling. We discontinued the program after 18 months due to staffing limitations and competing priorities. We estimated a cost of $9194 for meeting time to develop the project. Conclusions The project appeared feasible at its outset but could not be sustained past the first cycle of

  19. Formative evaluation of the telecare fall prevention project for older veterans.

    Science.gov (United States)

    Miake-Lye, Isomi M; Amulis, Angel; Saliba, Debra; Shekelle, Paul G; Volkman, Linda K; Ganz, David A

    2011-05-23

    Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage patients to appropriate services. Here we report the formative evaluation of this project. To evaluate the intervention we: 1) interviewed patient and employee stakeholders, 2) reviewed participating patients' electronic health record data and 3) abstracted information from meeting minutes. We describe the implementation process, including whether the project was implemented according to plan; identify barriers and facilitators to implementation; and assess the incremental benefit to the quality of health care for fall prevention received by patients in the project. We also estimate the cost of developing the pilot project. The project underwent multiple changes over its life span, including the addition of an option to mail patients educational materials about falls. During the project's lifespan, 113 patients were considered for inclusion and 35 participated. Patient and employee interviews suggested support for the project, but revealed that transportation to medical care was a major barrier in following up on fall risks identified by nurse telephone triage. Medical record review showed that the project enhanced usual medical care with respect to home safety counseling. We discontinued the program after 18 months due to staffing limitations and competing priorities. We estimated a cost of $9194 for meeting time to develop the project. The project appeared feasible at its outset but could not be sustained past the first cycle of evaluation due to insufficient resources and a waning of local

  20. Inhibition of multidrug efflux as a strategy to prevent biofilm formation.

    Science.gov (United States)

    Baugh, Stephanie; Phillips, Charlotte R; Ekanayaka, Aruna S; Piddock, Laura J V; Webber, Mark A

    2014-03-01

    We have recently shown that inactivation of any of the multidrug efflux systems of Salmonella results in loss of the ability to form a competent biofilm. The aim of this study was to determine the mechanism linking multidrug efflux and biofilm formation, and to determine whether inhibition of efflux is a viable antibiofilm strategy. Mutants lacking components of the AcrAB-TolC system in Salmonella enterica serovar Typhimurium were investigated for their ability to aggregate, produce biofilm matrix components and form a biofilm. The potential for export of a biofilm-relevant substrate via efflux pumps was investigated and expression of genes that regulate multidrug efflux and production of biofilm matrix components was measured. The ability of efflux inhibitors carbonyl cyanide m-chlorophenylhydrazone, chlorpromazine and phenyl-arginine-β-naphthylamide to prevent biofilm formation by Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus under static and flow conditions was assessed. Mutants of Salmonella Typhimurium that lack TolC or AcrB, but surprisingly not AcrA, were compromised in their ability to form biofilms. This defect was not related to changes in cellular hydrophobicity, aggregative ability or export of any biofilm-specific factor. The biofilm defect resulted from transcriptional repression of curli biosynthesis genes and consequent inhibition of production of curli. All three efflux inhibitors significantly reduced biofilm production in both static and flow biofilm assays, although different concentrations of each inhibitor were most active against each species. This work shows that both genetic inactivation and chemical inhibition of efflux pumps results in transcriptional repression of biofilm matrix components and a lack of biofilm formation. Therefore, inhibition of efflux is a promising antibiofilm strategy.

  1. Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Karras, Jenna R.; Paisie, Carolyn A.; Huebner, Kay, E-mail: kay.huebner@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210 (United States)

    2014-06-04

    The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome stability, oxidative stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is lost or reduced in many human cancers, is a tumor suppressor and genome caretaker whose loss initiates genome instability in preneoplastic lesions. Ongoing studies are seeking more detailed understanding of the role of FHIT in the cellular response to oxidative damage. This review discusses the relationship between FHIT, reactive oxygen species production, and DNA damage in the context of cancer initiation and progression.

  2. Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice

    DEFF Research Database (Denmark)

    Ge, Xiadong; Leung, Tung-Ming; Arriazu, Elena

    2014-01-01

    , tumor necrosis factor-α (TNFα) production, and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol-induced liver injury. Wild-type (WT), OPN knockout...... score, and the number of macrophages and TNFα+ cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed binding affinity for LPS which prevented macrophage activation, reactive oxygen, and nitrogen species generation...... by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation...

  3. Contribution of formative research to design an environmental program for obesity prevention in schools in Mexico City.

    Science.gov (United States)

    Bonvecchio, Anabelle; Théodore, Florence L; Safdie, Margarita; Duque, Tiffany; Villanueva, María Ángeles; Torres, Catalina; Rivera, Juan

    2014-01-01

    This paper describes the methods and key findings of formative research conducted to design a school-based program for obesity prevention. Formative research was based on the ecological model and the principles of social marketing. A mixed method approach was used. Qualitative (direct observation, indepth interviews, focus group discussions and photo-voice) and quantitative (closed ended surveys, checklists, anthropometry) methods were employed. Formative research key findings, including barriers by levels of the ecological model, were used for designing a program including environmental strategies to discourage the consumption of energy dense foods and sugar beverages. Formative research was fundamental to developing a context specific obesity prevention program in schools that seeks environment modification and behavior change.

  4. Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone formation in both rat skull and fibula bone defects.

    Science.gov (United States)

    Tsuda, Yoshifumi; Hattori, Hidemi; Tanaka, Yoshihiro; Ishihara, Masayuki; Kishimoto, Satoko; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi

    2013-09-01

    In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8 week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1α2 and α-smooth muscle actin (α-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1 week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Noritake, Hidenao [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kimura, Wataru; Wu, Yi-Xin [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kobayashi, Yoshimasa [Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Uezato, Tadayoshi [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Miura, Naoyuki, E-mail: nmiura@hama-med.ac.jp [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fifty percent of the mutant Rb transgenic mice produced liver tumors. Black-Right-Pointing-Pointer In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. Black-Right-Pointing-Pointer No increase in expression of the Myc-target genes was observed in the non-tumorous liver. Black-Right-Pointing-Pointer Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with {approx}50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  6. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    International Nuclear Information System (INIS)

    Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir; Noritake, Hidenao; Kimura, Wataru; Wu, Yi-Xin; Kobayashi, Yoshimasa; Uezato, Tadayoshi; Miura, Naoyuki

    2012-01-01

    Highlights: ► Fifty percent of the mutant Rb transgenic mice produced liver tumors. ► In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. ► No increase in expression of the Myc-target genes was observed in the non-tumorous liver. ► Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with ∼50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  7. Novel application for the prevention and treatment of Staphylococcus aureus biofilm formation

    Science.gov (United States)

    Traba, Christian

    Formation of bacterial biofilms at solid-liquid interfaces creates numerous problems in both industrial and biomedical sciences. In this dissertation, the application of plasma from two very different facets was studied. In part one, the susceptibility of pre-formed Staphylococcus aureus biofilms on biomaterials to different plasmas was investigated. It was found that the distinct chemical/physical properties of plasmas generated from oxygen, nitrogen, and argon all demonstrated very potent but very different anti-biofilm mechanisms of action. An in depth analysis of these results show: 1) different reactive species produced in each plasma demonstrate specific activity, and 2) the commonly associated etching effect could be manipulated and even controlled, depending on experimental conditions and the discharge gas. These studies provide insights into the anti-biofilm mechanisms of plasma as well as the effects of different reactive species on biofilm inactivation. Under experimental parameters, bacterial cells in Staphylococcus aureus biofilms were killed (>99.9%) by plasmas within minutes of exposure and no bacteria nor biofilm re-growth from discharge gas treated biofilms was observed throughout the life-span of the re-growth experiment. The decontamination ability of plasmas for the treatment of biofilm related infections on biomedical materials was confirmed and novel applications involving the use of low power argon and oxygen for the treatment of biofilm contaminated biomaterials and indwelling devices is proposed. The second facet of this dissertation explores the interaction between biofilm forming Staphylococcus aureus bacteria on different antibacterial/anti-biofilm surfaces. The antibiotic-free anti-fouling surfaces constructed in this study were generated from the plasma-assisted graft polymerization technique. These sophisticated surfaces were stable, biocompatible and capable of preventing biofilm formation on biomaterials and medical devices. Under

  8. CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation

    Directory of Open Access Journals (Sweden)

    Noelle E. Huskey

    2015-03-01

    Full Text Available Embryonic stem cells (ESCs have adopted an accelerated cell-cycle program with shortened gap phases and precocious expression of cell-cycle regulatory proteins, including cyclins and cyclin-dependent kinases (CDKs. We examined the effect of CDK inhibition on the pathways regulating proliferation and survival of ESCs. We found that inhibiting cyclin-dependent kinase 1 (CDK1 leads to activation of the DNA damage response, nuclear p53 stabilization, activation of a subset of p53 target genes including NOXA, and negative regulation of the anti-apoptotic protein MCL1 in human and mouse ESCs, but not differentiated cells. We demonstrate that MCL1 is highly expressed in ESCs and loss of MCL1 leads to ESC death. Finally, we show that clinically relevant CDK1 inhibitors prevent formation of ESC-derived tumors and induce necrosis in established ESC-derived tumors. Our data demonstrate that ES cells are uniquely sensitive to CDK1 inhibition via a p53/NOXA/MCL1 pathway.

  9. Brain and Spinal Tumors

    Science.gov (United States)

    ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ...

  10. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat

    NARCIS (Netherlands)

    Schwandt, LQ; Van Weissenbruch, R; Stokroos, [No Value; Van der Mei, HC; Busscher, HJ; Albers, FWJ

    Objective - To evaluate the preventive effect of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine on biofilm formation on voice prostheses in vitro. Material and Methods - Groningen button and Provox(R) 2 voice prostheses were inoculated with a mixture of bacteria and yeasts

  11. MR-based full-body preventative cardiovascular and tumor imaging: technique and preliminary experience

    International Nuclear Information System (INIS)

    Goyen, Mathias; Goehde, Susanne C.; Herborn, Christoph U.; Hunold, Peter; Vogt, Florian M.; Gizewski, Elke R.; Lauenstein, Thomas C.; Ajaj, Waleed; Forsting, Michael; Debatin, Joerg F.; Ruehm, Stefan G.

    2004-01-01

    Recent improvements in hardware and software, lack of side effects, as well as diagnostic accuracy make magnetic resonance imaging a natural candidate for preventative imaging. Thus, the purpose of the study was to evaluate the feasibility of a comprehensive 60-min MR-based screening examination in healthy volunteers and a limited number of patients with known target disease. In ten healthy volunteers (7 men, 3 women; mean age, 32.4 years) and five patients (4 men, 1 woman; mean age, 56.2 years) with proven target disease we evaluated the performance of a comprehensive MR screening strategy by combining well-established organ-based MR examination components encompassing the brain, the arterial system, the heart, the lungs, and the colon. All ten volunteers and five patients tolerated the comprehensive MR examination well. The mean in-room time was 63 min. In one volunteer, insufficient colonic cleansing on the part of the volunteer diminished the diagnostic reliability of MR colonography. All remaining components of the comprehensive MR examination were considered diagnostic in all volunteers and patients. In the five patients, the examination revealed the known pathologies [aneurysm of the anterior communicating artery (n=1), renal artery stenosis (n=1), myocardial infarct (n=1), and colonic polyp (n=2)]. The outlined MR screening strategy encompassing the brain, the arterial system, the heart, the lung, and the colon is feasible. Further studies have to show that MR-based screening programs are cost-effective in terms of the life-years saved. (orig.)

  12. hnRNP F directs formation of an exon 4 minus variant of tumor-associated NADH oxidase (ENOX2).

    Science.gov (United States)

    Tang, Xiaoyu; Kane, Vanessa D; Morré, Dorothy M; Morré, D James

    2011-11-01

    HUVEC or mouse 3T3 cells infected with SV-40 generate within 3 to 5 days post-infection an ENOX2 species corresponding to the exon-4 minus splice variant of a tumor-associated NADH oxidase (ENOX2 or tNOX) expressed at the cancer cell surface. This study was to seek evidence for splicing factors that might direct formation of the exon 4 minus ENOX2 splice variant. To determine if silencing of ENOX2 exon 4 occurs because of motifs located in exon 4, transfections were performed on MCF-10A (mammary non-cancer), BT-20 (mammary cancer), and HeLa (cervical cancer) cells using a GFP minigene construct containing either a constitutively spliced exon (albumin exon 2) or the alternatively spliced ENOX2 exon 4 between the two GFP halves. Removal of exon 4 from the processed RNA of the GFP minigene construct occurred with HeLa and to a lesser extent with BT-20 but not in non-cancer MCF-10A cells. The Splicing Rainbow Program was used to identify all of the possible hnRNPs binding sites of exon 4 of ENOX2. There are 8 Exonic Splicing Silencers (ESSs) for hnRNP binding in the exon 4 sequences. Each of these sites were mutated by site-directed mutagenesis to test if any were responsible for the splicing skip. Results showed MutG75 ESS mutation changed the GFP expression which is a sign of splicing silence, while other mutations did not. As MutG75 changed the ESS binding site for hnRNP F, this result suggests that hnRNP F directs formation of the exon 4 minus variant of ENOX2.

  13. Formative research to develop theory-based messages for a Western Australian child drowning prevention television campaign: study protocol.

    Science.gov (United States)

    Denehy, Mel; Crawford, Gemma; Leavy, Justine; Nimmo, Lauren; Jancey, Jonine

    2016-05-20

    Worldwide, children under the age of 5 years are at particular risk of drowning. Responding to this need requires the development of evidence-informed drowning prevention strategies. Historically, drowning prevention strategies have included denying access, learning survival skills and providing supervision, as well as education and information which includes the use of mass media. Interventions underpinned by behavioural theory and formative evaluation tend to be more effective, yet few practical examples exist in the drowning and/or injury prevention literature. The Health Belief Model and Social Cognitive Theory will be used to explore participants' perspectives regarding proposed mass media messaging. This paper describes a qualitative protocol to undertake formative research to develop theory-based messages for a child drowning prevention campaign. The primary data source will be focus group interviews with parents and caregivers of children under 5 years of age in metropolitan and regional Western Australia. Qualitative content analysis will be used to analyse the data. This study will contribute to the drowning prevention literature to inform the development of future child drowning prevention mass media campaigns. Findings from the study will be disseminated to practitioners, policymakers and researchers via international conferences, peer and non-peer-reviewed journals and evidence summaries. The study was submitted and approved by the Curtin University Human Research Ethics Committee. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Magnesium prevents vascular calcification in vitro by inhibition of hydroxyapatite crystal formation.

    NARCIS (Netherlands)

    Braake, A.D. ter; Tinnemans, P.T.; Shanahan, C.M.; Hoenderop, J.G.J.; Baaij, J.H.F. de

    2018-01-01

    Magnesium has been shown to effectively prevent vascular calcification associated with chronic kidney disease. Magnesium has been hypothesized to prevent the upregulation of osteoblastic genes that potentially drives calcification. However, extracellular effects of magnesium on hydroxyapatite

  15. Mesenchymal Stem Cells Engineered to Secrete Pigment Epithelium-Derived Factor Inhibit Tumor Metastasis and the Formation of Malignant Ascites in a Murine Colorectal Peritoneal Carcinomatosis Model.

    Science.gov (United States)

    Yang, Liping; Zhang, Yuwei; Cheng, Liuliu; Yue, Dan; Ma, Jinhu; Zhao, Da; Hou, Xiaoming; Xiang, Rong; Cheng, Ping

    2016-03-01

    The therapeutic effects of conventional treatments for advanced colorectal cancer with colorectal peritoneal carcinomatosis (CRPC) and malignant ascites are not very encouraging. Vascular endothelial growth factor-A/vascular permeability factors (VEGF-A/VPF) play key roles in the formation of malignant ascites. In previous work, we demonstrated that pigment epithelium-derived factor (PEDF) antagonized VEGF-A and could repress tumor growth and suppress metastasis in several cancer types. Thus, PEDF may be a therapeutic candidate for treating malignant ascites. Mesenchymal stem cells (MSCs) are promising tools for delivering therapeutic agents in cancer treatment. In the study, MSCs derived from bone marrow were efficiently engineered to secrete human PEDF by adenoviral transduction. Then, intraperitoneal Ad-PEDF-transduced MSCs were analyzed with respect to CRPC and malignant ascites in a CT26 CRPC model. MSCs engineered to secrete PEDF through adenoviral transduction significantly inhibited tumor metastasis and malignant ascites formation in CT26 CRPC mice. Antitumor mechanisms of MSCs-PEDF (MSCs transduced with Ad-PEDF: MOI 500) were associated with inhibiting tumor angiogenesis, inducing apoptosis, and restoring the VEGF-A/sFLT-1 ratio in ascites. Moreover, MSC-mediated Ad-PEDF delivery reduced production of adenovirus-neutralizing antibodies, prolonged PEDF expression, and induced MSCs-PEDF migration toward tumor cells. As a conclusion, MSCs engineered to secrete PEDF by adenoviral transduction may be a therapeutic approach for suppressing tumor metastasis and inhibiting malignant ascites production in CRPC.

  16. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

    Directory of Open Access Journals (Sweden)

    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  17. Gogo receptor contributes to retinotopic map formation and prevents R1-6 photoreceptor axon bundling.

    Directory of Open Access Journals (Sweden)

    Irina Hein

    Full Text Available BACKGROUND: Topographic maps form the basis of neural processing in sensory systems of both vertebrate and invertebrate species. In the Drosophila visual system, neighboring R1-R6 photoreceptor axons innervate adjacent positions in the first optic ganglion, the lamina, and thereby represent visual space as a continuous map in the brain. The mechanisms responsible for the establishment of retinotopic maps remain incompletely understood. RESULTS: Here, we show that the receptor Golden goal (Gogo is required for R axon lamina targeting and cartridge elongation in a partially redundant fashion with local guidance cues provided by neighboring axons. Loss of function of Gogo in large clones of R axons results in aberrant R1-R6 fascicle spacing. Gogo affects target cartridge selection only indirectly as a consequence of the disordered lamina map. Interestingly, small clones of gogo deficient R axons perfectly integrate into a proper retinotopic map suggesting that surrounding R axons of the same or neighboring fascicles provide complementary spatial guidance. Using single photoreceptor type rescue, we show that Gogo expression exclusively in R8 cells is sufficient to mediate targeting of all photoreceptor types in the lamina. Upon lamina targeting and cartridge selection, R axons elongate within their individual cartridges. Interestingly, here Gogo prevents bundling of extending R1-6 axons. CONCLUSION: Taken together, we propose that Gogo contributes to retinotopic map formation in the Drosophila lamina by controlling the distribution of R1-R6 axon fascicles. In a later developmental step, the regular position of R1-R6 axons along the lamina plexus is crucial for target cartridge selection. During cartridge elongation, Gogo allows R1-R6 axons to extend centrally in the lamina cartridge.

  18. Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Angel Descalzo, Miguel

    2007-06-15

    To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

  19. Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation.

    Science.gov (United States)

    Zuo, Jiangcheng; Yu, Yalan; Zhu, Man; Jing, Wei; Yu, Mingxia; Chai, Hongyan; Liang, Chunzi; Tu, Jiancheng

    2018-02-06

    Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

  20. Chemo prevention of Tea Polyphenols against Tumor Growth of Hepato-Colon Cancer Induced by Azoxy methane in Rats

    International Nuclear Information System (INIS)

    Heibashy, M.I.A.; Mazen, G.M.A.

    2008-01-01

    This investigation was conducted to evaluate the chemo prevention of tea polyphenols as anticancer agent in rats which were injected with azoxy methane (AOM) which is a potent hepato-colon carcinogen agents in rodents. The obtained data revealed a significant elevation in serum tumor markers, carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA 1 9.9) in carcinogenic rats in comparison to their corresponding normal control ones. Also, there was a significant increase in the content of cytochrome P 4 50 and the activity of alcohol dehydrogenase (ADH) in both liver and colon as well as a significant elevation in the activities of methoxyresorufin-O-dealkylase (MRD), ethoxyresorutin-O-dealkylase (ERD) and pentoxyresorufin-O- dealkylase (PRD) in liver microsomes. While, glutathione content (GSH) and glutathione peroxidase (Gp x ) activity were decreased significantly in liver and colon as a result of cancer induction. On the other hand, the supplementation of black or green tea before induction of cancer in rats led to a considerable correction in all previous parameters studied. These amelioration effects dependent on magic biochemical properties of flavanols (catechins) and type of tea. In conclusion, tea polyphenols have appreciable anti-cancer efficacy on hepato colon cancer in rats. The underlying mechanisms of through which tea counteracted hepato-colon cancer were discussed

  1. The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis.

    Science.gov (United States)

    Bonuccelli, Gloria; Castello-Cros, Remedios; Capozza, Franco; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Tsirigos, Aristotelis; Xuanmao, Jiao; Whitaker-Menezes, Diana; Howell, Anthony; Lisanti, Michael P; Sotgia, Federica

    2012-11-01

    Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we performed genome-wide transcriptional profiling. Interestingly, our results show that α-casein upregulates gene transcripts associated with interferon/STAT1 signaling and downregulates genes associated with "stemness." These findings were validated by immunoblot and FACS analysis, which showed the upregulation and hyperactivation of STAT1 and a decrease in the number of CD44(+) "cancer stem cells." These gene signatures were also able to predict clinical outcome in human breast cancer patients. Thus, we conclude that a lactation-based therapeutic strategy using recombinant α-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies.

  2. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  3. Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PIGF-1/VEGF heterodimers

    DEFF Research Database (Denmark)

    Eriksson, A.; Cao, R.; Pawliuk, R.

    2002-01-01

    , the biological function of its related homolog, placenta growth factor (PlGF), is poorly understood. Here we demonstrate that PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes VEGF-induced angiogenesis when both factors are coexpressed in murine fibrosarcoma cells. Overexpression of PlGF-1...... in VEGF-producing tumor cells results in the formation of PlGF-1/VEGF heterodimers and depletion of the majority of mouse VEGF homodimers. The heterodimeric form of PlGF-1/VEGF lacks the ability to induce angiogenesis in vitro and in vivo. Similarly, PlGF-1/VEGF fails to activate the VEGFR-2-mediated...... signaling pathways. Further, PlGF-1 inhibits the growth of a murine fibrosarcoma by approximately 90% when PlGF-1-expressing tumor cells are implanted in syngeneic mice. In contrast, overexpression of human VEGF in murine tumor cells causes accelerated and exponential growth of primary fibrosarcomas...

  4. Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhofer, Jörg; Berg, Christian Hededam

    2005-01-01

    The S100A4(mts1) protein stimulates metastatic spread of tumor cells. An elevated expression of S100A4 is associated with poor prognosis in many human cancers. Dynamics of tumor development were studied in S100A4-deficient mice using grafts of CSML100, highly metastatic mouse mammary carcinoma...

  5. Prevention of Addictive Behavior Based on the Formation of Teenagers' Resilience

    Science.gov (United States)

    Zeleeva, Vera P.; Shubnikova, Ekaterina G.

    2016-01-01

    The relevance of the study is due to the development of a new stage of prevention and the need to justify new educational goals and objectives of the pedagogical prevention of addictive behavior in the educational environment. The purpose of this article is to examine the totality of the necessary and sufficient individual resources, that are…

  6. Formation and utilization of acetoin, an unusual product of pyruvate metabolism by Ehrlich and AS30-D tumor mitochondria.

    Science.gov (United States)

    Baggetto, L G; Lehninger, A L

    1987-07-15

    [14C]Pyruvate was rapidly non-oxidatively decarboxylated by Ehrlich tumor mitochondria at a rate of 40 nmol/min/mg of protein in the presence or absence of ADP. A search for decarboxylation products led to significant amounts of acetoin formed when Ehrlich tumor mitochondria were incubated with 1 mM [14C] pyruvate in the presence of ATP. Added acetoin to aerobic tumor mitochondria was rapidly utilized in the presence of ATP at a rate of 65 nmol/min/mg of protein. Citrate has been found as a product of acetoin utilization and was exported from the tumor mitochondria. Acetoin has been found in the ascitic liquid of Ehrlich and AS30-D tumor-bearing animals. These unusual reactions were not observed in control rat liver mitochondria.

  7. Chondrosarcoma of the femur with histology-imaging correlation of tumor growth--preliminary observations concerning periosteal new bone formation and soft tissue extension.

    Science.gov (United States)

    Steiner, German C; Schweitzer, Mark E; Kenan, Samuel; Abdelwahab, Ibrahim F

    2011-01-01

    The objective of this study was, in chondrosarcoma (CHS) of the femur, to evaluate by radiologic-pathologic correlation, the degree of tumor growth, cortical destruction, periosteal reaction, and soft tissue extension present. Eight cases of histologically proven CHS of the femur were studied. All cases were resected, evaluated histologically with coronal slabs, and compared with radiographs and magnetic resonance imaging (MRI) scans. In two resected specimens, the tumors were studied in more detail; along with coronal slabs, axial sections of the remaining anterior and posterior halves of both tumors were taken, and the bone specimens were X-rayed and examined histologically. CHS initially involved the medullary cavity and subsequently destroyed the cortex; first, by endosteal scalloping and, second, by subsequent invasion and destruction of the cortex. During this process, there was periosteal new bone formation (PNBF), with increased cortical thickness, the degree of which often correlated with the degree of cortical destruction. In the areas of cortical thickening of three cases, a "grey line" was seen on MRI that separated the cortex from the periosteal new bone; the line, in reality,is a space between the two structures. The presence of this line suggests that the tumor does not extend beyond the cortex. PNBF occurred in all cases and varied in thickness. It frequently developed independent of direct periosteal tumor involvement. The periosteum of one case contained porotic bone with interposed marrow fat, which was easily misinterpreted as tumor extension on MRI. Expansion and remodeling of the femoral diaphysis in CHS, with widening of the medullary cavity, is usually due to extensive cortical destruction with PNBF. Soft tissue extension was present in five cases and apparently occurred by two different mechanisms: direct tumor destruction of the cortex and periosteum, with extension into the soft tissues; and subtle MRI occult tumor permeation through the

  8. LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Ken S. Rosenthal

    2017-01-01

    Full Text Available The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER consists of the murine HER-2/neu66–74 H-2d CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL (human β2 microglobulin38–50 peptide. The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of J-HER one week after challenge with TUBO breast cancer cells limited the spread of the tumors and the morbidity and the mortality in the challenged mice. The ability to elicit responses that prevent spread of the TUBO tumor by J-HER suggests its utility as a neoimmunoadjuvant therapy to surgery. Individual or mixtures of J-LEAPS vaccines can be readily prepared to include different CD8 T cell epitopes to optimize tumor therapy and customize treatment for individuals with different HLA types.

  9. Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis

    Science.gov (United States)

    Jian, Shiou-Ling; Chen, Wei-Wei; Su, Yu-Chia; Su, Yu-Wen; Chuang, Tsung-Hsien; Hsu, Shu-Ching; Huang, Li-Rung

    2017-01-01

    Immunotherapy aiming to rescue or boost antitumor immunity is an emerging strategy for treatment of cancers. The efficacy of immunotherapy is strongly controlled by the immunological milieu of cancer patients. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with immunosuppressive functions accumulating in individuals during tumor progression. The signaling mechanisms of MDSC activation have been well studied. However, there is little known about the metabolic status of MDSCs and the physiological role of their metabolic reprogramming. In this study, we discovered that myeloid cells upregulated their glycolytic genes when encountered with tumor-derived factors. MDSCs exhibited higher glycolytic rate than their normal cell compartment did, which contributed to the accumulation of the MDSCs in tumor-bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP), as a vital antioxidant agent able to prevent excess ROS production and therefore contributed to the survival of MDSCs. These findings suggest that glycolytic metabolites have important roles in the modulation of fitness of MDSCs and could be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in tumor-bearing individuals. PMID:28492541

  10. Formative evaluation of the telecare fall prevention project for older veterans

    OpenAIRE

    Miake-Lye, Isomi M; Amulis, Angel; Saliba, Debra; Shekelle, Paul G; Volkman, Linda K; Ganz, David A

    2011-01-01

    Abstract Background Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage pa...

  11. Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm- and adherence-specific mechanisms.

    Science.gov (United States)

    Rane, Hallie S; Bernardo, Stella M; Howell, Amy B; Lee, Samuel A

    2014-02-01

    Candida albicans is a common cause of nosocomial urinary tract infections (UTIs) and is responsible for increased morbidity and healthcare costs. Moreover, the US Centers for Medicare & Medicaid Services no longer reimburse for hospital-acquired catheter-associated UTIs. Thus, development of specific approaches for the prevention of Candida urinary infections is needed. Cranberry juice-derived proanthocyanidins (PACs) have efficacy in the prevention of bacterial UTIs, partially due to anti-adherence properties, but there are limited data on their use for the prevention and/or treatment of Candida UTIs. Therefore, we sought to systematically assess the in vitro effect of cranberry-derived PACs on C. albicans biofilm formation in artificial urine. C. albicans biofilms in artificial urine were coincubated with cranberry PACs at serially increasing concentrations and biofilm metabolic activity was assessed using the XTT assay in static microplate and silicone disc models. Cranberry PAC concentrations of ≥16 mg/L significantly reduced biofilm formation in all C. albicans strains tested, with a paradoxical effect observed at high concentrations in two clinical isolates. Further, cranberry PACs were additive in combination with traditional antifungals. Cranberry PACs reduced C. albicans adherence to both polystyrene and silicone. Supplementation of the medium with iron reduced the efficacy of cranberry PACs against biofilms. These findings indicate that cranberry PACs have excellent in vitro activity against C. albicans biofilm formation in artificial urine. We present preliminary evidence that cranberry PAC activity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation.

  12. Treating cancer as an infectious disease--viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology.

    Directory of Open Access Journals (Sweden)

    Xing Guo Wang

    2007-10-01

    Full Text Available Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers.Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC and Hepatitis B-associated hepatocellular carcinoma (HCC by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies.This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.

  13. Preventive effects of a phospholipid polymer coating on PMMA on biofilm formation by oral streptococci

    Science.gov (United States)

    Shibata, Yukie; Yamashita, Yoshihisa; Tsuru, Kanji; Ishihara, Kazuhiko; Fukazawa, Kyoko; Ishikawa, Kunio

    2016-12-01

    The regulation of biofilm formation on dental materials such as denture bases is key to oral health. Recently, a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) coating, was reported to inhibit sucrose-dependent biofilm formation by Streptococcus mutans, a cariogenic bacterium, on the surface of poly(methyl methacrylate) (PMMA) denture bases. However, S. mutans is a minor component of the oral microbiome and does not play an important role in biofilm formation in the absence of sucrose. Other, more predominant oral streptococci must play an indispensable role in sucrose-independent biofilm formation. In the present study, the effect of PMB coating on PMMA was evaluated using various oral streptococci that are known to be initial colonizers during biofilm formation on tooth surfaces. PMB coating on PMMA drastically reduced sucrose-dependent tight biofilm formation by two cariogenic bacteria (S. mutans and Streptococcus sobrinus), among seven tested oral streptococci, as described previously [N. Takahashi, F. Iwasa, Y. Inoue, H. Morisaki, K. Ishihara, K. Baba, J. Prosthet. Dent. 112 (2014) 194-203]. Streptococci other than S. mutans and S. sobrinus did not exhibit tight biofilm formation even in the presence of sucrose. On the other hand, all seven species of oral streptococci exhibited distinctly reduced glucose-dependent soft biofilm retention on PMB-coated PMMA. We conclude that PMB coating on PMMA surfaces inhibits biofilm attachment by initial colonizer oral streptococci, even in the absence of sucrose, indicating that PMB coating may help maintain clean conditions on PMMA surfaces in the oral cavity.

  14. Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

    Science.gov (United States)

    He, Y; Wu, A C; Harrington, B S; Davies, C M; Wallace, S J; Adams, M N; Palmer, J S; Roche, D K; Hollier, B G; Westbrook, T F; Hamidi, H; Konecny, G E; Winterhoff, B; Chetty, N P; Crandon, A J; Oliveira, N B; Shannon, C M; Tinker, A V; Gilks, C B; Coward, J I; Lumley, J W; Perrin, L C; Armes, J E; Hooper, J D

    2016-01-28

    Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC

  15. A new experimental method to prevent paraffin - wax formation on the crude oil wells: A field case study in Libya

    Directory of Open Access Journals (Sweden)

    Elhaddad Elnori E.

    2015-01-01

    Full Text Available Wax formation and deposition is one of the most common problems in oil producing wells. This problem occurs as a result of the reduction of the produced fluid temperature below the wax appearance temperature (range between 46°C and 50°C and the pour point temperature (range between 42°C and 44°C. In this study, two new methods for preventing wax formation were implemented on three oil wells in Libya, where the surface temperature is, normally, 29°C. In the first method, the gas was injected at a pressure of 83.3 bar and a temperature of 65°C (greater than the pour point temperature during the gas-lift operation. In the second method, wax inhibitors (Trichloroethylene-xylene (TEX, Ethylene copolymers, and Comb polymers were injected down the casings together with the gas. Field observations confirmed that by applying these techniques, the production string was kept clean and no wax was formed. The obtained results show that the wax formation could be prevented by both methods.

  16. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  17. Chlorhexidine efficacy in preventing lesion formation in enamel and dentine: an in situ study

    NARCIS (Netherlands)

    van Strijp, A.J.P.; Gerardu, V.A.M.; Buijs, M.J.; van Loveren, C.; ten Cate, J.M.

    2008-01-01

    Background: Clinical studies on the caries-preventive properties of chlorhexidine mouthrinses are limited and the results are inconclusive. Aim: The aim of this study was to elucidate the contribution of a 0.2% chlorhexidine mouthrinse to the protection of enamel and dentine against

  18. IL-3R-alpha blockade inhibits tumor endothelial cell-derived extracellular vesicle (EV)-mediated vessel formation by targeting the β-catenin pathway.

    Science.gov (United States)

    Lombardo, Giusy; Gili, Maddalena; Grange, Cristina; Cavallari, Claudia; Dentelli, Patrizia; Togliatto, Gabriele; Taverna, Daniela; Camussi, Giovanni; Brizzi, Maria Felice

    2018-03-01

    The proangiogenic cytokine Interleukin-3 (IL-3) is released by inflammatory cells in breast and ovarian cancer tissue microenvironments and also acts as an autocrine factor for human breast and kidney tumor-derived endothelial cells (TECs). We have previously shown that IL-3-treated endothelial cells (ECs) release extracellular vesicles (EVs), which serve as a paracrine mechanism for neighboring ECs, by transferring active molecules. The impact of an anti-IL-3R-alpha blocking antibody on the proangiogenic effect of EVs released from TECs (anti-IL-3R-EVs) has therefore been investigated in this study. We have found that anti-IL-3R-EV treatment prevented neovessel formation and, more importantly, also induced the regression of in vivo TEC-derived neovessels. Two miRs that target the canonical wingless (Wnt)/β-catenin pathway, at different levels, were found to be differentially regulated when comparing the miR-cargo of naive TEC-derived EVs (EVs) and anti-IL-3R-EVs. miR-214-3p, which directly targets β-catenin, was found to be upregulated, whereas miR-24-3p, which targets adenomatous polyposis coli (APC) and glycogen synthase kinase-3β (GSK3β), was found to be downregulated. In fact, upon their transfer into the cell, low β-catenin content and high levels of the two members of the "β-catenin destruction complex" were detected. Moreover, c-myc downregulation was found in TECs treated with anti-IL-3R-EVs, pre-miR-214-3p-EVs and antago-miR-24-3p-EVs, which is consistent with network analyses of miR-214-3p and miR-24-3p gene targeting. Finally, in vivo studies have demonstrated the impaired growth of vessels in pre-miR-214-3p-EV- and antago-miR-24-3p-EV-treated animals. These effects became much more evident when combo treatment was applied. The results of the present study identify the canonical Wnt/β-catenin pathway as a relevant mechanism of TEC-derived EV proangiogenic action. Furthermore, we herein provide evidence that IL-3R blockade may yield some

  19. Streptomyces lunalinharesii 235 prevents the formation of a sulfate-reducing bacterial biofilm

    Directory of Open Access Journals (Sweden)

    Juliana Pacheco da Rosa

    Full Text Available ABSTRACT Streptomyces lunalinharesii strain 235 produces an antimicrobial substance that is active against sulfate reducing bacteria, the major bacterial group responsible for biofilm formation and biocorrosion in petroleum reservoirs. The use of this antimicrobial substance for sulfate reducing bacteria control is therefore a promising alternative to chemical biocides. In this study the antimicrobial substance did not interfere with the biofilm stability, but the sulfate reducing bacteria biofilm formation was six-fold smaller in carbon steel coupons treated with the antimicrobial substance when compared to the untreated control. A reduction in the most probable number counts of planktonic cells of sulfate reducing bacteria was observed after treatments with the sub-minimal inhibitory concentration, minimal inhibitory concentration, and supra-minimal inhibitory concentration of the antimicrobial substance. Additionally, when the treated coupons were analyzed by scanning electron microscopy, the biofilm formation was found to be substantially reduced when the supra-minimal inhibitory concentration of the antimicrobial substance was used. The coupons used for the biofilm formation had a small weight loss after antimicrobial substance treatment, but corrosion damage was not observed by scanning electron microscopy. The absence of the dsrA gene fragment in the scraped cell suspension after treatment with the supra-minimal inhibitory concentration of the antimicrobial substance suggests that Desulfovibrio alaskensis was not able to adhere to the coupons. This is the first report on an antimicrobial substance produced by Streptomyces active against sulfate reducing bacteria biofilm formation. The application of antimicrobial substance as a potential biocide for sulfate reducing bacteria growth control could be of great interest to the petroleum industry.

  20. Controlled release of chlorhexidine from a mesoporous silica-containing macroporous titanium dental implant prevents microbial biofilm formation.

    Science.gov (United States)

    De Cremer, K; Braem, A; Gerits, E; De Brucker, K; Vandamme, K; Martens, J A; Michiels, J; Vleugels, J; Cammue, B P; Thevissen, K

    2017-01-11

    Roughened surfaces are increasingly being used for dental implant applications as the enlarged contact area improves bone cell anchorage, thereby facilitating osseointegration. However, the additional surface area also entails a higher risk for the development of biofilm associated infections, an etiologic factor for many dental ailments, including peri-implantitis. To overcome this problem, we designed a dental implant composed of a porous titanium-silica (Ti/SiO2) composite material and containing an internal reservoir that can be loaded with antimicrobial compounds. The composite material consists of a sol-gel derived mesoporous SiO2 diffusion barrier integrated in a macroporous Ti load-bearing structure obtained by powder metallurgical processing. The antimicrobial compounds can diffuse through the porous implant walls, thereby reducing microbial biofilm formation on the implant surface. A continuous release of µM concentrations of chlorhexidine through the Ti/SiO2 composite material was measured, without initial burst effect, over at least 10 days and using a 5 mM chlorhexidine solution in the implant reservoir. Metabolic staining, CFU counting and visualisation by scanning electron microscopy confirmed that Streptococcus mutans biofilm formation on the implant surface was almost completely prevented due to chlorhexidine release (preventive setup). Moreover, we demonstrated efficacy of released chlorhexidine against mature Streptococcus mutans biofilms (curative setup). In conclusion, we provide a proof of concept of the sustained release of chlorhexidine, one of the most widely used oral antiseptics, through the Ti/SiO2 material thereby preventing and eradicating biofilm formation on the surface of the dental implant. In principle, our flexible design allows for the use of any bioactive compound, as discussed.

  1. Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation.

    Science.gov (United States)

    Kasiri, Sahba; Ansari, Khairul I; Hussain, Imran; Bhan, Arunoday; Mandal, Subhrangsu S

    2013-01-01

    HOXC13 is a homeobox containing gene that plays crucial roles in hair development and origin of replication. Herein, we investigated the biochemical functions of HOXC13 and explored its potential roles in tumor cell viability. We have designed a phosphorothioate based antisense-oligonucleotide that specifically knockdown HOXC13 in cultured cells. Cell viability and cytotoxicity assays demonstrated that HOXC13 is essential for cell growth and viability. Antisense-mediated knockdown of HOXC13 affected the cell viability and induced apoptosis in cultured tumor cells. HOXC13 regulates the expression of cyclins and antisense-mediated knockdown of HOXC13 resulted in cell cycle arrest and apoptosis in colon cancer cells. Finally over expression of HOXC13 resulted in 3D-colony formation in soft-agar assay indicating its potential roles in cell proliferation and tumorigenesis.

  2. Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

    DEFF Research Database (Denmark)

    Wang, Z; Pedersen, Esben Ditlev Kølle; Basse, A

    2010-01-01

    Rac1 has a role in proliferation and survival of tumor cells in vitro. The exact effects of Rac1 on growth, apoptosis and corresponding signaling pathways during tumorigenesis in vivo, however, have not been explored yet. Using mice with a keratinocyte-restricted deletion of the Rac1 gene, we found...... that Rac1 is essential for DMBA/TPA-induced skin tumor formation. This corresponded to a decreased keratinocyte hyperproliferation, although apoptosis was not detectably altered. Activated Rac1 promoted Erk-dependent hyperproliferation by Pak1-mediated Mek activation independent of Mek1 phosporylation...... at serine 298. Rac1 was furthermore required for Pak2-dependent hyperactivation of Akt, which under in vivo condition was restricted to the suprabasal cell layers corresponding to a suprabasal-specific expression of Pak2. It is surprising that none of these signaling pathways was altered in untreated Rac1...

  3. Environment of estates and crime prevention through urban environment formation and modification

    Directory of Open Access Journals (Sweden)

    Matlovičová Kvetoslava

    2016-01-01

    Full Text Available Due to the significant impact of criminality on the quality of life in a particular territory, criminality is attracting more and more attention from local authorities which are trying to reduce it. In this respect, the concept of CPTED (Crime Prevention Through Environmental Design which is quite often used out­side of Slovakia and is based on prevention of criminality through the appropriate design of urban environments, seems to be useful. The study offers the characteristics of CPTED principles and also suggests possibilities for its application within innercity criminality on model territories of the city of Prešov (Slovakia as an usable way of reducing crime in other mainly East-central European cities.

  4. Corrosive inorganic contamination on wafer surfaces after nickel-iron electroplating formation mechanisms and prevention

    Energy Technology Data Exchange (ETDEWEB)

    Kritzer, P. [Freudenberg Nonwovens KG, Technical Nonwovens Div., Weinheim (Germany); Diel, W.; Barber, P.H. [IBM Speichersysteme Deutschland GmbH, Mainz (Germany); Romankiw, L.T. [IBM Watson Research Center, Yorktown Heights, NY (United States)

    2001-11-01

    Electroplating of Nickel-Iron alloys is widely used in the production of magnetic heads for storage systems. Usually, the plating process is performed in acidic, salt-containing solutions. After the plating step, a complete removal of the plating salts is necessary to receive a clean surface. In disadvantageous cases, a precipitation of sticky particles is observed that cannot be removed from the plated surface without damaging the surface. Some of these substances (esp. nickel sulfates) might lead to severe local corrosion and thus might act as ''time-bomb'' in the later product. Non-corrosive precipitations (i.e. nickel hydroxides) strongly hinder or even prevent the following production steps. In the present paper, the mechanisms of the origin of the different kinds of precipitation are described and the principle actions for their prevention are given. An outlook is given for other possible technical applications. (orig.)

  5. Control and Prevention of Ice Formation on the Surface of an Aluminum Alloy

    DEFF Research Database (Denmark)

    Rahimi, Maral

    In cold climates, mechanical ventilation systems with heat recovery, e.g. air-to-air exchangers, are often used to reduce energy demand for heating by recovering the heat from the exhausted air. This, however, creates a risk of ice accretion on the fins of the heat exchanger as warm and humid...... exhausted air cools down. Due to the reduction in heat exchanger efficiency due to ice formation, this phenomenon has been studied for many decades. There are two approaches to controlling ice formation on heat exchangers: active and passive. The active methods, e.g. bypass, recirculation, preheating etc......., require energy and consequently reduce the overall efficiency of the system. They are not addressed in this work and have already been studied extensively by many researchers. The passive methods, which are related to the surface characteristics of the heat exchanger fins and their effect on the initial...

  6. UV-Induced prevention of biofilm formation inside medical tubes and catheters

    DEFF Research Database (Denmark)

    Pedersen, Jens Kristian Mølgaard; Nielsen, Kristian; Bang, Ole

    2014-01-01

    Biofilm formation inside medical tubes and catheters may often cause unwanted infections, illness andimpaired wound healing during medical treatment, resulting in extended hospitalization and - in worst case– life threatening conditions of the patients. In fact, it is estimated, that the infectio......-light propagation or by other meansintegrating optical fiber technology into the tube walls, such as to gradually release UV-light into theinterior, efficiently killing off bacteria present inside....

  7. Kaempferide Prevents Titanium Particle Induced Osteolysis by Suppressing JNK Activation during Osteoclast Formation.

    Science.gov (United States)

    Jiao, Zixian; Xu, Weifeng; Zheng, Jisi; Shen, Pei; Qin, An; Zhang, Shanyong; Yang, Chi

    2017-11-30

    Kaempferide (KF) is an O-methylated flavonol, a natural plant extract, which is often found in Kaempferia galanga. It has a variety of effects including anti-carcinogenic, anti-inflammatory, anti-oxidant, anti-bacterial and anti-viral properties. In this study, we aimed to investigate whether KF effectively inhibits titanium particle induced calvarial bone loss via down regulation of the JNK signaling pathway. In the mice with titanium particle induced calvarial osteolysis, the Low dose of KF mildly reduced the resorption pits while in the high dose group, fewer scattered pits were observed on the surface of calvarium. Histological examination showed fewer osteoclasts formation in the KF group. In mouse bone marrow macrophages (BMMs) and RAW264.7 cells, KF significantly inhibited the osteoclast formation and bone resorption at 12.5 μM. However, KF does not affect the mature osteoclast F-actin ring formation. But when being co-treated with KF and anisomycin, BMMs differentiated into mature osteoclasts. At the molecular levels, the JNK phosphorylation was inhibited and the osteoclastogenesis-related specific gene expression including V-ATPase d2, TRAP, calcitonin receptor (CTR), c-Fos and NFATc1 was markedly suppressed. In conclusion, these results indicated that KF is a promising agent in the treatment of osteoclast-related diseases.

  8. Antioxidant Compounds in Traditional Indian Pickles May Prevent the Process-Induced Formation of Benzene.

    Science.gov (United States)

    Kharat, Mahesh M; Adiani, Vanshika; Variyar, Prasad; Sharma, Arun; Singhal, Rekha S

    2016-01-01

    Pickles in the Indian market contain ascorbic acid from the raw material used and benzoate as an added preservative that are involved in the formation of benzene in soft drinks. In this work, 24 market pickle samples were surveyed for benzene content, as well as its precursors and other constituents that influence its formation. The analysis showed that pickle samples were high in acid content (low pH) and showed significant amount of ascorbic acid, minerals (Cu and Fe), and benzoic acid present in them. Also, most samples exhibited high antioxidant activity that might be attributed to the ingredients used, such as fruits and spices. The solid-phase microextraction headspace gas chromatography-mass spectrometry method was developed in-house for benzene analysis. Eleven of 24 samples had benzene, with the highest concentration of 4.36 ± 0.82 μg of benzene per kg of pickle for a lime pickle that was also reported to have highest benzoic acid and considerably less hydroxyl radical ((•)OH) scavenging activity. However, benzene levels for all 11 samples were considerably below the World Health Organization regulatory limit of 10 μg/kg for benzene in mineral water. Studies on model systems revealed that the high antioxidant activity of Indian pickles may have had a strong inhibitory effect on benzene formation.

  9. Late administration of a specific COX-2 inhibitor does not treat and/or prevent progression of gastric tumors in rats submitted to duodenogastric reflux procedure

    Directory of Open Access Journals (Sweden)

    Paulo Antônio Rodrigues

    2013-06-01

    Full Text Available PURPOSE:To assess whether late introduction of a specific COX-2 inhibitor (Meloxicam can treat and/or prevent the progression of tumors in the stomach of rats submitted to duodenogastric reflux. METHODS: Seventy five male Wistar rats, weighing 150 grams, were submitted to the induction of duodenogastric reflux through the pylorus. At 36 weeks of follow-up were established three experimental groups: DGR36 sacrificed immediately, DGR54 and DGR54MLX both sacrificed at 54th week of follow-up . The animals of the latter group were fed with a rat chow premixed with Meloxicam (2.0 mg/ kg feed; 0.3 mg / kg bw / day and the other two with standard rat chow. The lesions found in the pyloric mucosa and gastrojejunal anastomosis were analyzed macroscopically and histologically. For statistical analysis was adjusted a generalized linear model assuming a binomial distribution with LOGIT link function. RESULTS: No significant differences were found when comparing the incidences of benign tumor lesions (Adenomatous Hyperplasia, p=0.4915, or malignant (Mucinous Adenocarcinoma, p=0.2731, among groups. CONCLUSION: Late introduction of specific COX-2 inhibitor (Meloxicam did not treat and was not able to prevent the progression of tumoral lesions induced by duodenogastric reflux in the rat stomachs.

  10. Multi-targeted DATS Prevents Tumor Progression and Promotes Apoptosis in an Animal Model of Glioblastoma via HDAC-inhibition

    Science.gov (United States)

    Wallace, Gerald C; Haar, Catherine P; Vandergrift, W Alex; Giglio, Pierre; Ray, Swapan K; Patel, Sunil J; Banik, Naren L; Das, Arabinda

    2015-01-01

    Glioblastoma, the most malignant and lethal of brain tumors, remains incurable despite aggressive chemotherapy and surgical interventions. Few new chemotherapeutics for glioblastoma therapy have been explored in preclinical models, and some agents approved for have reached the clinical setting. However success rates are not significant. Previous investigations involving diallyl trisulfide (DATS), a garlic constituent, have indicated significant anti-cancer effects in vitro, including: glioblastoma growth inhibition, extrinsic and intrinsic apoptotic pathway activation, and cell death. DATS has also been shown to inhibit histone deacetylase activity and impede glioblastoma tumor progression. We hypothesized that DATS would block ectopic U87MG induced tumors by inhibiting multiple pro-apoptotic pathways via HDAC. To this end, ectopic tumors were developed in SCID mice and subsequently treated with daily intraperitoneal injections of DATS. Results indicate that a range of DATS doses (10μg/kg-10mg/kg) dose-dependently reduced tumor volume and number of mitotic cells within tumors after seven days. Our histological and biochemical assays demonstrate that DATS reduces mitosis in tumors, decreases HDAC activity, increases in acetylation of H3 and H4, inhibits cell cycle progression, promotes apoptotic cascade activation (m-calpian, Bax, caspase-3) and decreases pro-survival markers (Survivin, Bcl-2, p-Akt, c-Myc, mTOR, EGFR, VEGF). Our data also demonstrates an increase in p21/WAF1 expression, which correlates with increased p53 expression and MDM2 degradation following DATS treatment. Finally, histological assessment and enzyme assays suggest that even the highest dose of DATS administered in this study did not negatively impact hepatic function. These in vivo findings strongly support orthotopic investigation into the therapeutic potential of DATS and further review of the epigenetic mechanisms behind its anti-cancer activities. PMID:23754639

  11. Mitochondrial oxidative stress drives tumor progression and metastasis: should we use antioxidants as a key component of cancer treatment and prevention?

    Directory of Open Access Journals (Sweden)

    Sotgia Federica

    2011-05-01

    Full Text Available Abstract The functional role of oxidative stress in cancer pathogenesis has long been a hotly debated topic. A study published this month in BMC Cancer by Goh et al., directly addresses this issue by using a molecular genetic approach, via an established mouse animal model of human breast cancer. More specifically, alleviation of mitochondrial oxidative stress, via transgenic over-expression of catalase (an anti-oxidant enzyme targeted to mitochondria, was sufficient to lower tumor grade (from high-to-low and to dramatically reduce metastatic tumor burden by >12-fold. Here, we discuss these new findings and place them in the context of several other recent studies showing that oxidative stress directly contributes to tumor progression and metastasis. These results have important clinical and translational significance, as most current chemo-therapeutic agents and radiation therapy increase oxidative stress, and, therefore, could help drive tumor recurrence and metastasis. Similarly, chemo- and radiation-therapy both increase the risk for developing a secondary malignancy, such as leukemia and/or lymphoma. To effectively reduce mitochondrial oxidative stress, medical oncologists should now re-consider the use of powerful anti-oxidants as a key component of patient therapy and cancer prevention. Please see related research article: http://www.biomedcentral.com/1471-2407/11/191

  12. Novel dural incision and closure procedure for preventing postoperative cerebrospinal fluid leakage during the surgical removal of dumbbell-shaped spinal tumors: technical note.

    Science.gov (United States)

    Ito, Kiyoshi; Aoyama, Tatsuro; Nakamura, Takuya; Hanaoka, Yoshiki; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro

    2016-11-01

    The authors report on a new method for removing dumbbell-shaped spinal tumors that avoids the risk of postoperative cerebrospinal fluid (CSF) leakage. Adequate visualization of the intra- and extradural components of the tumor is achieved with the use of separate dural incisions. First, the dura mater is opened along the dural theca to provide adequate visualization of the intradural portion of the mass; then, a second incision is made along the nerve root to remove the extradural component. Meticulous suturing is essential in intradural lesion cases; however, the dura mater is usually thin and fragile in such cases. During suturing with a needle and thread, the dura mater can become lacerated proximal to the needle holes and result in CSF leakage. In the authors' technique, instead of using a needle and thread, nonpenetrating vascular clips were used to close the dural incisions. When operating on dumbbell-shaped spinal tumors, the authors found that the "separate-dural-incision method" was preferable to the conventional T-shaped dural incision method because no dural defects occurred after the intradural procedure and meticulous dural closure with vascular clips was achieved. The authors conclude that the novel separate-dural-incision method for removing dumbbell-shaped tumors and the use of nonpenetrating vascular clips permits reliable dural closure, prevents postoperative CSF leakage, and promises good postoperative clinical results.

  13. Role of vitamin D3 in modulation of ΔNp63α expression during UVB induced tumor formation in SKH-1 mice.

    Directory of Open Access Journals (Sweden)

    Natasha T Hill

    Full Text Available ΔNp63α, a proto-oncogene, is up-regulated in non-melanoma skin cancers and directly regulates the expression of both Vitamin D receptor (VDR and phosphatase and tensin homologue deleted on chromosome ten (PTEN. Since ΔNp63α has been shown to inhibit cell invasion via regulation of VDR, we wanted to determine whether dietary Vitamin D3 protected against UVB induced tumor formation in SKH-1 mice, a model for squamous cell carcinoma development. We examined whether there was a correlation between dietary Vitamin D3 and ΔNp63α, VDR or PTEN expression in vivo in SKH-1 mice chronically exposed to UVB radiation and fed chow containing increasing concentrations of dietary Vitamin D3. Although we observed differential effects of the Vitamin D3 diet on ΔNp63α and VDR expression in chronically irradiated normal mouse skin as well as UVB induced tumors, Vitamin D3 had little effect on PTEN expression in vivo. While low-grade papillomas in mice exposed to UV and fed normal chow displayed increased levels of ΔNp63α, expression of both ΔNp63α and VDR was reduced in invasive tumors. Interestingly, in mice fed high Vitamin D3 chow, elevated levels of ΔNp63α were observed in both local and invasive tumors but not in normal skin suggesting that oral supplementation with Vitamin D3 may increase the proliferative potential of skin tumors by increasing ΔNp63α levels.

  14. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  15. PDZK1 prevents neointima formation via suppression of breakpoint cluster region kinase in vascular smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wan Ru Lee

    Full Text Available Scavenger receptor class B, type I (SR-BI and its adaptor protein PDZK1 mediate responses to HDL cholesterol in endothelium. Whether the receptor-adaptor protein tandem serves functions in other vascular cell types is unknown. The current work determined the roles of SR-BI and PDZK1 in vascular smooth muscle (VSM. To evaluate possible VSM functions of SR-BI and PDZK1 in vivo, neointima formation was assessed 21 days post-ligation in the carotid arteries of wild-type, SR-BI-/- or PDZK1-/- mice. Whereas neointima development was negligible in wild-type and SR-BI-/-, there was marked neointima formation in PDZK1-/- mice. PDZK1 expression was demonstrated in primary mouse VSM cells, and compared to wild-type cells, PDZK1-/- VSM displayed exaggerated proliferation and migration in response to platelet derived growth factor (PDGF. Tandem affinity purification-mass spectrometry revealed that PDZK1 interacts with breakpoint cluster region kinase (Bcr, which contains a C-terminal PDZ binding sequence and is known to enhance responses to PDGF in VSM. PDZK1 interaction with Bcr in VSM was demonstrated by pull-down and by coimmunoprecipitation, and the augmented proliferative response to PDGF in PDZK1-/- VSM was abrogated by Bcr depletion. Furthermore, compared with wild-type Bcr overexpression, the introduction of a Bcr mutant incapable of PDZK1 binding into VSM cells yielded an exaggerated proliferative response to PDGF. Thus, PDZK1 has novel SR-BI-independent function in VSM that affords protection from neointima formation, and this involves PDZK1 suppression of VSM cell proliferation via an inhibitory interaction with Bcr.

  16. Licochalcone A Prevents Platelet Activation and Thrombus Formation through the Inhibition of PLCγ2-PKC, Akt, and MAPK Pathways.

    Science.gov (United States)

    Lien, Li-Ming; Lin, Kuan-Hung; Huang, Li-Ting; Tseng, Mei-Fang; Chiu, Hou-Chang; Chen, Ray-Jade; Lu, Wan-Jung

    2017-07-12

    Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 μM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.

  17. Sustained prevention of biofilm formation on a novel silicone matrix suitable for medical devices

    DEFF Research Database (Denmark)

    Steffensen, Søren Langer; Merete H., Vestergaard,; Jensen, Minna Grønning

    2015-01-01

    ciprofloxacin was loaded into the polymer matrix by a post-polymerization loading procedure. Sustained release of ciprofloxacin was demonstrated, and the release could be controlled by varying the hydrogel content in the range 13–38% (w/w) and by changing the concentration of ciprofloxacin during loading...... in the range of 1–20 mg/mL. Devices containing 25% (w/w) hydrogel and loaded with ciprofloxacin displayed a strong antibacterial effect against Staphylococcus aureus bacterial colonization and subsequent biofilm formation on the device material was inhibited for 29 days. In conclusion, the hydrogel...

  18. Radiation-induced formation of 8-hydroxy-2'-deoxyguanosine and its prevention by scavengers

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Jeding, I B; Loft, S

    1994-01-01

    measured 8-OHdG formation in calf thymus DNA exposed to ionizing radiation under conditions generating either hydroxyl radicals (OH.), superoxide anions (O2-) or both. Additionally, we investigated the relationship between the scavenger effect of the drug 5-aminosalicylic acid (5-ASA) and increasing OH...... and 100 Gy radiation, i.e. within a wide range of OH. exposure, which is useful information considering clinical applications where the exact amount of ROS formed is unknown. Both 5-ASA and ascorbate at low concentrations (

  19. Biosurfactants prevent in vitro Candida albicans biofilm formation on resins and silicon materials for prosthetic devices.

    Science.gov (United States)

    Cochis, Andrea; Fracchia, Letizia; Martinotti, Maria Giovanna; Rimondini, Lia

    2012-06-01

    The aim of this study was to evaluate in vitro the preventive antiadhesion activity of biosurfactants against Candida albicans biofilm. Disks of silicon and acrylic resin for denture prostheses were precoated with increasing concentrations of biosurfactants obtained from endophyte biofilms selected from Robinia pseudoacacia and from Nerium oleander, and afterward infected with C. albicans cells. The number of biofilm cells were detected by colony-forming unit (CFU) counting, cell viability was established by the 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay, and biosurfactant cytotoxicity was evaluated by the [3-(4,5-dimethyliazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium] (MTT) assay. Chlorhexidine was used as control. Precoating with biosurfactants caused a greater reduction (P biosurfactants was observed at low concentrations (78.12 μg/mL and 156.12 μg/mL) which were noncytotoxic. This study demonstrated the preventive antiadhesion activity of biosurfactants against C. albicans biofilm. These agents are amphiphilic, interfere with microbial adhesion, and demonstrate cycompatibility with epithelial cells and fibroblasts. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. [Calculus formation in the prostatic cavity after transurethral resection of the prostate: causes, treatment and prevention].

    Science.gov (United States)

    Wei, Zhi-Feng; Xu, Xiao-Feng; Cheng, Wen; Zhou, Wen-Quan; Ge, Jing-Ping; Zhang, Zheng-Yu; Gao, Jian-Ping

    2012-05-01

    To study the causes, clinical manifestations, treatment and prevention of calculus that develops in the prostatic cavity after transurethral resection of the prostate. We reported 11 cases of calculus that developed in the prostatic cavity after transurethral resection or transurethral plasmakinetic resection of prostate. The patients complained of repeated symptoms of frequent micturition, urgent micturition and urodynia after operation, accompanied with urinary tract infection and some with urinary obstruction, which failed to respond to anti-infective therapies. Cystoscopy revealed calculi in the prostatic cavity, with eschar, sphacelus, uneven wound surface and small diverticula in some cases. After diagnosis, 1 case was treated by holmium laser lithotripsy and a second transurethral resection of the prostate, while the other 10 had the calculi removed under the cystoscope, followed by 1 -2 weeks of anti-infective therapy. After treatment, all the 11 cases showed normal results of routine urinalysis, and no more symptoms of frequent micturition, urgent micturition and urodynia. Three- to six-month follow-up found no bladder irritation symptoms and urinary tract infection. Repeated symptoms of frequent micturition, urgent micturition, urodynia and urinary tract infection after transurethral resection of the prostate should be considered as the indicators of calculus in the prostatic cavity, which can be confirmed by cystoscopy. It can be treated by lithotripsy or removal of the calculus under the cystoscope, or even a second transurethral resection of the prostate. For its prevention, excessive electric coagulation and uneven wound surface should be avoided and anti-infection treatment is needed.

  1. Extract of Ulmus macrocarpa Hance prevents thrombus formation through antiplatelet activity.

    Science.gov (United States)

    Yang, Won-Kyung; Lee, Jung-Jin; Sung, Yoon-Young; Kim, Dong-Seon; Myung, Chang-Seon; Kim, Ho Kyoung

    2013-09-01

    Ulmus macrocarpa Hance (Ulmaceae) has been used as a traditional oriental medicine for the treatment of edema, mastitis, gastric cancer and inflammation. The aim of this study was to investigate the effects of Ulmus macrocarpa extract (UME) on thrombus formation in vivo, platelet activation ex vivo and fibrinolytic activity in vitro. To identify the antithrombotic activity of UME in vivo, we used an arterial thrombosis model. UME delayed the occlusion time by 13.4 and 13.9 min at doses of 300 and 600 mg/kg, respectively. UME significantly inhibited ex vivo platelet aggregation induced by collagen and adenosine 5'-diphosphate (ADP), respectively, but did not affect the coagulation times following activated partial thromboplastin and prothrombin activation. Therefore, to investigate the antiplatelet effect of UME, the effect of UME on collagen and ADP-induced platelet aggregation in vitro was examined. UME exhibited antiplatelet aggregation activity, induced by ADP and collagen. Furthermore, the fibrinolytic activity of UME was investigated. The results showed that UME significantly increased fibrinolysis at 1,000 mg/ml. In conclusion, the results suggested that UME may significantly inhibit artery thrombus formation in vivo, potentially due to antiplatelet activity, and also exhibits potential as a clot‑dissolving agent for thrombolytic therapy.

  2. Improving Prevention Curricula: Lessons Learned Through Formative Research on the Youth Message Development Curriculum

    Science.gov (United States)

    GREENE, KATHRYN; CATONA, DANIELLE; ELEK, ELVIRA; MAGSAMEN-CONRAD, KATE; BANERJEE, SMITA C.; HECHT, MICHAEL L.

    2016-01-01

    This article describes formative research (a pilot study, interviews, and focus groups) conducted as part of a feasibility test of 2 versions (Analysis vs. Planning) of a brief media literacy intervention titled Youth Message Development (YMD). The intervention targets high school student alcohol use with activities to understand persuasion strategies, increase counter-arguing, and then apply these new skills to ad analysis or a more engaging ad poster planning activity. Based on the theory of active involvement (Greene, 2013), the Planning curriculum is proposed to be more effective than the Analysis curriculum. Overall, results of the formative research indicated that students (N = 182) and mentors/teachers (N = 53) perceived the YMD Planning curriculum as more interesting, involving, and novel, and these ratings were associated with increased critical thinking about the impact of advertising, lower alcohol use intentions, and fewer positive expectations about the effects of alcohol use. Qualitative feedback indicated a need to supplement alcohol-focused ad stimuli with ads targeting other advertising images, use incentives and competition-based activities to further enhance student motivation, and provide flexibility to enhance the appropriateness of the curriculum to various settings. These concerns led to the development of a revised curriculum and plans for further study. PMID:27684111

  3. Superhydrophilic nanopillar-structured quartz surfaces for the prevention of biofilm formation in optical devices

    Science.gov (United States)

    Han, Soo; Ji, Seungmuk; Abdullah, Abdullah; Kim, Duckil; Lim, Hyuneui; Lee, Donghyun

    2018-01-01

    Bacterial biofilm formation on optical devices such as contact lenses, optical glasses, endoscopic devices, and microscopic slides and lenses are major concerns in the field of medicine and biomedical engineering. To solve these problems, here we present the first report of superhydrophilic transparent nanopillar-structured surfaces with bactericidal properties. To construct bactericidal surfaces, we imitated a topological mechanism found in nature in which nanopillar-structured surfaces cause a mechanical disruption of the outer cell membranes of bacteria, resulting in bacterial cell death. We used nanosphere lithography to fabricate nanopillars with various sharpnesses and heights on a quartz substrate. Water contact angle and light reflectance measurements revealed superhydrophilic, antifogging and antireflective properties, which are important for use in optical devices. To determine bactericidal efficiency, the fabricated surfaces were incubated and tested against two Gram-negative bacteria associated with biofilm formation and various diseases in humans, Pseudomonas aeruginosa and Escherichia coli. The highest bactericidal activity was achieved with nanopillars that measured 300 nm in height and 10 nm in apex diameter. Quartz substrates patterned with such nanopillars killed ∼38,000 P. aeruginosa and ∼27,000 E. coli cells cm-2 min-1, respectively. Thus, the newly designed nanopillar-structured bactericidal surfaces are suitable for use in the development of superhydrophilic and transparent optical devices.

  4. Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma

    Science.gov (United States)

    Oberyszyn, Tatiana M.

    2013-01-01

    Ultraviolet B (UVB) light is the major environmental carcinogen contributing to non-melanoma skin cancer (NMSC) development. There are over 3.5 million NMSC diagnoses in two million patients annually, with men having a 3-fold greater incidence of squamous cell carcinoma (SCC) compared with women. Chronic inflammation has been linked to tumorigenesis, with a key role for the cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, currently is prescribed to patients as a short-term therapeutic agent to induce SCC precursor lesion regression. However, its efficacy as a preventative agent in patients without evidence of precursor lesions but with significant UVB-induced cutaneous damage has not been explored. We previously demonstrated in a murine model of UVB-induced skin carcinogenesis that when exposed to equivalent UVB doses, male mice had lower levels of inflammation but developed increased tumor multiplicity, burden and grade compared with female mice. Because of the discrepancy in the degree of inflammation between male and female skin, we sought to determine if topical treatment of previously damaged skin with an anti-inflammatory COX-2 inhibitor would decrease tumor burden and if it would be equally effective in the sexes. Our results demonstrated that despite observed sex differences in the inflammatory response, prolonged topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly, tumor burden was significantly decreased only in male mice. Our data suggest a new therapeutic use for currently available topical diclofenac as a preventative intervention for patients predisposed to cutaneous SCC development before lesions appear. PMID:23125227

  5. Photoprotection by Cichorum endivia extracts: prevention of UVB-induced erythema, pyrimidine dimer formation and IL-6 expression.

    Science.gov (United States)

    Enk, C D; Hochberg, M; Torres, A; Lev, O; Dor, I; Srebnik, M; Dembitsky, V M

    2004-01-01

    In the gradual process of evolution, plants have developed natural sun protecting substances that enable continuous survival under direct and intense ultraviolet (UV) radiation. As part of our studies of plant-derived pigments that might constitute an alternative to conventional sunscreens, we have tested the ethanolic extracts of roots, stalks, and inflorescences of populations of wild Cichorum endivia subsp. Divaricatum (Asteraceae) in terms of protection against sunburn, and in prevention of UVB-induced pyrimidine dimer formation and IL-6 mRNA expression in the human keratinocyte cell line, HaCaT. Using ELISA technique for detection of pyrimidine dimers and RT-PCR for detection of IL-6, we found that the ethanolic extract of C. endivia roots absorbs radiation in the UVB spectrum and partially prevents induction of pyrimidine dimers and IL-6 expression. Application of the root extract on the skin prior to UVB irradiation totally prevented erythema. Our findings suggest that C. endivia extracts might possess sun-protective qualities that make them useful as sunscreens. Copyright 2004 S. Karger AG, Basel

  6. Dental calculus: recent insights into occurrence, formation, prevention, removal and oral health effects of supragingival and subgingival deposits.

    Science.gov (United States)

    White, D J

    1997-10-01

    radius of plaque induced periodontal injury. Removal of subgingival plaque and calculus remains the cornerstone of periodontal therapy. Calculus formation is the result of petrification of dental plaque biofilm, with mineral ions provided by bathing saliva or crevicular fluids. Supragingival calculus formation can be controlled by chemical mineralization inhibitors, applied in toothpastes or mouthrinses. These agents act to delay plaque calcification, keeping deposits in an amorphous non-hardened state to facilitate removal with regular hygiene. Clinical efficacy for these agents is typically assessed as the reduction in tartar area coverage on the teeth between dental cleaning. Research shows that topically applied mineralization inhibitors can also influence adhesion and hardness of calculus deposits on the tooth surface, facilitating removal. Future research in calculus may include the development of improved supragingival tartar control formulations, the development of treatments for the prevention of subgingival calculus formation, the development of improved methods for root detoxification and debridement and the development and application of sensitive diagnostic methods to assess subgingival debridement efficacy.

  7. Measures to prevent foam formation in the anaerobic digestion of sugar beet in biogas plants

    Directory of Open Access Journals (Sweden)

    Lucie Moeller

    2017-01-01

    Full Text Available The occurrence of persistent foaming is observed in many anaerobic digesters that have sugar beet as their feedstock. The formation of foam entails a significant risk of damage to biogas plants, as gas pipes can become blocked. For this reason, foaming tests have been conducted to investigate which measures lead to reductions in foam development. It was found that generally available fertilizers such as urea, ammonium nitrate and calcium cyanamide have a foam-reducing effect. However, batch fermentation tests showed inhibition of biogas production at higher concentrations of these substances, which means that they should be used with care. Calcium cyanamide was found to be very unsuitable, as this substance inhibited biogas production even at low concentrations and caused the fermentation process to come to a complete stop at higher concentrations.

  8. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Directory of Open Access Journals (Sweden)

    Mércia Beluzi

    Full Text Available Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107 of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control and TP5 (tumor + PGZ/5 mg. Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group. The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01 when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01 on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05 and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT was entirely re

  9. Differential effect triggered by a heparan mimetic of the RGTA family preventing oral mucositis without tumor protection.

    Science.gov (United States)

    Mangoni, Monica; Yue, Xiaoli; Morin, Christophe; Violot, Dominique; Frascogna, Valerie; Tao, Yungan; Opolon, Paule; Castaing, Marine; Auperin, Anne; Biti, Giampaolo; Barritault, Denis; Vozenin-Brotons, Marie-Catherine; Deutsch, Eric; Bourhis, Jean

    2009-07-15

    Oral mucositis is a common side effect induced by radio/chemotherapy in patients with head and neck cancer. Although it dramatically impairs patient quality of life, no efficient and safe therapeutic solution is available today. Therefore, we investigated the protective efficacy of a new heparan mimetic biopolymer, RGTA-OTR4131, used alone or in combination with amifostine, for oral mucositis and simultaneously evaluated its effect on tumor growth in vitro and in vivo. A single dose of 16.5 Gy was selectively delivered to the snout of mice, and the effects of OTR4131 or amifostine-OTR4131 were analyzed by macroscopic scoring and histology. The effect of OTR4131 administration on tumor growth was then investigated in vitro and in xenograft models using two cell lines (HEP-2 and HT-29). Amifostine and OTR4131 significantly decreased the severity and duration of lip mucosal reactions. However, amifostine has to be administered before irradiation, whereas the most impressive protection was obtained when OTR4131 was injected 24 h after irradiation. In addition, OTR4131 was well tolerated, and the combination of amifostine and OTR4131 further enhanced mucosal protection. At the tumor level, OTR4131 did not modify HEP-2 cell line clonogenic survival in vitro or protect xenografted tumor cells from radiotherapy. Of interest, high doses of OTR4131 significantly decreased clonogenic survival of HT-29 cells. RGTAs-OTR4131 is a well-tolerated, natural agent that effectively reduces radio-induced mucositis without affecting tumor sensitivity to irradiation. This suggests a possible transfer into the clinic for patients' benefit.

  10. C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

    Science.gov (United States)

    Qi, Wenjing; Yan, Yijian; Pfeifer, Dietmar; Donner V Gromoff, Erika; Wang, Yimin; Maier, Wolfgang; Baumeister, Ralf

    2017-05-01

    Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

  11. C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

    Directory of Open Access Journals (Sweden)

    Wenjing Qi

    2017-05-01

    Full Text Available Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß/bone morphogenic protein (BMP signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

  12. Surface zwitterionization: Effective method for preventing oral bacterial biofilm formation on hydroxyapatite surfaces

    Science.gov (United States)

    Lee, Myoungjin; Kim, Heejin; Seo, Jiae; Kang, Minji; Kang, Sunah; Jang, Joomyung; Lee, Yan; Seo, Ji-Hun

    2018-01-01

    In this study, we conducted surface zwitterionization of hydroxyapatite (HA) surfaces by immersing them in the zwitterionic polymer solutions to provide anti-bacterial properties to the HA surface. Three different monomers containing various zwitterionic groups, i.e., phosphorylcholine (PC), sulfobetaine (SB), and carboxybetaine (CB), were copolymerized with the methacrylic monomer containing a Ca2+-binding moiety, using the free radical polymerization method. As a control, functionalization of the copolymer containing the Ca2+-binding moiety was synthesized using a hydroxy group. The stable immobilization of the zwitterionic functional groups was confirmed by water contact angle analysis and X-ray photoelectron spectroscopy (XPS) measurement conducted after the sonication process. The zwitterionized HA surface showed significantly decreased protein adsorption, whereas the hydroxyl group-coated HA surface showed limited efficacy. The anti-bacterial adhesion property was confirmed by conducting Streptococcus mutans (S. mutans) adhesion tests for 6 h and 24 h. When furanone C-30, a representative anti-quorum sensing molecule for S. mutans, was used, only a small amount of bacteria adhered after 6 h and the population did not increase after 24 h. In contrast, zwitterionized HA surfaces showed almost no bacterial adhesion after 6 h and the effect was retained for 24 h, resulting in the lowest level of oral bacterial adhesion. These results confirm that surface zwitterionization is a promising method to effectively prevent oral bacterial adhesion on HA-based materials.

  13. High wind speeds prevent formation of a distinct bacterioneuston community in the sea-surface microlayer.

    Science.gov (United States)

    Rahlff, Janina; Stolle, Christian; Giebel, Helge-Ansgar; Brinkhoff, Thorsten; Ribas-Ribas, Mariana; Hodapp, Dorothee; Wurl, Oliver

    2017-05-01

    The sea-surface microlayer (SML) at the boundary between atmosphere and hydrosphere represents a demanding habitat for bacteria. Wind speed is a crucial but poorly studied factor for its physical integrity. Increasing atmospheric burden of CO2, as suggested for future climate scenarios, may particularly act on this habitat at the air-sea interface. We investigated the effect of increasing wind speeds and different pCO2 levels on SML microbial communities in a wind-wave tunnel, which offered the advantage of low spatial and temporal variability. We found that enrichment of bacteria in the SML occurred solely at a U10 wind speed of ≤5.6 m s-1 in the tunnel and ≤4.1 m s-1 in the Baltic Sea. High pCO2 levels further intensified the bacterial enrichment in the SML during low wind speed. In addition, low wind speed and pCO2 induced the formation of a distinctive bacterial community as revealed by 16S rRNA gene fingerprints and influenced the presence or absence of individual taxonomic units within the SML. We conclude that physical stability of the SML below a system-specific wind speed threshold induces specific bacterial communities in the SML entailing strong implications for ecosystem functioning by wind-driven impacts on habitat properties, gas exchange and matter cycling processes. © FEMS 2017.

  14. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    Science.gov (United States)

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.

  15. Intraperitoneal tenoxicam to prevent abdominal adhesion formation in a rat peritonitis model.

    Science.gov (United States)

    Ezberci, Fikret; Bulbuloglu, Ertan; Ciragil, Pinar; Gul, Mustafa; Kurutas, Ergul Belge; Bozkurt, Serdar; Kale, I Taner

    2006-01-01

    We investigated the effects of intraperitoneal tenoxicam on the development of postoperative intra-abdominal adhesions and oxidative stress in a model of bacterial peritonitis. Bacterial peritonitis was induced in 24 rats by cecal ligation and puncture. The rats were randomly assigned to one of three groups. Group 1 (n = 8) received 2 ml saline intraperitoneally, group 2 (n = 8) received 2 ml (0.5 mg/kg) tenoxicam (Oksamen) intraperitoneally, and group 3 (n = 8) was a control, which did not receive any injection. All animals were killed 14 days later so we could assess the adhesion score and measure anastomotic bursting pressures. Tissue antioxidant levels were measured in 1-g tissue samples taken from the abdominal wall. The adhesion score was significantly lower in the tenoxicam group than in the saline and control groups. The anastomotic bursting pressures were higher in the saline and tenoxicam groups than in the control group. The catalase (CAT) levels were higher in the saline and tenoxicam groups than in the control group. The malondialdehyde (MDH) levels were higher in the saline group than in the tenoxicam and control groups. Intraperitoneal tenoxicam inhibited the formation of postoperative intra-abdominal adhesions without compromising wound healing in this bacterial peritonitis rat model. Tenoxicam also decreased the oxidative stress during peritonitis.

  16. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Directory of Open Access Journals (Sweden)

    Fiorella Faggi

    Full Text Available The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3 in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS, an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  17. Prevention of Bacterial Biofilm Formation on Soft Contact Lenses Using Natural Compounds.

    Science.gov (United States)

    El-Ganiny, Amira M; Shaker, Ghada H; Aboelazm, Abeer A; El-Dash, Heba A

    2017-12-01

    In eye care field, contact lenses (CL) have a great impact on improving vision, but their use can be limited by ocular infection. CL- associated infections can be reduced by good attention to CL storage case practice. CL-care solutions should be able to control microbial growth on CL. The aim of the study was to evaluate and compare the efficacy of CL-care solutions (found in Egyptian market) with some natural compounds in removal and inhibition of bacterial biofilm formed on soft CL. Clinical isolates were recovered from patients having conjunctivitis from Benha University Hospital and identified microbiologically. Quantification of biofilm was done using microtiter plate assay. Three multipurpose CL-care solutions were examined for their ability to remove and inhibit biofilm. Also four natural extracts having antibacterial activity and are safe on eye were tested for their anti-biofilm activity. The major bacterial isolates from eye infections were Pseudomonas aeruginosa (36%) and Staphylococcus spp. (37.8%). Only 33.3% of isolates showed ability to produce weak to moderate biofilm. The tested multi-purpose CL-care solutions showed moderate ability to remove preformed biofilm. Among the tested natural compounds, Calendula officinalis and Buddleja salviifolia extracts showed an excellent efficacy in inhibition of biofilm and also removal of preformed biofilm. This study demonstrated that isolates from infected eye and CL-cases showed weak to moderate biofilm formation. Calendula officinalis and Buddleja salviifolia extracts showed excellent effect on inhibition and removal of biofilm, these extracts could be added into CL-care solutions which could markedly reduce eye-infections during CL-wear.

  18. Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

    Science.gov (United States)

    Danigo, Aurore; Nasser, Mohamad; Bessaguet, Flavien; Javellaud, James; Oudart, Nicole; Achard, Jean-Michel; Demiot, Claire

    2015-02-18

    Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.

  19. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride......, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION...

  20. ENOX2 (or tNOX): a new and old molecule with cancer activity involved in tumor prevention and therapy.

    Science.gov (United States)

    Ronconi, G; Lessiani, G; Spinas, E; Kritas, S K; Caraffa, Al; Saggini, A; Antinolfi, P; Pizzicannella, J; Toniato, E; Conti, P

    2016-01-01

    Cancer includes a number of related diseases due to abnormal cell proliferation that spreads to nearby tissues. Many compounds (physical, chemical and biological) have been used to try to halt this abnormal proliferation, but the therapeutic results are poor, due also to the side effects. It has been reported that ecto-nicotinamide adenine dinucleotide oxidase di-sulfide-thiol exchanger 2 (ENOX2), also known as tumor-associated nicotinamide adenine dinucleotide oxidase (tNOX), was found to be located on the cancer cell surface, essential for cancer cell growth. Capsaicin and other anti-oxidants are capable of inhibiting tNOX, causing apoptosis of cells, exerting anti-tumor activity. It is interesting that some authors reported that ENOX2 is present in the serum of cancer patients several years before the clinical symptoms of the tumor. However, this result has to be confirmed. In this article we discuss ENOX2 and its inhibition as a hope of improving cancer therapy.

  1. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yiting; Wu, Dan; Xia, Fengjie; Xian, Hongyu; Zhu, Xinyue [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, 400716 (China); Huang, Zhenping, E-mail: huangzhenping19633@163.com [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China)

    2016-04-29

    Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma. - Highlights: • High expression of HDAC9 correlates with poor patient prognosis. • Downregulation of HDAC9 inhibits cell proliferation in retinoblastoma cells. • Downregulation of HDAC9 induces cell cycle arrest at G1 phase in retinoblastoma cells. • Downregulation of HDAC9 suppresses tumor growth in nude mice.

  2. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma

    International Nuclear Information System (INIS)

    Zhang, Yiting; Wu, Dan; Xia, Fengjie; Xian, Hongyu; Zhu, Xinyue; Cui, Hongjuan; Huang, Zhenping

    2016-01-01

    Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma. - Highlights: • High expression of HDAC9 correlates with poor patient prognosis. • Downregulation of HDAC9 inhibits cell proliferation in retinoblastoma cells. • Downregulation of HDAC9 induces cell cycle arrest at G1 phase in retinoblastoma cells. • Downregulation of HDAC9 suppresses tumor growth in nude mice.

  3. Prevention of parastomal hernias with 3D funnel meshes in intraperitoneal onlay position by placement during initial stoma formation.

    Science.gov (United States)

    Köhler, G; Hofmann, A; Lechner, M; Mayer, F; Wundsam, H; Emmanuel, K; Fortelny, R H

    2016-02-01

    In patients with terminal ostomies, parastomal hernias (PSHs) occur on a frequent basis. They are commonly associated with various degrees of complaints and occasionally lead to life-threatening complications. Various strategies and measures have been tested and evaluated, but to date there is a lack of published evidence with regard to the best surgical technique for the prevention of PSH development. We conducted a retrospective analysis of prospectively collected data of eighty patients, who underwent elective permanent ostomy formation between 2009 and 2014 by means of prophylactic implantation of a three-dimensional (3D) funnel mesh in intraperitoneal onlay (IPOM) position. PSH developed in three patients (3.75%). No mesh-related complications were encountered and none of the implants had to be removed. Ostomy-related complications had to be noted in seven (8.75%) cases. No manifestation of ostomy prolapse occurred. Follow-up time was a median 21 (range 3-47) months. The prophylactical implantation of a specially shaped, 3D mesh implant in IPOM technique during initial formation of a terminal enterostomy is safe, highly efficient and comparatively easy to perform. As opposed to what can be achieved with flat or keyhole meshes, the inner boundary areas of the ostomy itself can be well covered and protected from the surging viscera with the 3D implants. At the same time, the vertical, tunnel-shaped part of the mesh provides sufficient protection from an ostomy prolapse. Further studies will be needed to compare the efficacy of various known approaches to PSH prevention.

  4. Comparative evaluation of turmeric and chlorhexidine gluconate mouthwash in prevention of plaque formation and gingivitis: a clinical and microbiological study.

    Science.gov (United States)

    Waghmare, P F; Chaudhari, A U; Karhadkar, V M; Jamkhande, A S

    2011-07-01

    To compare the efficacy of turmeric mouthwash and chlorhexidine gluconate mouthwash in prevention of gingivitis and plaque formation. A total of 100 randomly selected subjects visiting the Department of Periodontology at Bharati Vidyapeeth Deemed University, Dental College and Hospital, were considered for the study. The gingival index (GI) by Loe and Silness was recorded which was followed by Turesky- Gilmore-Glickman modification of Quigley Hein plaque index (TQHPI) at 0, 14 and 21 days. Individuals who gave an informed consent, subjects in the age group of 25 to 35 years with having fair and poor gingival index scores and a score >1 for plaque index, were included in the study. Results showed statistically significant reduction (p plaque index (PI) with chlorhexidine gluconate mouthwash when compared with turmeric mouthwash. No significant difference in mean gingival index (GI) was seen when chlorhexidine mouthwash was compared with turmeric mouthwash. Significant reduction in total microbial count (p chlorhexidine mouthwash was compared with turmeric mouthwash. From the above observations, it can be concluded that chlorhexidine gluconate as well as turmeric mouthwash can be effectively used as an adjunct to mechanical plaque control methods in prevention of plaque and gingivitis. Chlorhexidine gluconate has been found to be more effective when antiplaque property was considered. From this study, it could be stated that turmeric is definitely a good adjunct to mechanical plaque control. Further studies are required on turmeric based mouthwash to establish it as a low cost plaque control measure.

  5. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation

    Directory of Open Access Journals (Sweden)

    Bakhrouf Amina

    2011-04-01

    Full Text Available Abstract Background Thymoquinone is an active principle of Nigella sativa seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections. Methods The antibacterial activity of Thymoquinone (TQ and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT reduction assay. Results TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml especially Gram positive cocci (Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510. Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50 was reached with 22 and 60 μg/ml for Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface. Conclusion The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.

  6. A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in ApcMin/+mice.

    Science.gov (United States)

    Ni, Y; Wong, V H Y; Tai, W C S; Li, J; Wong, W Y; Lee, M M L; Fong, F L Y; El-Nezami, H; Panagiotou, G

    2017-03-01

    To investigate the in vivo effects of Lactobacillus rhamnosus GG (LGG) on intestinal polyp development and the interaction between this single-organism probiotic and the gut microbiota therein. The Apc Min/+ mouse model was used to study the potential preventive effect of LGG on intestinal polyposis, while shotgun metagenomic sequencing was employed to characterize both taxonomic and functional changes within the gut microbial community. We found that the progression of intestinal polyps in the control group altered the community functional profile remarkably despite small variation in the taxonomic diversity. In comparison, the consumption of LGG helped maintain the overall functional potential and taxonomic profile in the resident microbes, thereby leading to a 25% decrease of total polyp counts. Furthermore, we found that LGG enriched those microbes or microbial activities related to short-chain fatty acid production (e.g. Roseburia and Coprococcus), as well as suppressed the ones that can lead to inflammation (e.g. Bilophila wadsworthia). Our study using shotgun metagenomics highlights how single probiotic LGG may exert its beneficial effects and decrease polyp formation in mice by maintaining gut microbial functionality. This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human. © 2016 The Society for Applied Microbiology.

  7. Early intervention with a small molecule inhibitor for tumor nefosis factor-α prevents cognitive deficits in a triple transgenic mouse model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Gabbita S

    2012-05-01

    Full Text Available Abstract Background Chronic neuroinflammation is an important component of Alzheimer’s disease and could contribute to neuronal dysfunction, injury and loss that lead to disease progression. Multiple clinical studies implicate tumor necrosis factor-α as an inflammatory mediator of neurodegeneration in patients with Alzheimer’s because of elevated levels of this cytokine in the cerebrospinal fluid, hippocampus and cortex. Current Alzheimer’s disease interventions are symptomatic treatments with limited efficacy that do not address etiology. Thus, a critical need exists for novel treatments directed towards modifying the pathophysiology and progression. Methods To investigate the effect of early immune modulation on neuroinflammation and cognitive outcome, we treated triple transgenic Alzheimer’s disease mice (harboring PS1M146V, APPSwe, and tauP301L transgenes with the small molecule tumor necrosis factor-α inhibitors, 3,6′-dithiothalidomide and thalidomide, beginning at four months of age. At this young age, mice do not exhibit plaque or tau pathology but do show mild intraneuronal amyloid beta protein staining and a robust increase in tumor necrosis factor-α. After 10 weeks of treatment, cognitive performance was assessed using radial arm maze and neuroinflammation was assessed using biochemical, stereological and flow cytometric endpoints. Results 3,6′-dithiothalidomide reduced tumor necrosis factor-α mRNA and protein levels in the brain and improved working memory performance and the ratio of resting to reactive microglia in the hippocampus of triple transgenic mice. In comparison to non-transgenic controls, triple transgenic Alzheimer’s disease mice had increased total numbers of infiltrating peripheral monomyelocytic/granulocytic leukocytes with enhanced intracytoplasmic tumor necrosis factor-α, which was reduced after treatment with 3,6′-dithiothalidomide. Conclusions These results suggest that modulation of tumor

  8. Formative research and strategic development of a physical activity component to a social marketing campaign for obesity prevention in preschoolers.

    Science.gov (United States)

    Bellows, Laura; Anderson, Jennifer; Gould, Susan Martin; Auld, Garry

    2008-06-01

    The prevalence of overweight in childhood, including preschoolers, continues to rise. While efforts focusing on school-aged children are encouraging, obesity prevention programs to address nutrition and physical activity in the child care center are lacking. Food Friends is a successfully evaluated nutrition program aimed at enhancing preschoolers' food choices, the addition of a physical activity program would improve the programs overall efforts to establish healthful habits early in life. This study describes the formative research conducted with secondary influencers of preschoolers-teachers and parents-for the development of a physical activity program. Key informant interviews and focus group discussions were conducted with preschool teachers and parents, respectively, to examine current physical activity practices, as well as attitudes, opinions, and desired wants and needs for physical activity materials. Findings illustrate that teachers provided physical activity; however, most did not use a structured program. Teachers identified time, space and equipment as barriers to providing activity in their classroom. Focus group findings identified activities of preschoolers', parents' perceptions of the adequacy of activity levels, and items to help parents engage their children in more physical activity. Barriers were also identified by parents and included time, safety, inclement weather, and lack of knowledge and self-efficacy. Findings from this formative research were used to develop a marketing strategy to guide the development of a physical activity component, Food Friends Get Movin' with Mighty Moves , as part of a larger social marketing campaign aimed to decrease the risk for obesity in low-income preschoolers.

  9. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat.

    Science.gov (United States)

    Schwandt, Leonora Q; Van Weissenbruch, Ranny; Stokroos, Ietse; Van der Mei, Henny C; Busscher, Henk J; Albers, Frans W J

    2004-08-01

    To evaluate the preventive effect of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine on biofilm formation on voice prostheses in vitro. Groningen button and Provox 2 voice prostheses were inoculated with a mixture of bacteria and yeasts isolated from previously explanted Groningen button voice prostheses. After 5 h, separate throats were flushed with buttermilk, Yakult Light fermented milk drink, N-acetylcysteine or phosphate-buffered saline, which served as a control. After 7 days, the microflora on each voice prosthesis was determined. On Groningen button voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine all reduced the amount of both bacteria and yeasts. On Provox 2 voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine reduced the amount of bacteria but, conversely, increased the amount of yeasts. These in vitro experiments demonstrate that biofilm formation on voice prostheses is reduced in an artificial throat by the use of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine. However, the structural differences between the type of voice prostheses may influence the ultimate effects.

  10. Pathobiology of cholesterol gallstone disease: from equilibrium ternary phase diagram to agents preventing cholesterol crystallization and stone formation.

    Science.gov (United States)

    Portincasa, Piero; Moschetta, Antonio; Calamita, Giuseppe; Margari, Antonio; Palasciano, Giuseppe

    2003-03-01

    The primum movens in cholesterol gallstone formation is hypersecretion of hepatic cholesterol, chronic surpersaturation of bile with cholesterol and rapid precipitation of cholesterol crystals in the gallbladder from cholesterol-enriched vesicles. Associated events include biochemical defects (increased biliary mucin, and increased proportions of hydrophobic bile salts in the intestine and gallbladder), motility defects (gallbladder smooth muscle hypocontractility in vitro and gallbladder stasis in vivo, sluggish intestinal transit), and an abnormal genetic background. The study of physical-chemical factors and pathways leading to cholesterol crystallization in bile has clinical relevance and the task can be carried out in different ways. The lithogenicity of bile is investigated in artificial model biles made by three biliary lipids - cholesterol, bile salts and phospholipids - variably combined in systems plotting within the equilibrium ternary phase diagram; also, crystallization propensity of ex vivo incubated human bile is studied by biochemical analysis of precipitated crystals, polarizing quantitative light microscopy and turbidimetric methods. The present review will focus on the recent advances in the field of pathobiology of cholesterol gallstones, by underscoring the role of early events like water transport, lipid transport, crystallization phenomena - including a genetic background - in gallstone pathogenesis. Agents delaying or preventing precipitation of cholesterol crystals and gallstone formation in bile will also be discussed.

  11. A combined road weather forecast system to prevent road ice formation in the Adige Valley (Italy)

    Science.gov (United States)

    Di Napoli, Claudia; Piazza, Andrea; Antonacci, Gianluca; Todeschini, Ilaria; Apolloni, Roberto; Pretto, Ilaria

    2016-04-01

    Road ice is a dangerous meteorological hazard to a nation's transportation system and economy. By reducing the pavement friction with vehicle tyres, ice formation on pavements increases accident risk and delays travelling times thus posing a serious threat to road users' safety and the running of economic activities. Keeping roads clear and open is therefore essential, especially in mountainous areas where ice is likely to form during the winter period. Winter road maintenance helps to restore road efficiency and security, and its benefits are up to 8 times the costs sustained for anti-icing strategies [1]. However, the optimization of maintenance costs and the reduction of the environmental damage from over-salting demand further improvements. These can be achieved by reliable road weather forecasts, and in particular by the prediction of road surface temperatures (RSTs). RST is one of the most important parameters in determining road surface conditions. It is well known from literature that ice forms on pavements in high-humidity conditions when RSTs are below 0°C. We have therefore implemented an automatic forecast system to predict critical RSTs on a test route along the Adige Valley complex terrain, in the Italian Alps. The system considers two physical models, each computing heat and energy fluxes between the road and the atmosphere. One is Reuter's radiative cooling model, which predicts RSTs at sunrise as a function of surface temperatures at sunset and the time passed since then [2]. One is METRo (Model of the Environment and Temperature of Roads), a road weather forecast software which also considers heat conduction through road material [3]. We have applied the forecast system to a network of road weather stations (road weather information system, RWIS) installed on the test route [4]. Road and atmospheric observations from RWIS have been used as initial conditions for both METRo and Reuter's model. In METRo observations have also been coupled to

  12. A randomised controlled trial on melatonin and rosiglitazone for prevention of adhesion formation in a rat uterine horn model.

    Science.gov (United States)

    Aksakal, Orhan; Yilmaz, Bulent; Gungor, Tayfun; Sirvan, Levent; Sut, Necdet; Inan, Ismet; Kalyoncu, Senol; Mollamahmutoglu, Leyla

    2010-07-01

    To investigate the effectiveness of melatonin and rosiglitazone in reducing postoperative adhesion formation in a rat uterine horn model. Thirty non-pregnant female Wistar albino rats, weighing 180-220 g, were used as a model for postoperative adhesion formation. The rats were randomised into three groups after seven standard lesions were inflicted in a 2-cm segment of each uterine horn and lower abdominal sidewall using bipolar cauterisation. The rats were treated with 10 mg/kg, intraperitoneal melatonin, and 1 mg/kg per day peroral rosiglitazone. No medication was given to the control group. As much as 20 uterine horns of 10 rats were evaluated in each group. Extent, severity, and degree of the adhesions to the uterine horns and, inflammation and fibrosis scores (histopathologically) were evaluated after 2 weeks of the treatment. There was no mortality in the groups and all of the rats recovered without incident after operation. Rosiglitazone group had lower adhesion scores [median (min-max ranges)] regarding extent, severity, and degree of the adhesions [0 (0-3), 0 (0-3) and 0 (0-3), respectively], which were significantly different (P < 0.001, P < 0.05 and P < 0.01, respectively) from those of the controls [1 (0-3), 2 (0-2) and 2 (0-3), respectively]; however, there were no statistically significant differences between rosiglitazone versus melatonin groups [1 (0-4), 2 (0-3) and 1 (0-3), respectively] and melatonin versus control groups. Moreover, no significant differences were determined between groups regarding histopathologic findings. Rosiglitazone, but not melatonin, is effective in prevention of adhesion formation in a rat uterine horn model.

  13. Thyroid tumor formation in the male mouse induced by fluopyram is mediated by activation of hepatic CAR/PXR nuclear receptors.

    Science.gov (United States)

    Rouquié, D; Tinwell, H; Blanck, O; Schorsch, F; Geter, D; Wason, S; Bars, R

    2014-12-01

    Fluopyram, a broad spectrum fungicide, caused an increased incidence of thyroid follicular cell (TFC) adenomas in males at the highest dose evaluated (750ppm equating to 105mg/kg/day) in the mouse oncogenicity study. A series of short-term mechanistic studies were conducted in the male mouse to characterize the mode of action (MOA) for the thyroid tumor formation and to determine if No Observed Effect Levels (NOELs) exist for each key event identified. The proposed MOA consists of an initial effect on the liver by activating the constitutive androstane (Car) and pregnane X (Pxr) nuclear receptors causing increased elimination of thyroid hormones followed by an increased secretion of thyroid stimulating hormone (TSH). This change in TSH secretion results in an increase of TFC proliferation which leads to hyperplasia and eventually adenomas after chronic exposure. Car/Pxr nuclear receptors were shown to be activated as indicated by increased activity of specific Phase I enzymes (PROD and BROD, respectively). Furthermore, evidence of increased T4 metabolism was provided by the induction of phase II enzymes known to preferentially use T4 as a substrate. Additional support for the proposed MOA was provided by demonstrating increased Tsh β transcripts in the pituitary gland. Finally, increased TFC proliferation was observed after 28days of treatment. In these dose-response studies, clear NOELs were established for phase 2 liver enzyme activities, TSH changes and TFC proliferation. Furthermore, compelling evidence for Car/Pxr activation being the molecular initiating event for these thyroid tumors was provided by the absence of the sequential key events responsible for the TCF tumors in Car/Pxr KO mice when exposed to fluopyram. In conclusion, fluopyram thyroid toxicity is mediated by activation of hepatic Car/Pxr receptors and shows a threshold dependent MOA. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers.

    Science.gov (United States)

    De Vlieghere, Elly; Carlier, Charlotte; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-03-01

    This data paper contains information about the in vivo model for peritoneal implants used in the paper "Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells" (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included.

  15. Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers

    Directory of Open Access Journals (Sweden)

    Elly De Vlieghere

    2016-03-01

    Full Text Available This data paper contains information about the in vivo model for peritoneal implants used in the paper “Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells” (De Vlieghere et al., 2015 [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included.

  16. Digital Bangladesh: Using Formative Research to Develop Phone Messages for the Prevention and Control of Diabetes in Rural Bangladesh.

    Directory of Open Access Journals (Sweden)

    Hannah Maria Jennings

    2015-10-01

    Full Text Available Background: As with many low-income countries, diabetes is an increasing issue in Bangladesh affecting an estimated 20% to 30% of the population either as intermediate hyperglycaemia or fully expressed diabetes mellitus (Bhowmik et al., 2012. The Bangladesh D-MAGIC project is a cluster randomised control trial to test the effectiveness of interventions to improve detection, management and control of diabetes in rural Bangladesh. One of these interventions is an mHealth intervention, which involves sending health promotion voice messages to individuals’ mobile phones to target diabetes prevention and management. In-depth formative research (interviews and focus group discussions has been undertaken in rural Faridpur District in order to gain a greater understanding of people’s beliefs, practices and behaviour regarding diabetes prevention and control and their access to and use of mobile phones. The findings of the research, used within the COM-B framework (Michie et al 2011, are being used to inform and appropriately tailor the voice messages to the needs of the target population. This presentation will highlight key findings of the formative research and discuss how these findings are being used to design the mHealth intervention. Aim: To identify key issues for the content and delivery of voice messages regarding the prevention and control of diabetes in rural Bangladesh through in-depth formative research. Methods: We conducted sixteen semi-structured interviews with purposively sampled diabetics, non-diabetics and health professionals. In addition, nine focus group discussions with diabetics and non-diabetics were conducted in villages in three sub-districts of Faridpur. We explored beliefs and behaviour regarding diet, exercise, smoking, stress and care-seeking. The findings from the interviews and focus group discussions were analysed thematically, and specific enablers and barriers to behaviour change related to diabetes identified

  17. Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors

    International Nuclear Information System (INIS)

    Voisin, Laure; Basik, Mark; Meloche, Sylvain; Julien, Catherine; Duhamel, Stéphanie; Gopalbhai, Kailesh; Claveau, Isabelle; Saba-El-Leil, Marc K; Rodrigue-Gervais, Ian Gaël; Gaboury, Louis; Lamarre, Daniel

    2008-01-01

    The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established. Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells. We found that expression of activated MEK1 or MEK2 is sufficient to morphologically transform intestinal epithelial cells, dysregulate cell proliferation and induce the formation of high-grade adenocarcinomas after orthotopic transplantation in mice. A large proportion of these intestinal tumors metastasize to the liver and lung. Mechanistically, activation of MEK1 or MEK2 up-regulates the expression of matrix metalloproteinases, promotes invasiveness and protects cells from undergoing anoikis. Importantly, we show that silencing of MEK2 expression completely suppresses the proliferation of human colon carcinoma cell lines, whereas inactivation of MEK1 has a much weaker effect. MEK1 and MEK2 isoforms have similar transforming properties and are able to induce the formation of metastatic intestinal tumors in mice. Our results suggest that MEK2 plays a more important role than MEK1 in sustaining the proliferation of human colorectal cancer cells

  18. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma.

    Science.gov (United States)

    Zhang, Yiting; Wu, Dan; Xia, Fengjie; Xian, Hongyu; Zhu, Xinyue; Cui, Hongjuan; Huang, Zhenping

    2016-04-29

    Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Role of ultraviolet irradiation and oxidative stress in cataract formation-medical prevention by nutritional antioxidants and metabolic agonists.

    Science.gov (United States)

    Varma, Shambhu D; Kovtun, Svitlana; Hegde, Kavita R

    2011-07-01

    Cataract is a significant cause of visual disability with relatively high incidence. It has been proposed that such high incidence is related to oxidative stress induced by continued intraocular penetration of light and consequent photochemical generation of reactive oxygen species, such as superoxide and singlet oxygen and their derivatization to other oxidants, such as hydrogen peroxide and hydroxyl radical. The latter two can also interact to generate singlet oxygen by Haber-Weiss reaction. It has been proposed that in addition to the endogenous enzymatic antioxidant enzymes, the process can be inhibited by many nutritional and metabolic oxyradical scavengers, such as ascorbate, vitamin E, pyruvate, and xanthine alkaloids, such as caffeine. Initial verification of the hypothesis has been done primarily by rat and mouse lens organ culture studies under ambient as well as ultraviolet (UV) light irradiation and determining the effect of such irradiation on its physiology in terms of its efficiency of active membrane transport activity and the levels of certain metabolites such as glutathione and adenosine triphosphate as well as in terms of apoptotic cell death. In vivo studies on the possible prevention of oxidative stress and cataract formation have been conducted by administering pyruvate and caffeine orally in drinking water and by their topical application using diabetic and galactosemic animal models. Photosensitized damage to lens caused by exposure to visible light and UVA has been found to be significantly prevented by ascorbate and pyruvate. Caffeine has been found be effective against UVA and UVB. Oral or topical application of pyruvate has been found to inhibit the formation of cataracts induced by diabetes and galactosemia. Caffeine has also been found to inhibit cataract induced by sodium selenite and high levels of galactose. Studies with diabetes are in progress. Various in vitro and in vivo studies summarized in this review strongly support the

  20. GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women.

    Science.gov (United States)

    Iepsen, Eva W; Lundgren, Julie R; Hartmann, Bolette; Pedersen, Oluf; Hansen, Torben; Jørgensen, Niklas R; Jensen, Jens-Erik B; Holst, Jens J; Madsbad, Sten; Torekov, Signe S

    2015-08-01

    Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. Randomized control study. Outpatient research hospital clinic. Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years. After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.

  1. Expression of Tumor Necrosis Factor Receptor 2 Characterizes TLR9-Driven Formation of Interleukin-10-Producing B Cells

    Directory of Open Access Journals (Sweden)

    Olga Ticha

    2018-01-01

    Full Text Available B cell-derived interleukin-10 (IL-10 production has been described as a hallmark for regulatory function in B lymphocytes. However, there is an ongoing debate on the origin of IL-10-secreting B cells and lack of specific surface markers has turned into an important obstacle for studying human B regulatory cells. In this study, we propose that tumor necrosis factor receptor 2 (TNFR2 expression can be used for enrichment of IL-10-secreting B cells. Our data confirm that IL-10 production can be induced by TLR9 stimulation with CpG ODN and that IL-10 secretion accompanies differentiation of peripheral blood B cells into plasma blasts. We further show that CpG ODN stimulation induces TNFR2 expression, which correlates with IL-10 secretion and terminal differentiation. Indeed, flow cytometric sorting of TNFR2+ B cells revealed that TNFR2+ and TNFR2− fractions correspond to IL-10+ and IL-10− fractions, respectively. Furthermore, CpG-induced TNFR2+ B cells were predominantly found in the IgM+ CD27+ B cell subset and spontaneously released immunoglobulin. Finally, our data corroborate the functional impact of TNFR2 by demonstrating that stimulation with a TNFR2 agonist significantly augments IL-10 and IL-6 production in B cells. Altogether, our data highlight a new role for TNFR2 in IL-10-secreting human B lymphocytes along with the potential to exploit this finding for sorting and isolation of this currently ill-defined B cell subset.

  2. Curcumin Prevents Formation of Polyglutamine Aggregates by Inhibiting Vps36, a Component of the ESCRT-II Complex

    Science.gov (United States)

    Verma, Meenakshi; Sharma, Abhishek; Naidu, Swarna; Bhadra, Ankan Kumar; Kukreti, Ritushree; Taneja, Vibha

    2012-01-01

    Small molecules with antioxidative properties have been implicated in amyloid disorders. Curcumin is the active ingredient present in turmeric and known for several biological and medicinal effects. Adequate evidence substantiates the importance of curcumin in Alzheimer's disease and recent evidence suggests its role in Prion and Parkinson's disease. However, contradictory effects have been suggested for Huntington's disease. This difference provided a compelling reason to investigate the effect of curcumin on glutamine-rich (Q-rich) and non-glutamine-rich (non Q-rich) amyloid aggregates in the well established yeast model system. Curcumin significantly inhibited the formation of htt72Q-GFP (a Q-rich) and Het-s-GFP (a non Q-rich) aggregates in yeast. We show that curcumin prevents htt72Q-GFP aggregation by down regulating Vps36, a component of the ESCRT-II (Endosomal sorting complex required for transport). Moreover, curcumin disrupted the htt72Q-GFP aggregates that were pre-formed in yeast and cured the yeast prion, [PSI +]. PMID:22880132

  3. Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps.

    Science.gov (United States)

    Manfredi, Angelo A; Rovere-Querini, Patrizia; D'Angelo, Armando; Maugeri, Norma

    2017-09-01

    The protection exerted by neutrophils against invading microbes is partially mediated via the generation of neutrophil extracellular traps (NETs). In sterile conditions NETs are damaging species, enriched in autoantigens and endowed with the ability to damage the vessel wall and bystander tissues, to promote thrombogenesis, and to impair wound healing. To identify and reposition agents that can be used to modulate the formation of NETs is a priority in the research agenda. Low molecular weight heparins (LMWH) are currently used, mostly on an empirical basis, in conditions in which NETs play a critical role, such as pregnancy complications associated to autoimmune disease. Here we report that LMWHs induce a profound change in the ability of human neutrophils to generate NETs and to mobilize the content of the primary granules in response to unrelated inflammatory stimuli, such as IL-8, PMA and HMGB1. Autophagy consistently accompanies NET generation in our system and autophagy inhibitors, 3-MA and wortmannin, prevent NET generation. Pretreatment with LMWH in vitro critically jeopardizes neutrophil ability to activate autophagy, a mechanism that might contribute to neutrophil unresponsiveness. Finally, we verified that treatment of healthy volunteers with a single prophylactic dose of parnaparin abrogated the ability of neutrophils to activate autophagy and to generate NETs. Together, these results support the contention that neutrophils, and NET generation in particular, might represent a preferential target of the anti-inflammatory action of LMWH. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

    Science.gov (United States)

    Batra, Rishi; Suh, Melissa K; Carson, Jeffrey S; Dale, Matthew A; Meisinger, Trevor M; Fitzgerald, Matthew; Opperman, Patrick J; Luo, Jiangtao; Pipinos, Iraklis I; Xiong, Wanfen; Baxter, B Timothy

    2018-02-01

    Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β -/- and TNF-α -/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α -/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β -/- macrophages. Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases. © 2017 American Heart Association, Inc.

  5. Constitutive transgene expression of Stem Cell Antigen-1 in the hair follicle alters the sensitivity to tumor formation and progression

    Directory of Open Access Journals (Sweden)

    Rikke Christensen

    2017-08-01

    Full Text Available The cell surface protein Stem Cell Antigen-1 (Sca-1 marks stem or progenitor cells in several murine tissues and is normally upregulated during cancer development. Although the specific function of Sca-1 remains unknown, Sca-1 seems to play a role in proliferation, differentiation and cell migration in a number of tissues. In the skin epithelium, Sca-1 is highly expressed in the interfollicular epidermis but is absent in most compartments of the hair follicle; however, the function of Sca-1 in the skin has not been investigated. To explore the role of Sca-1 in normal and malignant skin development we generated transgenic mice that express Sca-1 in the hair follicle stem cells that are normally Sca-1 negative. Development of hair follicles and interfollicular epidermis appeared normal in Sca-1 mutant mice; however, follicular induction of Sca-1 expression in bulge region and isthmus stem cells reduced the overall yield of papillomas in a chemical carcinogenesis protocol. Despite that fewer papillomas developed in transgenic mice a higher proportion of the papillomas underwent malignant conversion. These findings suggest that overexpression of Sca-1 in the hair follicle stem cells contributes at different stages of tumour development. In early stages, overexpression of Sca-1 decreases tumour formation while at later stages overexpression of Sca-1 seems to drive tumours towards malignant progression.

  6. The use of silicone occlusive sheeting (Sil-K) and silicone occlusive gel (epiderm) in the prevention of hypertrophic scar formation

    NARCIS (Netherlands)

    Niessen, FB; Spauwen, PHM; Robinson, PH; Fidler, [No Value; Kon, M

    1998-01-01

    The development of hypertrophic scars and keloids is an unsolved problem in the process of found healing. For this reason, a successful treatment to prevent excessive scar formation still has not been found. Over the last decade, however, a promising new treatment has been introduced. Silicone

  7. RAS interaction with PI3K p110α is required for tumor-induced angiogenesis.

    Science.gov (United States)

    Murillo, Miguel Manuel; Zelenay, Santiago; Nye, Emma; Castellano, Esther; Lassailly, Francois; Stamp, Gordon; Downward, Julian

    2014-08-01

    Direct interaction of RAS with the PI3K p110α subunit mediates RAS-driven tumor development: however, it is not clear how p110α/RAS-dependant signaling mediates interactions between tumors and host tissues. Here, using a murine tumor cell transfer model, we demonstrated that disruption of the interaction between RAS and p110α within host tissue reduced tumor growth and tumor-induced angiogenesis, leading to improved survival of tumor-bearing mice, even when this interaction was intact in the transferred tumor. Furthermore, functional interaction of RAS with p110α in host tissue was required for efficient establishment and growth of metastatic tumors. Inhibition of RAS and p110α interaction prevented proper VEGF-A and FGF-2 signaling, which are required for efficient angiogenesis. Additionally, disruption of the RAS and p110α interaction altered the nature of tumor-associated macrophages, inducing expression of markers typical for macrophage populations with reduced tumor-promoting capacity. Together, these results indicate that a functional RAS interaction with PI3K p110α in host tissue is required for the establishment of a growth-permissive environment for the tumor, particularly for tumor-induced angiogenesis. Targeting the interaction of RAS with PI3K has the potential to impair tumor formation by altering the tumor-host relationship, in addition to previously described tumor cell-autonomous effects.

  8. c-Jun N-terminal kinase 2 prevents luminal cell commitment in normal mammary glands and tumors by inhibiting p53/Notch1 and breast cancer gene 1 expression

    Science.gov (United States)

    Pfefferle, Adam D.; Perou, Charles M.; Van Den Berg, Carla Lynn

    2015-01-01

    Breast cancer is a heterogeneous disease with several subtypes carrying unique prognoses. Patients with differentiated luminal tumors experience better outcomes, while effective treatments are unavailable for poorly differentiated tumors, including the basal-like subtype. Mechanisms governing mammary tumor subtype generation could prove critical to developing better treatments. C-Jun N-terminal kinase 2 (JNK2) is important in mammary tumorigenesis and tumor progression. Using a variety of mouse models, human breast cancer cell lines and tumor expression data, studies herein support that JNK2 inhibits cell differentiation in normal and cancer-derived mammary cells. JNK2 prevents precocious pubertal mammary development and inhibits Notch-dependent expansion of luminal cell populations. Likewise, JNK2 suppresses luminal populations in a p53-competent Polyoma Middle T-antigen tumor model where jnk2 knockout causes p53-dependent upregulation of Notch1 transcription. In a p53 knockout model, JNK2 restricts luminal populations independently of Notch1, by suppressing Brca1 expression and promoting epithelial to mesenchymal transition. JNK2 also inhibits estrogen receptor (ER) expression and confers resistance to fulvestrant, an ER inhibitor, while stimulating tumor progression. These data suggest that therapies inhibiting JNK2 in breast cancer may promote tumor differentiation, improve endocrine therapy response, and inhibit metastasis. PMID:25970777

  9. Bone tumor

    Science.gov (United States)

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

  10. Formative research to develop a community-based intervention for chronic disease prevention in Guatemalan school-age children.

    Science.gov (United States)

    Letona, Paola; Ramirez-Zea, Manuel; Caballero, Benjamin; Gittelsohn, Joel

    2014-01-31

    Noncommunicable diseases (NCD) are the most common causes of morbidity and mortality worldwide, even in low- and middle-income countries (LMIC). Recent trends in health promotion emphasize community-based interventions as an important strategy for improving health outcomes. The aim of this study was to conduct formative research regarding the perceptions of NCD risk factors, their influencing factors, and community resources available to aid the development and implementation of a community-based intervention with school-age children. Focus group discussions (n = 18), home visits (n = 30), and individual semi-structured interviews (n = 26) were conducted in three urban communities in Guatemala with school-age children (10-12 years of age), teachers, parents, and local community members (i.e., school principals, school food kiosk vendors, religious leaders, authority representatives). All focus groups and interviews were transcribed verbatim for thematic analysis. Children, parents, and teachers have general knowledge about modifiable risk factors. Adults worried more about tobacco use, as compared to unhealthy diet and physical inactivity in children. Participants identified features at the intrapersonal (e.g., negative emotional state), interpersonal (e.g., peers as role models), and organizational and community levels (e.g., high levels of crime) that influence these risk factors in children. School committees, religious leaders, and government programs and activities were among the positive community resources identified. These findings should help researchers in Guatemala and similar LMIC to develop community-based interventions for NCD prevention in school-age children that are effective, feasible, and culturally acceptable.

  11. THEOS-2 Orbit Design: Formation Flying in Equatorial Orbit and Damage Prevention Technique for the South Atlantic Magnetic Anomaly (SAMA)

    Science.gov (United States)

    Pimnoo, Ammarin

    2016-07-01

    Geo-Informatics and Space Technology Development Agency (GISTDA) has initiative THEOS-2 project after the THEOS-1 has been operated for more than 7 years which is over the lifetime already. THEOS-2 project requires not only the development of earth observation satellite(s), but also the development of the area-based decision making solution platform comprising of data, application systems, data processing and production system, IT infrastructure improvement and capacity building through development of satellites, engineering model, and infrastructures capable of supporting research in related fields. The developing satellites in THEOS-2 project are THAICHOTE-2 and THAICHOTE-3. This paper focuses the orbit design of THAICHOTE-2 & 3. It discusses the satellite orbit design for the second and third EOS of Thailand. In this paper, both THAICHOTE will be simulated in an equatorial orbit as a formation flying which will be compared the productive to THAICHOTE-1 (THEOS-1). We also consider a serious issue in equatorial orbit design, namely the issue of the geomagnetic field in the area of the eastern coast of South America, called the South Atlantic Magnetic Anomaly (SAMA). The high-energy particles of SAMA comprise a radiation environment which can travel through THAICHOTE-2 & 3 material and deposit kinetic energy. This process causes atomic displacement or leaves a stream of charged atoms in the incident particles' wake. It can cause damage to the satellite including reduction of power generated by solar arrays, failure of sensitive electronics, increased background noise in sensors, and exposure of the satellite devices to radiation. This paper demonstrates the loss of ionizing radiation damage and presents a technique to prevent damage from high-energy particles in the SAMA.

  12. Prevention and control of sequels in the mouth of patients treated with radiation therapy for head and neck tumors

    International Nuclear Information System (INIS)

    Cardoso, Maria de Fatima Aparecida; Novikoff, Silviene; Tresso, Adriana; Segreto, Roberto Araujo; Cervantes, Onivaldo

    2005-01-01

    Surgery and radiation therapy are de main treatments for head and neck cancer. The side effects of the interaction of ionizing radiation on the tissues include dermatitis, mucositis, xerostomia, candidiasis, dysgeusia, dysphagia, caries, trismus, osteoradionecrosis. Objective: To assess dental condition of the patients using a protocol which allows avoiding or reducing the effects of radiation in the tissues of the oral cavity. Materials And Methods: Dental follow-up was performed before, during and up to 180 days after radiation therapy in 12 patients submitted to surgery and radiation therapy or radiation therapy alone. Results: The proportion of effects such as dermatitis, mucositis, dysgeusia, and dysphagia increased from the second week of the treatment until the end of the administrations. There was a clear decrease at the end of the treatment which was close to baseline values after 180 days. The reduction of xerostomia was slower and less effective. No case of caries, trismus, and osteoradionecrosis were observed during the assessment period. Conclusion: Regular dental follow-up associated with preventive measures such as prophylactic management of dental and oral diseases, adequate hygiene, mouth-washing with bicarbonate water and chamomile tea, and topic fluorine application contributed to improve the recovery conditions of patients with cancer of head and neck submitted to radiation therapy. (author)

  13. [Clinical effects of pedicled omentum covering and wrapping the ureteral anastomosis to prevent ureteral anastomotic leakage after surgery of abdominal and pelvic tumors].

    Science.gov (United States)

    Wang, Gangcheng; Han, Guangsen; Ren, Yingkun; Cheng, Yong; Xu, Yongchao; Zhao, Yuzhou; Zhang, Jian; Lu, Chaomin

    2014-03-01

    To explore the clinical effects of pedicled omentum covering and wrapping the ureteral anastomosis to prevent ureteral anastomotic leakage after surgery of abdominal and pelvic tumors. Clinical data of 64 patients with ureteral anastomosis after surgery of abdominal and pelvic tumors treated in our department from May 2005 to May 2012 were retrospectively analyzed. They were assigned into 2 groups. There were 23 patients of ureteral anastomosis combined with pedicled omentum surrounding and wrapping the anastomotic site (optimization group), and 41 cases of ureteral anastomosis alone (control group). The clinical data of all the 64 patients were reviewed and the therapeutic effects of the two treatment approaches were compared. At one week after the operation, there were 8 cases (34.8%, 8/23) with ureteral anastomotic fistula in the optimization group and 31 cases (75.6%, 31/41) in the control group (P = 0.010). In the postoperative days 1-3, the average drainage everyday from abdominal tube around the anastomotic site was 260.4 ml and 320.8 ml, respectively (P = 0.446). The average drainage volume everyday was 80.5 ml and 160.5 ml from the postoperative day 4 to day 7 (P = 0.015). The average time of removal of the peritoneal cavity drainage tube was 18.5 d in the optimization group and 32.6 d postoperatively in the control group (P = 0.015). Covering and wrapping the ureteral anastomosis with pedicled omentum can promote the rapid adhesion of surrounding tissues to reduce urine leakage and postoperative complications, and shorten the surgical treatment cycle.

  14. SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.

    Directory of Open Access Journals (Sweden)

    Weina Zhao

    Full Text Available Significant insight into the signaling pathways leading to activation of the Rel transcription factor family, collectively termed NF-κB, has been gained. Less well understood is how subsets of NF-κB-dependent genes are regulated in a signal specific manner. The SIMPL protein (signaling molecule that interacts with mouse pelle-like kinase is required for full Tumor Necrosis Factor-α (TNFα induced NF-κB activity. We show that SIMPL is required for steady-state hematopoiesis and the expression of a subset of TNFα induced genes whose products regulate hematopoietic cell activity. To gain insight into the mechanism through which SIMPL modulates gene expression we focused on the Tnf gene, an immune response regulator required for steady-state hematopoiesis. In response to TNFα SIMPL localizes to the Tnf gene promoter where it modulates the initiation of Tnf gene transcription. SIMPL binding partners identified by mass spectrometry include proteins involved in transcription and the interaction between SIMPL and MED1 was characterized in more detail. In response to TNFα, SIMPL is found in p65-MED1 complexes where SIMPL enhances p65/MED1/SIMPL complex formation. Together our results indicate that SIMPL functions as a TNFα-dependent p65 co-activator by facilitating the recruitment of MED1 to p65 containing transcriptional complexes to control the expression of a subset of TNFα-induced genes.

  15. How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

    Directory of Open Access Journals (Sweden)

    Peter Gál

    2017-10-01

    Full Text Available It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

  16. How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair.

    Science.gov (United States)

    Gál, Peter; Varinská, Lenka; Fáber, Lenka; Novák, Štepán; Szabo, Pavol; Mitrengová, Petra; Mirossay, Andrej; Mučaji, Pavel; Smetana, Karel

    2017-10-26

    It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

  17. Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α.

    Science.gov (United States)

    Sewing, A Charlotte P; Kantores, Crystal; Ivanovska, Julijana; Lee, Alvin H; Masood, Azhar; Jain, Amish; McNamara, Patrick J; Tanswell, A Keith; Jankov, Robert P

    2012-07-01

    Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed in human infants with severe bronchopulmonary dysplasia. Inhalation of CO(2) (therapeutic hypercapnia) has been described to limit cytokine production and to have anti-inflammatory effects on the injured lung; we therefore hypothesized that therapeutic hypercapnia would prevent bleomycin-induced lung injury. Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or saline vehicle from postnatal days 1-14 while being continuously exposed to 5% CO(2) (Pa(CO(2)) elevated by 15-20 mmHg), 7% CO(2) (Pa(CO(2)) elevated by 35 mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%, CO(2), had significantly attenuated lung tissue macrophage influx and PHT, as evidenced by normalized pulmonary vascular resistance and right ventricular systolic function, decreased right ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. The level of CO(2) neither prevented increased tissue neutrophil influx nor led to improvements in decreased lung weight, septal thinning, impaired alveolarization, or decreased numbers of peripheral arteries. Bleomycin led to increased expression and content of lung tumor necrosis factor (TNF)-α, which was found to colocalize with tissue macrophages and to be attenuated by exposure to 7% CO(2). Inhibition of TNF-α signaling with the soluble TNF-2 receptor etanercept (0.4 mg/kg ip from days 1-14 on alternate days) prevented bleomycin-induced PHT without decreasing tissue macrophages and, similar to CO(2), had no effect on arrested alveolar development. Our findings are consistent with a preventive effect of therapeutic hypercapnia with 7% CO(2) on bleomycin-induced PHT via attenuation of macrophage-derived TNF-α. Neither tissue macrophages nor TNF-α appeared to contribute to arrested lung development induced by bleomycin. That 7% CO(2

  18. Mediastinal tumor

    Science.gov (United States)

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

  19. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

    OpenAIRE

    McGee, Meghan E.; Maki, Aaron J.; Johnson, Steven E.; Lynne Nelson, O.; Robbins, Charles T.; Donahue, Seth W.

    2007-01-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. ...

  20. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  1. Role of antioxidants in prevention of pyrimidine dimer formation in UVB irradiated human HaCaT keratinocytes.

    Science.gov (United States)

    Hochberg, Malka; Kohen, Ron; Enk, Claes D

    2006-06-01

    The objective of the present study was to study the role of reactive oxygen species (ROS) in UVB induced cyclobutane pyrimidine dimer (CPD) formation in human keratinocytes, and to examine the modulating activity of low molecular weight antioxidants. To demonstrate the involvement of ROS, we examined the protective capacity of alpha-tocopherol, tempamine, and diethyldithiocarbamate (DDC) on CPD formation in intact cells and naked DNA. HaCaT cells and naked DNA in water solution were irradiated with UVB in the presence of the antioxidants and CPD was determined by ELISA. We found that all three antioxidants provided protection against UVB induced CPD formation. The protection was observed in intact cells only and not in naked DNA. Since some of the tested antioxidants do not possess UV absorbing qualities, our findings suggest that in a cellular environment ROS play a role in CPD formation.

  2. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

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

    2015-01-01

    , decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts......BACKGROUND: The tumor microenvironment plays a determinative role in stimulating tumor progression and metastasis. Notably, tumor-stroma signals affect the pattern of infiltrated immune cells and the profile of tumor-released cytokines. Among the known molecules that are engaged in stimulating...... the metastatic spread of tumor cells is the S100A4 protein. S100A4 is known as an inducer of inflammatory processes and has been shown to attract T-cells to the primary tumor and to the pre-metastatic niche. The present study aims to examine the immunomodulatory role of S100A4 in vivo and in vitro and assess...

  3. SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets.

    Science.gov (United States)

    Kim, Yun Hak; Bae, Jin Ung; Kim, In Suk; Chang, Chulhun L; Oh, Sae Ock; Kim, Chi Dae

    2016-12-01

    SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH 4 Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.

  4. The Impact Of Oral Vitamin E In Preventing Mucositis (Bucal Mucous Inflammation Resulting From The Radiotherapy In Tumors Of Head And Neck

    Directory of Open Access Journals (Sweden)

    Bahador M

    2004-07-01

    Full Text Available Background: Mucositis [bucal Mucous inflamation] is the most common complication resulting from the radiotherapy in tumors of head and neck. These malignancies are often curable through radiotherapy. This complication, however, may impair the treatment process and cause malnutrition. So far no medicine has been Known to prevent this complication. Vitamin E is a stabilizer of cell membrane and is also used in mucositis treatment. The survey of oral vitamin E effect on mucositis prophylaxis in radiotherapy of head and neck malignancies. Materials and Methods: Seventy patients afflicted with head and neck malignancies referring to Imam Khomeini Hospital were randomly divided into 2groups, two of whom died during treatment process. The first group (The case group consisting of 34 patients Consumed oral vitamin E 200 mg daily for seven days. The second group (The control group did not use any medicine at all. The two group underwent radiotherapy. They were compared and contrasted as to mucositis severity and dysphagia during treatment. Results: In the first group, since the fourth week up to the end of the treatment, there was a lower frequency and grade of mucositis in contrast with the control group. In the fourth week, the grade two mucositis in the first group (Case group was 20.6% and 47.5% in the control group the difference was statistically significant (P=0.024. There was also a lower frequency and grade of dysphagia in the case group since the fourth week versus the control group. In the fourth week, moderate dysphagia was 29.4% in the case group and 55.9% in the control group. The difference was statistically significant (P=0.023. Conclusion: Oral vitamin E has Proved to be effective in the Prophylaxis of Moderate and severe mucositis and dysphagia resulting from radiotherapy. It is advisable to conduct more research with more cases, lengthier duration and heavier doses.

  5. Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α, prevents retinal ganglion cell loss in a rat model of glaucoma.

    Directory of Open Access Journals (Sweden)

    Miin Roh

    Full Text Available Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death.Episcleral vein cauterization (EVC caused intraocular pressure (IOP to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH. Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs.Ocular hypertension (OHT triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.

  6. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

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

    Directory of Open Access Journals (Sweden)

    Gregory J. Baker

    2014-07-01

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

  8. Communicating the benefits of chronic preventive therapy: does the format of efficacy data determine patients' acceptance of treatment?

    Science.gov (United States)

    Hux, J E; Naylor, C D

    1995-01-01

    Patients' informed acceptance of chronic medical therapy hinges on communicating the potential benefits of drugs in quantitative terms. In a hypothetical scenario of treatment initiation, the authors assessed how three different formats of the same data affected the willingness of 100 outpatients to take what were implied to be three different lipid-lowering drugs. Side-effects were declared negligible and costs insured. Subjects make a "yes-no" decision about taking such a medication, and graded the decision on a certainty scale. Advised of a relative risk reduction--"34% reduction in heart attacks"--88% of the patients assented to therapy. All other formats elicited significantly more refusals (p benefits are presented. Multiple complementary formats may be most appropriate. The results imply that many patients may decline treatment if briefed on the likelihood or extent of benefit.

  9. Formation of students of higher educational institutions ready to use injury-prevention knowledge in professional work.

    Directory of Open Access Journals (Sweden)

    Gavrilenko I.V.

    2011-01-01

    Full Text Available The article explains the theoretical model of the readiness of future teachers of physical culture to use injury-prevention knowledge in professional work. Professional readiness of future teachers to teaching involves his professional qualifications and a set of personal qualities and properties. In order to assess the effectiveness of the model components have been identified as signs proving the degree of quality training for students. Efficiency of the model is evaluated on specific indicators, taking into account the level of preparedness for future professionals in injury-prevention activities.

  10. Suppression of Tumor Angiogenesis by Nonsteroidal Anti-Inflammatory Drugs: A New Function for Old Drugs

    Directory of Open Access Journals (Sweden)

    Curzio Raegg

    2001-01-01

    Full Text Available There is solid epidemiological evidence demonstrating that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs reduces the risk of developing colorectal cancer, and to a lesser extent gastric and esophageal cancers[1]. Importantly, NSAIDs suppress colon polyp formation and progression in patients diagnosed with familial adenomatous polyposis coli (APC[2]. In many animal studies, NSAIDs have been shown to prevent tumor formation and slow tumor progression, thus confirming and extending the clinical observations[3,4,5]. Recent findings have demonstrated that NSAIDs inhibit angiogenesis, suggesting that the tumor suppressive activity of these drugs may be due, at least in part, to their ability to inhibit tumor angiogenesis[6]. The study of the mechanism by which NSAIDs suppress tumor angiogenesis, is matter of intense research.

  11. Formative assessment in the development of an obesity prevention component for the Expanded Food and Nutrition Education Program in Texas

    Science.gov (United States)

    This study conducted formative research (surveys, focus groups); to assess the nutrition education needs of clients in the Texas Expanded Food and Nutrition Education Program prior to curriculum revision. Current participants in the Expanded Food and Nutrition Education Program from 3 Texas cities (...

  12. A Formative Evaluation of Healthy Heroes: A Photo Comic Book-Social Cognitive Theory Based Obesity Prevention Program

    Science.gov (United States)

    Branscum, Paul; Housley, Alexandra; Bhochhibhoya, Amir; Hayes, Logan

    2016-01-01

    Purpose: Low consumption of fruits and vegetables is often associated with poor diet quality, and childhood obesity. The purpose of this study was to assess the feasibility, and conduct a formative evaluation, of Healthy Heroes, an innovative, social cognitive theory-based program that uses child created photo-comic books to promote fruit and…

  13. 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.

  14. Using culture-centered qualitative formative research to design broadcast messages for HIV prevention for African American adolescents.

    Science.gov (United States)

    Horner, Jennifer R; Romer, Daniel; Vanable, Peter A; Salazar, Laura F; Carey, Michael P; Juzang, Ivan; Fortune, Thierry; Diclemente, Ralph; Farber, Naomi; Stanton, Bonita; Valois, Robert F

    2008-06-01

    The need for formative research in designing mass media health-education messages is widely accepted; however, distinct methodologies for developing such messages are less well documented. This article describes a culture-centered approach for developing messages to promote sexual risk reduction in urban African American adolescents. The method uses qualitative formative research to identify "competing narratives" that support healthy behavior despite the dominance of messages that favor risk-taking behavior. The method is illustrated using qualitative analysis of semistructured interviews with 124 adolescents. Analysis focuses on two barriers to sexual risk reduction: (a) social pressure for early initiation of sexual intercourse and (b) perceptions that condoms reduce sexual pleasure. We demonstrate how competing narratives identified in the analysis can be featured in radio and television messages advocating healthy behavior by modeling risk-reducing negotiation skills.

  15. Prevention of melanin formation during aryl alcohol oxidase production under growth-limited conditions using an Aspergillus nidulans cell factory.

    Science.gov (United States)

    Pardo-Planas, Oscar; Prade, Rolf A; Müller, Michael; Atiyeh, Hasan K; Wilkins, Mark R

    2017-11-01

    An Aspergillus nidulans cell factory was genetically engineered to produce an aryl alcohol oxidase (AAO). The cell factory initiated production of melanin when growth-limited conditions were established using stationary plates and shaken flasks. This phenomenon was more pronounced when the strain was cultured in a trickle bed reactor (TBR). This study investigated different approaches to reduce melanin formation in fungal mycelia and liquid medium in order to increase the enzyme production yield. Removal of copper from the medium recipe reduced melanin formation in agar cultures and increased enzyme activities by 48% in agitated liquid cultures. Copper has been reported as a key element for tyrosinase, an enzyme responsible for melanin production. Ascorbic acid (0.44g/L) stopped melanin accumulation, did not affect growth parameters and resulted in AAO activity that was more than two-fold greater than a control treatment with no ascorbic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Hydrate formation in drilling fluids: prevention and countering; Formacao de hidratos em fluidos de perfuracao: prevencao e controle

    Energy Technology Data Exchange (ETDEWEB)

    Villas Boas, Mario Barbosa [PETROBRAS, Macae, RJ (Brazil). Distrito de Perfuracao do Sudeste. Setor de Fluidos de Perfuracao

    1988-12-31

    The possibility of hydrates forming during deep water well drilling is analyzed under conditions typical of the state of Rio de Janeiro`s coastal ocean bed. Relying on an extensive review of technical literature, an effort has been made to ascertain the conditions which favor the occurrence of such hydrates in gas-contaminated water-based drilling muds. Based on this study, methods are proposed for preventing and countering this problem. (author) 58 refs., 10 figs.

  17. [Glomus jugulare tumor: perioperative management].

    Science.gov (United States)

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

    1996-12-01

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

  18. Role of dietary fiber in formation and prevention of small intestinal ulcers induced by nonsteroidal anti-inflammatory drug.

    Science.gov (United States)

    Satoh, Hiroshi

    2010-01-01

    Recent advances in endoscopic techniques such as capsule endoscopy have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. Although the pathogenesis of NSAID-induced intestinal ulcer has been widely studied, dietary factors have seldom been considered. In the present review, the role of dietary fiber (DF) in the formation of NSAID-induced intestinal ulcers is discussed. In previous studies, small intestinal lesions were not observed when NSAIDs were administered to fasted rats, dogs, and cats, but were observed in conventionally-fed animals, suggesting the importance of feeding in the formation of intestinal lesions induced by NSAIDs. However, in animals fed diets containing low or no DF, indomethacin (IND) did not produce lesions in the small intestine, but did produce lesions in animals fed diets supplemented with insoluble dietary fiber (IDF, cellulose). The results suggest that IDF in the diet plays an important role in the formation of NSAID-induced intestinal lesions. On the other hand, addition of soluble dietary fibers (SDFs) such as pectin or mucin to regular diet markedly decreased NSAID-induced intestinal lesions. Thus, IDF and SDF have opposing effects on IND-induced intestinal lesions, i.e., IDF is harmful while SDF is protective. SDFs potentially represent a novel and safe means for protecting the small intestine against NSAID-induced intestinal lesions.

  19. Simultaneous siRNA targeting of Src and downstream signaling molecules inhibit tumor formation and metastasis of a human model breast cancer cell line.

    Directory of Open Access Journals (Sweden)

    Jeffrey D Bjorge

    2011-04-01

    Full Text Available Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3 and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research.Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a reduced ability to form primary tumors in NOD/SCID mice. In addition, direct intra-tumoral injection of siRNAs targeting these signaling molecules resulted in a substantial inhibition of tumor metastases as well as of primary tumor growth. Simultaneous knock-down of Src and Stat3, and/or Myc exhibited the greatest effects resulting in substantial inhibition of primary tumor growth and metastasis.These findings demonstrate the effectiveness of simultaneous targeting of Src and the downstream signaling partners Stat3 and/or cMyc to inhibit the growth and oncogenic properties of a human cancer cell line. This knowledge may be very useful in the development of future therapeutic approaches involving targeting of specific genes products involved in tumor growth and metastasis.

  20. Pre-Cancer Atlas (PCA) and Other Human Tumor Atlas Network (HTAN) Funding Opportunity Announcements (FOAs) Released | Division of Cancer Prevention

    Science.gov (United States)

    There are 3 new funding opportunity announcements about the Pre-Cancer Atlas associated with the Beau Biden Cancer MoonshotSM Initiative that are intended to accelerate cancer research. The purpose of the FOAs is to promote research that results in a comprehensive view of the dynamic, multidimensional tumor ecosystem and is a direct response to the Moonshot Blue Ribbon Panel recommendation to generate human tumor atlases. |

  1. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

    Science.gov (United States)

    Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

    2017-03-01

    Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.

    Science.gov (United States)

    Verma, Dheeraj; Moghimi, Babak; LoDuca, Paul A; Singh, Harminder D; Hoffman, Brad E; Herzog, Roland W; Daniell, Henry

    2010-04-13

    To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.

  3. Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in a mouse model of secondhand smoke induced erectile dysfunction.

    Science.gov (United States)

    Bivalacqua, Trinity J; Sussan, Thomas E; Gebska, Melina A; Strong, Travis D; Berkowitz, Dan E; Biswal, Shyam; Burnett, Arthur L; Champion, Hunter C

    2009-02-01

    We determined the effect of passive secondhand cigarette smoke on 1) erectile function in vivo, 2) molecular mechanisms involved in penile vascular function, and 3) erectile function and penile molecular signaling in the presence of phosphodiesterase type 5 inhibitor therapy. Four groups of mice were used, including group 1--controls, group 2--mice exposed to 3 weeks of secondhand smoke (5 hours per day for 5 days per week), group 3--control plus sildenafil (100 mg/kg per day) and group 4--smoke exposed plus sildenafil (100 mg/kg per day). Cavernous nerve electrical stimulation and intracavernous injection of acetylcholine were done to assess erectile function. Constitutive and inducible nitric oxide synthase activity, reactive oxygen species generation, nitrotyrosine formation and superoxide anion levels were assessed. Decreased erectile responses to cavernous nerve electrical stimulation and impaired endothelium dependent erectile responses to ACh in mice exposed to secondhand smoke were observed. Superoxide anion was increased in endothelial and corporeal smooth muscle cells of smoking mouse penises. In mice exposed to secondhand smoke constitutive nitric oxide synthase activity was decreased, and inducible nitric oxide synthase activity, reactive oxygen species generation and nitrotyrosine formation increased. Sildenafil therapy restored constitutive nitric oxide synthase activity in the penis of smoking mice, decreased inducible nitric oxide synthase activity, reactive oxygen species generation and nitrotyrosine formation, and improved erectile responses to cavernous nerve electrical stimulation and acetylcholine. Short-term exposure to secondhand smoke impairs erectile function through excessive penile reactive oxygen species signaling and inducible nitric oxide synthase activity. Decreased penile constitutive nitric oxide synthase activity may be attributable to the decreased endothelial nitric oxide synthase activity resulting from increased oxidative

  4. Preventive effects of an original combination of grape seed polyphenols with amine fluoride on dental biofilm formation and oxidative damage by oral bacteria.

    Science.gov (United States)

    Furiga, A; Roques, C; Badet, C

    2014-04-01

    To investigate the preventive effects of an original combination of a grape seed extract (GSE) with an amine fluoride (Fluorinol(®) ) on dental plaque formation and oxidative damage caused by oral bacteria. The antibacterial activity of the compounds was assessed using the broth macrodilution method, and their antiplaque activity was evaluated on a multispecies biofilm grown on saliva-coated hydroxyapatite discs. The effect on glucosyltransferases activity was analysed through reductions in the overall reaction and the quantity of insoluble glucan synthesized. The combination of 2000 μg ml(-1) of GSE with 10·2 mg ml(-1) of Fluorinol(®) significantly decreased the biofilm formation (up to 4·76 log10 of reduction) and inhibited by 97·4% the insoluble glucan synthesis by glucosyltransferases. The antioxidant activity of this combination, alone or incorporated into a formulated mouthwash (Eludril daily(®) ), was determined using the Trolox equivalent antioxidant capacity assay (TEAC), and both showed significantly greater antioxidant capacity than vitamin C. The GSE/Fluorinol(®) combination showed both a significant antiplaque activity and an important antioxidant capacity in vitro, without any bactericidal effects. This is, to our knowledge, the first report on the properties of an original combination of a polyphenolic extract with amine fluoride that could be used for the prevention of oral diseases and oxidative damage associated. © 2013 The Society for Applied Microbiology.

  5. Radiation-induced glomerular thrombus formation and nephropathy are not prevented by the ADP receptor antagonist clopidogrel

    International Nuclear Information System (INIS)

    Poele, Johannes A.M. te; Kleef, Ellen M. van; Wal, Anja F. van der; Dewit, Luc G.H.; Stewart, Fiona A.

    2001-01-01

    Purpose: To assess the effects of kidney irradiation on glomerular adenosine diphosphatase (ADPase) activity and intraglomerular microthrombus formation, and their correlation to the development of renal functional impairment. Methods and Materials: C3H/HenAf-nu + mice were given single-dose or fractionated kidney irradiations. Glomerular ADPase activity was measured using a cerium-based histochemical method. Microthrombus formation within the glomeruli was assessed by a semiquantitative immunohistochemical analysis of fibrinogen/fibrin deposits. Renal function was assessed by the [ 51 Cr]EDTA retention assay. Results: The ADPase activity was significantly reduced, to approximately 50% of pretreatment value, 4-40 weeks after 10-16 Gy single-dose irradiation and at 44 weeks after 20x2 Gy. No dose-effect relationship was found. An approximately fourfold increase in glomerular fibrinogen/fibrin staining was observed at 1 year after irradiation. This increase was not influenced by treating the mice with daily, oral clopidogrel, a platelet ADP receptor antagonist, which reduced platelet aggregation by more than 75%. Radiation-induced impairment of glomerular filtration was also not affected by the clopidogrel treatment. Conclusion: These data indicate that irradiation significantly reduced glomerular ADPase activity, which correlated with an increased glomerular fibrinogen/fibrin deposition. We were not able to reduce these prothrombotic changes, nor to protect against radiation nephropathy, by pharmacological intervention with an ADP-receptor antagonist

  6. The cellular RNA helicase UAP56 is required for prevention of double-stranded RNA formation during influenza A virus infection.

    Science.gov (United States)

    Wisskirchen, Christian; Ludersdorfer, Thomas H; Müller, Dominik A; Moritz, Eva; Pavlovic, Jovan

    2011-09-01

    The cellular DEAD box RNA helicase UAP56 plays a pivotal role in the efficient transcription/replication of influenza A virus. UAP56 is recruited by the nucleoprotein (NP) of influenza A viruses, and recent data revealed that the RNA helicase is required for the nuclear export of a subset of spliced and unspliced viral mRNAs. The fact that influenza viruses do not produce detectable amounts of double-stranded RNA (dsRNA) intermediates during transcription/replication suggests the involvement of cellular RNA helicases. Hence, we examined whether the RNA-unwinding activity of UAP56 or its paralog URH49 plays a role in preventing the accumulation of dsRNA during infection. First, our data showed that not only UAP56 but also its paralog URH49 can interact with NPs of avian and human influenza A viruses. The small interfering RNA (siRNA)-mediated depletion of either RNA helicase reduced the transport of M1 and hemagglutinin (HA) mRNAs and, to a lesser extent, NP and NS1 mRNAs into the cytoplasm. Moreover, we found that virus infection of UAP56-depleted cells leads to the rapid accumulation of dsRNA in the perinuclear region. In parallel, we observed a robust virus-mediated activation of dsRNA-dependent protein kinase R (PKR), indicating that the cellular RNA helicase UAP56 may be recruited by influenza virus to prevent dsRNA formation. The accumulation of dsRNA was blocked when actinomycin D or cycloheximide was used to inhibit viral transcription/replication or translation, respectively. In summary, we demonstrate that UAP56 is utilized by influenza A viruses to prevent the formation of dsRNA and, hence, the activation of the innate immune response.

  7. The use of additive ceramic hollow spheres on cement slurry to prevent lost circulation in formation `X' having low pressure fracture

    Science.gov (United States)

    Rita, Novia; Mursyidah, Syahindra, Michael

    2018-03-01

    When drilling, if the hydrostatic pressure is higher than formation pressure (fracture pressure) it will cause lost circulation during cementing process. To solve this problem, hydrostatic pressure of slurry can be decreased by lowering the slurry density by using some additives. Ceramic Hollow Spheres (CHS) is lightweight additive. This additive comes with low specific gravity so it can lowered the slurry density. When the low-density slurry used in cementing process, it can prevent low circulation and fractured formation caused by cement itself. Class G cement is used in this experiment with the standard density of this slurry is 15.8 ppg. With the addition of CHS, slurry density lowered to 12.5 ppg. CHS not only used to lower the slurry density, it also used to make the same properties with the standard slurry even the density has been lowered. Both thickening time and compressive strength have not change if the CHS added to the slurry. With addition of CHS, thickening time at 70 Bc reached in 03 hours 12 minutes. For the compressive strength, 2000 psi reached in 07 hours 07 minutes. Addition of CHS can save more time in cementing process of X formation.

  8. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

    DEFF Research Database (Denmark)

    Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette

    2015-01-01

    bone mass reductions. DESIGN: Randomized control study. SETTING: Out-patient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), age 46±2 years. INTERVENTION: After a low-calorie diet-induced 12% weight loss, participants were randomized to treatment......CONTEXT: Recent studies indicate that glucagon-like peptide 1 (GLP-1) regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. OBJECTIVE: To investigate the role of GLP-1 RAs on bone formation and weight loss induced...... markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic and arm-leg BMC decreased during weight maintenance...

  9. Small RNA Library Preparation Method for Next-Generation Sequencing Using Chemical Modifications to Prevent Adapter Dimer Formation.

    Science.gov (United States)

    Shore, Sabrina; Henderson, Jordana M; Lebedev, Alexandre; Salcedo, Michelle P; Zon, Gerald; McCaffrey, Anton P; Paul, Natasha; Hogrefe, Richard I

    2016-01-01

    For most sample types, the automation of RNA and DNA sample preparation workflows enables high throughput next-generation sequencing (NGS) library preparation. Greater adoption of small RNA (sRNA) sequencing has been hindered by high sample input requirements and inherent ligation side products formed during library preparation. These side products, known as adapter dimer, are very similar in size to the tagged library. Most sRNA library preparation strategies thus employ a gel purification step to isolate tagged library from adapter dimer contaminants. At very low sample inputs, adapter dimer side products dominate the reaction and limit the sensitivity of this technique. Here we address the need for improved specificity of sRNA library preparation workflows with a novel library preparation approach that uses modified adapters to suppress adapter dimer formation. This workflow allows for lower sample inputs and elimination of the gel purification step, which in turn allows for an automatable sRNA library preparation protocol.

  10. Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats.

    Science.gov (United States)

    Kobaek-Larsen, Morten; El-Houri, Rime B; Christensen, Lars P; Al-Najami, Issam; Fretté, Xavier; Baatrup, Gunnar

    2017-03-22

    Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 μg FaOH per g feed and 7 μg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.

  11. Pirfenidone vs. sodium hyaluronate/carboxymethylcellulose as prevention of the formation of intra-abdominal adhesions after colonic surgery. A randomized study in an experimental model.

    Science.gov (United States)

    Bello-Guerrero, Jorge Alberto; Cruz-Santiago, César Alberto; Luna-Martínez, Javier

    2016-01-01

    Up to 93% of patients undergoing abdominal surgery will develop intra-abdominal adhesions with the subsequent morbidity that they represent. Various substances have been tested for the prevention of adhesions with controversial results; the aim of our study is to compare the capability of pirfenidone in adhesion prevention against sodium hyaluronate/carboxymethylcellulose. A randomized, prospective, longitudinal experimental study with Winstar rats. They were divided into 3 groups. The subjects underwent an exploratory laparotomy and they had a 4cm(2) cecal abrasion. The first group received saline on the cecal abrasion, and groups 2 and 3 received pirfenidone and sodium hyaluronate/carboxymethylcellulose respectively. All rats were sacrificed on the 21st day after surgery and the presence of adhesions was evaluated with the modified Granat scale. Simple frequency, central tendency and dispersion measures were recorded. For the statistical analysis we used Fisher's test. To evaluate adhesions we used the Granat's modified scale. The control group had a median adhesion formation of 3 (range 0-4). The pirfenidone group had 1.5 (range 0-3), and the sodium hyaluronate/carboxymethylcellulose group had 0 (range 0-1). There was a statistically significant difference to favor sodium hyaluronate/carboxymethylcellulose against saline and pirfenidone (P<0.009 and P<.022 respectively). The use of sodium hyaluronate/carboxymethylcellulose is effective for the prevention of intra-abdominal adhesions. More experimental studies are needed in search for the optimal adhesion prevention drug. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism.

    Science.gov (United States)

    Sureban, Sripathi M; Madhoun, Mohammad F; May, Randal; Qu, Dongfeng; Ali, Naushad; Fazili, Javid; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ding, Kai; Lightfoot, Stanley A; Houchen, Courtney W

    2015-11-10

    Tumor stem cell marker Doublecortin-like kinase1 (DCLK1) is upregulated in several solid tumors. The role of DCLK1 in hepatocellular carcinoma (HCC) is unclear. We immunostained tissues from human livers with HCC, cirrhosis controls (CC), and non-cirrhosis controls (NCC) for DCLK1. Western blot and ELISA analyses for DCLK1 were performed with stored plasma samples. We observed increased immunoreactive DCLK1 in epithelia and stroma in HCC and CCs compared with NCCs, and observed a marked increase in plasma DCLK1 from patients with HCC compared with CC and NCC. Analysis of the Cancer Genome Atlas' HCC dataset revealed that DCLK1 is overexpressed in HCC tumors relative to adjacent normal tissues. High DCLK1-expressing cells had more epithelial-mesenchymal transition (EMT). Various tumor suppressor miRNAs were also downregulated in HCC tumors. We evaluated the effects of DCLK1 knockdown on Huh7.5-derived tumor xenograft growth. This was associated with growth arrest and a marked downregulation of cMYC, and EMT transcription factors ZEB1, ZEB2, SNAIL, and SLUG via let-7a and miR-200 miRNA-dependent mechanisms. Furthermore, upregulation of miR-143/145, a corresponding decrease in pluripotency factors OCT4, NANOG, KLF4, and LIN28, and a reduction of let-7a, miR-143/145, and miR-200-specific luciferase activity was observed. These findings suggest that the detection of elevated plasma DCLK1 may provide a cost-effective, less invasive tool for confirmation of clinical signs of cirrhosis, and a potential companion diagnostic marker for patients with cirrhosis and HCC. Our results support evaluating DCLK1 as a biomarker for detection and as a therapeutic target for eradicating HCC.

  13. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Harford-Wright

    Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

  14. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Science.gov (United States)

    Harford-Wright, Elizabeth; Lewis, Kate M; Ghabriel, Mounir N; Vink, Robert

    2014-01-01

    The neuropeptide substance P (SP) has been implicated in the disruption of the blood-brain barrier (BBB) and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg), dexamethasone (8 mg/kg) or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05). Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants further

  15. Red strain oryza sativa-unpolished thai rice prevents oxidative stress and colorectal aberrant crypt foci formation in rats.

    Science.gov (United States)

    Tammasakchai, Achiraya; Reungpatthanaphong, Sareeya; Chaiyasut, Chaiyavat; Rattanachitthawat, Sirichet; Suwannalert, Prasit

    2012-01-01

    Oxidative stress has been proposed to be involved in colorectal cancer development. Many dark pigments of plants have potent oxidative stress preventive properties. In this study, unpolished Thai rice was assessed for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Red strain unpolished Thai rice was also administered to rats exposed to azoxymethane (AOM) for induction of aberrant crypt foci (ACF). Serum malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) were investigated for cellular oxidative stress and serum antioxidants, respectively. Red pigment unpolished Thai rice demonstrated high antioxidant activity and was found to significantly and dose dependently decrease the total density and crypt multiplicity of ACF. Consumption of Thai rice further resulted in high serum antioxidant activity and low MDA cellular oxidative stress. Interestingly, the density of ACF was strongly related to MDA at r=0.964, while it was inversely related with FRAP antioxidants (r=-0.915, pred strain of unpolished Thai rice may exert potentially beneficial effects on colorectal cancer through decrease in the level of oxidative stress.

  16. Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1.

    Science.gov (United States)

    Jin, Haojie; Wang, Cun; Jin, Guangzhi; Ruan, Haoyu; Gu, Dishui; Wei, Lin; Wang, Hui; Wang, Ning; Arunachalam, Einthavy; Zhang, Yurong; Deng, Xuan; Yang, Chen; Xiong, Yi; Feng, Hugang; Yao, Ming; Fang, Jingyuan; Gu, Jianren; Cong, Wenming; Qin, Wenxin

    2017-09-01

    xenograft tumors, with fewer metastases and blood vessels, than control HCC cells. In HCC cells, RCAN1.4 inhibited expression of insulin-like growth factor 1 and vascular endothelial growth factor A by reducing calcineurin activity and blocking nuclear translocation of nuclear factor of activated T cells (NFAT1). HCC cells incubated with the calcineurin inhibitor cyclosporin A had decreased nuclear level of NFAT1. HCC cells had hypermethylation of a CpG island in the 5' regulatory region of RCAN1.4, which reduced its expression. RCAN1.4 is down-regulated in HCC tissues, compared with non-tumor liver tissues. RCAN1.4 prevents cell proliferation, migration, and invasion in vitro; overexpressed RCAN1.4 in HCC cells prevents growth, angiogenesis, and metastases of xenograft tumors by inhibiting calcineurin activity and nuclear translocation of NFAT1. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

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

  18. Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation

    OpenAIRE

    Kasiri, Sahba; Ansari, Khairul I.; Hussain, Imran; Bhan, Arunoday; Mandal, Subhrangsu S.

    2012-01-01

    HOXC13 is a homeobox containing gene that plays crucial roles in hair development and origin of replication. Herein, we investigated the biochemical functions of HOXC13 and explored its potential roles in tumor cell viability. We have designed a phosphorothioate based antisense-oligonucleotide that specifically knockdown HOXC13 in cultured cells. Cell viability and cytotoxicity assays demonstrated that HOXC13 is essential for cell growth and viability. Antisense-mediated knockdown of HOXC13 a...

  19. Abdominal closure reinforcement by using polypropylene mesh functionalized with poly-ε-caprolactone nanofibers and growth factors for prevention of incisional hernia formation.

    Science.gov (United States)

    Plencner, Martin; East, Barbora; Tonar, Zbyněk; Otáhal, Martin; Prosecká, Eva; Rampichová, Michala; Krejčí, Tomáš; Litvinec, Andrej; Buzgo, Matej; Míčková, Andrea; Nečas, Alois; Hoch, Jiří; Amler, Evžen

    2014-01-01

    Incisional hernia affects up to 20% of patients after abdominal surgery. Unlike other types of hernia, its prognosis is poor, and patients suffer from recurrence within 10 years of the operation. Currently used hernia-repair meshes do not guarantee success, but only extend the recurrence-free period by about 5 years. Most of them are nonresorbable, and these implants can lead to many complications that are in some cases life-threatening. Electrospun nanofibers of various polymers have been used as tissue scaffolds and have been explored extensively in the last decade, due to their low cost and good biocompatibility. Their architecture mimics the natural extracellular matrix. We tested a biodegradable polyester poly-ε-caprolactone in the form of nanofibers as a scaffold for fascia healing in an abdominal closure-reinforcement model for prevention of incisional hernia formation. Both in vitro tests and an experiment on a rabbit model showed promising results.

  20. Clinical Tumor Dimensions May Be Useful to Prevent Geographic Miss in Conventional Radiotherapy of Uterine Cervix Cancer-A Magnetic Resonance Imaging-Based Study

    International Nuclear Information System (INIS)

    Justino, Pitagoras Baskara; Baroni, Ronaldo; Blasbalg, Roberto; Andrade Carvalho, Heloisa de

    2009-01-01

    Purpose: To evaluate the risk of geographic miss associated with the classic four-field 'box' irradiation technique and to define the variables that predict this risk. Materials and Methods: The study population consisted of 80 patients with uterine cervix cancer seen between 2001 and 2006. Median age was 55 years (23-82 years), and 72 (90%) presented with squamous cell carcinoma. Most patients (68.7%) presented with locally advanced disease (IIb or more). Magnetic resonance imaging findings from before treatment were compared with findings from simulation of the conventional four-field 'box' technique done with rectal contrast. Study variables included tumor volume; involvement of vagina, parametrium, bladder, or rectum; posterior displacement of the anterior rectal wall; and tumor anteroposterior diameter (APD). Margins were considered adequate when the target volume (primary tumor extension, whole uterine body, and parametrium) was included within the field limits and were at least 1 cm in width. Results: Field limits were inadequate in 45 (56%) patients: 29 (36%) patients at the anterior and 28 (35%) at the posterior border of the lateral fields. Of these, 12 patients had both anterior and posterior miss, and this risk was observed in all stages of the disease (p = 0.076). Posterior displacement of the anterior rectal wall beyond S2-S3 was significantly correlated with the risk of geographic miss (p = 0.043). Larger tumors (APD 6 cm or above and volume above 50 cm 3 ) were also significantly correlated with this risk (p = 0.004 and p = 0.046, respectively). Conclusions: Posterior displacement of the anterior rectal wall, tumor APD, and volume can be used as guidance in evaluating the risk of geographic miss.

  1. Pharmacological blockade of aquaporin-1 water channel by AqB013 restricts migration and invasiveness of colon cancer cells and prevents endothelial tube formation in vitro.

    Science.gov (United States)

    Dorward, Hilary S; Du, Alice; Bruhn, Maressa A; Wrin, Joseph; Pei, Jinxin V; Evdokiou, Andreas; Price, Timothy J; Yool, Andrea J; Hardingham, Jennifer E

    2016-02-24

    Aquaporins (AQP) are water channel proteins that enable fluid fluxes across cell membranes, important for homeostasis of the tissue environment and for cell migration. AQP1 knockout mouse models of human cancers showed marked inhibition of tumor-induced angiogenesis, and in pre-clinical studies of colon adenocarcinomas, forced over-expression of AQP1 was shown to increase angiogenesis, invasion and metastasis. We have synthesized small molecule antagonists of AQP1. Our hypothesis is that inhibition of AQP1 will reduce migration and invasiveness of colon cancer cells, and the migration and tube-forming capacity of endothelial cells in vitro. Expression of AQP1 in cell lines was assessed by quantitative (q) PCR, western blot and immunofluorescence, while expression of AQP1 in human colon tumour tissue was assessed by immunohistochemistry. The effect of varying concentrations of the AQP1 inhibitor AqB013 was tested on human colon cancer cell lines expressing high versus low levels of AQP1, using wound closure (migration) assays, matrigel invasion assays, and proliferation assays. The effect of AqB013 on angiogenesis was tested using an endothelial cell tube-formation assay. HT29 colon cancer cells with high AQP1 levels showed significant inhibition of migration compared to vehicle control of 27.9% ± 2.6% (p colon cancer.

  2. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

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

  3. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

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

  4. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

    Full Text Available Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 persons/year. The most common benign brain tumor in adults is meningioma, which is most present in women, and the most common malignant tumor is glioblastoma, which is most present in adult men. Due to high mortality, especially in patients diagnosed with glioblastoma and significant brain tumor morbidity, there is a constant interest in understanding its etiology in order to possibly prevent tumor occurrence in future and enable more efficient treatment strategies for this fatal brain disease. Despite the continuously growing number of epidemiological studies on possible factors of tumor incidence, the etiology remains unclear. The only established environmental risk factor of gliomas is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor of brain tumor development. However, studies have been inconsistent and inconclusive, so more definite results are still expected.

  5. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    Science.gov (United States)

    Kim, Junghyun; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Chan-Sik; Kim, Jin Sook

    2016-01-01

    Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID:27657123

  6. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2016-09-01

    Full Text Available Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE against damage to retinal vascular cells were investigated in streptozotocin (STZ-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB and inducible nitric oxide synthase (iNOS were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

  7. Prevention of Bone Bridge Formation Using Transplantation of the Autogenous Mesenchymal Stem Cells to Physeal Defects: An Experimental Study in Rabbits

    Directory of Open Access Journals (Sweden)

    L. Plánka

    2007-01-01

    Full Text Available Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold. The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs, the bone

  8. Inflammatory cytokine-mediated evasion of virus-induced tumors from NK cell control.

    Science.gov (United States)

    Mishra, Rabinarayan; Polic, Bojan; Welsh, Raymond M; Szomolanyi-Tsuda, Eva

    2013-07-15

    Infections with DNA tumor viruses, including members of the polyomavirus family, often result in tumor formation in immune-deficient hosts. The complex control involved in antiviral and antitumor immune responses during these infections can be studied in murine polyomavirus (PyV)-infected mice as a model. We found that NK cells efficiently kill cells derived from PyV-induced salivary gland tumors in vitro in an NKG2D (effector cell)-RAE-1 (target cell)-dependent manner; but in T cell-deficient mice, NK cells only delay but do not prevent the development of PyV-induced tumors. In this article, we show that the PyV-induced tumors have infiltrating functional NK cells. The freshly removed tumors, however, lack surface RAE-1 expression, and the tumor tissues produce soluble factors that downregulate RAE-1. These factors include the proinflammatory cytokines IL-1α, IL-1β, IL-33, and TNF. Each of these cytokines downregulates RAE-1 expression and susceptibility to NK cell-mediated cytotoxicity. CD11b(+)F4/80(+) macrophages infiltrating the PyV-induced tumors produce high amounts of IL-1β and TNF. Thus, our data suggest a new mechanism whereby inflammatory cytokines generated in the tumor environment lead to evasion of NK cell-mediated control of virus-induced tumors.

  9. Vasculogenic mimicry and tumor metastasis.

    Science.gov (United States)

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

    2016-01-01

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

  10. Spinal tumors

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  11. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

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

  12. Brain Tumors

    Science.gov (United States)

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

  13. TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice.

    Science.gov (United States)

    Uthaya Kumar, Dinesh Babu; Chen, Chia-Lin; Liu, Jian-Chang; Feldman, Douglas E; Sher, Linda S; French, Samuel; DiNorcia, Joseph; French, Samuel W; Naini, Bita V; Junrungsee, Sunhawit; Agopian, Vatche Garen; Zarrinpar, Ali; Machida, Keigo

    2016-03-01

    Obesity and alcohol consumption contribute to steatohepatitis, which increases the risk for hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCCs). Mouse hepatocytes that express HCV-NS5A in liver up-regulate the expression of Toll-like receptor 4 (TLR4), and develop liver tumors containing tumor-initiating stem-like cells (TICs) that express NANOG. We investigated whether the TLR4 signals to NANOG to promote the development of TICs and tumorigenesis in mice placed on a Western diet high in cholesterol and saturated fat (HCFD). We expressed HCV-NS5A from a transgene (NS5A Tg) in Tlr4-/- (C57Bl6/10ScN), and wild-type control mice. Mice were fed a HCFD for 12 months. TICs were identified and isolated based on being CD133+, CD49f+, and CD45-. We obtained 142 paraffin-embedded sections of different stage HCCs and adjacent nontumor areas from the same patients, and performed gene expression, immunofluorescence, and immunohistochemical analyses. A higher proportion of NS5A Tg mice developed liver tumors (39%) than mice that did not express HCV NS5A after the HCFD (6%); only 9% of Tlr4-/- NS5A Tg mice fed HCFD developed liver tumors. Livers from NS5A Tg mice fed the HCFD had increased levels of TLR4, NANOG, phosphorylated signal transducer and activator of transcription (pSTAT3), and TWIST1 proteins, and increases in Tlr4, Nanog, Stat3, and Twist1 messenger RNAs. In TICs from NS5A Tg mice, NANOG and pSTAT3 directly interact to activate expression of Twist1. Levels of TLR4, NANOG, pSTAT3, and TWIST were increased in HCC compared with nontumor tissues from patients. HCFD and HCV-NS5A together stimulated TLR4-NANOG and the leptin receptor (OB-R)-pSTAT3 signaling pathways, resulting in liver tumorigenesis through an exaggerated mesenchymal phenotype with prominent Twist1-expressing TICs. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Marine fish oil is more potent than plant-based n-3 polyunsaturated fatty acids in the prevention of mammary tumors.

    Science.gov (United States)

    Liu, Jiajie; Abdelmagid, Salma A; Pinelli, Christopher J; Monk, Jennifer M; Liddle, Danyelle M; Hillyer, Lyn M; Hucik, Barbora; Silva, Anjali; Subedi, Sanjeena; Wood, Geoffrey A; Robinson, Lindsay E; Muller, William J; Ma, David W L

    2017-12-27

    Marine-derived n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit mammary carcinogenesis. However, evidence regarding plant-based α-linolenic acid (ALA), the major n-3 PUFA in the Western diet, remains equivocal. The objective of this study was to examine the effect of lifelong exposure to plant- or marine-derived n-3 PUFAs on pubertal mammary gland and tumor development in MMTV-neu(ndl)-YD5 mice. It is hypothesized that lifelong exposure to n-3 PUFA reduces terminal end buds during puberty leading to delayed tumor onset, volume and multiplicity. It is further hypothesized that plant-derived n-3 PUFAs will exert dose-dependent effects. Harems of MMTV-FVB males were bred with wild-type females and fed either a (1) 10% safflower (10% SF, n-6 PUFA, control), (2) 10% flaxseed (10% FS), (3) 7% safflower plus 3% flaxseed (3% FS) or (4) 7% safflower plus 3% menhaden (3% FO) diet. Female offspring were maintained on parental diets. Compared to SF, 10% FS and 3% FO reduced (P<.05) terminal end buds at 6 weeks and tumor volume and multiplicity at 20 weeks. A dose-dependent reduction of tumor volume and multiplicity was observed in mice fed 3% and 10% FS. Antitumorigenic effects were associated with altered HER2, pHER-2, pAkt and Ki-67 protein expression. Compared to 10% SF, 3% FO significantly down-regulated expression of genes involved in eicosanoid synthesis and inflammation. From this, it can be estimated that ALA was 1/8 as potent as EPA+DHA. Thus, marine-derived n-3 PUFAs have greater potency versus plant-based n-3 PUFAs. Copyright © 2018. Published by Elsevier Inc.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  16. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

    The Brain Tumor Epidemiology Consortium is an open scientific forum organized to foster the development of multi-center, international and inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes, and prevention of brain tumors.

  17. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

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

  18. Hydrate prevention during formation test of gas in deep water; Prevencao de formacao de hidratos durante teste de formacao de poco de gas em lamina d'agua profunda

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Renato Cunha [PETROBRAS, Rio de Janeiro, RJ (Brazil)

    2008-07-01

    This work shows a scenery of formation test in deep water, for a well of gas, for which, there were made simulations with objective of identifying possible pairs of points (Pressure x Temperature), favorable to the hydrates formation. Besides, they were made comparisons of the values obtained in the simulation with the values registered during the formation test for the well Alfa of the field Beta. Of ownership of those information, we made an evaluation of the real needs of injection of inhibitors with intention of preventing the hydrates formation in each phase of the test. In an including way, the work has as objective recommends the volumes of hydrates inhibitors to be injected in each phase of a test of formation of well of gas in deep water, in way to assure that the operations are made without there is risk of hydrates formation. (author)

  19. Hydrates prevention during deep-water formation gas well test; Prevencao de formacao de hidratos durante teste de formacao de poco de gas em lamina d'agua profunda

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Renato Cunha [Unidade de Operacoes de Exploracao e Producao do Espirito Santo. Engenharia de Producao. Gerencia de Engenharia de Poco, ES (Brazil)], e-mail: renatocr@petrobras.com.br; Freitas, Alexandre Mussumeci Valim de [Centro de Pesquisas da Petrobras (CENPES). Gerencia de Tecnologia de Elevacao e Escoamento da Producao (Brazil)], e-mail: amfreitas@petrobras.com.br; Nishimura, Nelson Satiro [E and P Engenharia de Producao. Reservas e Reservatorios. Gerencia de Avaliacao de Reservatorios (Brazil)], e-mail: nishimura@petrobras.com.br

    2010-06-15

    This study examines the situation of a deep water formation test for a gas well in which simulations were made to identify possible pairs of points (Pressure versus Temperature), favorable to hydrate formation. Furthermore, the values obtained in the simulation were compared with the values registered during the formation test for the Alfa well in the Beta Field. With this information, an evaluation was made of the necessity to inject inhibitors intended to prevent hydrate formation in each test phase. In a wider sense, the study's objective was to recommend the volumes of hydrate inhibitors to be injected in each phase of a deep water formation test of a gas well to assure the operation be done without the risk of hydrate formation. (author)

  20. Phenotypic characterization of drug resistance and tumor initiating cancer stem cells from human bone tumor osteosarcoma cell line OS-77

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2014-08-01

    Full Text Available The cancer stem cell theory suggest that presence of small subpopulation of cancer stem cells are the major implication in the cancer treatment and also responsible for tumor recurrence. Based on Hoechst 33342 dye exclusion technique, we have identified about 3.3% of cancer stem like side population (SP cells from human osteosarcoma OS-77 cell line whose prevalence is significantly reduced to 0.3% after treatment with verapamil. The sphere formation assay revealed that osteosarcoma SP cells are highly capable to form tumor spheres (sarcospheres. Further by immunocytochemistry and RT-PCR, we show that OS-77 SP cells have enhanced expression of stem cell surface markers such as CD44, Nanog and ATP-binding cassette (ABC transporter gene (ABCG2 which contributes to self-renewal and drug resistance, respectively. Our findings help to designing a novel therapeutic drug which could effectively target the cancer stem cells and prevent the tumor relapse.

  1. Modeling of formation and prevention of a pure water zone in capillary isoelectric focusing with narrow pH range carrier ampholytes.

    Science.gov (United States)

    Takácsi-Nagy, Anna; Kilár, Ferenc; Thormann, Wolfgang

    2017-03-01

    This paper comprises a continuation of computer simulation studies dealing with carrier ampholyte based CIEF in presence of narrow pH gradients. With this technique, amphoteric sample components with pI values outside the pH gradient are migrating isotachophoretically toward the cathode or anode whereas components with pI values within the gradient become focused. In order to understand the processes occurring in presence of the electric field, the behavior of both carrier ampholytes and amphoteric sample components is investigated by computer modeling. Characteristics of two pH unit gradients with end components having pI values at or around 7.00 and conditions that lead to the formation of a water zone at neutrality were investigated. Data obtained reveal that a zone of water is formed in focusing with carrier ampholytes when the applied pH range does not cover the neutral region, ends at pH 7.00 or begins at pH 7.00. The presence of additional amphoteric components that cover the neutrality region prevent water zone formation under current flow. This situation is met in experiments with narrow pH gradients that end or begin around neutrality. Simulation data reveal that no water zone evolves when atmospheric carbon dioxide dissolved in the catholyte causes the migration of carbonic acid (in the form of carbonate and/or hydrogen carbonate ions) from the catholyte through the focusing structure. An electrolyte change in the electrode solution does not have an impact on the focusing part but does change the isotachophoretic pattern migrating behind the leading ion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

    Science.gov (United States)

    Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

    2016-09-01

    Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

  3. Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells.

    Science.gov (United States)

    Chakrabarti, Mrinmay; Ray, Swapan K

    2015-12-10

    Glioblastoma is the most lethal brain tumor. Failure of conventional chemotherapies prompted the search for natural compounds for treatment of glioblastoma. Plant-derived flavonoids could be alternative medicine for inhibiting not only glioblastoma cells but also glioblastoma stem cells (GSC). Two plant-derived flavonoids are luteolin (LUT) and silibinin (SIL). We investigated anti-tumor mechanisms of LUT and SIL in different human glioblastoma cells and GSC and found significant synergistic inhibition of human glioblastoma LN18 and SNB19 cells and GSC following treatment with combination of 20µM LUT and 50µM SIL. Combination of 20µM LUT and 50µM SIL was more effective than a conventional chemotherapeutic agent (BCNU or TMZ). We continued our studies with SNB19 cells and GSC and found dramatic inhibition of cell migration from spheroids and also cell invasion through matrigel following treatment with combination of LUT and SIL. This combination was highly effective to block angiogenesis and survival pathways leading to induction of apoptosis. Inhibition of PKCα, XIAP, and iNOS ultimately caused induction of extrinsic and intrinsic pathways of apoptosis. Collectively, synergistic efficacy of LUT and SIL could be a promising therapy to inhibit cell migration and invasion and induce apoptosis in different glioblastoma cells including GSC. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Kerathocyst odontogenic tumor: Importance of selection the best treatment modality and a periodical follow-up to prevent from recurrence: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Nasim Jafaripozve

    2013-01-01

    Full Text Available The keratocystic odontogenic tumor (KCOT is a relatively common oral and maxillofacial lesion with specific characteristics such us rapid growth, extension into the surrounding tissues and high rates of recurrence. Various treatment modalities have been reported. Due to the very thin and friable lining characteristic of the tumor, enucleation can be difficult undertaken and for this reason it is associated with the highest recurrence rates. A 22-year-old male referred to our clinic due to a slight expansion in the right mandible from 2 years ago. He has a history of occurrence of KCOT in this region that was treated surgically by enucleation and curettage 5 years ago. Cone beam computed tomography showed a multilocular radiolucent lesion that extended from the angle of the mandible to the symphysis. Incisional biopsy showed a KCOT recurrence that surgically treated with resection of the right mandible by continuity preservation. Selection of the best treatment modality and also a periodical lifelong follow-up is very important to reduce the rate of recurrence and morbidity of the patient.

  5. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Directory of Open Access Journals (Sweden)

    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.

  6. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-04-30

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

  8. Comparison of drug and cell-based delivery: engineered adult mesenchymal stem cells expressing soluble tumor necrosis factor receptor II prevent arthritis in mouse and rat animal models.

    Science.gov (United States)

    Liu, Linda N; Wang, Gang; Hendricks, Kyle; Lee, Keunmyoung; Bohnlein, Ernst; Junker, Uwe; Mosca, Joseph D

    2013-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with unknown etiology where tumor necrosis factor-α (TNFα) plays a critical role. Etanercept, a recombinant fusion protein of human soluble tumor necrosis factor receptor II (hsTNFR) linked to the Fc portion of human IgG1, is used to treat RA based on the rationale that sTNFR binds TNFα and blocks TNFα-mediated inflammation. We compared hsTNFR protein delivery from genetically engineered human mesenchymal stem cells (hMSCs) with etanercept. Blocking TNFα-dependent intercellular adhesion molecule-1 expression on transduced hMSCs and inhibition of nitric oxide production from TNFα-treated bovine chondrocytes by conditioned culture media from transduced hMSCs demonstrated the functionality of the hsTNFR construction. Implanted hsTNFR-transduced mesenchymal stem cells (MSCs) reduced mouse serum circulating TNFα generated from either implanted TNFα-expressing cells or lipopolysaccharide induction more effectively than etanercept (TNFα, 100%; interleukin [IL]-1α, 90%; and IL-6, 60% within 6 hours), suggesting faster clearance of the soluble tumor necrosis factor receptor (sTNFR)-TNFα complex from the animals. In vivo efficacy of sTNFR-transduced MSCs was illustrated in two (immune-deficient and immune-competent) arthritic rodent models. In the antibody-induced arthritis BalbC/SCID mouse model, intramuscular injection of hsTNFR-transduced hMSCs reduced joint inflammation by 90% compared with untransduced hMSCs; in the collagen-induced arthritis Fischer rat model, both sTNFR-transduced rat MSCs and etanercept inhibited joint inflammation by 30%. In vitro chondrogenesis assays showed the ability of TNFα and IL1α, but not interferon γ, to inhibit hMSC differentiation to chondrocytes, illustrating an additional negative role for inflammatory cytokines in joint repair. The data support the utility of hMSCs as therapeutic gene delivery vehicles and their potential to be used in alleviating inflammation

  9. A randomized controlled study of the efficacy of misoprostol and hyaluronic acid in preventing adhesion formation after gynecological surgery: a rat uterine horn model.

    Science.gov (United States)

    Kaya, Cihan; Sever, Nurten; Cengiz, Hüseyin; Yıldız, Şükrü; Ekin, Murat; Yaşar, Levent

    2014-05-01

    To investigate the effect of misoprostol in the reduction of adhesion formation after gynecological surgery. A double blind, randomized controlled experimental study was designed. Twenty-one female Wistar Hannover rats were divided into three groups as control, misoprostol and Hyalobarrier(®) groups. A uterine horn adhesion model was created. After anesthesia induction, 1.5-2cm injuries were made to the each uterine horn by cautery. The control group received no special medications except for the standard surgical procedure. The misoprostol group received 10μcg/kg misoprostol in addition to the standard surgical procedure, and the Hyalobarrier(®) group received 1cm(3) ready-for-use Hyalobarrier(®) gel intraperitoneally in addition to the standard surgical procedure. After 14 days from the first surgical procedure, adhesion scores were evaluated. The extent (p<0.001), severity (p<0.001), degree (p<0.001) and total adhesion score (p<0.001) values of the control group were statistically higher than the values of misoprostol and Hyalobarrier(®) groups. The inflammation score value of misoprostol group was statistically lower than control and Hyalobarrier(®) groups (p<0.001). In this study, we have found a new therapeutic potential of misoprostol that may be useful in preventing pelvic adhesion and reducing inflammation scores. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Gender-related effects of 17-{beta}-estradiol and B-hexachlorocyclohexane on liver tumor formation in medaka (Oryzias latipes)

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1994-12-31

    When medaka were acutely exposed to diethylnitrosamine (DEN), greater incidence of hepatocarcinoma was seen in female versus male fish. This is possibly related to elevated female endogenous estrogens, which increase liver weight and production of vitellogenin. To examine roles of estrogens in tumor modulation, 21-day old medaka were exposed to DEN (200 ppm for 24 hr.), then fed purified diets containing the estrogenic compound {beta}-hexachlorocyclohexane ({beta}-HCH) or 17-{beta}estradiol (E2) for 6 months. Incidences of basophilic preneoplastic foci of cellular alteration in females receiving DEN and 0.01, 0.1, or 1.0 ppm E2 were three times the incidences in similarly-treated males. Also, incidences of basophilic foci in DEN + 0.1 ppm E2 males were significantly increased over DEN-only males and were equal to incidences in DEN-only females. Liver weights and hepatosomatic indices of males given 0.1 ppm E2 were not significantly different than females fed control diet. Females fed 0.01-10.0 ppm {beta}-HCH after DEN had 4--5 times greater incidences of basophilic foci as males. Gender-related effects on kinetics of growth rates and volumes of foci are being examined.

  11. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  12. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

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

  13. Carcinoid Tumors

    Science.gov (United States)

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

  14. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

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

  15. Prevention and control of sequels in the mouth of patients treated with radiation therapy for head and neck tumors; Prevencao e controle das sequelas bucais em pacientes irradiados por tumores de cabeca e pescoco

    Energy Technology Data Exchange (ETDEWEB)

    Cardoso, Maria de Fatima Aparecida; Novikoff, Silviene; Tresso, Adriana; Segreto, Roberto Araujo [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Setor de Odontologia; Cervantes, Onivaldo [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Medicina. Setor de Radioterapia

    2005-04-01

    Surgery and radiation therapy are de main treatments for head and neck cancer. The side effects of the interaction of ionizing radiation on the tissues include dermatitis, mucositis, xerostomia, candidiasis, dysgeusia, dysphagia, caries, trismus, osteoradionecrosis. Objective: To assess dental condition of the patients using a protocol which allows avoiding or reducing the effects of radiation in the tissues of the oral cavity. Materials And Methods: Dental follow-up was performed before, during and up to 180 days after radiation therapy in 12 patients submitted to surgery and radiation therapy or radiation therapy alone. Results: The proportion of effects such as dermatitis, mucositis, dysgeusia, and dysphagia increased from the second week of the treatment until the end of the administrations. There was a clear decrease at the end of the treatment which was close to baseline values after 180 days. The reduction of xerostomia was slower and less effective. No case of caries, trismus, and osteoradionecrosis were observed during the assessment period. Conclusion: Regular dental follow-up associated with preventive measures such as prophylactic management of dental and oral diseases, adequate hygiene, mouth-washing with bicarbonate water and chamomile tea, and topic fluorine application contributed to improve the recovery conditions of patients with cancer of head and neck submitted to radiation therapy. (author)

  16. Antimicrobial GL13K peptide coatings killed and ruptured the wall of Streptococcus gordonii and prevented formation and growth of biofilms.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available Infection is one of the most prevalent causes for dental implant failure. We have developed a novel antimicrobial peptide coating on titanium by immobilizing the antimicrobial peptide GL13K. GL13K was developed from the human salivary protein BPIFA2. The peptide exhibited MIC of 8 µg/ml against planktonic Pseudonomas aeruginosa and their biofilms were reduced by three orders of magnitude with 100 µg/ml GL13K. This peptide concentration also killed 100% of Streptococcus gordonii. At 1 mg/ml, GL13K caused less than 10% lysis of human red blood cells, suggesting low toxicity to mammalian cells. Our GL13K coating has also previously showed bactericidal effect and inhibition of biofilm growth against peri-implantitis related pathogens, such as Porphyromonas gingivalis. The GL13K coating was cytocompatible with human fibroblasts and osteoblasts. However, the bioactivity of antimicrobial coatings has been commonly tested under (quasistatic culture conditions that are far from simulating conditions for biofilm formation and growth in the oral cavity. Oral salivary flow over a coating is persistent, applies continuous shear forces, and supplies sustained nutrition to bacteria. This accelerates bacteria metabolism and biofilm growth. In this work, the antimicrobial effect of the coating was tested against Streptococcus gordonii, a primary colonizer that provides attachment for the biofilm accretion by P. gingivalis, using a drip-flow biofilm bioreactor with media flow rates simulating salivary flow. The GL13K peptide coatings killed bacteria and prevented formation and growth of S. gordonii biofilms in the drip-flow bioreactor and under regular mild-agitation conditions. Surprisingly the interaction of the bacteria with the GL13K peptide coatings ruptured the cell wall at their septum or polar areas leaving empty shell-like structures or exposed protoplasts. The cell wall rupture was not detected under regular culture conditions, suggesting that cell

  17. Pretreatment with a γ-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Toshiki Okubo

    2016-10-01

    Full Text Available Neural stem/progenitor cells (NS/PCs derived from human induced pluripotent stem cells (hiPSCs are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.

  18. Rationale and approaches to the prevention of smoking-related diseases: overview of recent studies on chemoprevention of smoking-induced tumors in rodent models.

    Science.gov (United States)

    De Flora, Silvio; Izzotti, Alberto; D'Agostini, Francesco; La Maestra, Sebastiano; Micale, Rosanna T; Ceccaroli, Chiara; Steele, Vernon E; Balansky, Roumen

    2014-01-01

    Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of other chronic diseases. It is the leading cause of death in developed countries, and the global burden of cancer is escalating in less developed regions. For a rational implementation of strategies exploitable for the prevention smoking-related diseases, it is crucial to elucidate both the mechanisms of action of cigarette smoke and the protective mechanisms of the host organism. The imperative primary prevention goal is to avoid any type of exposure to smoke. Epidemiological studies have shown that a decrease in the consumption of cigarettes can be successful in attenuating the epidemic of lung cancer in several countries. Chemoprevention by means of dietary and/or pharmacological agents provides a complementary strategy aimed at decreasing the risk of developing smoking-associated diseases in addicted current smokers, who are unable to quit smoking, and especially in involuntary smokers and ex-smokers. The availability of new animal models that are suitable to detect the carcinogenicity of cigarette smoke and to assess the underlying molecular mechanisms provides new tools for evaluating both safety and efficacy of putative chemopreventive agents.

  19. Tumor Markers

    Science.gov (United States)

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

  20. Tumor Grade

    Science.gov (United States)

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

  1. Cryoablation for pulmonary tumor

    International Nuclear Information System (INIS)

    Kawamura, Masafumi; Izumi, Yotaro; Tsukada, Norimasa; Asakura, Keisuke; Nakatsuka, Seishi; Yashiro, Hideki; Inoue, Masanori; Kuribayashi, Sachio; Kobayashi, Koichi

    2008-01-01

    We have experienced more than 200 sessions for mainly metastatic lung tumor and small number of primary lung cancer since 2002. Cryo-probe is inserted percutaneously with local anesthesia under CT scan guide. Co-axial technique is adopted to prevent from hemorrhage and massive air leakage. The average of hospital stay after treatment is 2.6 days. Although pneumothorax was associated with more than half patients, 5% of them experienced chest tube insertion. Local recurrence 1 year after treatment was found 10% of tumors of 10 mm or less diameter, 30% of 11-20 mm diameter, and 40% of 20-30 mm diameter and 100% of 31 mm or more diameter. In case of large vessels (3 mm or more diameter) running within 4 mm from tumor, recurrence rate was higher compared with the same sized tumors without large vessels running nearby. We are eager for the development of 3D-simulation system considering the distribution of caloric value is strongly requested to improve the local control power of cryoablation for lung tumor. (author)

  2. Glioblastoma: a pathogenic crosstalk between tumor cells and pericytes.

    Directory of Open Access Journals (Sweden)

    Elisabetta M Caspani

    Full Text Available Cancers likely originate in progenitor zones containing stem cells and perivascular stromal cells. Much evidence suggests stromal cells play a central role in tumor initiation and progression. Brain perivascular cells (pericytes are contractile and function normally to regulate vessel tone and morphology, have stem cell properties, are interconvertible with macrophages and are involved in new vessel formation during angiogenesis. Nevertheless, how pericytes contribute to brain tumor infiltration is not known. In this study we have investigated the underlying mechanism by which the most lethal brain cancer, Glioblastoma Multiforme (GBM interacts with pre-existing blood vessels (co-option to promote tumor initiation and progression. Here, using mouse xenografts and laminin-coated silicone substrates, we show that GBM malignancy proceeds via specific and previously unknown interactions of tumor cells with brain pericytes. Two-photon and confocal live imaging revealed that GBM cells employ novel, Cdc42-dependent and actin-based cytoplasmic extensions, that we call flectopodia, to modify the normal contractile activity of pericytes. This results in the co-option of modified pre-existing blood vessels that support the expansion of the tumor margin. Furthermore, our data provide evidence for GBM cell/pericyte fusion-hybrids, some of which are located on abnormally constricted vessels ahead of the tumor and linked to tumor-promoting hypoxia. Remarkably, inhibiting Cdc42 function impairs vessel co-option and converts pericytes to a phagocytic/macrophage-like phenotype, thus favoring an innate immune response against the tumor. Our work, therefore, identifies for the first time a key GBM contact-dependent interaction that switches pericyte function from tumor-suppressor to tumor-promoter, indicating that GBM may harbor the seeds of its own destruction. These data support the development of therapeutic strategies directed against co-option (preventing

  3. Prevention: Exercise

    Medline Plus

    Full Text Available ... Injuries Sports Injuries Whiplash and Whiplash Associated Disorder Infections & Tumors Spinal Infections Spinal Tumors Extradural and Intradural Tumors TREATMENTS Assessment ...

  4. Prevention: Exercise

    Medline Plus

    Full Text Available ... Sports Injuries Whiplash and Whiplash Associated Disorder Infections & Tumors Spinal Infections Spinal Tumors Extradural and Intradural Tumors TREATMENTS Assessment Tools Lumbar ...

  5. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature

    NARCIS (Netherlands)

    Huang, XM; Molema, G; King, S; Watkins, L; Edgington, TS; Thorpe, PE

    1997-01-01

    Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor Vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally

  6. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

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

  7. Advances in the Relationship Between Tumor Cell Metabolism and Tumor Metastasis

    Directory of Open Access Journals (Sweden)

    Yalong ZHANG

    2014-11-01

    Full Text Available Intracellular nutrients and the rate of energy flowing in tumor cells are often higher than that in normal cells due to the prolonged stress of tumor-specific microenvironment. In this context, the metabolism of tumor cells provides the fuel of bio-synthesis and energy required for tumor metastasis. Consistent with this, the abnormal metabolism such as extremely active glucose metabolism and excessive accumulating of fatty acid is also discovered in metastatic tumors. Previous Studies have confirmed that the regulation of tumor metabolism can affect the tumor metastasis, and some of these have been successfully applied in clinical effective, positive way. Thus, targeting metabolism of tumor cells might be an effectively positive way to prevent the metastasis of tumor. So, our review is focused on the research development of the relationship between tumor metabolism and metastasis as well as the underlying mechanism.

  8. The significance of fertile pigs vaccination against porcine parvovirus infection in the prevention of intrauterine infection and formation of colostrum piglets immunity

    Directory of Open Access Journals (Sweden)

    Stojanac Nenad

    2014-01-01

    Full Text Available The aim of this study was to come closer to the knowledge of piglets protection during intrauterine life, as well as formation of colostrum immunity against Porcine Parvovirus Infection (PPV, on the basis of detailed antibody titer analysis from the blood serum of pigs 7 days before previous weaning, 30 days before mating and their piglets during first 3 days of life. The research included 60 fertile pigs and 300 of their offspring. For that purpose we have examined antibody titer specific for PPV in blood serum of vaccinated fertile pigs on 70th and 113th day of gestation, and in the blood serum of piglets originated from itemized fertile pigs during first day of life, before colostrums consummation and also during 3rd day of life. On the 70th day of gestation, in the fertile pigs blood serum, average antibody titer specific for PPV, value of 12.60 was determined, what represents adequate level for solid protection against PPV infection. This was confirmed undoubtedly by examination results of antibodies in the blood serum of piglets before colostrum consummation, which was 100% negative. Titer drop in the blood serum of fertile pigs, on 113th day of gestation (on the level of 8.7 came as a result of specific antibodies transfer from the mother’s blood flow to the colostrum. The above-mentioned is supported by the fact that on the 3rd day of life there was confirmed high average body titer level (13.37 in newborn piglets body serum has been confirmed. The principle of fertile pigs vaccination 7 days before weaning and one month before gilts insemination is an efficient measure which prevents intrauterine infection occurrence during the entire gestation process. The level of antibodies specific for PPV which is determined in gilts blood serum after vaccination can be a result of both primary and secondary immune response (animal infected before first vaccination, as well as absence of gilts revaccination, what is usually recommended by

  9. Abdominal closure reinforcement by using polypropylene mesh functionalized with poly-Ԑ-caprolactone nanofibers and growth factors for prevention of incisional hernia formation

    Directory of Open Access Journals (Sweden)

    Plencner M

    2014-07-01

    architecture mimics the natural extracellular matrix. We tested a biodegradable polyester poly-Ԑ-caprolactone in the form of nanofibers as a scaffold for fascia healing in an abdominal closure-reinforcement model for prevention of incisional hernia formation. Both in vitro tests and an experiment on a rabbit model showed promising results. Keywords: nanofibers, growth factors, surgical mesh, hernia regeneration, in vivo

  10. Mediastinal tumors

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  11. Tumor lysis syndrome in children

    International Nuclear Information System (INIS)

    Suarez, Amaranto

    2004-01-01

    Tumor lysis syndrome is a metabolic emergency characterized by electrolyte alteration with or without acute renal failure. It occurs mainly in patients with malignant tumors that have a high growth fraction, or after cytotoxic therapy, as a result of the massive degradation of malignant cells and the release of high amounts of intracellular elements that exceed the capacity of renal excretion. The objective of the treatment is the prevention of nephropathy due to uric acid deposits, and the correction of metabolic acidosis and electrolyte alterations. This paper reviews the incidence, the physiopathology, and the treatment of tumor lysis syndrome in children

  12. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

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

  13. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  14. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  15. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  16. Chemokines in tumor proximal fluids.

    Science.gov (United States)

    Kotyza, Jaromir

    2017-03-01

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

  17. Phase 1 trial of ontuxizumab (MORAb-004) in children with relapsed or refractory solid tumors: A report from the Children's Oncology Group Phase 1 Pilot Consortium (ADVL1213).

    Science.gov (United States)

    Norris, Robin E; Fox, Elizabeth; Reid, Joel M; Ralya, Andrew; Liu, Xiaowei W; Minard, Charles; Weigel, Brenda J

    2018-05-01

    Ontuxizumab is a humanized IgG monoclonal antibody that targets the cell-surface glycoprotein endosialin (tumor endothelial marker-1[TEM-1]/CD248) found on activated mesenchymal cells and certain tumors. Ontuxizumab binding to endosialin may interfere with platelet-derived growth factor signaling, prevent tumor stroma organization, and prevent new vessel formation. Ontuxizumab was administered intravenously on days 1, 8, 15, and 22 of a 28-day cycle at three dose levels (4, 8, and 12 mg/kg). Further dose escalation to 16 mg/kg was planned if the maximum tolerated dose (MTD) was not reached and the ontuxizumab systemic clearance was ≥30% higher in children compared to adults. Following determination of the MTD/recommended phase 2 dose, an additional cohort of six patients (children with relapsed or refractory solid tumors. The PK of ontuxizumab does not appear to be significantly different in children compared to adults. © 2018 Wiley Periodicals, Inc.

  18. Adequate antigen availability: a key issue for novel approaches to tumor vaccination and tumor immunotherapy.

    Science.gov (United States)

    Accolla, Roberto S; Tosi, Giovanna

    2013-03-01

    A crucial parameter for activation of the anti-tumor immune response is an adequate antigen availability (AAA) defined here as the optimal tumor antigen dose and related antigen processing and MHC-II-restricted presentation necessary to efficiently trigger tumor-specific TH cells. We will discuss two distinct experimental systems: a) a preventive anti-tumor vaccination system; b) a therapy-induced anti-tumor vaccination approach. In the first case tumor cells are rendered constitutively MHC-II+ by transfecting them with the MHC-II transcriptional activator CIITA. Here AAA is generated by the function of tumor's newly expressed MHC-II molecules to present tumor-associated antigens to tumor-specific TH cells. In the second case, AAA is generated by treating established tumors with neovasculature-targeted TNFα. In conjuction with Melphalan, targeted TNFα delivery produces extensive areas of tumor necrosis that generate AAA capable of optimally activate tumor-specific TH cells which in turn activate CTL immune effectors. In both experimental systems tumor rejection and persistent and long-lived TH cell anti-tumor memory, responsible of defending the animals from subsequent challenges with tumor cells, are achieved. Based on these and other investigators' results we propose that AAA is a key element for triggering adaptive immune functions resulting in subversion from a pro-tumor to an anti-tumor microenvironment, tumor rejection and acquisition of anti-tumor immune memory. Hypotheses of neuro-immune networks involved in these approaches are discussed. These considerations are important also for the comprehension of how chemotherapy and/or radiation therapies may help to block and/or to eradicate the tumor and for the construction of suitable anti-tumor vaccine strategies.

  19. Encouraging early preventive dental visits for preschool-aged children enrolled in Medicaid: using the extended parallel process model to conduct formative research.

    Science.gov (United States)

    Askelson, Natoshia M; Chi, Donald L; Momany, Elizabeth; Kuthy, Raymond; Ortiz, Cristina; Hanson, Jessica D; Damiano, Peter

    2014-01-01

    Preventive dental visits for preschool-aged children can result in better oral health outcomes, especially for children from lower income families. Many children, however, still do not see a dentist for preventive visits. This qualitative study examined the potential for the Extended Parallel Process Model (EPPM) to be used to uncover potential antecedents to parents' decisions about seeking preventive dental care. Seventeen focus groups including 41 parents were conducted. The focus group protocol centered on constructs (perceived severity, perceived susceptibility, perceived self-efficacy, and perceived response efficacy) of the EPPM. Transcripts were analyzed by three coders who employed closed coding strategies. Parents' perceptions of severity of dental issues were high, particularly regarding negative health and appearance outcomes. Parents perceived susceptibility of their children to dental problems as low, primarily because most children in this study received preventive care, which parents viewed as highly efficacious. Parents' self-efficacy to obtain preventive care for their children was high. However, they were concerned about barriers including lack of dentists, especially dentists who are good with young children. Findings were consistent with EPPM, which suggests this model is a potential tool for understanding parents' decisions about seeking preventive dental care for their young children. Future research should utilize quantitative methods to test this model. © 2012 American Association of Public Health Dentistry.

  20. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  1. Tumor bioengineering using a transglutaminase crosslinked hydrogel.

    Directory of Open Access Journals (Sweden)

    Josephine Y Fang

    Full Text Available Development of a physiologically relevant 3D model system for cancer research and drug development is a current challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel to mimic the tumor 3D microenvironment. The system has several unique advantages over other alternatives including presenting cell-matrix interaction sites from collagen-derived peptides, geometry-initiated multicellular tumor spheroids, and metabolic gradients in the tumor microenvironment. Also it provides a controllable wide spectrum of gel stiffness for mechanical signals, and technical compatibility with imaging based screening due to its transparent properties. In addition, the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals enhancing tumor cell uptake rate. Overall, this distinctive 3D system could offer a platform to more accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo.

  2. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  3. Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+phenotype: a promising target for preventing progression of TNBC.

    Science.gov (United States)

    Brugnoli, Federica; Grassilli, Silvia; Lanuti, Paola; Marchisio, Marco; Al-Qassab, Yasamin; Vezzali, Federica; Capitani, Silvano; Bertagnolo, Valeria

    2017-09-04

    The malignant potential of triple negative breast cancer (TNBC) is also dependent on a sub-population of cells with a stem-like phenotype. Among the cancer stem cell markers, CD133 and EpCAM strongly correlate with breast tumor aggressiveness, suggesting that simultaneous targeting of the two surface antigens may be beneficial in treatment of TNBC. Since in TNBC-derived cells we demonstrated that PLC-β2 induces the conversion of CD133 high to CD133 low cells, here we explored its possible role in down-modulating the expression of both CD133 and EpCAM and, ultimately, in reducing the number of TNBC cells with a stem-like phenotype. A magnetic step-by-step cell isolation with antibodies directed against CD133 and/or EpCAM was performed on the TNBC-derived MDA-MB-231 cell line. In the same cell model, PLC-β2 was over-expressed or down-modulated and cell proliferation and invasion capability were evaluated by Real-time cell assays. The surface expression of CD133, EpCAM and CD44 in the different experimental conditions were measured by multi-color flow cytometry immunophenotyping. A CD133 + /EpCAM + sub-population with high proliferation rate and invasion capability is present in the MDA-MB-231 cell line. Over-expression of PLC-β2 in CD133 + /EpCAM + cells reduced the surface expression of both CD133 and EpCAM, as well as proliferation and invasion capability of this cellular subset. On the other hand, the up-modulation of PLC-β2 in the whole MDA-MB-231 cell population reduced the number of cells with a CD44 + /CD133 + /EpCAM + stem-like phenotype. Since selective targeting of the cells with the highest aggressive potential may have a great clinical importance for TNBC, the up-modulation of PLC-β2, reducing the number of cells with a stem-like phenotype, may be a promising goal for novel therapies aimed to prevent the progression of aggressive breast tumors.

  4. Tumors and tumor-like lesions of the heart valves

    Directory of Open Access Journals (Sweden)

    Jacob Lavee

    2009-12-01

    Full Text Available Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5% valvular lesions were papillary fibroelastomas, one (9.1% was myxoma, 2 (18.2% were organized thrombi, and 3 (27.3% were calcification lesions. There was a total of 5 (45.5% atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5% semilunar valvular lesions were from the aortic valve. One (9.1% lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events.

  5. Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis.

    Science.gov (United States)

    Choi, Suk Hyun; Lee, Jue Yeon; Suh, Jin Sook; Park, Yoon Shin; Chung, Chong Pyoung; Park, Yoon Jeong

    Angiogenesis plays a critical role in the growth and metastasis of cancer, and growth factors released from cancer promote blood-vessel formation in the tumor microenvironment. The angiogenesis is accelerated via interactions of growth factors with the high-affinity receptors on cancer cells. In particular, heparan sulfate proteoglycans (HSPGs) on the surface of cancer cells have been shown to be important in many aspects of determining a tumor's phenotype and development. Specifically, the regulation of the interactions between HSPGs and growth factors results in changes in tumor progression. A peptide with heparin-binding (HBP) activity has been developed and synthesized to inhibit tumor growth via the prevention of angiogenesis. We hypothesized that HBP could inhibit the interaction of growth factors and HSPGs on the surface of cancer cells, decrease paracrine signaling in endothelial cells (ECs), and finally decrease angiogenesis in the tumor microenvironment. In this study, we found that HBP had antiangiogenic effects in vitro and in vivo. The conditioned media obtained from a breast cancer cell line treated with HBP were used to culture human umbilical vein ECs (HUVECs) to evaluate the antiangiogenic effect of HBP on ECs. HBP effectively inhibited the migration, invasion, and tube formation of HUVECs in vitro. In addition, the expressions of angiogenesis-mediating factors, including ERK, FAK, and Akt, were considerably decreased. HBP also decreased the levels of invasive factors, including MMP2 and MMP9, secreted by the HUVECs. We demonstrated significant suppression of tumor growth in a breast cancer xenograft model and enhanced distribution of HBP at the site of tumors. Taken together, our results show that HBP has antiangiogenic effects on ECs, and suggest that it may serve as a potential antitumor agent through control of the tumor microenvironment.

  6. Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth

    Science.gov (United States)

    Xie, Qifa; Gan, Lu; Wang, Jianxia; Wilson, Ingred; Li, Liwu

    2010-01-01

    IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M−/− mice are resistant to tumor growth upon inoculation with transplantable tumor cells. Immune cells from IRAK-M−/− mice are responsible for the anti-tumor effect, since adoptive transfer of splenocytes from IRAK-M−/− mice to wild type mice can transfer the tumor-resistant phenotype. Upon tumor cell challenge, there are elevated populations of CD4+ and CD8+ T cells and a decreased population of CD4+ CD25+Foxp3+ regulatory T cells in IRAK-M −/− splenocytes. Furthermore, we observe that IRAK-M deficiency leads to elevated proliferation and activation of T cells and B cells. Enhanced NFκB activation directly caused by IRAK-M deficiency may explain elevated activation of T and B cells. In addition, macrophages from IRAK-M−/− mice exhibit enhanced phagocytic function toward acetylated LDL and apoptotic thymocytes. Collectively, we demonstrate that IRAK-M is directly involved in the regulation of both innate and adaptive immune signaling processes, and deletion of IRAK-M enhances host anti-tumor immune response. PMID:17477969

  7. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  8. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  9. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  10. Prevention of adhesion formation in Wistar-albino rats by increased bowel movements achieved with oral Ricinus oil use for 8 days postoperatively: an experimental study.

    Science.gov (United States)

    Kahyaoglu, Serkan; Timur, Hakan; Kaba, Metin; Kahyaoglu, Inci; Sirvan, Levent; Cicek, Mahmut Nedim

    2012-12-01

    Adhesion formation frequently occurs after abdominopelvic surgery and can cause significant morbidity for patients. Meticulous hemostasis, minimal access surgery and utilization of surgical adjuvants intraoperatively are clinically useful measures to minimize adhesion formation. We investigated the clinical efficiency of oral Ricinus oil treatment for 8 days postoperatively to decrease adhesion formation in this case-control study in a rat model. Following computer-generated randomization, 24 female Wistar-albino rats were operated on, with 10 standard cautery lesions on the right uterine horn and two simple suture lesions on left uterine horn generated with absorbable material. Half (n=12) the rats received 0.13 g (0.2 ml) Ricinus oil emulsion (40 g/60 ml) via the oral route during the first 8 days postoperatively, and the remaining rats (n=11) were considered as controls. The extent, severity, degree, total adhesion scores and histopathological features of the adhesions were the main outcome measures. The degree and total adhesion formation scores in the Ricinus oil group and control group revealed significant differences in adhesion extent and severity. The total adhesion scores of the Ricinus oil and control groups were 3.00 ± 2.21 and 5.18 ± 2.78 respectively (P0.05). Ricinus oil treatment following abdominopelvic surgery for the 8-day period that covers the completion of tissue healing process may be a promising, cheap and cost-effective treatment strategy for patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Biopsy in Musculoskeletal Tumors

    Directory of Open Access Journals (Sweden)

    Mohammad Gharehdaghi

    2014-09-01

    other anatomic structures? (4 Carcinomas are homogeneous, and a simple CNB is usually sufficient for diagnosis, but in soft tissue sarcomas, the periphery of the tumor is the growing part and usually represents the authentic underlying malignancy. The center of the tumor may be hemorrhagic or necrotic, thus taking biopsy from this part may distract from the correct diagnosis.Extraosseus part of a bone sarcoma is as representative as bony component of the tumor. Violating the bone and weakening the cortex may predispose it to pathologic fracture, so biopsy of an extraosseus part is sufficient for the diagnosis if present (3. The biopsy tract “open or CNB” is contaminated by tumor cells and should be widely excised if a wide excision or amputation is performed. For this reason, excision of the biopsy incision or needle entrance should be planned along with the definitive tumor excision to prevent complications and the need for altering the treatment strategy (Figure A, B, C. Open incisional biopsy provides sufficient material for microscopic diagnosis as well as immune- histochemical, cytogenetic, or electron microscopic studies. It has some disadvantages such as wound healing problems, infection, tumor cell contamination, and nerve and vessel injuries (1. For open biopsies, the incision should be as small as necessary and longitudinal. Transverse incisions are not advisable. To perform an intraosseus biopsy, the window should be circular or oblong, and as small as needed to prevent a pathologic fracture. Closing this window by PMMA prevents tumor cell contamination. Compressing the PMMA exceeds the chance of metastasis. As a rule, culture what you biopsy and biopsy what you culture. Use of a tourniquet without exsanguinations helps better visualization and meticulous hemostasis which prevents spreading of the tumor cells in hematoma. Importantly, it should be deflated before closing the wound (3. The port of entry of drains, if necessary, must be in line and

  12. Sustained Angiopoietin-2 Expression Disrupts Vessel Formation and Inhibits Glioma Growth

    Directory of Open Access Journals (Sweden)

    Ok-Hee Lee

    2006-05-01

    Full Text Available Systematic analyses of the expression of angiogenic regulators in cancer models should yield useful information for the development of novel therapies for malignant gliomas. In this study, we analyzed tumor growth, vascularization, and angiopoietin-2 (Ang2 expression during the development of U-87 MG xenografts. We found that tumoral angiogenesis in this model follows a multistage process characterized by avascular, prolific peripheral angiogenesis, and late vascular phases. On day 4, we observed an area of central necrosis, a peripheral ring of Ang2-positive glioma cells, and reactive Ang2-positive vascular structures in the tumor/brain interface. When the tumor had developed a vascular network, Ang2 was expressed only in peripheral vascular structures. Because Ang2 expression was downmodulated in the late stages of development, probably to maintain a stable tumoral vasculature, we next studied whether sustained Ang2 expression might impair vascular development and, ultimately, tumor growth. Ang2 prevented the formation of capillary-like structures and impaired angiogenesis in a chorioallantoic membrane chicken model. Finally, we tested the effect of sustained Ang2 expression on U-87 MG xenograff development. Ang2 significantly prolonged the survival of intracranial U-87 MG tumor-bearing animals. Examination of Ang2treated xenograffs revealed areas of tumor necrosis and vascular damage. We therefore conclude that deregulated Ang2 expression during gliomagenesis hindered successful angiogenesis and that therapies that sustain Ang2 expression might be effective against malignant gliomas.

  13. Severe acute tumor lysis syndrome in patients with germ-cell tumors

    Directory of Open Access Journals (Sweden)

    Guilherme Alvarenga Feres

    2008-01-01

    Full Text Available Germ-cell tumors are a high-proliferative type of cancer that may evolve to significant bulky disease. Tumor lysis syndrome is rarely reported in this setting. The reports of three patients with germ-cell tumors who developed severe acute tumor lysis syndrome following the start of their anticancer therapy are presented. All patients developed renal dysfunction and multiorgan failure. Patients with extensive germ-cell tumors should be kept on close clinical and laboratory monitoring. Physicians should be aware of this uncommon but severe complication and consider early admission to the intensive care unit for the institution of measures to prevent acute renal failure.

  14. Prevention: Exercise

    Medline Plus

    Full Text Available ... Osteoporosis Spondylolysis and Spondylolysthesis Injuries Spinal Cord Injuries Sports Injuries Whiplash and Whiplash Associated Disorder Infections & Tumors Spinal Infections Spinal Tumors Extradural and Intradural ...

  15. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

    Directory of Open Access Journals (Sweden)

    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  16. Uncertainces in tumor target definition using PET

    International Nuclear Information System (INIS)

    Kirov, A.

    2013-01-01

    Full text: Introduction: PET entered into the clinics for radiation therapy as a means of displaying the metabolically active part of the tumor. However this advantage, PET has a number of shortcomings that prevent its use for precise determination of the tumor boundaries. What you will learn: The aim of the lecture is to present: the requirements for the accuracy of the determination of tumor boundaries in radiation therapy; the main phenomena which bring uncertainty using PET and a brief overview of methods for segmentation of tumors and their problems

  17. Bone formation in axial spondyloarthritis.

    Science.gov (United States)

    Lories, Rik J; Haroon, Nigil

    2014-10-01

    The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Unreduced gamete formation in wheat × Aegilops spp. hybrids is genotype specific and prevented by shared homologous subgenomes.

    Science.gov (United States)

    Fakhri, Zhaleh; Mirzaghaderi, Ghader; Ahmadian, Samira; Mason, Annaliese S

    2016-05-01

    The presence of homologous subgenomes inhibited unreduced gamete formation in wheat × Aegilops interspecific hybrids. Unreduced gamete rates were under the control of the wheat nuclear genome. Production of unreduced gametes is common among interspecific hybrids, and may be affected by parental genotypes and genomic similarity. In the present study, five cultivars of Triticum aestivum and two tetraploid Aegilops species (i.e. Ae. triuncialis and Ae. cylindrica) were reciprocally crossed to produce 20 interspecific hybrid combinations. These hybrids comprised two different types: T. aestivum × Aegilops triuncialis; 2n = ABDU(t)C(t) (which lack a common subgenome) and T. aestivum × Ae. cylindrica; 2n = ABDD(c)C(c) (which share a common subgenome). The frequency of unreduced gametes in F1 hybrids was estimated in sporads from the frequency of dyads, and the frequency of viable pollen, germinated pollen and seed set were recorded. Different meiotic abnormalities recorded in the hybrids included precocious chromosome migration to the poles at metaphase I and II, laggards in anaphase I and II, micronuclei and chromosome stickiness, failure in cell wall formation, premature cytokinesis and microspore fusion. The mean frequency of restitution meiosis was 10.1 %, and the mean frequency of unreduced viable pollen was 4.84 % in T. aestivum × Ae. triuncialis hybrids. By contrast, in T. aestivum × Ae. cylindrica hybrids no meiotic restitution was observed, and a low rate of viable gametes (0.3 %) was recorded. This study present evidence that high levels of homologous pairing between the D and D(c) subgenomes may interfere with meiotic restitution and the formation of unreduced gametes. Variation in unreduced gamete production was also observed between T. aestivum × Ae. triuncialis hybrid plants, suggesting genetic control of this trait.

  19. Ossifying renal tumor of infancy

    International Nuclear Information System (INIS)

    El-Husseini, Tareq K.; Al-Orf, Ali M.; Egail, Siddig A.; Mostert, C.

    2005-01-01

    Ossifying renal tumor of infancy ORTI is a benign neoplasm, which presents with gross hematuria and less frequently as an abdominal mass, histologically it comprises a large cell with an epithelial nature and osteoid formation. We report a case of a 10-month-old girl who developed ORTI as non-opacified upper calyces of left kidney on excretory urography. We outlined the calcific and tumors nature of the lesion by ultrasound and computed tomography. The macroscopic and histological features were pathognomonic. (author)

  20. Combination of grafted Schwann cells and lentiviral-mediated prevention of glial scar formation improve recovery of spinal cord injured rats.

    Science.gov (United States)

    Do-Thi, Anh; Perrin, Florence E; Desclaux, Mathieu; Saillour, Paulette; Amar, Lahouari; Privat, Alain; Mallet, Jacques

    2016-10-01

    The present study was intended to combine three therapeutic approaches in a well-defined rat model of spinal cord injury, a lateral hemisection at thoracic level. A guidance channel was implanted at the lesion site. This channel was seeded with native Schwann cells or Schwann cells that had been previously transduced with a lentiviral vector carrying the GDNF gene. Thereafter, these experiences were reproduced in animals injected with lentiviral vectors carrying a shRNA for GFAP (Lv-shGFAP), which has recently been shown to block glial scar formation. Functional evaluations showed that Lv-shGFAP induced a significant improvement in recovery in animals grafted with Schwann cells. Histological studies demonstrated the outgrowth of axons in the guidance channel containing Schwann cells transduced or not with GDNF. This axonal growth was enhanced in rats receiving Lv-shGFAP vector. Also, a significant increase of serotonergic innervation of the injured hemicord, distal to the lesion, was found only in animals treated with Lv-shGFAP vectors. Importantly, this study confirms that glial scar formation is a major impediment for axonal sprouting after spinal cord injury, and emphasizes the importance of serotonergic innervation for locomotor function. Moreover we show a significant additive effect of a combinatorial approach to axonal regeneration in the injured spinal cord. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Use of a Fibrinogen/Thrombin-Based Collagen Fleece (TachoComb, TachoSil) With a Stapled Closure to Prevent Pancreatic Fistula Formation Following Distal Pancreatectomy.

    Science.gov (United States)

    Mita, Kazuhito; Ito, Hideto; Murabayashi, Ryo; Asakawa, Hideki; Nabetani, Masashi; Kamasako, Akira; Koizumi, Kazuya; Hayashi, Takashi

    2015-12-01

    Postoperative pancreatic fistula formation remains a source of significant morbidity following distal pancreatectomy. The aim of this study was to evaluate the rate of clinically significant fistulas (International Study Group on Pancreatic Fistula grade B and grade C) after distal pancreatectomy using a fibrinogen/thrombin-based collagen fleece (TachoComb, TachoSil) with a stapled closure. Seventy-five patients underwent distal pancreatectomy at our institution between January 2005 and March 2014. A fibrinogen/thrombin-based collagen fleece was applied to the staple line of the pancreas before stapling. Twenty-six patients (34.7%) developed a pancreatic fistula, 8 patients (10.7%) developed a grade B fistula, and no patients developed a grade C fistula. The duration of the drain was significantly different in patients with or without a pancreatic fistula (8.0 ± 4.5 vs. 5.4 ± 1.3 days, P = .0003). Histological analysis showed that there was a tight covering with the fibrinogen/thrombin-based collagen fleece. The fibrinogen/thrombin-based collagen fleece (TachoComb, TachoSil) with a stapled closure has low rates of fistula formation and provides a safe alternative to the conventional stapled technique in distal pancreatectomy. © The Author(s) 2015.

  2. EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model

    Science.gov (United States)

    Yang, Su-Geun; Tsauo, Jiaywei; Kim, Kun Yung; Kim, Min Tae; Gang, Sung Gwon; Kim, Dae-Kee; Kim, Dong-Hyun; Song, Ho-Young

    2018-01-01

    Purpose To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS) for suppressing granulation tissue formation after stent placement in a canine urethral model. Materials and methods All experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS) group received NFCSs and the drug stent (DS) group received EW-7197 (1000 μg)-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test. Results Stent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p 0.05). Conclusion The EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model. PMID:29447198

  3. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2017-03-01

    Full Text Available In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR. Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM. Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

  4. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Lee, Chang Hoon; Yoon, Kwon-Ha; Lee, Myeung Su

    2017-03-07

    In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca 2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca 2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

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

    Science.gov (United States)

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

    1996-08-01

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

  6. Granular cell tumor of the orbit.

    Science.gov (United States)

    Salour, Hossein; Tavakoli, Mehdi; Karimi, Saeed; Rezaei Kanavi, Mozhgan; Faghihi, Mohammad

    2013-10-01

    To report a case of granular cell tumor as a rare orbital pathology. A 50-year-old female presented with a 4-year history of diplopia, right ocular displacement and a firm nontender mass in her right lower lid. Computed tomography (CT) scan of the orbit disclosed a well-defined mass in the right inferior orbit involving the right inferior rectus. Subtotal excision of the mass was performed, and histopathologic and immunohistochemical studies revealed granular cell tumor. Subsequently, the tumor recurred and exenteration was required as multiple sessions of radiotherapy failed to prevent the residual tumor from growing. Granular cell tumor, though very rare in the orbit, should be considered in patients with orbital masses especially in cases with involvement of the inferior rectus muscle. Infiltrative tumors may be impossible to completely resect and can rapidly recur following surgery.

  7. Granular Cell Tumor of the Orbit

    Directory of Open Access Journals (Sweden)

    Hossein Salour

    2013-01-01

    Full Text Available Purpose: To report a case of granular cell tumor as a rare orbital pathology. Case report: A 50-year-old female presented with a 4-year history of diplopia, right ocular displacement and a firm nontender mass in her right lower lid. Computed tomography (CT scan of the orbit disclosed a well-defined mass in the right inferior orbit involving the right inferior rectus. Subtotal excision of the mass was performed, and histopathologic and immunohistochemical studies revealed granular cell tumor. Subsequently, the tumor recurred and exenteration was required as multiple sessions of radiotherapy failed to prevent the residual tumor from growing. Conclusion: Granular cell tumor, though very rare in the orbit, should be considered in patients with orbital masses especially in cases with involvement of the inferior rectus muscle. Infiltrative tumors may be impossible to completely resect and can rapidly recur following surgery.

  8. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  9. Production of a low calorie mandarin juice by enzymatic conversion of constituent sugars to oligosaccharides and prevention of insoluble glucan formation.

    Science.gov (United States)

    Nguyen, Thi Thanh Hanh; Cho, Jae-Young; Seo, Ye-Seul; Woo, Hye-Jin; Kim, Hwa-Kyoung; Kim, Ghahyun J; Jhon, Deok-Young; Kim, Doman

    2015-03-01

    Over 99% of sucrose in mandarin juice (57.1 g/l in original juice to 428.4 g/l in concentrated juice) was enzymatically converted to glucooligosaccharides using 3 U dextransucrase/ml prepared from Leuconostoc mesenteroides at 28 °C. The oligosaccharide synthesis yields were 51 and 47% for the original and the concentrated mandarin juice, respectively. The degree of polymerization of oligosaccharides in the enzyme-modified juice was 2-7. Calories in the original and modified mandarin juice were 433 and 301 kcal/l (30.5% reduction). Compared with the original juice, the enzyme-modified juice showed 82% decrease of insoluble glucan formation by mutansucrase from Streptococcus mutans. A sensory evaluation of the juices revealed that the original and modified mandarin juices had sweetness values of 4.5 and 4.9 and the same values for overall acceptability.

  10. The efficacy of different anti-microbial metals at preventing the formation of, and eradicating bacterial biofilms of pathogenic indicator strains.

    Science.gov (United States)

    Gugala, Natalie; Lemire, Joe A; Turner, Raymond J

    2017-06-01

    The emergence of multidrug-resistant pathogens and the prevalence of biofilm-related infections have generated a demand for alternative anti-microbial therapies. Metals have not been explored in adequate detail for their capacity to combat infectious disease. Metal compounds can now be found in textiles, medical devices and disinfectants-yet, we know little about their efficacy against specific pathogens. To help fill this knowledge gap, we report on the anti-microbial and antibiofilm activity of seven metals: silver, copper, titanium, gallium, nickel, aluminum and zinc against three bacterial strains, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. To evaluate the capacity of metal ions to prevent the growth of, and eradicate biofilms and planktonic cells, bacterial cultures were inoculated in the Calgary Biofilm Device (minimal biofilm eradication concentration) in the presence of the metal salts. Copper, gallium and titanium were capable of preventing planktonic and biofilm growth, and eradicating established biofilms of all tested strains. Further, we observed that the efficacies of the other tested metal salts displayed variable efficacy against the tested strains. Further, contrary to the enhanced resistance anticipated from bacterial biofilms, particular metal salts were observed to be more effective against biofilm communities versus planktonic cells. In this study, we have demonstrated that the identity of the bacterial strain must be considered before treatment with a particular metal ion. Consequent to the use of metal ions as anti-microbial agents to fight multidrug-resistant and biofilm-related infections increases, we must aim for more selective deployment in a given infectious setting.

  11. Glimepiride reduces the expression of PrPc, prevents PrPSc formation and protects against prion mediated neurotoxicity in cell lines.

    Directory of Open Access Journals (Sweden)

    Clive Bate

    Full Text Available BACKGROUND: A hallmark of the prion diseases is the conversion of the host-encoded cellular prion protein (PrP(C into a disease related, alternatively folded isoform (PrP(Sc. The accumulation of PrP(Sc within the brain is associated with synapse loss and ultimately neuronal death. Novel therapeutics are desperately required to treat neurodegenerative diseases including the prion diseases. PRINCIPAL FINDINGS: Treatment with glimepiride, a sulphonylurea approved for the treatment of diabetes mellitus, induced the release of PrP(C from the surface of prion-infected neuronal cells. The cell surface is a site where PrP(C molecules may be converted to PrP(Sc and glimepiride treatment reduced PrP(Sc formation in three prion infected neuronal cell lines (ScN2a, SMB and ScGT1 cells. Glimepiride also protected cortical and hippocampal neurones against the toxic effects of the prion-derived peptide PrP82-146. Glimepiride treatment significantly reduce both the amount of PrP82-146 that bound to neurones and PrP82-146 induced activation of cytoplasmic phospholipase A(2 (cPLA(2 and the production of prostaglandin E(2 that is associated with neuronal injury in prion diseases. Our results are consistent with reports that glimepiride activates an endogenous glycosylphosphatidylinositol (GPI-phospholipase C which reduced PrP(C expression at the surface of neuronal cells. The effects of glimepiride were reproduced by treatment of cells with phosphatidylinositol-phospholipase C (PI-PLC and were reversed by co-incubation with p-chloromercuriphenylsulphonate, an inhibitor of endogenous GPI-PLC. CONCLUSIONS: Collectively, these results indicate that glimepiride may be a novel treatment to reduce PrP(Sc formation and neuronal damage in prion diseases.

  12. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  13. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  14. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  15. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  16. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  17. Erastin-Like Anti-Warburg Agents Prevent Mitochondrial Depolarization Induced by Free Tubulin and Decrease Lactate Formation in Cancer Cells.

    Science.gov (United States)

    DeHart, David N; Lemasters, John J; Maldonado, Eduardo N

    2018-01-01

    In Warburg metabolism, suppression of mitochondrial metabolism contributes to a low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of metabolites across the mitochondrial outer membrane occurs through voltage-dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces VDAC closure and dynamically regulates mitochondrial membrane potential (ΔΨ). Erastin, a small molecule that binds to VDAC, antagonizes the inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact cells. Here, our aim was to identify novel compounds from the ChemBridge DIVERSet library that block the inhibitory effect of tubulin on ΔΨ using cell-based screening. HCC4006 cells were treated with nocodazole (NCZ) to increase free tubulin and decrease ΔΨ in the presence or absence of library compounds. Tetramethylrhodamine methylester (TMRM) fluorescence was assessed by high-content imaging to determine changes in ΔΨ. Compounds were considered positive if ΔΨ increased in the presence of NCZ. Using confocal microscopy, we identified and validated six lead molecules that antagonized the depolarizing effect of NCZ. Lead compounds and erastin did not promote microtubule stabilization, so changes in ΔΨ were independent of tubulin dynamics. The most potent lead compound also decreased lactate formation. These novel small molecules represent a potential new class of anti-Warburg drugs.

  18. Herbal Extracts Combination (WNK Prevents Decline in Spatial Learning and Memory in APP/PS1 Mice through Improvement of Hippocampal Aβ Plaque Formation, Histopathology, and Ultrastructure

    Directory of Open Access Journals (Sweden)

    Wei-hong Cong

    2012-01-01

    Full Text Available To investigate the cognitive enhancement effect of WNK, an extracts combination of P. ginseng,  G. biloba, and C. sativus L. and possible mechanisms, 5-month-old APP/PS1 transgenic mice were used in this study. After 3 months of administration, all mice received Morris water maze (MWM training and a probe test. Mouse brain sections were detected by immunohistochemistry, HE staining, and transmission electron microscopy. MWM results showed significant difference between transgenic mice and nontransgenic littermates (P<0.05, P<0.01. WNK-treated mice exhibited enhanced maze performance over the training progression, especially better spatial memory retention in probe test compared to transgenic mice (P<0.05, P<0.01 and better spatial learning and memory at the fourth day of MWM test compared to EGB761- (G. biloba extract- treated ones (P<0.05. Hippocampal Aβ plaque burden significantly differed between APP/PS1 and littermate mice (P<0.001, while decreased Aβ plaque appeared in WNK- or EGB761-treated transgenic brains (P<0.05. Neurodegenerative changes were evident from light microscopic and ultrastructural observations in transgenic brains, which were improved by WNK or EGB761 treatment. These data indicate WNK can reduce the decline in spatial cognition, which might be due to its effects on reducing Aβ plaque formation and ameliorating histopathology and ultrastructure in hippocampus of APP/PS1 mouse brain.

  19. The use of autologous platelet-leukocyte-enriched plasma to minimize drain burden and prevent seroma formation in latissimus dorsi breast reconstruction.

    Science.gov (United States)

    Harper, J Garrett; Elliott, L Franklyn; Bergey, Patti

    2012-05-01

    Seromas and drains are major sources of morbidity associated with latissimus dorsi breast reconstruction. Our goal was to look at an autologous platelet-leukocyte-enriched plasma spray and to assess its efficacy in reducing drain burden and seroma formation. We performed a single surgeon, patient-controlled, blinded study on bilateral latissimus dorsi breast reconstruction patients in which we applied autologous platelet-leukocyte-enriched plasma to one side and measured drain amounts, time to drain removal, and seroma rate. Twelve patients were included in this study. The average age was 41.1 years, and the average body mass index was 21.6 kg/m. Average volume of drain output showed neither difference (789 mL spray side vs. 790 mL control side) nor average time to drain removal (11.83 days spray side vs. 11.5 days control side). There were 2 complications reported: 1 hematoma (8.33%) and 1 seroma (8.33%) that required aspiration in a postoperative visit. It appears after 12 patients that there is no demonstrable difference regarding drain output, time to drain removal, or seroma incidence between the study and the control group. We feel a larger study population would add power and confirm these findings.

  20. Dietary feeding of freeze-dried whole cranberry inhibits intestinal tumor development in Apcmin/+ mice

    Science.gov (United States)

    Dong, Wenxiao; Zhang, Yujie; Wang, Sinan; Xie, Runxiang; Wang, Bangmao; Cao, Hailong

    2017-01-01

    It is increasingly perceived that dietary components have been linked with the prevention of intestinal cancer. Cranberry is a rich source of phenolic constituents and non-digestible fermentable dietary fiber, which shows anti-proliferation effect in colorectal cancer cells. Herein, we investigated the efficacy of long-term cranberry diet on intestinal adenoma formation in Apcmin/+ mice. Apcmin/+ mice were fed a basal diet or a diet containing 20% (w/w) freeze-dried whole cranberry powder for 12 weeks, and the number and size of tumors were recorded after sacrifice. Our results showed that cranberry strongly prevented the growth of intestinal tumors by 33.1%. Decreased cell proliferation and increased apoptosis were observed in tumors of cranberry-fed mice. Cranberry diet reduced the expression profile of colonic inflammatory cytokines (IFN-γ, IL-1β and TNF-α) accompanied with increased levels of anti-inflammatory cytokines (IL-4 and IL-10). Moreover, the number of colonic goblet cells and MUC2 production were increased, and the intestinal barrier function was also improved. In addition, cranberry diet increased caecal short chain fatty acids concentrations, and down-regulated epidermal growth factor receptor signaling pathway. These data firstly show the efficacy and associated mechanisms of cranberry diet on intestinal tumor growth in Apcmin/+ mice, suggesting its chemopreventive potential against intestinal cancer. PMID:29228651

  1. Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy schedules

    International Nuclear Information System (INIS)

    Anthony, P.; Keys, H.; Evarts, C.M.; Rubin, P.; Lush, C.

    1987-01-01

    Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As of February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. It historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients

  2. A systematic nurse-led approach to withdrawal risk screening, prevention and treatment among inpatients with an alcohol use disorder in an ear, nose, throat and jaw surgery department-A formative evaluation.

    Science.gov (United States)

    Leuenberger, Deborah Linda; Fierz, Katharina; Hinck, Andreas; Bodmer, Daniel; Hasemann, Wolfgang

    2017-02-01

    Among patients with head and neck cancer comorbid alcohol use disorder is frequent which contributes to higher risk of developing perioperative alcohol withdrawal syndrome/delirium or delirium due to medical conditions. Although guidelines emphasize prevention and treatment of alcohol withdrawal in hospitalized patients, a validated systematic approach for management of these patients is still lacking. Our aim was to formatively evaluate our newly developed systematic approach in view of nurses' adherence to screening patients for regular alcohol consumption and managing their withdrawal symptoms using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised. We conducted a formative evaluation to improve the project's design and performance and used a retrospective chart review in a consecutive sample of all adult inpatients with head and neck cancer being assigned for surgery in a university hospital. Our bundle of interventions consisted of nurses' screenings for regular alcohol consumption, withdrawal risk assessment, offering patients a substitution therapy, nurses' assessments of withdrawal symptoms and symptom oriented withdrawal management. Proximate endpoints were analyzed descriptively at each component of the bundle in terms of frequencies and severity of withdrawal symptoms, frequencies of nurses' and doctors' screenings and nurses' assessments performed as required. Between 2013 and 2014, 87 inpatients met inclusion criteria and screenings by doctors/ nurses revealed 49 alcohol consumers, where six screenings were omitted by nurses and six by doctors. Twenty-one consumers were at risk and six of them developed an alcohol withdrawal syndrome. None of the 87 showed an alcohol withdrawal delirium, but five developed a delirium due to medical conditions. Nurses correctly conducted all preventive elements of the intervention bundle in 14 (58%) patients at risk but overall, only performed 50% of the required assessments. Although nurses safely

  3. Melanoma prevention by MC1R selective small peptide analogs of alpha MSH | Division of Cancer Prevention

    Science.gov (United States)

    This revised application will test the hypothesis that small peptide analogs of ¿-melanocortin (¿-MSH) that are selective agonists of the melanocortin 1 receptor (MC1R) will prevent melanoma tumor formation in transgenic mouse melanoma models by enhancing repair of ultraviolet radiation (UV)-induced DNA damage and stimulating melanogenesis. We have pioneered the research on the MC1R and its agonist ¿-melanocyte stimulating hormone (¿-MSH), and discovered their role in reducing the extent of UV-induced DNA damage by activating DNA repair and antioxidant pathways. |

  4. von Hippel-Lindau disease: surveillance strategy for endolymphatic sac tumors

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael

    2011-01-01

    : Up to 16% of patients with the hereditary von Hippel-Lindau disease develop endolymphatic sac tumors of the inner ear. Early diagnosis and treatment of endolymphatic sac tumors can prevent audiovestibular morbidity, but optimal endolymphatic sac tumor surveillance strategy has yet to be determi...... to be determined. We aimed to evaluate endolymphatic sac tumor surveillance to determine the best surveillance strategy.......: Up to 16% of patients with the hereditary von Hippel-Lindau disease develop endolymphatic sac tumors of the inner ear. Early diagnosis and treatment of endolymphatic sac tumors can prevent audiovestibular morbidity, but optimal endolymphatic sac tumor surveillance strategy has yet...

  5. Choking Prevention

    Science.gov (United States)

    ... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations At Home ...

  6. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  7. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  8. 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

    Science.gov (United States)

    Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

    2016-12-01

    Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  10. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  11. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  12. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  13. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.; Dillmann, K.; Roth, C.; Backens, M.; Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie

    2007-06-15

    Magnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamartoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common subforms, especially of astrocytoma, will also be presented. (orig.)

  14. The Inhibition of Stat5 by a Peptide Aptamer Ligand Specific for the DNA Binding Domain Prevents Target Gene Transactivation and the Growth of Breast and Prostate Tumor Cells

    Science.gov (United States)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2013-01-01

    The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA) ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX) scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment. PMID:24276378

  15. The Inhibition of Stat5 by a Peptide Aptamer Ligand Specific for the DNA Binding Domain Prevents Target Gene Transactivation and the Growth of Breast and Prostate Tumor Cells

    Directory of Open Access Journals (Sweden)

    Vida Vafaizadeh

    2013-08-01

    Full Text Available The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment.

  16. Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice.

    Science.gov (United States)

    Wang, Xue; Wang, Jin; Wu, Wenbin; Li, Hongjun

    2016-11-01

    Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24 h later to interfere with the formation/recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.

  17. Adenomatoid odontogenic tumor in mandibular region

    International Nuclear Information System (INIS)

    Sanchez Cabrales, Ernesto; Vila Morales, Dadonim; Felipe Garmendia, Angel Mario; Serra Ortega, Alain; Torres Gomez de Cadiz, Alma

    2010-01-01

    The adenomatoid odontogenic tumor is an uncommon neoplasm derivative of the odontogenic epithelium containing canalicular structures with inductor modifications of variable intensity in the conjunctival tissue. It is a slow growth lesion and no much invasive but that may to be similar to other odontogenic lesions more aggressive including the dentigerous cyst and the ameloblastoma among others. Its classical location (upper canine area) guides us to diagnosis and its duct histological pattern is very typical of this tumor. Other tumors included in this group are the ameloblastic fibroma, the ameloblastic odontoma, the calcified odontogenic cyst and composed and complex odontomas. This group of lesions may or not to have formations of hard tissue inside. Thus, authors present the case of a patient presenting with this type of tumor making a histopathology study, a literature review on this benign odontogenic tumor and its clinical radiographic features, treatment, as well as the differential diagnoses to be into account. (author)

  18. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  19. [Wilms tumor in hemihypertrophy].

    Science.gov (United States)

    Sauer, O; Wemmer, U

    1977-04-07

    The case of a 4-year-old boy with Wilms' tumor and hemihypertrophy is described. Wilms' tumors are frequently associated with congenital malformations of the urinary tract, with aniridia and hemihypertrophy. Hemihypertrophy is a relatively rare malformation (1:14000) in the common population, but in patients with Wilms' tumors its frequency is about 1:49. Besides Wilms' tumors tumors of the adrenal cortex and hepatoblastomas are frequently observed together with hemihypertrophy.

  20. Update on Malignant Sweat Gland Tumors.

    Science.gov (United States)

    van der Horst, Michiel P J; Brenn, Thomas

    2017-06-01

    Malignant sweat gland tumors are rare cutaneous neoplasms, traditionally separated according to their behavior into low- and high-grade malignant. There is significant morphologic overlap, and outright malignant tumors may show relatively bland histologic features. They may, therefore, be mistaken easily for benign neoplasms. Recognition of these tumors and accurate diagnosis is important for early treatment to prevent aggressive behavior and adverse outcome. This article provides an overview of 4 important entities with emphasis on diagnostic pitfalls, differential diagnosis and recent developments. Microcystic adnexal carcinoma, squamoid eccrine ductal carcinoma, aggressive digital papillary adenocarcinoma, and spiradenocarcinoma are discussed in detail. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Tumors and tumor-like lesions

    International Nuclear Information System (INIS)

    Koesling, S.; Stoevesandt, D.; Knipping, S.

    2007-01-01

    Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There is a great variety of histological types, but only a small number of morphological patterns on imaging. Histology is an important point in therapeutic planning. In most cases it is obtained by sampling, which is not as difficult in the sinonasal area as in other regions of the body. The main task of imaging is an exact estimation of the extent and spread of a lesion. This article discusses the possibilities and limitations of CT and MRI in the assessment of the dignity and spread of paranasal tumors and tumor-like lesions in consideration of necessary therapeutic information. Additionally, an overview of features on imaging of different paranasal tumors and tumor-like lesions is given. (orig.)

  2. Broad targeting of angiogenesis for cancer prevention and therapy.

    Science.gov (United States)

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M; Arreola, Alexandra; Rathmell, W Kimryn; Generali, Daniele; Nagaraju, Ganji P; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I; Azmi, Asfar S; Bilsland, Alan; Keith, W Nicol; Jensen, Lasse D

    2015-12-01

    pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Glomus Tumor of the Hand

    Directory of Open Access Journals (Sweden)

    Won Lee

    2015-05-01

    Full Text Available BackgroundGlomus tumors were first described by Wood in 1812 as painful subcutaneous tubercles. It is an uncommon benign neoplasm involving the glomus body, an apparatus that involves in thermoregulation of cutaneous microvasculature. Glomus tumor constitutes 1%-5% of all hand tumors. It usually occurs at the subungual region and more commonly in aged women. Its classical clinical triad consists of pain, tenderness and temperature intolerance, especially cold sensitivity. This study reviews 15 cases of glomus tumor which were analyzed according to its anatomic location, surgical approach and histologic findings.MethodsFifteen patients with subungual glomus tumors of the hand operated on between January 2006 and March 2013, were retrospectively reviewed. Patients were evaluated preoperatively with standard physical examination including ice cube test and Love's test. Diagnostic imaging consisted of ultrasonography, computed tomography, and magnetic resonance imaging. All procedures were performed with tourniquet control under local anesthesia. Eleven patients underwent excision using the transungual approach, 3 patients using the volar approach and 1 patient using the lateral subperiosteal approach.ResultsTotal of 15 cases were reviewed. 11 tumors were located in the nail bed, 3 in the volar pulp and 1 in the radial aspect of the finger tip. After complete excision, patients remained asymptomatic in the immediate postoperative period. In the long term follow up, patients exhibited excellent cosmetic results with no recurrence.ConclusionsAccurate diagnosis should be made by physical, radiologic and pathologic examinations. Preoperative localization and complete extirpation is essential in preventing recurrence and subsequent nail deformity.

  4. MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Tinder, T L; Sterner, C J; Gendler, S J

    2001-03-01

    We have reported previously that MUC1 transgenic mice with spontaneous tumors of the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1-specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451-3460, 2000). From these MET mice, we have isolated, expanded, and cloned naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vbeta chains 5.1/5.2, 11, 13, and 2 and Valpha chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem repeat with highest affinity to APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a single Vbeta chain of 5.1/5.2 and Valpha2. It recognizes only the H-2Db class I-restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were effective in eradicating MUC1-expressing injected tumor cells including mammary gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation. To our knowledge, this is the first evidence that demonstrates that the naturally occurring MUC1-specific CTLs isolated from one tumor model has antitumor effects on other MUC1-expressing tumors in vivo. Therefore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.

  5. Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

    Directory of Open Access Journals (Sweden)

    Pelliccia Angela

    2007-10-01

    Full Text Available Abstract Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens

  6. Investigating Contingency Risk Factors of Brain Tumor in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    A Nazemi

    2014-12-01

    Conclusion: According to research results, several preventable and predictable factors are linked to pediatric brain tumors. Therefore, children prone to brain tumors are recommended to be examined and screened for these risk factors.

  7. A study of spinal cord tumors by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio.

    1989-01-01

    We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author)

  8. Desmoid tumor of bone with enchondromatous nodules, mistaken for chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Department of Orthopaedic Surgery, Uijongbu St. Mary' s Hospital, 65-1 Geumohdong, Uijongbu, Gyunggido, 480-130 (Korea); Kang, Yong-Koo; Lee, An-Hee [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Mirra, Joseph M. [Orthpaedic Oncology, Orthopaedic Hospital, Los Angeles, CA (United States)

    2003-04-01

    Desmoid tumor of bone, also termed desmoplastic fibroma or aggressive fibromatosis, is a rare, locally aggressive fibroblastic tumor. We present a 16-year-old male with a huge desmoid tumor involving the iliac wing. It was associated with enchondromatous nodules mimicking malignancy. The tumor in this patient was mistaken for chondrosarcoma and hemipelvectomy was performed. To our knowledge, such a case has not previously been documented fully in the English literature. The radiographic and pathologic findings and a possible mechanism of enchondromatous nodule formation in fibrous bone tumors are discussed. (orig.)

  9. Fever and abdominal tumoral masses

    Directory of Open Access Journals (Sweden)

    Augustin C. Dima

    2016-04-01

    Full Text Available 49 year-old man presented to our clinic for pain in the right hypochondrium, diarrhea, and fever. The clinical examination highlights a tumoral formation in the right side of the abdomen, with firm consistency, poorly defined margins, and present mobility in the deep structures. On biological exams, leukocytosis with neutrophilia, inflammatory syndrome, and hypoalbuminaemia were identified. The first computed tomography exam described parietal thickening of the ascending colon, with infiltrative aspect, and multiple local adenopathies, lomboaortic and interaortocave. Moreover, four nodular liver tumors, with hypodense image in native examination, were identified. The lab tests for infectious diseases were all inconclusives: three hemocultures, three stool samples, and three coproparasitological exams were all negatives. Interdisciplinary examinations, internal medicine and infectious diseases, sustained the diagnosis of colonic neoplasm with peritumoral abscess and liver pseudo-tumoral masses. The colonoscopy did not revealed any bowel lesions relevant for neoplasia. This result as well as the bio-clinical context imposed abstention from surgical intervention. Wide spectrum antibiotics and symptomatic treatment were initiated. But, ten days after hospitalization, the second computed tomography exam showed reduction of the ascending colon wall thickness associated with significant increases of the liver tumors is so revealed. The investigations for other possible etiologies were so continued.

  10. Hepatic tumors in children.

    Science.gov (United States)

    Stocker, J T

    2001-02-01

    Although they account for only 1% to 4% of solid tumors in children, hepatic tumors and pseudotumors offer a diagnostic challenge to the clinician seeing only an occasional case. Metastatic lesions such as neuroblastoma, Wilms' tumor, and lymphoma are the most common neoplasm seen in the liver, but 10 distinct primary tumors and pseudotumors of the liver occur with some regularity, and a few others may be seen rarely, including leiomyosarcoma, rhabdoid tumor, and endodermal sinus tumor. Five of these neoplasms--hepatoblastoma, infantile hemangio-endothelioma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, and embryonal rhabdomyosarcoma of the biliary tree--occur only in children and are the major focus of the article.

  11. Mathematical models of cytotoxic effects in endpoint tumor cell line assays: critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats.

    Science.gov (United States)

    Calhelha, Ricardo C; Martínez, Mireia A; Prieto, M A; Ferreira, Isabel C F R

    2017-10-23

    The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling

  12. Barriers and facilitators to the implementation of antenatal syphilis screening and treatment for the prevention of congenital syphilis in the Democratic Republic of Congo and Zambia: results of qualitative formative research.

    Science.gov (United States)

    Nkamba, Dalau; Mwenechanya, Musaku; Kilonga, Arlette Mavila; Cafferata, Maria Luisa; Berrueta, Amanda Mabel; Mazzoni, Agustina; Althabe, Fernando; Garcia-Elorrio, Ezequiel; Tshefu, Antoniette K; Chomba, Elwyn; Buekens, Pierre M; Belizan, Maria

    2017-08-14

    The impact of untreated syphilis during pregnancy on neonatal health remains a major public health threat worldwide. Given the high prevalence of syphilis during pregnancy in Zambia and Democratic Republic of Congo (DRC), the Preventive Congenital Syphilis Trial (PCS Trial), a cluster randomized trial, was proposed to increase same-day screening and treatment of syphilis during antenatal care visits. To design an accepted and feasible intervention, we conducted a qualitative  formative research. Our objective was to identify context-specific  barriers and facilitators to the implementation of antenatal screening and treatment during pregnancy. Qualitative research included in-depth semi-structured interviews with clinic administrators, group interviews with health care providers, and focus groups with pregnant women in primary care clinics (PCCs) in Kinshasa (DRC) and Lusaka (Zambia). A total of 112 individuals participated in the interviews and focus groups. Barriers for the implementation of syphilis testing and treatment were identified at the a) system level: fragmentation of the health system, existence of ANC guidelines in conflict with proposed intervention, poor accessibility of clinics (geographical and functional), staff and product shortages at the PCCs; b) healthcare providers' level: lack of knowledge and training about evolving best practices, reservations regarding same-day screening and treatment; c) Pregnant women level: late enrollment in ANC, lack of knowledge about consequences and treatment of syphilis, and stigma. Based on these results, we developed recommendations for the design of the PCS Trial intervention. This research allowed us to identify barriers and facilitators to improve the feasibility and acceptability of a behavioral intervention. Formative research is a critical step in designing appropriate and effective interventions by closing the "know-do gap".

  13. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    Science.gov (United States)

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B-LYN-p85 complex, which increased PI3K-Akt-mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice. Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Rape prevention

    Science.gov (United States)

    Date rape - prevention; Sexual assault - prevention ... Centers for Disease Control and Prevention website. Sexual assault and abuse and STDs. In: 2015 sexually transmitted diseases treatment guidelines 2015. www.cdc.gov/std/tg2015/sexual- ...

  15. Dengue Prevention

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Prevention Recommend on Facebook Tweet Share Compartir This photograph ... medications to treat a dengue infection. This makes prevention the most important step, and prevention means avoiding ...

  16. Aggressive malignant phyllodes tumor

    OpenAIRE

    Nathan Roberts; Dianne M. Runk

    2015-01-01

    Introduction: Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumo...

  17. Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

    Directory of Open Access Journals (Sweden)

    Wu Xianli

    2009-09-01

    Full Text Available Abstract Background Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB on formation of aberrant crypt foci (ACF in colons of male Fisher F344 rats (inbred strain. However, effects of BB on colon tumors and in both genders are unknown. Methods We examined efficacy of BB in inhibition of azoxymethane (AOM-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain. Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. Results Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P P P > 0.05 to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1 by BB. There was a tendency (0.1 > P > 0.05 for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P P Conclusion Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma by BB.

  18. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It ... KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous .... layer of the colon. The tumor cells are strongly positive to chromagranin and AE1/AE3. Features are those of carcinoid tumor of the colon. She was ...

  19. Granular Cell Tumor

    African Journals Online (AJOL)

    Necrosis within the tumor was absent, no mitosis was. Granular cell tumors are seldom diagnosed identified in the section and the edges of the accurately clinically. The lesion in this case was sample were tumor free (Figure 2). mistaken for a sebaceous cyst and following ulceration resembled carcinoma of the vulvar.

  20. Malignant tumors of childhood

    International Nuclear Information System (INIS)

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children

  1. Soft tissue mixed tumor

    Directory of Open Access Journals (Sweden)

    Eiichi Hiraishi

    2009-12-01

    Full Text Available Mixed tumors are relatively common in the skin and salivary glands, but extremely rare in soft tissues, often resulting in diagnostic problems. The occurrence of these tumors in the hand is especially limited. In this article we report the clinical, radiological, and histological features of a mixed tumor of the hypothenar region of the right hand.

  2. Tumor interstitial fluid

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

    2013-01-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secr...

  3. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It ... KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous .... layer of the colon. The tumor cells are strongly positive to chromagranin and AE1/AE3. Features are those of carcinoid tumor of the colon. She was ...

  4. Stellar formation

    CERN Document Server

    Reddish, V C

    1978-01-01

    Stellar Formation brings together knowledge about the formation of stars. In seeking to determine the conditions necessary for star formation, this book examines questions such as how, where, and why stars form, and at what rate and with what properties. This text also considers whether the formation of a star is an accident or an integral part of the physical properties of matter. This book consists of 13 chapters divided into two sections and begins with an overview of theories that explain star formation as well as the state of knowledge of star formation in comparison to stellar structure

  5. Plague Prevention

    Science.gov (United States)

    ... Healthcare Professionals Clinicians Public Health Officials Veterinarians Prevention History of Plague Resources FAQ Prevention Recommend on Facebook Tweet Share Compartir Reduce rodent habitat around your ...

  6. Curcumin and Turmeric Modulate the Tumor-Promoting Effects of Iron In Vitro.

    Science.gov (United States)

    Messner, Donald J; Robinson, Todd; Kowdley, Kris V

    2017-04-01

    Free or loosely chelated iron has tumor-promoting properties in vitro. Curcumin, a polyphenol derived from the food spice turmeric (Curcuma longa), is a potent antioxidant that binds iron. The primary aim of this study was to investigate whether curcuminoids prevent tumor-promoting effects of iron in T51B cells, a non-neoplastic rat liver epithelial cell line. Purified curcuminoids (curcumin) or a standardized turmeric extract similarly reduced oxidative stress and cytotoxicity associated with iron overload (IC 50 values near 10 μM, P turmeric for 16 wk in culture; subsequently assayed by soft agar colony formation) was nearly complete at 20 μM of total curcuminoids (P turmeric extract were taken up better by cells, had a longer half-life, and appeared more effective in blocking tumor promotion (P < 0.01), suggesting enhanced curcuminoid delivery to cells in culture. The primary finding that curcuminoids can inhibit tumor promotion caused by iron in T51B cells is tempered by evidence for an underlying increase in neoplastic transformation at lower concentrations.

  7. Agrobacterium tumefaciens promotes tumor induction by modulating pathogen defense in Arabidopsis thaliana.

    Science.gov (United States)

    Lee, Chil-Woo; Efetova, Marina; Engelmann, Julia C; Kramell, Robert; Wasternack, Claus; Ludwig-Müller, Jutta; Hedrich, Rainer; Deeken, Rosalia

    2009-09-01

    Agrobacterium tumefaciens causes crown gall disease by transferring and integrating bacterial DNA (T-DNA) into the plant genome. To examine the physiological changes and adaptations during Agrobacterium-induced tumor development, we compared the profiles of salicylic acid (SA), ethylene (ET), jasmonic acid (JA), and auxin (indole-3-acetic acid [IAA]) with changes in the Arabidopsis thaliana transcriptome. Our data indicate that host responses were much stronger toward the oncogenic strain C58 than to the disarmed strain GV3101 and that auxin acts as a key modulator of the Arabidopsis-Agrobacterium interaction. At initiation of infection, elevated levels of IAA and ET were associated with the induction of host genes involved in IAA, but not ET signaling. After T-DNA integration, SA as well as IAA and ET accumulated, but JA did not. This did not correlate with SA-controlled pathogenesis-related gene expression in the host, although high SA levels in mutant plants prevented tumor development, while low levels promoted it. Our data are consistent with a scenario in which ET and later on SA control virulence of agrobacteria, whereas ET and auxin stimulate neovascularization during tumor formation. We suggest that crosstalk among IAA, ET, and SA balances pathogen defense launched by the host and tumor growth initiated by agrobacteria.

  8. Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

    DEFF Research Database (Denmark)

    Andersen, Marie; Ruhwald, Morten; Thorn, Mette

    2003-01-01

    , suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides......Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after...... immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take...

  9. Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

    DEFF Research Database (Denmark)

    Andersen, Marie; Ruhwald, Morten; Thorn, Mette

    2003-01-01

    Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after...... immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take......, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides...

  10. TLR2-dependent induction of IL-10 and Foxp3+ CD25+ CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo.

    Directory of Open Access Journals (Sweden)

    Sayuri Yamazaki

    Full Text Available 16 S-[2,3-bis(palmitoylpropyl]cysteine (Pam2 lipopeptides act as toll-like receptor (TLR2/6 ligands and activate natural killer (NK cells and dendritic cells (DCs to produce inflammatory cytokines and cytotoxic NK activity in vitro. However, in this study, we found that systemic injection of Pam2 lipopeptides was not effective for the suppression of NK-sensitive B16 melanomas in vivo. When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner. The Pam2 lipopeptides increased the frequencies of Foxp3(+CD4(+ regulatory T (T reg cells in a TLR2- and IL-10- dependent manner. The T reg cells from Pam2-lipopeptide injected mice maintained suppressor activity. Pam2 lipopeptides, plus the depletion of T reg with an anti-CD25 monoclonal antibody, improved tumor growth compared with Pam2 lipopeptides alone. In conclusion, our data suggested that systemic treatment of Pam2 lipopeptides promoted IL-10 production and T reg function, which suppressed the effective induction of anti-tumor immunity in vivo. It is necessary to develop an adjuvant that does not promote IL-10 and T reg function in vivo for the future establishment of an anti-cancer vaccine.

  11. Cholecystokinin expression in tumors

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2016-01-01

    Cholecystokinin (CCK) is a classic gut hormone. CCK is also a complex system of peptides expressed in several molecular forms in enteroendocrine I cells, in cerebral and peripheral neurons, in cardiac myocytes and spermatozoa. CCK gene expression has now been found at protein or peptide level...... in different neuroendocrine tumors; cerebral gliomas and astrocytomas and specific pediatric tumors. Tumor hypersecretion of CCK was recently reported in a patient with a metastatic islet cell tumor and hypercholecystokininemia resulting in a novel tumor syndrome, the cholecystokininoma syndrome. This review...

  12. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

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

  13. Tumor-Penetrating Peptides

    Science.gov (United States)

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

    2013-01-01

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

  14. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  15. Dual-function synthetic peptide derived from BMP4 for highly efficient tumor targeting and antiangiogenesis

    Directory of Open Access Journals (Sweden)

    Choi SH

    2016-09-01

    Full Text Available Suk Hyun Choi,1,* Jue Yeon Lee,2,* Jin Sook Suh,1 Yoon Shin Park,3 Chong Pyoung Chung,2 Yoon Jeong Park1 1Department of Dental Regenerative Biotechnology, Dental Research Institute, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, School of Dentistry, Seoul National University, Seoul, 3Department in Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, South Korea *These authors contributed equally to this work Abstract: Angiogenesis plays a critical role in the growth and metastasis of cancer, and growth factors released from cancer promote blood-vessel formation in the tumor microenvironment. The angiogenesis is accelerated via interactions of growth factors with the high-affinity receptors on cancer cells. In particular, heparan sulfate proteoglycans (HSPGs on the surface of cancer cells have been shown to be important in many aspects of determining a tumor’s phenotype and development. Specifically, the regulation of the interactions between HSPGs and growth factors results in changes in tumor progression. A peptide with heparin-binding (HBP activity has been developed and synthesized to inhibit tumor growth via the prevention of angiogenesis. We hypothesized that HBP could inhibit the interaction of growth factors and HSPGs on the surface of cancer cells, decrease paracrine signaling in endothelial cells (ECs, and finally decrease angiogenesis in the tumor microenvironment. In this study, we found that HBP had antiangiogenic effects in vitro and in vivo. The conditioned media obtained from a breast cancer cell line treated with HBP were used to culture human umbilical vein ECs (HUVECs to evaluate the antiangiogenic effect of HBP on ECs. HBP effectively inhibited the migration, invasion, and tube formation of HUVECs in vitro. In addition, the expressions of angiogenesis-mediating factors, including ERK, FAK, and Akt, were considerably

  16. Estradiol-induced regression in T47D:A18/PKCalpha tumors requires the estrogen receptor and interaction with the extracellular matrix.

    Science.gov (United States)

    Zhang, Yiyun; Zhao, Huiping; Asztalos, Szilard; Chisamore, Michael; Sitabkhan, Yasmin; Tonetti, Debra A

    2009-04-01

    Several breast cancer tumor models respond to estradiol (E(2)) by undergoing apoptosis, a phenomenon known to occur in clinical breast cancer. Before the application of tamoxifen as an endocrine therapy, high-dose E(2) or diethystilbesterol treatment was successfully used, albeit with unfavorable side effects. It is now recognized that such an approach may be a potential endocrine therapy option. We have explored the mechanism of E(2)-induced tumor regression in our T47D:A18/PKCalpha tumor model that exhibits autonomous growth, tamoxifen resistance, and E(2)-induced tumor regression. Fulvestrant, a selective estrogen receptor (ER) down-regulator, prevents T47D:A18/PKCalpha E(2)-induced tumor growth inhibition and regression when given before or after tumor establishment, respectively. Interestingly, E(2)-induced growth inhibition is only observed in vivo or when cells are grown in Matrigel but not in two-dimensional tissue culture, suggesting the requirement of the extracellular matrix. Tumor regression is accompanied by increased expression of the proapoptotic FasL/FasL ligand proteins and down-regulation of the prosurvival Akt pathway. Inhibition of colony formation in Matrigel by E(2) is accompanied by increased expression of FasL and short hairpin RNA knockdown partially reverses colony formation inhibition. Classic estrogen-responsive element-regulated transcription of pS2, PR, transforming growth factor-alpha, C3, and cathepsin D is independent of the inhibitory effects of E(2). A membrane-impermeable E(2)-BSA conjugate is capable of mediating growth inhibition, suggesting the involvement of a plasma membrane ER. We conclude that E(2)-induced T47D:A18/PKCalpha tumor regression requires participation of ER-alpha, the extracellular matrix, FasL/FasL ligand, and Akt pathways, allowing the opportunity to explore new predictive markers and therapeutic targets.

  17. Extract of Perilla frutescens inhibits tumor proliferation of HCC via ...

    African Journals Online (AJOL)

    In this study, isoegomaketone(IK) was isolated from Perilla frutescens(L.), a Chinese herbal. The effects of IK were examined by cell viability assay, colony formation assay, xenograft tumor assay and western blotting in HCC cells. We found that IK inhibited cell viability, and its administration decreased tumor volume and ...

  18. Soil formation.

    NARCIS (Netherlands)

    Breemen, van N.; Buurman, P.

    1998-01-01

    Soil Formation deals with qualitative and quantitative aspects of soil formation (or pedogenesis) and the underlying chemical, biological, and physical processes. The starting point of the text is the process - and not soil classification. Effects of weathering and new formation of minerals,

  19. Integrin-Associated CD151 Drives ErbB2-Evoked Mammary Tumor Onset and Metastasis

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2012-08-01

    Full Text Available ErbB2+ human breast cancer is a major clinical problem. Prior results have suggested that tetraspanin CD151 might contribute to ErbB2-driven breast cancer growth, survival, and metastasis. In other cancer types, CD151 sometimes supports tumor growth and metastasis. However, a definitive test of CD151 effects on de novo breast cancer initiation, growth, and metastasis has not previously been done. We used CD151 gene-deleted mice expressing the MMTV-ErbB2 transgene to show that CD151 strongly supports ErbB2+ mammary tumor initiation and metastasis. Delayed tumor onset (by 70–100 days in the absence of CD151 was accompanied by reduced survival of mammary epithelial cells and impaired activation of FAK- and MAPK-dependent pathways. Both primary tumors and metastatic nodules showed smooth, regular borders, consistent with a less invasive phenotype. Furthermore, consistent with impaired oncogenesis and decreased metastasis, CD151-targeted MCF-10A/ErbB2 cells showed substantial decreases in three-dimensional colony formation, EGF-stimulated tumor cell motility, invasion, and transendothelial migration. These CD151-dependent functions were largely mediated through α6β4 integrin. Moreover, CD151 ablation substantially prevented PKC- and EGFR/ERK-dependent α6β4 integrin phosphorylation, consistent with retention of epithelial cell polarity and intermediate filament cytoskeletal connections, which helps to explain diminished metastasis. Finally, clinical data analyses revealed a strong correlation between CD151 and ErbB2 expression and metastasis-free survival of breast cancer patients. In conclusion, we provide strong evidence that CD151 collaborates with LB integrins (particularly α6β4 and ErbB2 (and EGFR receptors to regulate multiple signaling pathways, thereby driving mammary tumor onset, survival, and metastasis. Consequently, CD151 is a useful therapeutic target in malignant ErbB2+ breast cancer.

  20. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... markers . Most malignant germ cell tumors release tumor markers. The following tumor markers are used to detect extracranial germ cell tumors: ... testicular germ cell tumors, blood levels of the tumor markers help show if the tumor is a seminoma ...

  1. Activation of Apoptotic Signal in Endothelial Cells through Intracellular Signaling Molecules Blockade in Tumor-Induced Angiogenesis

    Directory of Open Access Journals (Sweden)

    Hossein Bazmara

    2015-01-01

    Full Text Available Tumor-induced angiogenesis is the bridge between avascular and vascular tumor growth phases. In tumor-induced angiogenesis, endothelial cells start to migrate and proliferate toward the tumor and build new capillaries toward the tumor. There are two stages for sprout extension during angiogenesis. The first stage is prior to anastomosis, when single sprouts extend. The second stage is after anastomosis when closed flow pathways or loops are formed and blood flows in the closed loops. Prior to anastomosis, biochemical and biomechanical signals from extracellular matrix regulate endothelial cell phenotype; however, after anastomosis, blood flow is the main regulator of endothelial cell phenotype. In this study, the critical signaling pathways of each stage are introduced. A Boolean network model is used to map environmental and flow induced signals to endothelial cell phenotype (proliferation, migration, apoptosis, and lumen formation. Using the Boolean network model, blockade of intracellular signaling molecules of endothelial cell is investigated prior to and after anastomosis and the cell fate is obtained in each case. Activation of apoptotic signal in endothelial cell can prevent the extension of new vessels and may inhibit angiogenesis. It is shown that blockade of a few signaling molecules in endothelial cell activates apoptotic signal that are proposed as antiangiogenic strategies.

  2. Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

    Science.gov (United States)

    Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

    2017-03-28

    Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

  3. Tumor detection with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.

    1984-01-01

    The most common primary ocular tumor in adults is malignant melanoma of the choroid. Metastatic tumors to the choroid occur with the same frequency. The radioactive phosphorous uptake test is used most often as a nuclear diagnostic test. The test does not differentiate melanomas from metastases, and it is necessary to perform surgery for proper placement of a detection device within a distance of 1-2 mm of the tumor. These deficiencies leave ophthalmologists with a pressing need for a gamma-emitting radiopharmaceutical that would facilitate noninvasive identification of choroidal melanoma. This need is made more urgent by the fact that recently, radiation therapy has been used to treat these tumors rather than enucleation. Eyes then harbor irradiated melanoma whose status is unknown. The tumor rarely decreases in size more than 25% to 50%. There is thus a need for a specific diagnostic test to assess the nature of the tumor and the effectiveness of therapy

  4. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  5. Imaging of pancreatic tumors

    International Nuclear Information System (INIS)

    Brambs, Hans-Juergen; Juchems, Markus

    2010-01-01

    Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

  6. Preparation and characterization of platinum(II) and (IV) complexes of 1,3-diaminepropane and 1,4-diaminebutane: circumvention of cisplatin resistance and DNA interstrand cross-link formation in CH1cisR ovarian tumor cells.

    Science.gov (United States)

    Alvarez-Valdés, Amparo; Pérez, José Manuel; López-Solera, Isabel; Lannegrand, Raúl; Continente, José Manuel; Amo-Ochoa, Pilar; Camazón, María José; Solans, Xavier; Font-Bardía, Mercè; Navarro-Ranninger, Carmen

    2002-04-25

    The reaction of Pt(dimethyl sulfoxide)(2)CBDCA (CBDCA = 1,1-cyclobutanedicarboxylate) with 1,4-diaminebutane and 1,3-diaminepropane ligands yields, under certain conditions, new [Pt(diamine)(2)]CBDCA complexes (1a,b), where the CBDCA ligand has been removed from the coordination sphere of the platinum atom by the diamine ligand, instead of forming the expected [Pt(diamine)CBDCA] complexes (1'a,b). The structure of complexes 1a and 1'b was solved by X-ray diffraction. Complex 1a crystallizes in the orthorhombic system, in the noncentrosymmetric C222 space group, with unit cell parameters: a = 20.053(2) A; b = 8.655(2) A, c = 5.711(3) A; V = 991.2(6) A(3); delta (calcd) = 1.627 mg/m(3); and R = 0.050. The Pt atom displays an unexpected distorted tetrahedral coordination with a N-Pt-N inner bond angle equal to 81(2) degrees for N atoms of the same 1,3-propanediamine ligand and a N-Pt-N bond angle for different ligands equal to 135.4(9) degrees. Complex 1'b crystallizes in the monoclinic system, in the centrosymmetric P2(1)/c space group, with unit cell parameters: a = 6.007(2) A; b = 15.336(4) A, c = 13.232(5) A; beta = 101.90(3) degrees; V = 1192.8(7) A(3); delta (calcd) = 2.369 mg/m(3); and R = 0.067. Cytotoxicity data show that of all the synthesized compounds, only complexes 1'a and 1'b exhibit remarkable cytotoxic properties. Thus, in contrast with carboplatin (cis-diammine-1,1-cyclobutane dicarboxilatoplatinum(II)), compounds 1'a and 1'b, which also contain the CBDCA ligand, are able to circumvent cisplatin (cis-diamminedichloroplatinum(II)) resistance in several tumor cells. Moreover, after 24 h of incubation of CH1cisR ovarian tumor cells with 10 microM of compounds 1'a and 1'b, the level of DNA interstrand cross-links (ICLs) induced by compounds 1'a and 1'b is 3.3 and 3.8 times higher, respectively, than that of carboplatin and 3.5 and 4.0 times higher, respectively, than that of cisplatin. Interestingly, under the same conditions, the intracellular

  7. Central nervous system tumors

    International Nuclear Information System (INIS)

    Curran, W.J. Jr.

    1991-01-01

    Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

  8. Aggressive malignant phyllodes tumor.

    Science.gov (United States)

    Roberts, Nathan; Runk, Dianne M

    2015-01-01

    Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3-0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10-30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumor will recur locally or metastasize. Distinguishing this subset of malignant phyllodes tumor is paramount. We present a case of malignant phyllodes which presented with metastatic disease. What is fascinating about this case is not only the initial presentation but also the aggressiveness of this variation of phyllodes tumor. The patient initially presented with a large mass which encompassed her whole right breast. On surgical pathology the mass measured roughly 31cm in diameter and weighed over 10kg. Within 5 weeks from surgery the patient had suffered brain metastases and also 6 local recurrent tumors. The patient passed roughly 11 weeks after her first visit to our office. Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. TUMORES ANEXIALES Y EMBARAZO

    OpenAIRE

    Tapia M.,Mauricio; Orellana H.,Ricardo; Cisterna C.,Patricio; Gazitúa P.,Raimundo; Sepúlveda A.,Rodrigo

    2005-01-01

    Objetivo: Evaluar la frecuencia de tumores anexiales en el embarazo, la histología tumoral y los resultados perinatales. Pacientes y método: Análisis retrospectivo de 33 pacientes con diagnóstico de tumor anexial y embarazo atendidas en el Servicio de Obstetricia del Hospital San Juan de Dios entre febrero de 2001 a julio de 2004. Resultados: La asociación tumor anexial y embarazo fue 1 en 424 embarazos. El tipo histológico más frecuente fue el cistoadenoma seroso (19,2%). La cirugía no alter...

  10. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  11. Adenomatoid odontogenic tumor, an uncommon tumor

    Directory of Open Access Journals (Sweden)

    K Vasudevan

    2012-01-01

    Full Text Available Here we report a case of adenomatoid odontogenic tumor (AOT in the maxilla in a young girl aged 14 years and its surgical management. We also review the literature and variations in the nomenclature and classifications of this interesting tumor. The review of literature gives an interesting picture regarding terminologies in the past and dilemma in classifying this tumor. The introduction of the name adenomatoid odontogenic tumour has resulted in the simpler and fruitful surgical management like enucleation and curettage with no reports of recurrences. In the past, similar lesion with the terminology like adeno ameloblastoma has resulted in unnecessary mutilating surgery. The conflicting views whether the lesion is being neoplasm or an anomalous hamartomatous growth is also being discussed.

  12. Short-term early exposure to lapatinib confers lifelong protection from mammary tumor development in MMTV-erbB-2 transgenic mice.

    Science.gov (United States)

    Ma, Zhikun; Parris, Amanda B; Xiao, Zhengzheng; Howard, Erin W; Kosanke, Stanley D; Feng, Xiaoshan; Yang, Xiaohe

    2017-01-06

    lapatinib suppressed the stemness of breast cancer cell lines, as evidenced by decreased tumorsphere formation and ALDH + cell populations. Taken together, these data demonstrate that brief treatment with EGFR/erbB-2-targeting agents before the onset of tumors may provide lifelong protection from mammary tumors, through the concurrent inhibition of erbB-2 and ER signaling pathways and consequential reprogramming. Our findings support further clinical testing to explore the benefit of shorter lapatinib exposure in the prevention of erbB-2-mediated carcinogenesis.

  13. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    Energy Technology Data Exchange (ETDEWEB)

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  14. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    Science.gov (United States)

    Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

    2013-01-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  15. A tumor profile in Patau syndrome (trisomy 13).

    Science.gov (United States)

    Satgé, Daniel; Nishi, Motoi; Sirvent, Nicolas; Vekemans, Michel; Chenard, Marie-Pierre; Barnes, Ann

    2017-08-01

    Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome. © 2017 Wiley Periodicals, Inc.

  16. Tumor carcinoide apendicular Appendiceal carcinoid tumor

    Directory of Open Access Journals (Sweden)

    Julio Vázquez Palanco

    2008-12-01

    Full Text Available El objetivo de este trabajo fue dar a conocer un interesante caso de tumor carcinoide que se presentó con cuadro clínico de apendicitis aguda. El paciente fue un varón de 8 años de edad, al cual se realizó apendicectomía a causa de una apendicitis aguda. El resultado anatomopatológico confirmó un tumor de células endocrinas (argentafinoma, tumor carcinoide en el tercio distal del órgano, que infiltraba hasta la serosa, y apendicitis aguda supurada. El paciente fue enviado a un servicio de oncohematología para tratamiento oncoespecífico. Por lo inusual de estos tumores en edades tempranas y por lo que puede representar para el niño una conducta no consecuente, decidimos presentar este caso a la comunidad científica nacional e internacional. Es extremadamente importante el seguimiento de los pacientes con apendicitis aguda y de las conclusiones del examen histológico, por lo que puede representar para el niño una conducta inadecuada en una situación como esta.The objective of this paper was to make known an interesting case of carcinoid tumor that presented a clinical picture of acute appendicitis.The patient was an eight-year-old boy that underwent appendectomy due to an acute appendicitis. The anatomopathological report confirmed an endocrine cell tumor (argentaffinoma, carcinoid tumor in the distal third of the organ that infiltrated up to the serosa, and acute suppurative appendicitis. The patient was referred to an oncohematology service for oncospecific treatment. As it is a rare tumor at early ages, and taking into account what a inconsequent behavior may represent for the child, it was decided to present this case to the national and international scientific community. The follow-up of the patients with acute appendicitis and of the conclusions of the histological examination is extremely important considering what an inadequate conduct may represent for the child in a situation like this.

  17. Preventing Addiction.

    Science.gov (United States)

    Moore, Susan Fordney

    The purpose of this paper is to provide the beginning counselor with an overview of prevention concepts. Prevention is a relatively new emphasis in community efforts to stem the rising costs of substance abuse and other high-risk behaviors. The paper discusses agent, host, and environmental prevention models and how they relate to causal theories…

  18. An exceptional collision tumor: gastric calcified stromal tumor and ...

    African Journals Online (AJOL)

    The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

  19. Prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Kew, Michael C

    2010-01-01

    Because of its frequency and grave prognosis, preventing hepatocellular carcinoma is an urgent priority. Prevention should be possible because environmental carcinogens-chronic hepatitis B and C virus infections, dietary exposure to aflatoxins, and iron overload-cause the great majority of these tumors. Chronic hepatitis B virus infection accounts for 55% of global hepatocellular carcinomas and 80% of those in the high-incidence Asia Pacific and sub-Saharan African regions. In these regions the infection that becomes chronic is predominantly acquired very early in life. A safe and effective vaccine against this virus is available and its universal inclusion in the immunization of infants has already resulted in a marked reduction of chronic infection and a 70% decrease in the occurrence of hepatocellular carcinoma in those immunized. Chronic hepatitis C virus infection is the major cause of hepatocellular carcinoma in industrialized countries. The infection is mainly acquired in adulthood and, until a vaccine becomes available, prevention will consist mainly of identifying, counselling, and treating chronically infected individuals, preventing spread of the virus by the use of safe injection practices (particularly in intravenous drug abusers), and screening all donated blood for the presence of the virus. 4.5 billion of the world.s population are exposed to dietary aflatoxins. Prevention involves treating susceptible crops to prevent fungal contamination, and handling the foodstuffs in such a way as to prevent contamination during storage. Iron overload in hereditary hemochromatosis can be prevented by repeated venesection and in African dietary iron overload by fermenting the home-brewed beer in iron-free containers.

  20. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    International Nuclear Information System (INIS)

    Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

  1. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    Pavel M.E., Baum U., Hahn E.G., Hensen J. Doxorubucin and streptozocin after failed biotherapy of Neuroendocrine tumors. Int J. Gastrointest Cancer 2005; 35 179-185. 33. Yao J.C., Phan A., Hoff P.M., et al. Targeting vas- cular endothelial growth factor in advanced carci- noid tumors: a random assignment phase II study.

  2. Keratinization in odontogenic tumors.

    Science.gov (United States)

    Regezi, J A; Courtney, R M; Kerr, D A

    1975-03-01

    The potential of odontogenic epithelium to keratinize in the form of ghost cells is demonstrated in the histologic variants of a number of odontongic tumors. Although the cells lack keratohyaline granules, they do contain abundant tonofilaments and probably represent an altered form of keratin. The presence of this material in odontogenic tumors does not appear to alter clinical occurence or clinical behavior.

  3. Ewing tumors in infants

    NARCIS (Netherlands)

    van den Berg, Henk; Dirksen, Uta; Ranft, Andreas; Jürgens, Heribert

    2008-01-01

    Malignancies in infancy are extremely rare. Ewing tumors are hardly ever noted in these children. Since it is generally assumed that malignancies in infancy have an extremely poor outcome, we wanted to investigate whether this was also the case in Ewing tumors. We identified in the Munster data

  4. Vanishing tumor in pregnancy

    Directory of Open Access Journals (Sweden)

    M V Vimal

    2012-01-01

    Full Text Available A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented.

  5. Children's Tumor Foundation

    Science.gov (United States)

    ... news and announcements in our newsletter: Children’s Tumor Foundation 120 Wall Street, 16th Floor New York, NY 10005-3904 1-800-323-7938 info@ctf.org © Children's Tumor Foundation - All rights reserved Privacy Policy

  6. Brain Tumors - Multiple Languages

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Brain Tumors URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Brain Tumors - Multiple Languages To use the sharing features on this page, ...

  7. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  8. Atypically localized glomus tumors

    Directory of Open Access Journals (Sweden)

    Meric Ugurlar

    2016-12-01

    Conclusion: When a painful mass is found in the body, glomus tumors should be kept in mind. The consideration of symptoms, including pain, temperature sensitivity, point tenderness, and discoloration, common characteristics of glomus tumors, may aid diagnosis. [Hand Microsurg 2016; 5(3.000: 112-117

  9. Pseudoanaplastic tumors of bone

    International Nuclear Information System (INIS)

    Bahk, Won-Jong; Mirra, Joseph M.

    2004-01-01

    To discuss the concept of pseudoanaplastic tumors of bone, which pathologically show hyperchromatism and marked pleomorphism with quite enlarged, pleomorphic nuclei, but with no to extremely rare, typical mitoses, and to propose guidelines for their diagnosis. From a database of 4,262 bone tumors covering from 1971 to 2001, 15 cases of pseudoanaplastic bone tumors (0.35% of total) were retrieved for clinical, radiographic and pathologic review. Postoperative follow-up after surgical treatment was at least 3 years and a maximum of 7 years. There were eight male and seven female patients. Their ages ranged from 10 to 64 years with average of 29.7 years. Pathologic diagnoses of pseudoanaplastic variants of benign bone tumors included: osteoblastoma (4 cases), giant cell tumor (4 cases), chondromyxoid fibroma (3 cases), fibrous dysplasia (2 cases), fibrous cortical defect (1 case) and aneurysmal bone cyst (1 case). Radiography of all cases showed features of a benign bone lesion. Six cases, one case each of osteoblastoma, fibrous dysplasia, aneurysmal bone cyst, chondromyxoid fibroma, giant cell tumor and osteoblastoma, were initially misdiagnosed as osteosarcoma. The remaining cases were referred for a second opinion to rule out sarcoma. Despite the presence of significant cytologic aberrations, no