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Sample records for cell-tumor fusion vaccines

  1. Identification of Novel Fusion Genes in Testicular Germ Cell Tumors.

    Science.gov (United States)

    Hoff, Andreas M; Alagaratnam, Sharmini; Zhao, Sen; Bruun, Jarle; Andrews, Peter W; Lothe, Ragnhild A; Skotheim, Rolf I

    2016-01-01

    Testicular germ cell tumors (TGCT) are the most frequently diagnosed solid tumors in young men ages 15 to 44 years. Embryonal carcinomas (EC) comprise a subset of TGCTs that exhibit pluripotent characteristics similar to embryonic stem (ES) cells, but the genetic drivers underlying malignant transformation of ECs are unknown. To elucidate the abnormal genetic events potentially contributing to TGCT malignancy, such as the existence of fusion genes or aberrant fusion transcript expression, we performed RNA sequencing of EC cell lines and their nonmalignant ES cell line counterparts. We identified eight novel fusion transcripts and one gene with alternative promoter usage, ETV6. Four out of nine transcripts were found recurrently expressed in an extended panel of primary TGCTs and additional EC cell lines, but not in normal parenchyma of the testis, implying tumor-specific expression. Two of the recurrent transcripts involved an intrachromosomal fusion between RCC1 and HENMT1 located 80 Mbp apart and an interchromosomal fusion between RCC1 and ABHD12B. RCC1-ABHD12B and the ETV6 transcript variant were found to be preferentially expressed in the more undifferentiated TGCT subtypes. In vitro differentiation of the NTERA2 EC cell line resulted in significantly reduced expression of both fusion transcripts involving RCC1 and the ETV6 transcript variant, indicating that they are markers of pluripotency in a malignant setting. In conclusion, we identified eight novel fusion transcripts that, to our knowledge, are the first fusion genes described in TGCT and may therefore potentially serve as genomic biomarkers of malignant progression. ©2015 American Association for Cancer Research.

  2. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... patterns that increase activation of the innate immune system. Importantly, viral-vectored vaccines that act through the induction of one or more of these factors also may benefit from cytokine coadministration and increased antigen presentation. In order to increase immunogenicity to the level achieved...

  3. Mouse x human heterohybridomas as fusion partners with human B cell tumors.

    Science.gov (United States)

    Carroll, W L; Thielemans, K; Dilley, J; Levy, R

    1986-05-01

    Surface idiotype (Id) of B cell malignancies is an excellent tumor-specific marker. We have, however, recently described heterogeneity of tumor Id in some cases. We therefore sought a way to isolate, reliably and efficiently, different species of idiotype from a potentially heterogeneous population. In this report we demonstrate our success using a series of mouse X human heterohybridomas as fusion partners with human B cell tumors. Three lines (K6H6/B5, K6H9/G12, SBC/H20) demonstrated excellent fusion efficiency with 75%-85% of wells plated containing hybrids. Two cell lines, K6H9/G12 and SBC/H20 had a tendency to secrete a single Ig chain (heavy or light chain), whereas the K6H6/B5 cell line secreted whole immunoglobulin (Ig) in greater than 80% of the hybrids. This line secreted significant amounts of Ig (2.73 micrograms/ml/10(6) cells) and was relatively stable in culture. Since this line has such a high fusion efficiency the products of normal B cells admixed with tumor may be recovered, allowing the opportunity of isolating host anti-tumor antibodies. In order to prove that hybrids were derived from the tumor, Southern blot analysis of rearranged DNA was performed in selected cases. Fusions with this line provide the potential for recovering many different species of idiotype in a mixed population. This will facilitate the production of mouse monoclonal anti-idiotype antibodies against many variants and against different idiotopes.

  4. Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children and young adults.

    Science.gov (United States)

    Philippe-Chomette, Pascale; Kabbara, Nabil; Andre, Nicolas; Pierron, Gaelle; Coulomb, Aurore; Laurence, Valérie; Blay, Jean-Yves; Delattre, Olivier; Schleiermacher, Gudrun; Orbach, Daniel

    2012-06-01

    The presence of the EWS-WT1 gene fusion transcript (GFT) is characteristic of desmoplastic small round cell tumor (DSRCT), a rare and very aggressive disease for which the treatment has not yet been clearly standardized. This was a retrospective national multicenter analysis of young patients <30 years with tumors expressing the EWS-WT1-GFT, designed to determine whether extensive surgery had an impact on survival. Between 1995 and 2006, a EWS-WT1-GFT was detected in the tumors of 38 patients, 17 (44.7%) of whom had had a different initial pathologic diagnosis prior to molecular testing. Mean age was 13.2 years (range: 4-29.7 years). Only 9 patients (24%) had localized disease. Treatment was heterogeneous. Nine patients had "limited" surgical resections and 22 underwent "extensive" surgery. Two-year event-free survival and overall survival were 14.4% and 50%, respectively. Among the five patients who were alive in complete remission, four had undergone extensive and complete surgery. Detection of the EWS-WT1-GFT plays a major role in the diagnosis of DSRCT. No survival difference was observed according to extent of surgery, but complete surgery seemed to offer the best chance of long-term survival. High-dose chemotherapy or local radiotherapy did not appear to improve survival in this retrospective analysis, but larger prospective studies are needed to provide definitive conclusions on the role of these treatments. Copyright © 2011 Wiley Periodicals, Inc.

  5. Generation of Tumor-specific T Lymphocytes Using Dendritic Cell/Tumor Fusions and Anti-CD3/CD28

    Science.gov (United States)

    Rosenblatt, Jacalyn; Wu, Zekui; Vasir, Baldev; Zarwan, Corrine; Stone, Richard; Mills, Heidi; Friedman, Thea; Konstantinopoulos, Panagiotis A.; Spentzos, Dimitrios; Ghebremichael, Musie; Stevenson, Kristen; Neuberg, Donna; Levine, James D.; Joyce, Robin; Tzachanis, Dimitrios; Boussiotis, Vassiliki; Kufe, Donald; Avigan, David

    2010-01-01

    Summary Adoptive immunotherapy with tumor-specific T cells represents a promising treatment strategy for patients with malignancy. However, the efficacy of T-cell therapy has been limited by the ability to expand tumor-reactive cells with an activated phenotype that effectively target malignant cells. We have developed an anticancer vaccine in which patient-derived tumor cells are fused with autologous dendritic cells (DCs), such that a wide array of tumor antigens are presented in the context of DC-mediated costimulation. In this study, we demonstrate that DC/tumor fusions induce T cells that react with tumor and are dramatically expanded by subsequent ligation of the CD3/CD28 costimulatory complex. These T cells exhibit a predominantly activated phenotype as manifested by an increase in the percentage of cells expressing CD69 and interferon γ. In addition, the T cells upregulate granzyme B expression and are highly effective in lysing autologous tumor targets. Targeting of tumor-specific antigen was demonstrated by the expansion of T cells with specificity for the MUC1 tetramer. Stimulation with anti-CD3/CD28 followed by DC/tumor fusions or either agent alone failed to result in a similar expansion of tumor-reactive T cells. Consistent with these findings, spectratyping analysis demonstrates selective expansion of T-cell clones as manifested by considerable skewing of the Vβ repertoire following sequential stimulation with DC/tumor fusions and anti-CD3/CD28. Gene expression analysis was notable for the upregulation of inflammatory pathways. These findings indicate that stimulation with DC/tumor fusions provides a unique platform for subsequent expansion with anti-CD3/CD28 in adoptive T-cell therapy of cancer. PMID:20145548

  6. Multivalent Fusion DNA Vaccine against Brucella abortus

    Science.gov (United States)

    Gómez, Leonardo; Llanos, Javiera; Escalona, Emilia; Sáez, Darwin; Álvarez, Francisco; Molina, Raúl; Flores, Manuel

    2017-01-01

    As an alternative brucellosis prevention method, we evaluated the immunogenicity induced by new multivalent DNA vaccines in BALB/c mice. We constructed the vaccines by fusion of BAB1_0273 and/or BAB1_0278 open reading frames (ORFs) from genomic island 3 (GI-3) and the Brucella abortus 2308 sodC gene with a link based on prolines and alanines (pV273-sod, pV278-sod, and pV273-278-sod, resp.). Results show that immunization with all tested multivalent DNA vaccines induced a specific humoral and cellular immune response. These novel multivalent vaccines significantly increased the production of IgM, IgG, and IgG2a antibodies as well as IFN-γ levels and the lymphoproliferative response of splenocytes. Although immunization with these multivalent vaccines induced a typical T-helper 1- (Th1-) dominated immune response, such immunogenicity conferred low protection levels in mice challenged with the B. abortus 2308 pathogenic strain. Our results demonstrated that the expression of BAB1_0273 and/or BABl_0278 antigens conjugated to SOD protein can polarize mice immunity to a Th1-type phenotype, conferring low levels of protection. PMID:29082252

  7. Multivalent Fusion DNA Vaccine against Brucella abortus

    Directory of Open Access Journals (Sweden)

    Leonardo Gómez

    2017-01-01

    Full Text Available As an alternative brucellosis prevention method, we evaluated the immunogenicity induced by new multivalent DNA vaccines in BALB/c mice. We constructed the vaccines by fusion of BAB1_0273 and/or BAB1_0278 open reading frames (ORFs from genomic island 3 (GI-3 and the Brucella abortus 2308 sodC gene with a link based on prolines and alanines (pV273-sod, pV278-sod, and pV273-278-sod, resp.. Results show that immunization with all tested multivalent DNA vaccines induced a specific humoral and cellular immune response. These novel multivalent vaccines significantly increased the production of IgM, IgG, and IgG2a antibodies as well as IFN-γ levels and the lymphoproliferative response of splenocytes. Although immunization with these multivalent vaccines induced a typical T-helper 1- (Th1- dominated immune response, such immunogenicity conferred low protection levels in mice challenged with the B. abortus 2308 pathogenic strain. Our results demonstrated that the expression of BAB1_0273 and/or BABl_0278 antigens conjugated to SOD protein can polarize mice immunity to a Th1-type phenotype, conferring low levels of protection.

  8. Purified dendritic cell-tumor fusion hybrids supplemented with non-adherent dendritic cells fraction are superior activators of antitumor immunity.

    Directory of Open Access Journals (Sweden)

    Yunfei Zhang

    Full Text Available BACKGROUND: Strong evidence supports the DC-tumor fusion hybrid vaccination strategy, but the best fusion product components to use remains controversial. Fusion products contain DC-tumor fusion hybrids, unfused DCs and unfused tumor cells. Various fractions have been used in previous studies, including purified hybrids, the adherent cell fraction or the whole fusion mixture. The extent to which the hybrids themselves or other components are responsible for antitumor immunity or which components should be used to maximize the antitumor immunity remains unknown. METHODS: Patient-derived breast tumor cells and DCs were electro-fused and purified. The antitumor immune responses induced by the purified hybrids and the other components were compared. RESULTS: Except for DC-tumor hybrids, the non-adherent cell fraction containing mainly unfused DCs also contributed a lot in antitumor immunity. Purified hybrids supplemented with the non-adherent cell population elicited the most powerful antitumor immune response. After irradiation and electro-fusion, tumor cells underwent necrosis, and the unfused DCs phagocytosed the necrotic tumor cells or tumor debris, which resulted in significant DC maturation. This may be the immunogenicity mechanism of the non-adherent unfused DCs fraction. CONCLUSIONS: The non-adherent cell fraction (containing mainly unfused DCs from total DC/tumor fusion products had enhanced immunogenicity that resulted from apoptotic/necrotic tumor cell phagocytosis and increased DC maturation. Purified fusion hybrids supplemented with the non-adherent cell population enhanced the antitumor immune responses, avoiding unnecessary use of the tumor cell fraction, which has many drawbacks. Purified hybrids supplemented with the non-adherent cell fraction may represent a better approach to the DC-tumor fusion hybrid vaccination strategy.

  9. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for ...

  10. Construction of a new fusion anti-caries DNA vaccine.

    Science.gov (United States)

    Niu, Y; Sun, J; Fan, M; Xu, Q-A; Guo, J; Jia, R; Li, Y

    2009-05-01

    Mutans streptococci (MS) are generally considered to be the principal etiological agent of dental caries. MS have two important virulence factors: cell- surface protein PAc and glucosyltransferases (GTFs). GTFs have two functional domains: an N-terminal catalytic sucrose-binding domain (CAT) and a C-terminal glucan-binding domain (GLU). A fusion anti-caries DNA vaccine, pGJA-P/VAX, encoding two important antigenic domains, PAc and GLU, of S. mutans, was successful in reducing the levels of dental caries caused by S. mutans in gnotobiotic animals. However, its protective effect against S. sobrinus infection proved to be weak. Does the DNA vaccine need an antigen of S. sobrinus to enhance its ability to inhibit infection? To answer this question, in this study, we cloned the catalytic (cat) fragment of S. sobrinus gtf-I, which demonstrated its ability to inhibit water-insoluble glucan synthesis by S. sobrinus, into pGJA-P/VAX to produce a new anti-caries DNA vaccine.

  11. Metaphyseal giant cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L.F.; Hemais, P.M.P.G.; Aymore, I.L.; Carmo, M.C.R. do; Cunha, M.E.P.R. da; Resende, C.M.C.

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed.

  12. Leydig cell tumor

    Science.gov (United States)

    Tumor - Leydig cell; Testicular tumor - Leydig; Testicular neoplasm ... The cause of this tumor is unknown. There are no known risk factors for this tumor. Unlike germ cell tumors of the testicles, this tumor ...

  13. Prevention and Treatment of Spontaneous Mammary Carcinoma with Dendritic Tumor Fusion Cell Vaccine

    National Research Council Canada - National Science Library

    Gong, Jianlin

    2002-01-01

    In the present study, the prevention of cancer development by vaccination with fusion cells was evaluated In a genetically engineered murine model which develops spontaneous mammary carcinomas. The mice (MMT...

  14. Granular Cell Tumor

    African Journals Online (AJOL)

    ultrastructure and immunochemical staining. 4 strongly suggest Schwann cell derivation . hyperplasia at the edges of the tumor. 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.

  15. Ovarian Germ Cell Tumors Treatment

    Science.gov (United States)

    ... Fallopian Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health Professional Version Key ...

  16. Immunogenicity of CTLA4 fusion anti-caries DNA vaccine in rabbits and monkeys.

    Science.gov (United States)

    Jia, Rong; Guo, Ji Hua; Fan, Ming Wen; Bian, Zhuan; Chen, Zhi; Fan, Bing; Yu, Fei; Xu, Qing An

    2006-06-12

    Enhancement of mucosal and systemic immune responses is still a challenge for the application of DNA vaccine. Here, we show anti-caries DNA vaccines, pGJA-P and pGJA-P/VAX, encoding Streptococcus mutans antigens fused to cytotoxic T lymphocyte antigen-4 (CTLA4), which binds to B7 molecule expressed on the surfaces of antigen-presenting cells. Rabbits and monkeys were immunized via intranasal or intramuscular routes. The fusion vaccine induced accelerated and increased specific antibody responses in serum and saliva compared with non-fusion DNA vaccine in rabbits. Significant specific serum IgG and salivary IgA levels could be detected in fusion vaccine-immunized monkeys. Therefore, this study demonstrates that fusing antigens to CTLA4 results in enhancing immune efficacy and strongly suggests that it may represent a promising approach to prevent dental caries or other mucosal infectious diseases. These findings also suggest that CTLA4 fusion anti-caries DNA vaccine may be effective immunogen in primates.

  17. Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.

    Directory of Open Access Journals (Sweden)

    Wen-Fang Cheng

    Full Text Available INTRODUCTION: Human papillomavirus (HPV has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII/E6 and PE(ΔIII/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. MATERIALS AND METHODS: In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. RESULTS: PE(ΔIII/E6+PE(ΔIII/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII/E6 group compared to 100% in the PE(ΔIII/E7 and PE(ΔIII/E6+PE(ΔIII/E7 groups. Mice vaccinated with the PE(ΔIII/E6+PE(ΔIII/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII/E6 or PE(ΔIII/E7 fusion proteins alone. CONCLUSION: Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies.

  18. Testicular germ cell tumors.

    Science.gov (United States)

    Diamantopoulos, N; Kortsaris, A

    2010-01-01

    Testicular cancer is the most frequent solid tumor in young male adults and a disease with elusive pathogenesis. Germ cell tumors represent 95% of all testicular cancers. There was an increasing incidence of testicular germ cell tumors during the second half of the 20th century. Despite their increased incidence, mortality is lower than 10% and the cure rate has reached 95%. Epidemiology of the disease shows remarkable geographic and racial variation. Known risk factors and the increased incidence during the last 50 years have led to the development of the two prevalent theories for the pathogenesis of the disease, Henderson theory and Rajpertde Meyts and Skakkebaek theory. Appropriate diagnosis and staging of the disease are crucial for successful management. Testicular ultrasound, CT scans, histological examination and serum tumor markers should be utilized in order to stratify the patient correctly. Treatment strategy is chosen according to the patient stage and prognostic group stratification. "Fine tuning" is needed in order to find the balance between treatment, cure and toxicity. Despite progress in therapeutic management, cure rates for poor risk patients do not exceed 50%. These patients should be encouraged to participate in clinical trials. Long-term toxicity of testicular germ cell tumors' treatment is also another issue that should be kept in mind during follow-up of these patients. This disease became the model of "curable" cancer and gave hope for cure of metastatic malignant diseases in general, as only 400 patients die from this disease in USA annually. More progress will be made only through well-designed clinical trials.

  19. Benign notochordal cell tumors.

    Science.gov (United States)

    Martínez Gamarra, C; Bernabéu Taboada, D; Pozo Kreilinger, J J; Tapia Viñé, M

    2017-08-01

    Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. [Construction and cellular expression of GTF-PAc fusion anti-caries DNA vaccine].

    Science.gov (United States)

    Jia, Rong; Fan, Mingwen; Bian, Zhuan; Guo, Jihua; Chen, Zhi; Du, Minquan

    2002-11-01

    To construct a fusion anti-caries DNA vaccine pGLUA-P carrying GLU fragment from gtfB gene of Streptococcus mutans GS-5 and A-P fragment including the A region and P region of PAc protein from a DNA anti-caries vaccine pCIA-P, and to investigate its expression in prokaryotic and eukaryotic cells. The sequence of GLU fragment in pGLU plasmid was testified by DNA sequencing. The fusion anti-caries DNA vaccine was constructed by ligating A-P fragment from pCIA-P to pGLU. The expression of GLUA-P fusion protein in E. coli BL21 (DE3) was induced by IPTG and checked by SDS-PAGE electrophoresis. pGLUA-P was transfected in vitro to cultured rat primary muscle cells by cation liposome Dosper, and immunohistochemical method was used to test the expression of GLUA-P fusion protein in cells. GLU sequence was identical with relative sequence of GTF-I (GS-5 strain) in Gene Bank. Recombinant eukaryotic expression plasmid pGLUA-P was confirmed to have both GLU and A-P fragment. After pGLUA-P was transferred into E. coli (DE3), it could express a new 115 000 protein by the induce of IPTG. Specific brown products could be found in the cytoplasm of cultured rat primary muscle cells transfected by pGLUA-P. Fusion anti-caries DNA vaccine pGLUA-P is successfully constructed and confirmed by sequencing and enzymes digestion. Fusion GLUA-P protein can be correctly expressed in prokaryotic and eukaryotic cells.

  1. Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines.

    Science.gov (United States)

    Moyle, Peter Michael

    Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their

  2. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... the mechanisms for manipulating the immune system, tumor immunotherapy, especially, targeting angiogenesis ... delivery system for transfection. The effects of resulting vaccine and underlying mechanism were investigated in ..... Genetic and epigenetic inactivation of T-cadherin in human hepatocellular ...

  3. Genetic Immunization with CDR3-Based Fusion Vaccine Confers Protection and Long-Term Tumor-Free Survival in a Mouse Model of Lymphoma

    Directory of Open Access Journals (Sweden)

    Sandra Iurescia

    2010-01-01

    Full Text Available Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. We have previously shown that CDR3-based DNA immunization can induce immune response against lymphoma and explored this strategy to provide protection in a murine B-cell lymphoma model. Here we performed vaccination employing as immunogen a naked DNA fusion product. The DNA vaccine was generated following fusion of a sequence derived from tetanus toxin fragment C to the VHCDR3109−116 epitope. Induction of tumor-specific immunity as well as ability to inhibit growth of the aggressive 38C13 lymphoma and to prolong survival of vaccinated mice has been tested. We determined that DNA fusion vaccine induced immune response, elicited a strong protective antitumor immunity, and ensured almost complete long-term tumor-free survival of vaccinated mice. Our results show that CDR3-based DNA fusion vaccines hold promise for vaccination against lymphoma.

  4. Malignant small round cell tumors

    Science.gov (United States)

    Rajwanshi, Arvind; Srinivas, Radhika; Upasana, Gautam

    2009-01-01

    Malignant small round cell tumors are characterised by small, round, relatively undifferentiated cells. They generally include Ewing's sarcoma, peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, hepatoblastoma, and nephroblastoma or Wilms’ tumor. Other differential diagnoses of small round cell tumors include small cell osteogenic sarcoma, undifferentiated hepatoblastoma, granulocytic sarcoma, and intraabdominal desmoplastic small round cell tumor. Differential diagnosis of small round cell tumors is particularly difficult due to their undifferentiated or primitive character. Tumors that show good differentiation are generally easy to diagnose, but when a tumor is poorly differentiated, identification of the diagnostic, morphological features is difficult and therefore, no definitive diagnosis may be possible. As seen in several study reports, fine needle aspiration cytology (FNAC) has become an important modality of diagnosis for these tumors. The technique yields adequate numbers of dissociated, viable cells, making it ideally suitable for ancillary techniques. Typically, a multimodal approach is employed and the principal ancillary techniques that have been found to be useful in classification are immunohistochemistry and immunophenotyping by flow cytometry, reverse transcriptase polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and electron microscopy. However, the recent characterization of chromosomal breakpoints and the corresponding genes involved in malignant small round cell tumors means that it is possible to use molecular genetic approaches for detection. PMID:21938141

  5. Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters.

    Science.gov (United States)

    Zhang, Feng; Li, Yu-hong; Fan, Ming-wen; Jia, Rong; Xu, Qing-an; Guo, Ji-hua; Yu, Fei; Tian, Qi-wei

    2007-08-01

    To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) fusion anti-caries DNA vaccines pGJA-P/VAX1, pGJA-P, and non-fusion anti-caries DNA construct pGLUA-P in hamsters. In addition, the ability of CTLA-4 to target pGJA-P/VAX1-encoding antigen to dendritic cells was tested in vitro. All DNA constructs contain genes encoding the A-P regions of a cell surface protein (PAc) and the glucan binding (GLU) domain of glucosyltransferases (GTFs) of cariogenic organism Streptococcus mutans. Human dendritic cells were mixed with the CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX1-transfected cells and analyzed by flow cytometry. Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration. Antibody responses to a representative antigen PAc were assayed by ELISA, and caries protection was evaluated by Keyes caries scores. A flow cytometric analysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of binding to human dendritic cells. pGJA-P/VAX1 and pGJA-P induced significantly higher specific salivary and serum anti-PAc antibody responses than pGLUA-P. Significantly fewer caries lesions were also observed in hamsters immunized with pGJA-P/VAX1 and pGJA-P. There was no significant difference in the anti-PAc antibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunized groups. Antigen encoded by CTLA-4 fusion anti-caries DNA vaccine pGJA-P/VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules. Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines.

  6. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

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    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  7. Sertoli-Leydig cell tumor

    Science.gov (United States)

    Sertoli-Leydig cell tumor (SLCT) is a rare cancer of the ovaries. The cancer cells produce and release a male sex hormone ... lead to cancer. SLCT starts in the female ovaries. The cancer cells release a male sex hormone. As a ...

  8. Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine.

    Science.gov (United States)

    Sun, Y; Shi, W; Yang, J Y; Zhou, D H; Chen, Y Q; Zhang, Y; Yang, Y; He, B X; Zhong, M H; Li, Y M; Cao, Y; Xiao, Y; Li, W; Yu, J; Li, Y H; Fan, M W; Yan, H M

    2012-10-01

    We previously demonstrated that an anti-caries DNA vaccine intranasally administered with recombinant flagellin protein as a mucosal adjuvant enhanced salivary IgA response and conferred better protection against caries. However, the relatively weak immunogenicity of DNA vaccines and the necessity for a large quantity of antigens remain significant challenges. Here, we fused the flagellin derived from E. coli (KF) and target antigen PAc containing the A-P fragment of PAc from S. mutans (rPAc) to produce a single recombinant protein (KF-rPAc). The abilities of KF-rPAc to induce rPAc-specific mucosal and systemic responses and protective efficiency against caries following intranasal immunization were compared with those of rPAc alone or a mixture of rPAc and KF (KF + rPAc) in rats. Results showed that KF-rPAc promoted significantly higher rPAc-specific antibodies in serum as well as in saliva than did an equivalent dose of rPAc alone or a mixture of KF + rPAc. Intranasal immunization of 8.5 µg KF-rPAc could achieve 64.2% reduction of dental caries in rats. In conclusion, our study demonstrated that flagellin and PAc fusion strategy is promising for anti-caries vaccine development, and KF-rPAc could be used as an anti-caries mucosal vaccine.

  9. Improved immunogenicity of Newcastle disease virus inactivated vaccine following DNA vaccination using Newcastle disease virus hemagglutinin-neuraminidase and fusion protein genes.

    Science.gov (United States)

    Firouzamandi, Masoumeh; Moeini, Hassan; Hosseini, Davood; Bejo, Mohd Hair; Omar, Abdul Rahman; Mehrbod, Parvaneh; Ideris, Aini

    2016-03-01

    The present study describes the development of DNA vaccines using the hemagglutinin-neuraminidase (HN) and fusion (F) genes from AF2240 Newcastle disease virus strain, namely pIRES/HN, pIRES/F and pIRES-F/HN. Transient expression analysis of the constructs in Vero cells revealed the successful expression of gene inserts in vitro. Moreover, in vivo experiments showed that single vaccination with the constructed plasmid DNA (pDNA) followed by a boost with inactivated vaccine induced a significant difference in enzyme-linked immunosorbent assay antibody levels (p inactivated vaccine alone. Taken together, these results indicated that recombinant pDNA could be used to increase the efficacy of the inactivated vaccine immunization procedure.

  10. Fusion

    CERN Document Server

    Mahaffey, James A

    2012-01-01

    As energy problems of the world grow, work toward fusion power continues at a greater pace than ever before. The topic of fusion is one that is often met with the most recognition and interest in the nuclear power arena. Written in clear and jargon-free prose, Fusion explores the big bang of creation to the blackout death of worn-out stars. A brief history of fusion research, beginning with the first tentative theories in the early 20th century, is also discussed, as well as the race for fusion power. This brand-new, full-color resource examines the various programs currently being funded or p

  11. Assessment of a recombinant F1-V fusion protein vaccine intended to protect Canada lynx (Lynx canadensis) from plague

    Science.gov (United States)

    Wolfe, Lisa L.; Shenk, Tanya M.; Powell, Bradford; Rocke, Tonie E.

    2011-01-01

    As part of an ongoing restoration program in Colorado, USA, we evaluated adverse reactions and seroconversion in captive Canada lynx (Lynx canadensis) after vaccination with a recombinant F1-V fusion protein vaccine against Yersinia pestis, the bacterium that causes plague. Ten adult female lynx received the F1-V vaccine; 10 source- and age-matched lynx remained unvaccinated as controls. All of the vaccinated and control lynx remained apparently healthy throughout the confinement period. We observed no evidence of injection site or systemic reactions to the F1-V vaccine. Among vaccinated lynx, differences in log10 reciprocal antibody titers measured in sera collected before and after vaccination (two doses) ranged from 1.2 to 5.2 for anti-F1 antibodies and from 0.6 to 5.2 for anti-V antibodies; titers in unvaccinated lynx did not change appreciably over the course of confinement prior to release, and thus differences in anti-F1 (P=0.003) and anti-V (P=0.0005) titers were greater among vaccinated lynx than among controls. Although our findings suggest that the F1-V fusion protein vaccine evaluated here is likely to stimulate antibody responses that may help protect Canada lynx from plague, we observed no apparent differences in survival between vaccinated and unvaccinated subject animals. Retrospectively, 22 of 50 (44%; 95% confidence interval 29–59%) unvaccinated lynx captured or recaptured in Colorado during 2000–08 had passive hemagglutination antibody titers >1:16, consistent with exposure to Y. pestis; paired pre- and postrelease titers available for eight of these animals showed titer increases similar in magnitude to those seen in response to vaccination, suggesting at least some lynx may naturally acquire immunity to plague in Colorado habitats.

  12. Assessment of a recombinant F1-V fusion protein vaccine intended to protect Canada lynx (Lynx canadensis) from plague.

    Science.gov (United States)

    Wolfe, Lisa L; Shenk, Tanya M; Powell, Bradford; Rocke, Tonie E

    2011-10-01

    As part of an ongoing restoration program in Colorado, USA, we evaluated adverse reactions and seroconversion in captive Canada lynx (Lynx canadensis) after vaccination with a recombinant F1-V fusion protein vaccine against Yersinia pestis, the bacterium that causes plague. Ten adult female lynx received the F1-V vaccine; 10 source- and age-matched lynx remained unvaccinated as controls. All of the vaccinated and control lynx remained apparently healthy throughout the confinement period. We observed no evidence of injection site or systemic reactions to the F1-V vaccine. Among vaccinated lynx, differences in log(10) reciprocal antibody titers measured in sera collected before and after vaccination (two doses) ranged from 1.2 to 5.2 for anti-F1 antibodies and from 0.6 to 5.2 for anti-V antibodies; titers in unvaccinated lynx did not change appreciably over the course of confinement prior to release, and thus differences in anti-F1 (P=0.003) and anti-V (P=0.0005) titers were greater among vaccinated lynx than among controls. Although our findings suggest that the F1-V fusion protein vaccine evaluated here is likely to stimulate antibody responses that may help protect Canada lynx from plague, we observed no apparent differences in survival between vaccinated and unvaccinated subject animals. Retrospectively, 22 of 50 (44%; 95% confidence interval 29-59%) unvaccinated lynx captured or recaptured in Colorado during 2000-08 had passive hemagglutination antibody titers >1:16, consistent with exposure to Y. pestis; paired pre- and postrelease titers available for eight of these animals showed titer increases similar in magnitude to those seen in response to vaccination, suggesting at least some lynx may naturally acquire immunity to plague in Colorado habitats.

  13. Vertebrectomy, bone allograft fusion, and antitumor vaccination for the treatment of vertebral fibrosarcoma in a dog.

    Science.gov (United States)

    Chauvet, A E; Hogge, G S; Sandin, J A; Lipsitz, D

    1999-01-01

    To describe the surgical technique of vertebrectomy with bone allograft fusion and the use of antitumor vaccine for the treatment of a primary vertebral neoplasm in a dog. Case Report. A 3 year old 32 kg female spayed mixed breed dog with progressive paraplegia. Myelography was performed to identify an L5 lytic lesion with spinal cord compression. A dorsal laminectomy was performed to decompress the spinal cord and obtain biopsies. Pathologic fracture of the vertebral body two days later was treated with L5 vertebrectomy, cortical allograft implantation, and bilateral plating from L4 to L6. Tumor samples were used to create an autologous cytokine-gene-engineered tumor cell vaccine. Recheck radiographs and neurologic examinations were obtained 1, 2, 7, and 13 months after surgery. The histopathologic diagnosis was fibrosarcoma. Although slight osteopenia of the allograft was noted thirteen months after surgery, the allograft and plate fixation remained stable. The patient tolerated the antitumor vaccination protocol well. Two years after the procedures the dog was able to ambulate normally but remained urinary and fecal incontinent. Vertebrectomy and cortical allograft implantation with plating permitted this patient to return to a functional lifestyle with its owners.

  14. Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans.

    Science.gov (United States)

    Guo, J H; Jia, R; Fan, M W; Bian, Z; Chen, Z; Peng, B

    2004-03-01

    Glucosyltransferases (GTFs) and A cell-surface protein (PAc) are two important virulence factors of the cariogenic organism Streptococcus mutans. They may mediate sucrose-independent or sucrose-dependent attachment of Streptococcus mutans to tooth surfaces, respectively. Thus, inhibiting both virulence factors is predicted to provide better protection against caries than inhibiting a single factor. To develop a highly efficient vaccine against caries, we constructed a fusion DNA vaccine, pGLUA-P, by cloning the GLU region of GTF into a DNA vaccine, pCIA-P, which encodes two highly conservative regions of PAc. In this report, we provide evidence that fewer caries lesions were observed in rats following subcutaneous injection of pGLUA-P, compared with pCIA-P, near the submandibular gland. Our findings suggest that a multigenic DNA vaccine may be more caries-preventive than a single-gene DNA vaccine.

  15. Correlation of haemagglutinin-neuraminidase and fusion protein content with protective antibody response after immunisation with inactivated Newcastle disease vaccines.

    NARCIS (Netherlands)

    Maas, R.A.; Komen, M.; Diepen, van M.; Oei, H.L.; Claassen, I.J.T.M.

    2003-01-01

    The correlation between the antigen content of inactivated Newcastle disease (ND) oil emulsion-vaccines and the serological response after immunisation was studied. The haemagglutinin-neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV) were quantified in 33 inactivated

  16. KMP11-HASPB fusion protein-expressing lentiviral vaccine protects BALB/c mice against Leishmania major infection

    Directory of Open Access Journals (Sweden)

    Nahid Mortazavidehkordi

    2016-12-01

    Full Text Available Hydrophilic acylated surface protein B (HASPB is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11 is another Leishmania antigen and considered as suitable candidate for vaccine development leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. In this study, KMP11 and HASPB coding sequences were cloned into a pCDH-cGFPlentiviral vector as a fusion protein to be used as a DNA vaccine against L.major. KMP11-HASPB fusion protein was successfully expressed as evidenced by RT-PCR and western blot assays. The effect of the vaccine was determined by evaluating the level of IFN-γ, IL-10, IgG1, and IgG2a performed using ELISA as well as determining the parasite load after challenge with L.major in vaccinated mice. The results revealed that IFN-γ, IL-10, IgG1, and IgG2a significantly increased after vaccination using KMP11-HASPB-expressing lentiviruses in BALB/c mice. It is noteworthy that the level of IFN-γ and IgG2a was higher than that of IL-10 and IgG1, respectively, which indicates the activation Th1 cells, macrophages, and cellular immunity. Moreover, the parasite load in the spleen and liver of vaccinated mice after challenge was significantly lower than that of controls.

  17. Vindesine in plasma cell tumors.

    Science.gov (United States)

    Salvagno, L; Paccagnella, A; Chiarion Sileni, V; De Besi, P; Frizzarin, M; Casara, D; Fiorentino, M V

    1985-12-31

    Twenty-one patients with plasma cell tumors received vindesine (VDS) at the dose of 3 mg/m2 i.v. on day 1 plus prednisone at the dose of 100 mg p.o. from day 1 to 5, recycling every 8 days 3 times and then every 10-12 days. In 3 patients with gastric or duodenal ulcer prednisone was not administered. All but one patient were heavily pretreated and resistant to M-2 regimen. Overall there were 4 objective responses (19%): 2 among 15 patients (13%) with multiple myeloma and 2 among 6 patients (33%) with extramedullary plasmacytoma (EMP). The responses lasted for 2, 12, 15 and 48+ months. One previously untreated EMP patient received VDS without prednisone and obtained a complete long-lasting remission. The association of VDS with high-dose prednisone seems to have some activity in plasma cell tumors; probably in multiple myeloma the objective responses are due to the high dose of cortisone rather than to VDS. On the contrary, in EMP patients, VDS may be an active agent, even if administered without cortisone.

  18. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  19. Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein in Piglets.

    Directory of Open Access Journals (Sweden)

    Shanshan Zhu

    Full Text Available In a recent study, we reported that a recombinant protein from fusion expression of flagellin to porcine circovirus type 2 (PCV2 Cap induced robust humoral and cell-mediated immunity that afforded full protection for PCV2 infection using BALB/c mice. Here, we further evaluated the immunogenicity and protection of the recombinant protein using specific pathogen free (SPF pigs. Twenty-five 3-week-old piglets without passively acquired immunity were divided into 5 groups. All piglets except negative controls were challenged with a virulent PCV2 at 21 days after booster vaccination and necropsied at 21 days post-challenge. Vaccination of piglets with the recombinant protein without adjuvant induced strong humoral and cellular immune responses as observed by high levels of PCV2-specific IgG antibodies and neutralizing antibodies, as well as frequencies of PCV2-specific IFN-γ-secreting cells that conferred good protection against PCV2 challenge, with significant reduced PCV2 viremia, mild lesions, low PCV2 antigen-positive cells, as well as improved body weight gain, comparable to piglets vaccinated with a commercial PCV2 subunit vaccine. These results further demonstrated that the recombinant flagellin-Cap fusion protein is capable of inducing solid protective humoral and cellular immunity when administered to pigs, thereby becoming an effective PCV2 vaccine candidate for control of PCV2 infection.

  20. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease.

    Science.gov (United States)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-07-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. Copyright © 2016. Published by Elsevier Inc.

  1. Granular cell tumors of the tracheobronchial tree.

    NARCIS (Netherlands)

    Maten, van der J; Blaauwgeers, JL; Sutedja, G.; Kwa, HB; Postmus, P.E.; Wagenaar, SS

    2003-01-01

    OBJECTIVE: To describe the population-based incidence and clinical characteristics of granular cell tumors of the tracheobronchial tree. METHODS: All newly registered tracheobronchial granular cell tumors in the Dutch Network and National Database for Pathology for 10 consecutive years (1990-1999)

  2. Poor immune responses of newborn rhesus macaques to measles virus DNA vaccines expressing the hemagglutinin and fusion glycoproteins.

    Science.gov (United States)

    Polack, Fernando P; Lydy, Shari L; Lee, Sok-Hyong; Rota, Paul A; Bellini, William J; Adams, Robert J; Robinson, Harriet L; Griffin, Diane E

    2013-02-01

    A vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8(+) CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection.

  3. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.

    Directory of Open Access Journals (Sweden)

    Lili Gan

    Full Text Available Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4 with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6. pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.

  4. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.

    Science.gov (United States)

    Gan, Lili; Jia, Rong; Zhou, Lili; Guo, Jihua; Fan, Mingwen

    2014-01-01

    Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4) with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6). pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.

  5. Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity.

    Directory of Open Access Journals (Sweden)

    Natalija Budimir

    Full Text Available BACKGROUND: The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV vaccine, that can target conserved internal antigens such as the nucleoprotein (NP and/or matrix protein (M1 need to be explored. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs, protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA severely compromises fusion activity of the virus, while inactivation with β-propiolactone (BPL preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. CONCLUSION/SIGNIFICANCE: The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane

  6. SYNOVIAL GIANT CELL TUMOR OF THE KNEE.

    Science.gov (United States)

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2009-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  7. Granular cell tumor of the urinary bladder

    OpenAIRE

    Bedir, Recep; Yılmaz, Rukiye; Özdemir, Oğuzhan; Uzun, Hakkı

    2017-01-01

    Granular cell tumors (GCTs) are extremely rare neoplasms of the bladder. In the literature, there are only a few reported cases. We present a GCT case with clinical, radiological, histomorphological, immünohistochemical findings and its differential diagnosis.

  8. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... with testicular germ cell tumors are treated in pediatric cancer centers, but the treatment is much like the ... with Cancer Questions to Ask Your Doctor about Cancer For Survivors and Caregivers About This PDQ Summary About PDQ ...

  9. General Information about Ovarian Germ Cell Tumors

    Science.gov (United States)

    ... Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping ... Ovarian germ cell tumors usually occur in teenage girls or young women and most often affect just ...

  10. Treatment Option Overview (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping ... Ovarian germ cell tumors usually occur in teenage girls or young women and most often affect just ...

  11. Recombinant cholera toxin B subunit and gene fusion proteins for oral vaccination.

    Science.gov (United States)

    Sanchez, J; Johansson, S; Löwenadler, B; Svennerholm, A M; Holmgren, J

    1990-01-01

    The B subunit portion of cholera toxin (CTB) is a safe and effective oral immunizing agent in humans, affording protection against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli producing heat-labile toxin (LT) (Clemens et al., 1986; 1988). CTB may also be used as a carrier of various "foreign" antigens suitable for oral administration. To facilitate large-scale production of CTB for vaccine development purposes, we have constructed recombinant overexpression systems for CTB proteins in which the CTB gene is under the control of strong foreign (non-cholera) promoters and in which it is also possible to fuse oligonucleotides to the CTB gene and thereby achieve overexpression of hybrid proteins (Sanchez and Holmgren, 1989; Sanchez et al., 1988). We here expand these findings by describing overexpression of CTB by a constitutive tacP promoter as well as by the T7 RNA-polymerase promoter, and also by describing gene fusions leading to overexpression of several hybrid proteins between heat-stable E. coli enterotoxin (STa)-related peptides to either the amino or carboxy ends of CTB. Each of the hybrid proteins, when tested as immunogens in rabbits, stimulated significant anti-STa as well as anti-CTB antibody formation, although the anti-STa antibody levels attained (c.a. 1-15 micrograms/ml specific anti-STa immunoglobulin) were too low to give more than partial neutralization of STa intestinal challenge in baby mice. The hybrid proteins also had a near-native conformation, as apparent from their oligomeric nature and their strong reactivity with both a neutralizing antibody against the B subunit and a neutralizing monoclonal antibody (mAb) against STa.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.

    Directory of Open Access Journals (Sweden)

    Alexandra J Spencer

    Full Text Available The orthodox role of the invariant chain (CD74; Ii is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA, higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.

  13. [Protective efficacy of a new fusion anti-caries DNA vaccine encoding antigens of both Streptococcus mutans and Streptococcus sobrinus].

    Science.gov (United States)

    Sun, Jing-hua; Niu, Yu-mei; Fan, Ming-wen; Xu, Qing-an; Yang, Xue-chao

    2009-08-25

    To construct a new fusion anti-caries DNA vaccine pGJGAC/VAX encoding antigens of both S. mutans and S. sobrinus so as to enhance the protective effect of DNA vaccine against S. sobrinus infection. The CAT fragment of S. sobrinus OMZ176 gtf-I was amplified by semi-nest PCR and then inserted into the plasmid pGJA-P/VAX to construct the recombinant plasmid pGJGAC/VAX. The CHO cell was transfected and the expression of fusion protein detected using cellular immunohistochemistry and Western blot. Mice were immunized with pGJGAC/VAX and control plasmids via the intramuscular (i.m) or intranasal (i.n) routes. During the experiment, blood and saliva samples were collected at a 2-week interval for antibody assay by ELISA. Rats were orally challenged with S. mutans Ingbritt or S. sobrinus 6715 and then immunized i.n with pGJGAC/VAX, pGJA-P/VAX or pVAX1. The Keyes method was used to determine the caries activity. (1) CAT sequence was identical to the related sequence of gtf-I (OMZ176) in GenBank. The recombinant plasmid pGJGAC/VAX encoded the genes of antigens of both S. mutans and S. sobrinus. The expressed protein could respond to specific anti-PAc, anti-GLU and anti-CAT antibodies respectively. (2) As for antibody reactions, mice in the experiment group had significantly higher levels of anti-PAc, anti-GLU and anti-CAT IgG antibodies than those in the pVAX1 group (P 0.05). A new fusion anti-caries DNA vaccine pGJGAC/VAX encoding antigens of both S. mutans and S. sobrinus is constructed successfully and expressed correctly in eukaryotic cells. It induces effective mucosal and systematic humoral responses so as to provide a better protection against S. sobrinus.

  14. Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice.

    Directory of Open Access Journals (Sweden)

    Corinne Cayatte

    Full Text Available Respiratory syncytial virus (RSV is recognized as an important cause of lower and upper respiratory tract infections in older adults, and a successful vaccine would substantially lower morbidity and mortality in this age group. Recently, two vaccine candidates based on soluble purified glycoprotein F (RSV F, either alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE, failed to reach their primary endpoints in clinical efficacy studies, despite demonstrating the desired immunogenicity profile and efficacy in young rodent models. Here, one of the RSV F vaccine candidates (post-fusion conformation, RSV post-F, and a stabilized pre-fusion form of RSV F (RSV pre-F, DS-Cav1 were evaluated in aged BALB/c mice. Humoral and cellular immunogenicity elicited after immunization of naïve, aged mice was generally lower compared to young animals. In aged mice, RSV post-F vaccination without adjuvant poorly protected the respiratory tract from virus replication, and addition of GLA-SE only improved protection in the lungs, but not in nasal turbinates. RSV pre-F induced higher neutralizing antibody titers compared to RSV post-F (as previously reported but interestingly, RSV F-specific CD8 T cell responses were lower compared to RSV post-F responses regardless of age. The vaccines were also tested in RSV seropositive aged mice, in which both antigen forms similarly boosted neutralizing antibody titers, although GLA-SE addition boosted neutralizing activity only in RSV pre-F immunized animals. Cell-mediated immune responses in the aged mice were only slightly boosted and well below levels induced in seronegative young mice. Taken together, the findings suggest that the vaccine candidates were not able to induce a strong anti-RSV immune response in recipient mice with an aged immune system, in agreement with recent human clinical trial results. Therefore, the aged mouse model could be a useful tool to evaluate improved vaccine

  15. Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection.

    Directory of Open Access Journals (Sweden)

    Sridhar Arumugam

    2016-04-01

    Full Text Available The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious.Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi, respectively, and vaccination with Bm-RAL-2 resulted in worm reductions of 42%, 22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion protein comprised of Bm-103 and Bm-RAL-2 resulted in improved efficacy with significant reduction of worm burden of 51% and 49% at 90 dpi, as did the concurrent vaccination with Bm-103 and Bm-RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with Bm-103 and Bm-RAL-2 as a fusion protein or concurrently not only induced a significant worm reduction of 61% and 42%, respectively, at 150 dpi, but also significantly reduced the fecundity of female worms as determined by embryograms. Elevated levels of antigen-specific IgG were observed in all vaccinated gerbils. Serum from gerbils vaccinated with Bm-103 and Bm-RAL-2 individually, concurrently or as a fusion protein killed third stage larvae in vitro when combined with peritoneal exudate cells.Although vaccination with Bm-103 and Bm-RAL-2 individually conferred protection against B. malayi infection in gerbils, a more consistent and enhanced protection was induced by vaccination with Bm-103 and Bm-RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted.

  16. The anti-tumour effect of a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12

    Directory of Open Access Journals (Sweden)

    Sha Wen

    2016-09-01

    Full Text Available Because of tumour dependence on angiogenesis, anti-angiogenic therapy has become the most attractive area of basic and clinical study in the field of cancer research. In order to create a synergistic effect on angiogenesis and immune regulation, we designed and constructed a new type of DNA vaccine that can express VEGFR2 (vascular endothelial growth factor receptor 2 and the prostate cancer antigen IL-12 (interleukin 12 in the same reading frame. The aim of this study was to investigate the anti-tumour activity of a eukaryotic expression plasmid carrying a fusion gene of human VEGFR2 and IL-12. According to the gene sequences in GenBank, we synthesized the human VEGFR2 and IL-12 genes. VEGFR2 and IL-12 were joined by a sequence encoding a Furin recognition site and a 2A cleavage site, and the resulting fusion gene was cloned into the eukaryotic expression vector pVAX1 to construct the expression plasmid pVAX1-VEGFR2-F2A-IL-12. The expression of VEGFR2 and IL-12 could be detected in 293T cells transfected with pVAX1-VEGFR2-F2A-IL-12 by enzyme-linked immunosorbent assay. Each of these proteins, and in particular co-expression of both proteins, can result in humoral and cellular immune responses in C57BL/6 mice. After injection into the tumour-bearing mouse model, the plasmid showed stronger inhibition of tumour growth than a plasmid expressing VEGFR2 alone. Our results demonstrate that a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12 could represent a promising approach for tumour immunotherapy.

  17. Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

    Directory of Open Access Journals (Sweden)

    Daniel Y. Bargieri

    2011-01-01

    Full Text Available In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines.

  18. Arthroplasty for tenosynovial giant cell tumors

    NARCIS (Netherlands)

    Verspoor, F.G.; Hannink, G.; Scholte, A.; Geest, I.C. van der; Schreuder, H.W.

    2016-01-01

    Background and purpose - Tenosynovial giant cell tumors (t-GCTs) can behave aggressively locally and affect joint function and quality of life. The role of arthroplasty in the treatment of t-GCT is uncertain. We report the results of arthroplasty in t-GCT patients. Patients and methods - t-GCT

  19. Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein

    Directory of Open Access Journals (Sweden)

    Jia Lu

    2011-01-01

    Full Text Available Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A expressing the fusion protein of Ag85A and ESAT-6 (r685A and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST- positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulent Mycobacterium tuberculosis H37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

  20. Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice.

    Science.gov (United States)

    Hu, Zixi; Chen, Jiaojiao; Zhou, Sufang; Yang, Nuo; Duan, Siliang; Zhang, Zhenghua; Su, Jing; He, Jian; Zhang, Zhiyong; Lu, Xiaoling; Zhao, Yongxiang

    2017-01-01

    Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

  1. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development....

  2. Cloning, expression and characterization of recombinant exotoxin A-flagellin fusion protein as a new vaccine candidate against Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Tanomand, Asghar; Farajnia, Safar; Najar Peerayeh, Shahin; Majidi, Jafar

    2013-01-01

    Infections due to Pseudomonas aeruginosa are among the leading causes of morbidity and mortality in patients who suffer from impaired immune responses and chronic diseases such as cystic fibrosis. At present, aggressive antibiotic therapy is the only choice for management of P. aeruginosa infections, but emergence of highly resistant strains necessitated the development of novel alternative therapeutics including an effective vaccine. Several P. aeruginosa antigens have been tested for vaccine development, including lipopolysaccharide alone, polysaccharides alginate, extracellular proteins, exotoxin A (exo A) and killed whole cell. However, none of them are currently available clinically. In this research, recombinant exoA-flagellin (fliC) fusion protein as a cocktail antigen was expressed and purified and its antigenic characteristics were evaluated. Expression of recombinant fusion protein by E. coli using pET22b vector resulted in production of exoA-fliC fusion protein in high concentration. Based on Western-blotting results, recombinant fusion protein showed a good antigenic interaction with sera from patients with various P. aeruginosa infections. These results suggested that recombinant exoA-fliC fusion protein can be produced in the laboratory, and tested as a candidate vaccine in P. aeruginosa infections.

  3. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy

    Science.gov (United States)

    Hart, Bryan E.

    2016-01-01

    Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine. PMID:27941982

  4. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

    Directory of Open Access Journals (Sweden)

    Bryan E Hart

    2016-12-01

    Full Text Available Buruli ulcer (BU vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

  5. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

    Science.gov (United States)

    Hart, Bryan E; Lee, Sunhee

    2016-12-01

    Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

  6. Vaccination with Dendritic Cell Myeloma Fusions in Conjuction with Stem Cell Transplantation and PD-1 Blockade

    Science.gov (United States)

    2015-07-01

    initiated study treatment. One participant died on 11/5/10 after suffering a cardiac arrest in his home; the event was reported to the Dana Farber...2013 1 Unrelated Possible None Resolved PM29 Vaccine Site Reaction 3/11/2013 1 Unrelated Definitely None Resolved PM29 Ecchymosis, vaccine site...3/13/2013 1 Unrelated Definitely None Resolved PM29 Facial Flushing 3/10/2013 1 Unrelated Possible None Resolved PM29 ANC 3/14/2013 1 Unrelated

  7. [Construction of genetically modified dendritic cell vaccine expressing bcr/abl fusion gene and inducing specific cytotoxic T lymphocytes to kill K562 cells in vitro].

    Science.gov (United States)

    Wang, Wen-Wen; Huang, Ren-Wei; Hu, Yuan; Li, Xu-Dong; Wang, Dong-Ning; He, Yi; Liu, Jia-Jun

    2009-06-01

    Specific immunological effect mediated by T lymphocytes plays an important role in treating chronic myelocytic leukemia (CML). Dendritic cells (DCs)-based immunotherapy has become popular in treating tumors. This study was to construct DC vaccines by transducing with replication-defective recombinant adenoviruses expressing bcr/abl fusion gene of CML, observe the lethal effects of specific cytotoxic T lymphocytes (CTLs) triggered by genetically modified DC vaccines expressing bcr/abl fusion gene against K562 cells in vitro. DNA fragment of bcr/abl fusion gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) to construct a recombinant adenovirus vector and produce recombinant adenoviruses. DCs were induced from peripheral blood monocytes in vitro, and transfected with recombinant adenoviruses or pulsed with peptide to induce specific CTLs. The lethal effect of CTLs against leukemic K562 cells in vitro was observed. We successfully constructed the replication-defective recombinant adenoviral vector expressing bcr/abl fusion gene. The recombinant adenoviruses we produced had a high virus titer of 2.0 x 10(10) pfu/mL. Transfection efficiency of DCs in vitro was 50%-60%. DC vaccines expressing bcr/abl fusion gene were successfully prepared and used to induce specific CTLs. With effector:target cell ratios of 40:1 and 20:1, the killing rates of K562 cells by CTLs were (47.6+/-4.7)% and (47.5+/-1.6)% in genetically modified DCs group, (25.8+/-4.4)% and (24.6+/-6.3)% in peptide-pulsed DCs group, and were (5.7+/-1.3)% and (4.5+/-1.6)% in control DCs group. The differences between every two groups were significant (all P<0.05). Genetically modified DC vaccine expressing bcr/abl fusion gene has a stronger contribution than peptide-pulsed DCs in triggering specific CTLs against K562 cells.

  8. Alga-Produced Cholera Toxin-Pfs25 Fusion Proteins as Oral Vaccines

    Science.gov (United States)

    Gregory, James A.; Topol, Aaron B.; Doerner, David Z.

    2013-01-01

    Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678

  9. A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats.

    Science.gov (United States)

    Rostad, Christina A; Stobart, Christopher C; Gilbert, Brian E; Pickles, Ray J; Hotard, Anne L; Meng, Jia; Blanco, Jorge C G; Moin, Syed M; Graham, Barney S; Piedra, Pedro A; Moore, Martin L

    2016-08-15

    Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10 total PFU and 2.7 log10 PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by

  10. Cranial vault metastasis of giant cell tumor.

    Science.gov (United States)

    Notarianni, Christina; Abreo, Fluerette; Nanda, Anil

    2008-08-01

    Giant cell tumors are benign bony tumors involving the epiphysis of long bones. Here, we present a case of giant cell tumor involving the parietal bone that had metastasized from the sacrum. A 36-year-old healthy woman presented to neurosurgery clinic in April 2005 reporting a "bump" over the left parietal area that had been increasing in size over the past 6 months. The lesion was nontender, and the patient had no other associated neurological symptoms. As we have presented here, cranial vault metastases can occur and should be considered in a differential diagnosis of bony lesions found in this location. These distant metastases, although relatively uncommon, must be managed aggressively. Newer radiation treatments seem to be a promising favorable adjunct to wide local resection and should be investigated further for these tumors.

  11. Multicentric giant cell tumor around the knee

    Directory of Open Access Journals (Sweden)

    Salgia Anil

    2007-01-01

    Full Text Available A case of multicentric giant cell tumor with synchronous occurrence in all three bones around the knee is reported here in view of its rarity. A 33-year-old average built male reported with complaints of severe pain, gradually increasing swelling around the right knee. A 3 x 2 cm swelling was present on the lateral aspect of the distal end of the right femur and a 3 x 3 cm swelling on the proximal part of the right tibia. Plain X-ray of right knee showed subarticular eccentrically located expansile lytic lesion in the lateral tibia condyle, lateral condyle of femur and patella. Fine needle aspiration cytology and subsequent histology ascertained the diagnosis of giant cell tumor of the bone. The patient was treated successfully with curettage, bone grafting and methyl methacrylate cementing (Sandwich technique.

  12. Enhanced Growth of Influenza Vaccine Seed Viruses in Vero Cells Mediated by Broadening the Optimal pH Range for Virus Membrane Fusion

    Science.gov (United States)

    Murakami, Shin; Ito, Mutsumi; Takano, Ryo; Katsura, Hiroaki; Shimojima, Masayuki

    2012-01-01

    Vaccination is one of the most effective preventive measures to combat influenza. Prospectively, cell culture-based influenza vaccines play an important role for robust vaccine production in both normal settings and urgent situations, such as during the 2009 pandemic. African green monkey Vero cells are recommended by the World Health Organization as a safe substrate for influenza vaccine production for human use. However, the growth of influenza vaccine seed viruses is occasionally suboptimal in Vero cells, which places limitations on their usefulness for enhanced vaccine production. Here, we present a strategy for the development of vaccine seed viruses with enhanced growth in Vero cells by changing an amino acid residue in the stem region of the HA2 subunit of the hemagglutinin (HA) molecule. This mutation optimized the pH for HA-mediated membrane fusion in Vero cells and enhanced virus growth 100 to 1,000 times in the cell line, providing a promising strategy for cell culture-based influenza vaccines. PMID:22090129

  13. Evaluation of a novel lentiviral vaccine expressing KMP11-HASPB fusion protein against Leishmania infantum in BALB/c mice.

    Science.gov (United States)

    Mortazavidehkordi, N; Farjadfar, A; Khanahmad, H; Ghayour Najafabadi, Z; Hashemi, N; Fallah, A; Najafi, A; Kia, V; Hejazi, S H

    2016-11-01

    Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania protein against which antibodies are produced in the sera of cutaneous and visceral Leishmaniasis (VL) patients. Kinetoplastid membrane protein 11 (KMP11) is another protein antigen of Leishmania which is reported as a promising candidate for vaccination of VL. It is a highly conserved surface protein present in all members of kinetoplastid family and is expressed in both promastigotes and amastigotes. In this study, the coding sequence of KMP11 and HASPB was cloned into a pCDH-cGFP lentiviral vector as a fusion protein. The gene expression was confirmed using RT-PCR and Western blot methods. After injection of the recombinant KMP11-HASPB-expressing lentiviruses to BALB/c mice, using ELISA technique, a significant increase in IFN-γ and IL-4 as well as IgG1 and IgG2a was observed compared to the control group. Furthermore, the number of parasites in the liver and spleen of vaccinated mice decreased significantly compared with the control group. © 2016 John Wiley & Sons Ltd.

  14. Stalking influenza by vaccination with pre-fusion headless HA mini-stem

    Science.gov (United States)

    Valkenburg, Sophie A.; Mallajosyula, V. Vamsee Aditya; Li, Olive T. W.; Chin, Alex W. H.; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L. M.

    2016-01-01

    Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity. PMID:26947245

  15. Adult type granulosa cell tumor - morphological features

    OpenAIRE

    Ioana Buda; Raluca Balan; Crauciuc Eduard; Ovidiu Toma

    2008-01-01

    Adult granulosa cell tumors (AGCT) account for approximately 1-2% of all ovarian tumors and 95% of all GCT. They occur more often in postmenopausal women, with a peak incidence between 50 and 55 years. Nine cases of AGCT were diagnosed in the Clinical Hospital of Obstetrics and Gynecology Iasi, in a 10 years period. The age of the patients ranged between 35 and 67 years, 4 of them (44.44%) being postmenopausal. The macroscopical appearance showed that all were unilateral tumors – ...

  16. Cytokine-neuroantigen fusion proteins as a new class of tolerogenic, therapeutic vaccines for treatment of inflammatory demyelinating disease in rodent models of multiple sclerosis.

    Science.gov (United States)

    Mannie, Mark D; Blanchfield, J Lori; Islam, S M Touhidul; Abbott, Derek J

    2012-01-01

    Myelin-specific induction of tolerance represents a promising means to modify the course of autoimmune inflammatory demyelinating diseases such as multiple sclerosis (MS). Our laboratory has focused on a novel preclinical strategy for the induction of tolerance to the major encephalitogenic epitopes of myelin that cause experimental autoimmune encephalomyelitis (EAE) in rats and mice. This novel approach is based on the use of cytokine-NAg (neuroantigen) fusion proteins comprised of the native cytokine fused either with or without a linker to a NAg domain. Several single-chain cytokine-NAg fusion proteins were tested including GMCSF-NAg, IFNbeta-NAg, NAgIL16, and IL2-NAg. These cytokine-NAg vaccines were tolerogenic, therapeutic vaccines that had tolerogenic activity when given as pre-treatments before encephalitogenic immunization and also were effective as therapeutic interventions during the effector phase of EAE. The rank order of inhibitory activity was as follows: GMCSF-NAg, IFNbeta-NAg > NAgIL16 > IL2-NAg > MCSF-NAg, IL4-NAg, IL-13-NAg, IL1RA-NAg, and NAg. Several cytokine-NAg fusion proteins exhibited antigen-targeting activity. High affinity binding of the cytokine domain to specific cytokine receptors on particular subsets of APC resulted in the concentrated uptake of the NAg domain by those APC which in turn facilitated the enhanced processing and presentation of the NAg domain on cell surface MHC class II glycoproteins. For most cytokine-NAg vaccines, the covalent linkage of the cytokine domain and NAg domain was required for inhibition of EAE, thereby indicating that antigenic targeting of the NAg domain to APC was also required in vivo for tolerogenic activity. Overall, these studies introduced a new concept of cytokine-NAg fusion proteins as a means to induce tolerance and to inhibit the effector phase of autoimmune disease. The approach has broad application for suppressive vaccination as a therapy for autoimmune diseases such as MS.

  17. Cytokine-neuroantigen fusion proteins as a new class of tolerogenic, therapeutic vaccines for treatment of inflammatory demyelinating disease in rodent models of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mark D. Mannie

    2012-08-01

    Full Text Available Myelin-specific induction of tolerance represents a promising means to modify the course of autoimmune inflammatory demyelinating diseases such as multiple sclerosis (MS. Our laboratory has focused on a novel preclinical strategy for the induction of tolerance to the major encephalitogenic epitopes of myelin that cause experimental autoimmune encephalomyelitis (EAE in rats and mice. This novel approach is based on the use of cytokine-NAg (neuroantigen fusion proteins comprised of the native cytokine fused either with or without a linker to a NAg domain. Several single-chain cytokine-NAg fusion proteins were tested including GMCSF-NAg, IFNbeta-NAg, NAgIL16, and IL2-NAg. These cytokine-NAg vaccines were tolerogenic, therapeutic vaccines that had tolerogenic activity when given as pre-treatments before encephalitogenic immunization and also were effective as therapeutic interventions during the effector phase of EAE. The rank order of inhibitory activity was: GMCSF-NAg, IFNbeta-NAg > NAgIL16 > IL2-NAg > MCSF-NAg, IL4-NAg, IL13-NAg, IL1RA-NAg, and NAg. Several cytokine-NAg fusion proteins exhibited antigen-targeting activity. High affinity binding of the cytokine domain to specific-cytokine receptors on particular subsets of APC resulted in the concentrated uptake of the NAg domain by those APC which in turn facilitated the enhanced processing and presentation of the NAg domain on cell surface MHC class II (MHCII glycoproteins. For most cytokine-NAg vaccines, the covalent linkage of the cytokine domain and NAg domain was required for inhibition of EAE, thereby indicating that antigenic targeting of the NAg domain to APC was also required in vivo for tolerogenic activity. Overall, these studies introduced a new concept of cytokine-NAg fusion proteins as a means to induce tolerance and to inhibit the effector phase of autoimmune disease. The approach has broad application for suppressive vaccination as a therapy for autoimmune diseases such as MS.

  18. Giant Cell Tumor of Bone - an Overview

    Directory of Open Access Journals (Sweden)

    Anshul Sobti

    2016-01-01

    Full Text Available Giant Cell tumors (GCT are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor.

  19. Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis

    Science.gov (United States)

    Rocke, Tonie E.; Smith, Susan; Marinari, Paul E.; Kreeger, J.; Enama, J.T.; Powell, B.S.

    2008-01-01

    Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

  20. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Mallika Sastry

    Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

  1. First Litopenaeus vannamei WSSV 100% oral vaccination protection using CotC::Vp26 fusion protein displayed on Bacillus subtilis spores surface.

    Science.gov (United States)

    Valdez, A; Yepiz-Plascencia, G; Ricca, E; Olmos, J

    2014-08-01

    Litopenaeus vannamei do not have an adaptive immune response system. White spot syndrome virus (WSSV) is the most severe pathogen in shrimps. Bacillus subtilis spores carrying heterologous antigens on its surface have been evaluated as a vaccine inducing specific systemic responses on vertebrates. Orally administrated Vp28 vaccines have been investigated in crustaceans. Vp26 is also an important constituent of WSSV structure but little is known about its oral vaccination capacity in L. vannamei. In this study, for first time, L. vannamei WSSV protection was carried out using B. subtilis recombinant spores (RS), displaying CotC::Vp26 fusion protein (FP) on its surface. RS-expressing FP were coated on shrimp food pellets and used to feed L. vannamei. Results have shown that orally administered B. subtilis RS protected 100% L. vannamei against WSSV infection. Bacillus subtilis spores orally administrated expressing CotC::Vp26 fusion protein on its surface demonstrated the great capacity of Vp26 to induce immune protection, equally or even greater than Vp28 in L. vannamei. The biotechnological process developed represents an easy to produce, practical to handle, environmentally stable, human-safe and economically feasible opportunity to apply a new Vp26 vaccine in a massively way in shrimp farms. © 2014 The Society for Applied Microbiology.

  2. Mixed germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    Pradhan M Pagaro

    2013-01-01

    Full Text Available Germ cell tumors arise in the ovaries and testis and rarely in other tissues. Mixed germ cell tumors are rare. We report two cases of mixed germ cell tumors, one consisting of seminoma and immature teratoma in the testis of a 30-year-old male and second consisting of a yolk sac tumor and immature teratoma in the ovary of a 17-year-old female. Many combinations of mixed germ cell tumors have been reported but very few cases of the above-mentioned combinations have been reported in literature.

  3. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  4. Giant cell tumor of dorsal vertebral body

    Directory of Open Access Journals (Sweden)

    Rakesh Redhu

    2012-01-01

    Full Text Available A 30-year-old female patient presented with complaints of backache, weakness in both lower limbs and bladder/bowel dysfunction. Imaging showed an osteolytic lesion at tenth dorsal (D10 vertebra with anterior compression on the spinal cord. Complete intralesional tumor excision with reconstruction was carried out using the anterolateral extrapleural approach. Histopathological examination was suggestive of giant cell tumor (GCT. Because of complete intralesional tumor excision and fear of post-radiation osteonecrosis of bone used for delayed bony union, a conservative approach was used, and radiation therapy was not given. After one year of follow-up patient is doing well without any recurrence of the tumor and is ambulant with support. GCT of dorsal vertebral body is an uncommon entity and total en bloc excision is difficult. Therefore, the treatment strategy is not well-defined. We discuss in brief about incidence, presentation and various treatment modalities available for spinal GCT.

  5. Perivascular Epithelioid Cell Tumor in the Stomach

    Directory of Open Access Journals (Sweden)

    Sun Ah Shin

    2017-07-01

    Full Text Available Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST, and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

  6. DNA fusion vaccine designs to induce tumor-lytic CD8+ T-cell attack via the immunodominant cysteine-containing epitope of NY-ESO 1.

    Science.gov (United States)

    Campos-Perez, Juan; Rice, Jason; Escors, David; Collins, Mary; Paterson, Alex; Savelyeva, Natalia; Stevenson, Freda K

    2013-09-15

    The cancer/testis antigen NY-ESO-1 contains an immunodominant HLA-A2-binding peptide (SLLMWITQC), designated S9C, an attractive target for vaccination against several human cancers. As cysteine contains a reactive -SH, the oxidation status of exogenous synthetic peptide is uncertain. We have designed tolerance-breaking DNA fusion vaccines incorporating a domain of tetanus toxin fused to tumor-derived peptide sequences (p.DOM-peptide), placed at the C-terminus for optimal immunogenicity. In a "humanized" HLA-A2 preclinical model, p.DOM-S9C primed S9C-specific CD8+ T cells more effectively than adjuvanted synthetic peptide. A DNA vaccine encoding the full NY-ESO-1 sequence alone induced only weak S9C-specific responses, amplified by addition of DOM sequence. The analog peptide (SLLMWITQL) also primed peptide-specific CD8+ T cells, again increased by DNA delivery. Importantly, T cells induced by S9C-encoding DNA vaccines killed tumor cells expressing endogenous NY-ESO-1. Only a fraction of T cells induced by the S9L-encoding DNA vaccines was able to recognize S9C and kill tumor cells. These data indicate that DNA vaccines mimic posttranslational modifications of -SH-containing peptides expressed by tumor cells. Instability of synthetic peptides and the potential dangers of analog peptides contrast with the ability of DNA vaccines to induce high levels of tumor-lytic peptide-specific CD8+ T cells. These findings encourage clinical exploration of this vaccine strategy to target NY-ESO-1. Copyright © 2013 UICC.

  7. Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice.

    Science.gov (United States)

    Gomez-Gutierrez, Jorge G; Elpek, Kutlu G; Montes de Oca-Luna, Roberto; Shirwan, Haval; Sam Zhou, H; McMasters, Kelly M

    2007-07-01

    Cervical cancer remains a leading cause of cancer-related mortality in women, particularly in developing countries. The causal association between genital human papilloma virus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Vaccines targeting the oncogenic proteins, E6 and E7 of HPV-16 and -18 are the focus of current vaccine development. Previous studies have shown that calreticulin (CRT) enhances the MHC class I presentation of linked peptide/protein and may serve as an effective vaccination strategy for antigen-specific cancer treatment. Two replication-deficient adenoviruses, one expressing HPV-16 E7 (Ad-E7) and the other expressing CRT linked to E7 (Ad-CRT/E7), were assessed for their ability to induce cellular immune response and tested for prophylactic and therapeutic effects in an E7-expressing mouse tumor model. Vaccination with Ad-CRT/E7 led to a dramatic increase in E7-specific T cell proliferation, interferon (IFN)-gamma-secretion, and cytotoxic activity. Immunization of mice with Ad-CRT/E7 was effective in preventing E7-expressing tumor growth, as well as eradicating established tumors with long-term immunological memory. Vaccination with an adenoviral vector expressing CRT-E7 fusion protein represents an effective strategy for immunotherapy of cervical cancer in rodents, with possible therapeutic potential in clinical settings.

  8. Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350.

    Science.gov (United States)

    Mok, Hoyin; Cheng, Xing; Xu, Qi; Zengel, James R; Parhy, Bandita; Zhao, Jackie; Wang, C Kathy; Jin, Hong

    2012-01-01

    Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3(rd) position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.

  9. Cytogenetics of testicular germ cell tumors of adults

    NARCIS (Netherlands)

    van Echten, J; de Jong, B

    1998-01-01

    In this article, not intended to be a review of the literature, we present our view about the oncogenesis, pathogenesis and tumor progression of testicular germ cell tumors of adults. This view is based on our cytogenetic analyses df primary testicular germ cell tumors (seminomas and non-seminomas),

  10. Granular Cell Tumor Of The Esophagus: An Unusual Cause Of ...

    African Journals Online (AJOL)

    We report an uncommon case of dysphagia caused by a granular cell tumor in a 38 year old black female. Previously documented granular cell tumors are reported as being small and treated endoscopically. This is probably the largest reported in literature and possibly the fi rst documented in the West African subregion.

  11. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

    Directory of Open Access Journals (Sweden)

    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  12. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

    Science.gov (United States)

    Chen, Man; Joyce, M. Gordon; Kong, Wing-Pui; Chuang, Gwo-Yu; Ko, Kiyoon; Kumar, Azad; Silacci, Chiara; Thom, Michelle; Salazar, Andres M.; Corti, Davide; Lanzavecchia, Antonio; Taylor, Geraldine; Mascola, John R.; Graham, Barney S.

    2017-01-01

    Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but

  13. A Malignant Granular Cell Tumor Excised with Mohs Micrographic Surgery

    Directory of Open Access Journals (Sweden)

    David Crowe

    2012-01-01

    Full Text Available Malignant granular cell tumors are extremely rare, aggressive neoplasms displaying rapid growth and frequent associated metastatic disease. Excision and evaluation for metastatic disease are mandatory. We present a 54-year-old patient with a malignant granular cell tumor, treated with Mohs micrographic surgery. Cutaneous granular cell tumors are uncommon neoplasms, likely of perineural origin. Most follow a benign and uneventful course, with wide local excision being the treatment of choice (Enzinger, 1988. The malignant granular cell tumor is an extremely rare, aggressive variant, which provides a diagnostic challenge and management dilemma, especially with early presentation when it may be mistaken for other entities. There is also controversy regarding surgical management and follow-up of both benign and malignant granular cell tumors.

  14. Baldness, acne and testicular germ cell tumors

    Science.gov (United States)

    Trabert, Britton; Sigurdson, Alice J.; Sweeney, Anne M.; Amato, Robert J.; Strom, Sara S.; McGlynn, Katherine A.

    2013-01-01

    Androgen levels during critical periods of testicular development may be involved in the etiology of testicular germ cell tumors (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls (OR, 0.6; 95% CI, 0.4, 1.0). Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR, 0.5; 95% CI, 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake. PMID:21128977

  15. Granular cell tumors of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Kayani Naila

    2007-03-01

    Full Text Available Abstract Background Granular cell tumors (GCTs are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. Materials and methods We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. Results Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100 and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13, neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin and sarcoma (desmin, vimentin markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. Conclusion We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively.

  16. Desmoplastic Small Round Cell Tumor of Stomach

    Directory of Open Access Journals (Sweden)

    Ahmed Abu-Zaid

    2013-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is an extremely uncommon, highly aggressive, and malignant mesenchymal neoplasm of undetermined histogenesis. Less than 200 case reports have been documented in literature so far. Herein, we report a 26-year-old otherwise healthy female patient who presented with a 1-month history of epigastric pain. On physical examination, a palpable, slightly mobile, and tender epigastric mass was detected. All laboratory tests were normal. A chest, abdominal, and pelvic contrast-enhanced computed tomography (CT scans showed a 3.8 × 7.2 × 8.7 cm ill-defined mass, involving gastric fundus and extending into gastric cardia and lower gastroesophageal junction. It was associated with multiple enlarged gastrohepatic lymph nodes; the largest measured 1.2 cm. There was no evidence of ascites or retroperitoneal or mesenteric lymphatic metastases. Patient underwent total gastrectomy with D2 lymphadenectomy, splenectomy, and antecolic Roux-en-Y esophagojejunal anastomosis. Histopathological examination revealed coexpression of mesenchymal, epithelial, and neural markers. The characteristic chromosomal translocation (t(11; 22(p13; q12 was demonstrated on fluorescence in situ hybridization (FISH technique. Diagnosis of DSRCT of stomach was confirmed. Patient received no postoperative radiotherapy or chemotherapy. A postoperative 3-month followup failed to show any recurrence. In addition, a literature review on DSRCT is included.

  17. A DNA vaccine expressing CFP21 and MPT64 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Wang, Chun; Chen, Zhenhua; Fu, Ruiling; Zhang, Ying; Chen, Lingxia; Huang, Li; Li, Jinjin; Shi, Chunwei; Fan, Xionglin

    2011-08-01

    The efficacy of Bacillus Calmette-Guérin (BCG) vaccine in preventing adult tuberculosis (TB) is highly variable. Genetic differences between BCG vaccine substrains, which can be divided into early strains and late strains based on the loss of region of difference two (RD2), may result in the variability and BCG substrains. The effect of lack of RD2 on the protective efficacy of BCG substrains against TB remains unknown. In this study, we demonstrated that CFP21 and MPT64(rCM) fusion protein, encoded by RD2 of Mycobacterium tuberculosis, could stimulate higher level of interferon (IFN)-γ in tuberculin skin test (TST)-positive healthy population than in TST-negative healthy population. Compared with naive mice challenged with virulent M. tuberculosis H37Rv, C57BL/6 mice vaccinated with pcD2164 DNA expressing rCM protein resulted in a greater decrease in the bacterial load of lung. Moreover, pcD2164 could boost the protective immunity in mice primed by BCG than BCG alone or DNA vaccination alone, as evidenced by lower bacterial load in the lung tissue and reduced lung pathology. The protection induced by BCG prime-DNA vaccine boost strategy was associated with significant increases in rCM protein-specific IFN-γ. Therefore, our results clearly indicate that the loss of RD2 has an important influence on the protective efficacy of different BCG substrains. These findings will benefit the optimal choice of BCG substrain for neonatal immunization and rational design of new vaccines for the prevention of TB.

  18. Delayed menopause due to granulosa cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Bhushan Murkey

    2011-01-01

    Full Text Available A 52-year-old patient presented with complaints of menorrhagia. Endometrial biopsy revealed simple hyperplasia of the endometrium. Total abdominal hysterectomy with bilateral oophorectomy was carried out. The ovaries looked grossly normal, but histopathology reported granulosa cell tumor of the right ovary. Granulosa cell tumors belong to the sexcord stromal category and account for approximately 2% of all ovarian tumors. We review the features and treatment of granulosa cell tumors and the importance of screening for ovarian tumors in a case of endometrial hyperplasia and delayed menopause.

  19. Vaccinations

    Science.gov (United States)

    ... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...

  20. Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors.

    Science.gov (United States)

    Lae, Marick E; Roche, Patrick C; Jin, Long; Lloyd, Ricardo V; Nascimento, Antonio G

    2002-07-01

    Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young male patients and is characterized by a reciprocal translocation t(11;22)(p13;q12) associated with the EWS-WT1 gene fusion transcript. Clinical, histopathologic, immunohistochemical, and molecular genetics features were reviewed for 32 tumors. There were 29 male and three female patients, with ages from 6 to 54 years (mean, 25 years). The main clinical signs and symptoms included abdominal pain (eight patients), weight loss (five patients), and presence of umbilical hernia (four patients). Two tumors primarily involved the ethmoid sinus and the soft tissues of the scalp; the other tumors (mean size, 10 cm) involved the abdominal cavity (88%). One patient presented initially with an axillary lymph node metastasis. Generally, all tumors showed the typical histologic findings of variably sized clusters of small, round, or spindled cells lying in a desmoplastic stroma. The neoplastic cells in formalin-fixed, paraffin-embedded tissue sections were positive for desmin (dot pattern) (81% of the cases), WT1 (91%), keratin (87%), neuron-specific enolase (84%), CD99 (23%), and actin (3%). The EWS-WT1 gene fusion transcript was detected in 29 of 30 tumors. One tumor with typical clinicopathologic and immunohistochemical features did not show the gene fusion. Follow-up for 27 patients showed that 19 patients (70%) died of uncontrolled, local, or widespread metastatic disease 3-46 months (mean, 20 months) after diagnosis, and eight patients were alive with known evidence of disease. Occasionally, desmoplastic small round cell tumor lacks the classic clinical, histologic, and immunohistochemical features. This study emphasizes the utility of analysis of the EWS-WT1 gene fusion transcript, which was performed on paraffin-embedded tissues, to confirm the diagnosis.

  1. A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants.

    Science.gov (United States)

    Tameris, M; Hokey, D A; Nduba, V; Sacarlal, J; Laher, F; Kiringa, G; Gondo, K; Lazarus, E M; Gray, G E; Nachman, S; Mahomed, H; Downing, K; Abel, B; Scriba, T J; McClain, J B; Pau, M G; Hendriks, J; Dheenadhayalan, V; Ishmukhamedov, S; Luabeya, A K K; Geldenhuys, H; Shepherd, B; Blatner, G; Cardenas, V; Walker, R; Hanekom, W A; Sadoff, J; Douoguih, M; Barker, L; Hatherill, M

    2015-06-09

    Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16-26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Mixed Germ Cell Tumor of the Testis with Post- Chemotherapy ...

    African Journals Online (AJOL)

    bleomycin, etoposide and cisplatinum) chemotherapy after left orchiectomy for mixed seminomatous and non- seminomatous germ cell tumor of the testis. He presented four months post-chemotherapy with a left scrotal mass which was excised and ...

  3. General Information about Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... with testicular germ cell tumors are treated in pediatric cancer centers, but the treatment is much like the ... with Cancer Questions to Ask Your Doctor about Cancer For Survivors and Caregivers About This PDQ Summary About PDQ ...

  4. Treatment Options for Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... with testicular germ cell tumors are treated in pediatric cancer centers, but the treatment is much like the ... with Cancer Questions to Ask Your Doctor about Cancer For Survivors and Caregivers About This PDQ Summary About PDQ ...

  5. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping ... Ovarian germ cell tumors usually occur in teenage girls or young women and most often affect just ...

  6. Retroperitoneal Extragonadal Nonseminomatous Germ Cell Tumor with Synchronous Orbital Metastasis

    Directory of Open Access Journals (Sweden)

    Ali Fuat Atmaca

    2009-01-01

    Full Text Available A huge retroperitoneal tumor with a right orbital mass was detected and proved to be an extragonadal nonseminomatous germ cell tumor on biopsy. BEP chemotherapy caused some regression in orbital mass however no change in retroperitoneal tumor size as well as serum tumor marker levels occurred. Herein, we present a rarely seen entity of extragonadal retroperitoneal nonseminomatous germ cell tumor with synchronous orbital metastases and discuss its diagnosis and management.

  7. Osteoclastic giant cell tumor of the pancreas: an immunohistochemical study

    DEFF Research Database (Denmark)

    Dizon, M A; Multhaupt, H A; Paskin, D L

    1996-01-01

    A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor.......A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor....

  8. Activity of nintedanib in germ cell tumors.

    Science.gov (United States)

    Steinemann, Gustav; Jacobsen, Christine; Gerwing, Mirjam; Hauschild, Jessica; von Amsberg, Gunhild; Höpfner, Michael; Nitzsche, Bianca; Honecker, Friedemann

    2016-02-01

    Germ cell tumors (GCTs) are the most frequent malignancy in male patients between 15 and 45 years of age. Cisplatin-based chemotherapy shows excellent cure rates, but patients with cisplatin-resistant GCTs have a poor prognosis. Nintedanib (BIBF 1120, Vargatef) inhibits the receptor classes vascular endothelial growth factor receptor, platelet derived growth factor receptor, and fibroblast growth factor receptor, and has shown activity against many tumors, as well as in idiopathic lung fibrosis and bleomycin-induced lung injury. Here, we investigated the antineoplastic and antiangiogenic properties of nintedanib in cisplatin-resistant and cisplatin-sensitive GCT cells, both alone and in combination with classical cytotoxic agents such as cisplatin, etoposide, and bleomycin. The half-maximal inhibitory concentration (IC50) of nintedanib was 4.5 ± 0.43 μmol/l, 3.1 ± 0.45 μmol/l, and 3.6 ± 0.33 μmol/l in cisplatin-sensitive NTERA2, 2102Ep, and NCCIT cells, whereas the IC50 doses of the cisplatin-resistant counterparts were 6.6 ± 0.37 μmol/l (NTERA2-R), 4.5 ± 0.83 μmol/l (2102Ep-R), and 6.1 ± 0.41 μmol/l (NCCIT-R), respectively. Single treatment with nintedanib induced apoptosis and resulted in a sustained reduction in the capacity of colony formation in both cisplatin-sensitive and cisplatin-resistant GCT cells. Cell cycle analysis showed that nintedanib induced a strong G0/G1-phase arrest in all investigated cell lines. Combination treatment with cisplatin did not result in additive, synergistic, or antagonistic effects. The in-vivo activity was studied using the chorioallantoic membrane assay and indicated the antiangiogenic potency of nintedanib with markedly reduced microvessel density. Topical treatment of inoculated tumor plaques resulted in a significant reduction of the tumor size. This indicates that nintedanib might be a promising substance in the treatment of GCT.

  9. Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults.

    Science.gov (United States)

    Fries, Louis; Shinde, Vivek; Stoddard, Jeffrey J; Thomas, D Nigel; Kpamegan, Eloi; Lu, Hanxin; Smith, Gale; Hickman, Somia P; Piedra, Pedro; Glenn, Gregory M

    2017-01-01

    A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults

  10. Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection.

    Directory of Open Access Journals (Sweden)

    Qian-Fei Zuo

    Full Text Available Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla. Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

  11. Effect of viral membrane fusion activity on antibody induction by influenza H5N1 whole inactivated virus vaccine

    NARCIS (Netherlands)

    Geeraedts, Felix; ter Veer, Wouter; Wilschut, Jan; Huckriede, Anke; de Haan, Aalzen

    2012-01-01

    Whole inactivated virus (WIV) influenza vaccines are more immunogenic in unprimed individuals than split-virus or subunit vaccines. In mice, this superior immunogenicity has been linked to the recognition of the viral ssRNA by endosomal TLR7 receptors in immune cells, leading to IFN alpha production

  12. A DNA vaccine encoding mutated HPV58 mE6E7-Fc-GPI fusion antigen and GM-CSF and B7.1

    Directory of Open Access Journals (Sweden)

    Wang H

    2015-10-01

    Full Text Available He Wang,1 Jiyun Yu,2 Li Li1 1Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 2Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, People’s Republic of China Background: Persistent infection with high-risk human papillomavirus (HPV is a predominant cause of cervical cancer, and HPV58 is the third most common virus detected in the patients with cervical cancer in Asia. E6 and E7 are the viral oncogenes which are constitutively expressed in HPV-associated tumor cells and can be used as target antigens for related immunotherapy. In this study, we modified the HPV58 E6 and E7 oncogenes to eliminate their oncogenic potential and constructed a recombinant DNA vaccine that coexpresses the sig-HPV58 mE6E7-Fc-GPI fusion antigen in addition to granulocyte-macrophage colony-stimulating factor (GM-CSF and B7.1 as molecular adjuvants (PVAX1-HPV58 mE6E7FcGB for the treatment of HPV58 (+ cancer. Methods: PVAX1-HPV58 mE6E7FcGB recombinant DNA vaccine was constructed to express a fusion protein containing a signal peptide, a modified HPV58 mE6E7 gene, and human IgG Fc and glycosylphosphatidylinositol (GPI-anchoring sequences using the modified DNA vaccine vector PVAX1-IRES-GM/B7.1 that coexpresses GM-CSF, and B7.1. C57BL/6 mice were challenged by HPV58 E6E7-expressing B16-HPV58 E6E7 cells, followed by immunization by PVAX1-HPV58 mE6E7FcGB vaccine on days 7, 14, 21 after tumor challenge. The cellular immune responses in immunized mice were assessed by measuring IFN-γ production in splenocytes upon stimulation by HPV58 E6E7-GST protein and the lysis of B16-HPV58 E6E7 target cells by splenocytes after restimulation with HPV58 E6E7-GST protein. The antitumor efficacy was evaluated by monitoring the growth of the tumor. Results: PVAX1-HPV58 mE6E7FcGB elicited varying levels of IFN-lsgdB58onn T-cell immune responses and lysis of target cell in mice in response to the

  13. Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

    Science.gov (United States)

    Saljoughian, Noushin; Taheri, Tahereh; Zahedifard, Farnaz; Taslimi, Yasaman; Doustdari, Fatemeh; Bolhassani, Azam; Doroud, Delaram; Azizi, Hiva; Heidari, Kazem; Vasei, Mohammad; Namvar Asl, Nabiollah; Papadopoulou, Barbara; Rafati, Sima

    2013-01-01

    Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE))) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE)-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE)-recombinant L. tarentolae as a safe live vaccine candidate against VL.

  14. Development of Novel Prime-Boost Strategies Based on a Tri-Gene Fusion Recombinant L. tarentolae Vaccine against Experimental Murine Visceral Leishmaniasis

    Science.gov (United States)

    Saljoughian, Noushin; Taheri, Tahereh; Zahedifard, Farnaz; Taslimi, Yasaman; Doustdari, Fatemeh; Bolhassani, Azam; Doroud, Delaram; Azizi, Hiva; Heidari, Kazem; Vasei, Mohammad; Namvar Asl, Nabiollah; Papadopoulou, Barbara; Rafati, Sima

    2013-01-01

    Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB-CTE)) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL. PMID:23638195

  15. Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Noushin Saljoughian

    Full Text Available Visceral leishmaniasis (VL is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L. tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL.

  16. Expression of HPV-16 L1 capsomeres with glutathione-S-transferase as a fusion protein in tobacco plastids: an approach for a capsomere-based HPV vaccine.

    Science.gov (United States)

    Hassan, Syed Waqas; Waheed, Mohammad Tahir; Müller, Martin; Clarke, Jihong Liu; Shinwari, Zabta Khan; Lössl, Andreas Günter

    2014-01-01

    Human Papillomavirus (HPV) is the main cause of cervical cancer, which is the second most severe cancer of women worldwide, particularly in developing countries. Although vaccines against HPV infection are commercially available, they are neither affordable nor accessible to women in low income countries e.g. Africa. Thus, alternative cost-effective vaccine production approaches need to be developed. This study uses tobacco plants to express pentameric capsomeres of HPV that have been reported to generate elevated immune responses against HPV. A modified HPV-16 L1 (L1_2xCysM) protein has been expressed as a fusion protein with glutathione-S-transferase (GST) in tobacco chloroplasts following biolistic transformation. In total 7 transplastomic lines with healthy phenotypes were generated. Site specific integration of the GST-L1_2xCysM and aadA genes was confirmed by PCR. Southern blot analysis verified homogenous transformation of all transplastomic lines. Antigen capture ELISA with the conformation-specific antibody Ritti01, showed protein expression as well as the retention of immunogenic epitopes of L1 protein. In their morphology, GST-L1 expressing tobacco plants were identical to wild type plants and yielded fertile flowers. Taken together, these data enrich knowledge for future development of cost-effective plant-made vaccines against HPV.

  17. Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2017-01-20

    Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  18. Vaccination with TAT-antigen fusion protein induces protective, CD8(+) T cell-mediated immunity against Leishmania major

    National Research Council Canada - National Science Library

    Kronenberg, Katharina; Brosch, Sven; Butsch, Florian; Tada, Yayoi; Shibagaki, Naotaka; Udey, Mark C; von Stebut, Esther

    2010-01-01

    ...; induction of CD8 responses has proven to be difficult. We evaluated the immunogenicity of fusion proteins comprising the protein transduction domain of HIV-1 TAT and the Leishmania antigen LACK...

  19. A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2 - A GLURP-MSP3 fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Lousada-Dietrich, Susana; Jogdand, Prajakta S; Jepsen, Søren

    2011-01-01

    of Type 1 cytokine responses (IFN-¿), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, GLA helps to elicit a vaccine-specific Type 1 antibody profile together with high levels of LLPC, both of which are thought to be essential...

  20. Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection.

    Science.gov (United States)

    Haigh, O; Kattenbelt, J; Cochrane, M; Thomson, S; Gould, A; Tindle, R

    2010-10-01

    We describe the construction and evaluation of a recombinant hepatitis B surface antigen (HBsAg)-vectored DNA vaccine encoding the E7 and E6 tumor-associated oncoproteins of human papillomavirus (HPV) type 16. We show the induction of effector and memory cytotoxic T lymphocyte responses to E7 and E6 class I-restricted epitopes after a single immunization, which were associated with tumor prevention and therapy. The findings vindicate the use of a HBsAg-based DNA vaccine as a vehicle to elicit responses to co-encoded tumor antigens, and have specific implications for the development of a therapeutic vaccine for HPV-associated squamous carcinomas.

  1. Diffuse-type giant cell tumor of the subcutaneous thigh

    Energy Technology Data Exchange (ETDEWEB)

    Sanghvi, D.A. [KEM Hospital, Department of Radiology, Parel, Mumbai (India); Purandare, N.C. [Tata Memorial Hospital, Bio Imaging Unit, Parel, Mumbai (India); Jambhekar, N.A.; Agarwal, A. [Tata Memorial Hospital, Department of Pathology, Parel, Mumbai (India); Agarwal, M.G. [Tata Memorial Hospital, Bone and Soft Tissue Unit, Parel, Mumbai (India)

    2007-04-15

    Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms. (orig.)

  2. Extraordinarily Prolonged Disease Recurrence in a Granulosa Cell Tumor Patient

    Directory of Open Access Journals (Sweden)

    Lisa N. Abaid

    2010-09-01

    Full Text Available Background: Granulosa cell tumors are rare sex cord stromal lesions that comprise approximately 3% of all ovarian neoplasms. The vast majority of granulosa cell tumors are considered indolent but in spite of aggressive management, delayed recurrence is of significant concern. Case Report: We describe a case involving a 67-year-old woman who presented with abdominal pain, bloody stools, and mild nausea. Following a CT scan of the abdomen and pelvis, a 19-cm pelvic mass was identified. Her prior medical history included a hysterectomy for uterine fibroids 40 years ago and a bilateral salpingo-oophorectomy for a presumed granulosa cell tumor 20 years ago. Final pathology revealed granulosa cell tumor with small bowel mesentery involvement. The patient underwent surgical resection and adjuvant chemotherapy; she is currently doing well. Conclusion: Granulosa cell tumors are considered to be of low malignant potential but they have the capacity to recur, even several years following initial patient management. This case exemplifies the disease’s capacity for prolonged recurrence and further accentuates the significance of long-term follow-up in these patients.

  3. T cell responses induced by adenoviral vectored vaccines can be adjuvanted by fusion of antigen to the oligomerization domain of C4b-binding protein.

    Directory of Open Access Journals (Sweden)

    Emily K Forbes

    Full Text Available Viral vectored vaccines have been shown to induce both T cell and antibody responses in animals and humans. However, the induction of even higher level T cell responses may be crucial in achieving vaccine efficacy against difficult disease targets, especially in humans. Here we investigate the oligomerization domain of the α-chain of C4b-binding protein (C4 bp as a candidate T cell "molecular adjuvant" when fused to malaria antigens expressed by human adenovirus serotype 5 (AdHu5 vectored vaccines in BALB/c mice. We demonstrate that i C-terminal fusion of an oligomerization domain can enhance the quantity of antigen-specific CD4(+ and CD8(+ T cell responses induced in mice after only a single immunization of recombinant AdHu5, and that the T cells maintain similar functional cytokine profiles; ii an adjuvant effect is observed for AdHu5 vectors expressing either the 42 kDa C-terminal domain of Plasmodium yoelii merozoite surface protein 1 (PyMSP1(42 or the 83 kDa ectodomain of P. falciparum strain 3D7 apical membrane antigen 1 (PfAMA1, but not a candidate 128kDa P. falciparum MSP1 biallelic fusion antigen; iii following two homologous immunizations of AdHu5 vaccines, antigen-specific T cell responses are further enhanced, however, in both BALB/c mice and New Zealand White rabbits no enhancement of functional antibody responses is observed; and iv that the T cell adjuvant activity of C4 bp is not dependent on a functional Fc-receptor γ-chain in the host, but is associated with the oligomerization of small (<80 kDa antigens expressed by recombinant AdHu5. The oligomerization domain of C4 bp can thus adjuvant T cell responses induced by AdHu5 vectors against selected antigens and its clinical utility as well as mechanism of action warrant further investigation.

  4. Multicentric Giant Cell Tumor of Bone: Synchronous and Metachronous Presentation

    Directory of Open Access Journals (Sweden)

    Reiner Wirbel

    2013-01-01

    Full Text Available A 27-year-old man treated 2.5 years ago for synchronous multicentric giant cell tumor of bone located at the right proximal humerus and the right 5th finger presented now with complaints of pain in his right hip and wrist of two-month duration. Radiology and magnetic resonance revealed multicentric giant cell tumor lesions of the right proximal femur, the left ileum, the right distal radius, and the left distal tibia. The patient has an eighteen-year history of a healed osteosarcoma of the right tibia that was treated with chemotherapy, resection, and allograft reconstruction. A literature review establishes this as the first reported case of a patient with synchronous and metachronous multicentric giant cell tumor who also has a history of osteosarcoma.

  5. Prenatal diagnosis of juvenile granulosa cell tumor of the testis.

    Science.gov (United States)

    Peterson, Chad; Skoog, Steven

    2008-12-01

    Juvenile granulosa cell tumor is a rare benign neoplasm of the testicular stroma that accounts for 1-5% of all prepubertal testis tumors [Metcalfe PD, Farivar-Mohseni H, Farhat W, McLorie G, Khoury A, Bagli DJ. Pediatric testicular tumors: contemporary incidence and efficacy of testicular preserving surgery. J Urol 2003;170:2412-2416; Ross JH, Rybicki L, Kay R. Clinical behavior and a contemporary management algorithm for prepubertal testis tumors: a summary of the prepubertal testis tumor registry. J Urol 2002;168:1675-1679]. A prior case series retrospectively identified a cystic testis tumor on prenatal ultrasound images which was subsequently diagnosed as a juvenile granulosa cell tumor [Bryan DE, Cain MP, Casale AJ. Juvenile granulosa-theca cell (sex cord-stromal) tumor of the infant testis. J Urol 2003;169:1497-1498]. We report a case of a prenatally diagnosed testis tumor which was subsequently diagnosed as a juvenile granulosa cell tumor.

  6. Current Management of Refractory Germ Cell Tumors and Future Directions.

    Science.gov (United States)

    Allen, J Clayton; Kirschner, Austin; Scarpato, Kristen R; Morgans, Alicia K

    2017-02-01

    We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients. Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors. Studies aiming to identify those patients who may benefit from more intensive treatment up front to prevent the development of refractory disease are also in progress. Testicular germ cell tumors are among the most curable of all solid tumor malignancies, with cure being possible even in the refractory, metastatic setting. Treatment of refractory disease remains a challenging clinical scenario, but potentially practice changing studies are ongoing.

  7. Impact of primary metastatic bone disease in germ cell tumors

    DEFF Research Database (Denmark)

    Oing, C; Oechsle, K; Necchi, A

    2017-01-01

    Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectiv......Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis...

  8. Intraoperative scrape cytology: Adult granulosa cell tumor of ovary

    Directory of Open Access Journals (Sweden)

    Prabal Deb

    2011-01-01

    Full Text Available Adult granulosa cell tumor is often a hormonally active stromal cell neoplasm of the ovary with malignant potential. Intra-operative pathological assessment is a valuable tool in guiding optimal surgical treatment in patients. Of the various intra-operative cytological diagnostic modalities, scrape smear cytology is an effective, economical, simple, fast and reliable method with results comparable with frozen section diagnosis. We describe a case of adult granulosa cell tumor in a 30-years-old lady diagnosed on intra-operative scrape cytology, and further reconfirmed on frozen section and histopathology.

  9. A recurrent giant cell tumor of bone treated with denosumab

    Directory of Open Access Journals (Sweden)

    Nicola Stadler

    2015-02-01

    Full Text Available Although the giant cell tumor of bone is generally classified as a benign tumor it can rarely metastasize and has a potential risk of local recurrence. We want to report about a female patient who suffered from a recurrence of a giant cell tumor of bone after the implantation of a total endoprosthesis of the knee joint. We have treated her with denosumab, which is a receptor activator of nuclear factor kappa-B ligand inhibitor. In this case report we want to present a new option to treat this kind of neoplasm.

  10. Granular cell tumor masquerading as a chalazion: a case report.

    Science.gov (United States)

    Scruggs, Ryan T; Black, Evan H

    2015-01-01

    Granular cell tumors were first described in the 1920s and since then have been commonly found throughout the body. They are rarely found in periorbital, orbital, and ocular structures. The authors present a patient with a 2-year history of a lesion that had been previously excised as a presumed chalazion without pathologic analysis. The lesion recurred, and histopathological analysis following complete resection revealed a granular cell tumor. This case is an example of a rare periocular tumor. Although only an isolated case, it provides support for the recommendation that excised lesions be sent to pathologic study, particularly those with an atypical clinical course.

  11. [Clinical and pathological analysis on ovarian granulosa cell tumors].

    Science.gov (United States)

    You, Xiao-Lin; Yin, Ru-Tie; Li, Ke-Min; Wang, Dan-Qing; Li, Lei; Yang, Kai-Xuan

    2010-05-01

    To identify different clinical and pathological features for adult and juvenile granulosa cell tumors. The clinical records of 42 patients with granulosa cell tumors of ovary, including pathological features, treatments and follow up results between April 2001 and September 2009 were reviewed. 1) There were 38 newly diagnosed cases after 2001, and 4 cases were relapsed cases diagnosed before 2001. The 38 cases accounted for 3.13% of ovarian cancer cases treated in our hospital. 2) Twenty nine of the 38 cases (76.3%) were Adult Type, while the other 9 (23.7%) were Juvenile Type. The median onset age were 53 and 25 years old for the Adult Type and Juvenile Type, respectively, which shows significant difference (z = -2.990, P = 0.003). 3) The most common symptoms and signs were abdominal pain (44.7%), vaginal bleeding (42.1%), and abdominal mass (76.3%). The most common complications were endometrial hyperplasia (52.6%) and hysteromyoma (21.1%). 4) Stage I, II and III comprised 73.7%, 23.7% and 2.6% of the 38 cases, respectively. Ten patients ng the underwent conservative unilateral oophorectomy or ovarian enucleation. Twenty patients underwent total abdominal hysterectomy plus bilateral salpingo-oophorectomy. Eight patients underwent cytoreductive surgery. The 42 patients had been followed up for 7 to 175 months, with 14 patients lost of contact. No death was recorded. Inhibin, calretinin, and vimentin were demonstrated to be useful for the diagnosis of granulose cell tumors. With low incidence rate, ovarian granulosa cell tumor is a low-grade malignant and functional tumor. Most are unilateral diseases. Most Adult-type granulosa cell tumors occur in middle aged and elderly people, while most juvenile granulosa cell tumors occur in adolescents and children. Acute abdomen symptom may occur but ascites are less likely to occur in patients with granular cell tumors than those with epithelial ovarian cancers. Ovarian granulosa cell tumors are usually detected early, but

  12. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

  13. Granular cell tumor with orbital involvement in a child

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Fabiano [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Radiologia; Iyeyasu, Josie Naomi; Carvalho, Keila Monteiro de [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Oftalmo-Otorrinolaringologia; Altemani, Albina Messias [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Anatomia Patologica

    2011-09-15

    The authors report a rare case of granular cell tumor in the left medial rectus muscle of a seven-year-old boy. Clinical, pathologic and radiologic findings of the present case are described and a brief literature review is undertaken. (author)

  14. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

    NARCIS (Netherlands)

    D. Chadha; C.J. Cornelisse; A. Schabert (A.)

    1990-01-01

    textabstractAbstract The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or

  15. Giant cell tumor of bone and tenosynovial tissue : surgical outcome

    NARCIS (Netherlands)

    Heijden, Lizz van der

    2014-01-01

    Giant cell tumor of bone (GCTB) is an intermediate, locally aggressive but rarely metastasizing tumor. Radiologically, GCTB shows typical lytic lesions. MR imaging is required to evaluate extent of GCTB for surgical planning. Preferred treatment for GCTB is extended curettage with local adjuvants,

  16. Hormone therapy in ovarian granulosa cell tumors: a systematic review

    NARCIS (Netherlands)

    van Meurs, Hannah S.; van Lonkhuijzen, Luc R. C. W.; Limpens, Jacqueline; van der Velden, Jacobus; Buist, Marrije R.

    2014-01-01

    This systematic review assessed the effectiveness of hormone therapy (HT) in patients with a granulosa cell tumor (GCT) of the ovary. Medline (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), prospective trial registers and PubMed (as supplied by publisher-subset)

  17. Enxtraoviarian granulosa cell tumor: a case report | Jai | Pan African ...

    African Journals Online (AJOL)

    One such rare case of extraovarian granulosa cell tumor was encountered in a 60-year-old female patient who presented with a large intra-abdominal mass. Computerized tomography revealed a large retroperitoneal mass measuring 11 x 10 x 8cm in size. Her past medical history was irrelevant. She underwent exploration ...

  18. Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1/RSV Vaccine

    Science.gov (United States)

    Mackow, Natalie; Amaro-Carambot, Emérito; Liang, Bo; Surman, Sonja; Lingemann, Matthias; Yang, Lijuan; Collins, Peter L.

    2015-01-01

    ABSTRACT Live attenuated recombinant human parainfluenza virus type 1 (rHPIV1) was investigated as a vector to express the respiratory syncytial virus (RSV) fusion (F) glycoprotein, to provide a bivalent vaccine against RSV and HPIV1. The RSV F gene was engineered to include HPIV1 transcription signals and inserted individually into three gene locations in each of the two attenuated rHPIV1 backbones. Each backbone contained a single previously described attenuating mutation that was stabilized against deattenuation, specifically, a non-temperature-sensitive deletion mutation involving 6 nucleotides in the overlapping P/C open reading frames (ORFs) (CΔ170) or a temperature-sensitive missense mutation in the L ORF (LY942A). The insertion sites in the genome were pre-N (F1), N-P (F2), or P-M (F3) and were identical for both backbones. In vitro, the presence of the F insert reduced the rate of virus replication, but the final titers were the same as the final titer of wild-type (wt) HPIV1. High levels of RSV F expression in cultured cells were observed with rHPIV1-CΔ170-F1, -F2, and -F3 and rHPIV1-LY942A-F1. In hamsters, the rHPIV1-CΔ170-F1, -F2, and -F3 vectors were moderately restricted in the nasal turbinates, highly restricted in lungs, and genetically stable in vivo. Among the CΔ170 vectors, the F1 virus was the most immunogenic and protective against wt RSV challenge. The rHPIV1-LY942A vectors were highly restricted in vivo and were not detectably immunogenic or protective, indicative of overattenuation. The CΔ170-F1 construct appears to be suitably attenuated and immunogenic for further development as a bivalent intranasal pediatric vaccine. IMPORTANCE There are no vaccines for the pediatric respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in particular are difficult to develop due to their poor growth and physical instability, but these obstacles could be

  19. Gingival Granular Cell Tumor of the Newborn: A Case Report and Review of Literature

    OpenAIRE

    Adalat HASANOV; Jamal MUSAYEV; Binnur ÖNAL; Chingiz RAHİMOV; Ismayil FARZALIYEV

    2011-01-01

    The etiology and histogenesis of granular cell tumor are still debated. Granular cell tumor of the newborn is considered to be a different entity than the adult form of this lesion with different immunohistochemical features. We present a case of a rare gingival granular cell tumor in a newborn and review the literature. Gingival granular cell tumor must be clinically differentiated from teratoma, congenital dermoid cyst, congenital fibrosarcoma, hemangioma, lymphangioma, leiomyoma, rhabdomyo...

  20. Mediastinal germ cell tumors: a radiologic-pathologic review

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, A. [Dept. of Radiology, Aristoteles Univ., Thessaloniki (Greece); Palladas, P. [Dept. of Radiology, G. Papanicolaou Hospital, Thessaloniki (Greece); Scordalaki, A. [Dept. of Pathology, G. Papanicolaou Hospital, Thessaloniki (Greece)

    2001-10-01

    Germ cell tumors of the mediastinum are histologically identical to those found in the testes and ovaries. Early diagnosis and treatment improve the survival rate. Imaging studies of teratoma demonstrate a rounded, often lobulated heterogeneous mass containing soft tissue elements with fluid and fat attenuation. Calcification is present in 20-43% of cases. Seminomas are large masses of homogeneous soft tissue attenuation. Malignant nonseminomatous germ cell tumors are heterogeneous tumors with irregular borders due to invasion of adjacent structures. CT shows the location and extent of the tumors as well as intrinsic elements including soft tissue, fat, fluid, and calcification. CT is the modality of choice for the diagnostic evaluation of these tumors. MRI reveals masses of heterogeneous signal intensity, is more sensitive in depicting infiltration of the adjacent structures by fat plane obliteration, and is performed as an ancillary study. (orig.)

  1. Germ cell tumors of the testicle among aircraft repairmen.

    Science.gov (United States)

    Ducatman, A M; Conwill, D E; Crawl, J

    1986-10-01

    A cluster of testicular germ cell tumors occurred among 3 of 153 white men who worked in a shop engaged in repair of exterior surfaces and electrical components of the airframes of F4 Phantom Jet aircraft. Evaluation of an occupationally identical shop at a second F4 rework facility at which there had been no previous reports of excess neoplasms revealed 4 additional men with a history of testicular germ cell tumors (p less than 0.01, Poisson, compared to the expected number of cases based on national incidence rates). Our investigation raises but does not prove a hypothesis of association between subsequent development of testicular germ cell cancer and history of extensive exposure to a mixture containing dimethylformamide, which had been used in F4 repair work at these facilities in the 1960s and 1970s. This represents the first report of 2 corresponding mini-epidemics of testicular tumors among workers in occupationally identical industrial settings.

  2. CT in primary malignant germ cell tumors of the retroperitoneum

    Energy Technology Data Exchange (ETDEWEB)

    Blomlie, V.; Lien, H.H.; Fossaa, S.D.; Jacobsen, A.B.; Stenwig, A.E. (Norske Radiumhospital, Oslo (Norway). Dept. of Diagnostic Radiology Norske Radiumhospital, Oslo (Norway). Dept. of Medical Oncology Norske Radiumhospital, Oslo (Norway). Dept. of Radiotherapy Norske Radiumhospital, Oslo (Norway). Dept. of Pathology)

    1991-03-01

    Malignant germ cell tumors may exist as a primary entity in the retroperitoneum. In a CT study of 14 males with this condition (2 seminomas and 12 non-seminomatous tumors) all masses were large, lobulated and of mixed density. Fat plane obliteration against adjacent structures was frequent. The aorta was embedded in 9 patients and the inferior vena cava was affected in 7, 2 of whom had signs of compromised caval blood flow. Distant metastases were found in the lungs (7 patients), liver (n=4), posterior mediastinum (n=3), and in brain and supraclavicular lymph nodes in one patient each. Serum biomarkers were elevated in 11 patients. An extragonadal germ cell tumor should be considered when CT of the abdomen reveals a large retroperitoneal mass with mixed density. (orig.).

  3. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2018-02-05

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  4. Antigen capsid-display on human adenovirus 35 via pIX fusion is a potent vaccine platform

    Science.gov (United States)

    van der Helm, Esmeralda; Spek, Dirk; Vorthoren, Lars; Serroyen, Jan; Kuipers, Harmjan; Schuitemaker, Hanneke; Zahn, Roland; Custers, Jerome; Vellinga, Jort

    2017-01-01

    Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings. PMID:28362809

  5. Giant cell tumor of tendon sheath: Spectrum of radiologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Karasick, D.; Karasick, S. (Jefferson Medical Coll., Philadelphia, PA (United States) Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States))

    1992-05-01

    Giant cell tumor of tendon sheath is the second most common tumor of the hand. It can also occur in larger joints. Radiologic features include a soft-tissue mass with or without osseous erosion. Less commonly, it can cause periostitis or permeative osseous invasion; it may rarely calcify. The entire imaging spectrum of this lesion is presented, with emphasis on atypical appearances which can mimic other lesions. (orig.).

  6. Circulating tumor cells in patients with testicular germ cell tumors.

    Science.gov (United States)

    Nastały, Paulina; Ruf, Christian; Becker, Pascal; Bednarz-Knoll, Natalia; Stoupiec, Małgorzata; Kavsur, Refik; Isbarn, Hendrik; Matthies, Cord; Wagner, Walter; Höppner, Dirk; Fisch, Margit; Bokemeyer, Carsten; Ahyai, Sascha; Honecker, Friedemann; Riethdorf, Sabine; Pantel, Klaus

    2014-07-15

    Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers. CTCs were enriched from peripheral blood (n = 143 patients) and testicular vein blood (TVB, n = 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system. In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P = 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of α-fetoprotein (AFP; P = 0.025), β-human chorionic gonadotropin (βHCG; P = 0.002), and lactate dehydrogenase (LDH; P = 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood. The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery. ©2014 American Association for Cancer Research.

  7. Giant cell tumor of the frontal sinus: case report

    Energy Technology Data Exchange (ETDEWEB)

    Matushita, Joao Paulo, E-mail: jpauloejulieta@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Hospital das Clinicas; Matushita, Julieta S.; Matushita Junior, Joao Paulo Kawaoka [Centro de Diagnostico por Imagem Dr. Matsushita, Belo Horizonte, MG (Brazil); Matushita, Cristina S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Hospital Universitario Clementino Fraga Filho; Simoes, Luiz Antonio Monteiro; Carvalho Neto, Lizando Franco de

    2013-06-15

    The authors report the case of a giant cell tumor of the frontal sinus in a 54-year-old male patient. This tumor location is rare, and this is the third case reported in the literature with radiographic documentation and histopathological confirmation. The patient underwent surgery, with curettage of frontal sinus and placement of a prosthesis. He died because a voluntary abrupt discontinuation of corticosteroids. (author)

  8. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    Science.gov (United States)

    2017-10-05

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  9. Leydig cell tumor in grey zone: A case report.

    Science.gov (United States)

    Muheilan, Muheilan Mustafa; Shomaf, Maha; Tarawneh, Emad; Murshidi, Muayyad Mujalli; Al-Sayyed, Manar Rizik; Murshidi, Mujalli Mhailan

    2017-01-01

    Leydig cell tumor constitutes only about 1-3% of testicular neoplasms. There is apparently increased incidence in the last few years; one possible explanation for this phenomenon is the widespread use of ultrasound technology and the subsequent increased early detection of smaller lesions that have not been found in historical series. We report a case of Leydig cell tumor of testis in a patient presenting with painless long standing slowly growing left scrotal mass who found to have intrapulmonary nodule and multiple enlarged retroperitoneal lymph nodes on staging work up. The mass was managed by radical orchiectomy. Pathological diagnosis was Leydig cell tumor. Orchiectomy is the accepted mode of treatment but follow-up every 3-6 months with physical examination, hormone assays, scrotal and abdominal ultrasonography, chest radiography, and CT scans is essential in such a case with a potential for malignant behavior. Inguinal orchiectomy is the therapeutic decision of choice and long-term follow-up is necessary to exclude recurrence or metastasis. Cases which fall in the grey zone like ours need to be followed up carefully for metastasis instead of rushing into an early retroperitoneal lymph node dissection, with its potential risks and complications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10.  An Uncommon Presentation of Giant Cell Tumor

    Directory of Open Access Journals (Sweden)

    Gopal Malhotra

    2011-09-01

    Full Text Available  Giant Cell Tumors commonly occur at the ends of long bones. However in rare cases, they can occur in the bones of the hands and feet. Tumors in these locations occur in younger patients; in addition, these tumors are more commonly multifocal and are associated with a higher risk for local recurrence than tumors at the ends of long bones. Since lesions in the small bones may be multifocal, a patient with a giant cell tumor of the small bones should undergo a skeletal survey to exclude similar lesions elsewhere. Primary surgical treatment ranges from curettage or excision with or without bone grafting to amputation. The success of surgical treatment depends on the completeness with which the tumor was removed. We are presenting a case report of a 34 year old female, who presented with a swelling in the right hand, following trauma. X-ray of the hand showed an osteolytic expansile lesion at the base of the 1st metacarpal bone. The lesion was initially curetted and then treated by local resection with bone grafting. Histological examination revealed a typical benign giant cell tumor composed of closely packed stromal cells with a variable admixture of giant cells. Follow up at the end of one year did not reveal any recurrence of the tumor.

  11. Effects of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in rats with caries.

    Science.gov (United States)

    Liu, Chang; Fan, Mingwen; Bian, Zhuan; Chen, Zhi; Li, Yuhong

    2008-12-02

    Our previously prophylactic studies have proved that the anti-caries DNA vaccine pGJA-P/VAX could generate effective immune response by intramuscular (i.m.) and intranasal (i.n.) administration in rats without caries. In the present, we determine whether it also could produce efficacy in rats with caries. By immunized with pGJA-P/VAX, rats were elicited both significantly higher anti-Streptococcus mutans serum IgG and salivary SIgA responses, compared to those with pVAX1. Correspondingly, rats immunized with pGJA-P/VAX via i.n. displayed significantly fewer enamel, dentinal lesions compared to those with pVAX1 via i.n. However, there was no significant difference in dental caries lesions between pGJA-P/VAX (i.m.) and pVAX1 (i.m.). These findings suggest that DNA vaccination via i.n., with bupivacaine delivery system, could be a promising alternatives for slowing down caries development in rat models.

  12. Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate.

    Science.gov (United States)

    Liang, Bo; Ngwuta, Joan O; Surman, Sonja; Kabatova, Barbora; Liu, Xiang; Lingemann, Matthias; Liu, Xueqiao; Yang, Lijuan; Herbert, Richard; Swerczek, Joanna; Chen, Man; Moin, Syed M; Kumar, Azad; McLellan, Jason S; Kwong, Peter D; Graham, Barney S; Collins, Peter L; Munir, Shirin

    2017-08-01

    Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. A live attenuated chimeric bovine/human parainfluenza virus type 3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naive children, rB/HPIV3 was well tolerated but the immunogenicity of wild-type RSV F was unsatisfactory. We previously modified RSV F with a designed disulfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently packaged in the vector virion. Here, we further stabilized pre-F by adding both disulfide and cavity-filling mutations (DS-Cav1), and we also modified RSV F codon usage to have a lower CpG content and a higher level of expression. This RSV F open reading frame was evaluated in rB/HPIV3 in three forms: (i) pre-F without vector-packaging signal, (ii) pre-F with vector-packaging signal, and (iii) secreted pre-F ectodomain trimer. Despite being efficiently expressed, the secreted pre-F was poorly immunogenic. DS-Cav1 stabilized pre-F, with or without packaging, induced higher titers of pre-F specific antibodies in hamsters, and improved the quality of RSV-neutralizing serum antibodies. Codon-optimized RSV F containing fewer CpG dinucleotides had higher F expression, replicated more efficiently in vivo, and was more immunogenic. The combination of DS-Cav1 pre-F stabilization, optimized codon usage, reduced CpG content, and vector packaging significantly improved vector immunogenicity and protective efficacy against RSV. This provides an improved vectored RSV vaccine candidate suitable for pediatric clinical evaluation.IMPORTANCE RSV and HPIV3 are the first and second leading viral causes of severe pediatric respiratory disease worldwide. Licensed vaccines or suitable antiviral drugs are not available. We

  13. Expression of an endotoxin-free S-layer/allergen fusion protein in gram-positive Bacillus subtilis 1012 for the potential application as vaccines for immunotherapy of atopic allergy

    Directory of Open Access Journals (Sweden)

    Egelseer Eva

    2011-02-01

    Full Text Available Abstract Background Genetic fusion of the major birch pollen allergen (Bet v1 to bacterial surface-(S-layer proteins resulted in recombinant proteins exhibiting reduced allergenicity as well as immunomodulatory capacity. Thus, S-layer/allergen fusion proteins were considered as suitable carriers for new immunotherapeutical vaccines for treatment of Type I hypersensitivity. Up to now, endotoxin contamination of the fusion protein which occurred after isolation from the gram-negative expression host E. coli had to be removed by an expensive and time consuming procedure. In the present study, in order to achieve expression of pyrogen-free, recombinant S-layer/allergen fusion protein and to study the secretion of a protein capable to self-assemble, the S-layer/allergen fusion protein rSbpA/Bet v1 was produced in the gram-positive organism Bacillus subtilis 1012. Results The chimaeric gene encoding the S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177 as well as Bet v1 was cloned and expressed in B. subtilis 1012. For that purpose, the E. coli-B. subtilis shuttle vectors pHT01 for expression in the B. subtilis cytoplasm and pHT43 for secretion of the recombinant fusion protein into the culture medium were used. As shown by western blot analysis, immediately after induction of expression, B. subtilis 1012 was able to secret rSbpA/Bet v1 mediated by the signal peptide amyQ of Bacillus amyloliquefaciens. Electron microscopical investigation of the culture medium revealed that the secreted fusion protein was able to form self-assembly products in suspension but did not recrystallize on the surface of the B. subtilis cells. The specific binding mechanism between the N-terminus of the S-layer protein and a secondary cell wall polymer (SCWP, located in the peptidoglycan-containing sacculi of Ly. sphaericus CCM 2177, could be used for isolation and purification of the secreted fusion protein from the culture medium. Immune reactivity of rSbpA/Bet v1

  14. Enhancement of immunostimulatory properties of exosomal vaccines by incorporation of fusion-competent G protein of vesicular stomatitis virus.

    Science.gov (United States)

    Temchura, Vladimir V; Tenbusch, Matthias; Nchinda, Godwin; Nabi, Ghulam; Tippler, Bettina; Zelenyuk, Maryna; Wildner, Oliver; Uberla, Klaus; Kuate, Seraphin

    2008-07-04

    Exosomes have been proposed as candidates for therapeutic immunization. The present study demonstrates that incorporation of the G protein of vesicular stomatitis virus (VSV-G) into exosome-like vesicles (ELVs) enhances their uptake and induces the maturation of dendritic cells. Targeting of VSV-G and ovalbumin as a model antigen to the same ELVs increased the cross-presentation of ovalbumin via an endosomal acidification mechanism. Immunization of mice with VSV-G and ovalbumin containing ELVs led to an increased IgG2a antibody response, expansion of antigen-specific CD8 T cells, strong in vivo CTL responses, and protection from challenge with ovalbumin expressing tumor cells. Thus, incorporation of VSV-G and targeting of antigens to ELVs are attractive strategies to improve exosomal vaccines.

  15. Giant cell tumor-like lesion of the urinary bladder: a report of two cases and literature review; giant cell tumor or undifferentiated carcinoma?

    Directory of Open Access Journals (Sweden)

    Oznur Meltem

    2009-12-01

    Full Text Available Summary Giant cell tumor, excluding its prototype in bone, is usually a benign but local aggressive neoplasm originating from tendon sheath or soft tissue. Malignant behavior is uncommon. Visceral organ involvement including urinary bladder is rare. Giant cell tumors in visceral organs usually accompany epithelial tumors and the clinical behavior of giant cell tumor in urinary bladder is similar to its bone counterpart. Here, we report two cases of giant cell tumor located in urinary bladder in comparison with nine reported cases in the English literature. Concurrent noninvasive urothelial carcinoma was also described in all these previous reports and only one patient with follow-up died of disease. One of the two cases we present had no concurrent urothelial tumor at the time of diagnosis but had a history of a low grade noninvasive urothelial carcinoma with three recurrences. The histology of these two cases was similar to the giant cell tumor of bone and composed of oval to spindle mononuclear cells with evenly spaced osteoclast-like giant cells. Immunohistochemically, the giant cells showed staining with osteoclastic markers including CD68, TRAP, and LCA. Immunohistochemical expression of vimentin, CD68, LCA, and smooth muscle actin in mononuclear cells supported a mesenchymal origin with histiocytic lineage. The histologic and immunohistochemical properties in our cases as well as their clinical courses were consistent with a giant cell tumor. Consequently, tumors in urinary bladder showing features of giant cell tumor of bone may also be considered and termed "giant cell tumor".

  16. Expression of P450 Aromatase in Granulosa Cell Tumors and Sertoli-Stromal Cell Tumors of the Ovary: Which Cells Are Responsible for Estrogenesis?

    Science.gov (United States)

    Kato, Noriko; Uchigasaki, Shinya; Fukase, Masayuki; Kurose, Akira

    2016-01-01

    Granulosa cell tumors are representative of estrogenic ovarian tumors, and some Sertoli-stromal cell tumors are also estrogenic. The exact cells that are responsible for estrogenesis, however, have yet to be identified. In the present study, 25 sex cord-stromal tumors (20 granulosa cell tumors, 4 Sertoli-Leydig cell tumors, and a Sertoli cell tumor) were immunohistochemically examined for expression of P450 aromatase, which is critical for estrogenesis. All of the tumors had been evaluated for estrogenic function, including contemporaneous endometrial hyperplasia and/or elevation of serum estradiol. Eleven of 14 estrogenic granulosa cell tumors showed sparse or aggregated immunoreactivity for aromatase, whereas 5 of 6 nonestrogenic tumors did not. Aromatase was selectively expressed by plump granulosa cells with eosinophilic or vacuolated cytoplasm, resembling luteinized granulosa cells. Such a localization of aromatase is analogous to that in normal ovaries. Aromatase expression in primary tumors was recapitulated by recurrent tumors. In Sertoli-stromal cell tumors, either undifferentiated plump cells or well-differentiated Sertoli cells expressed aromatase. In conclusion, the expression of P450 aromatase corresponds to specific cell morphology in sex cord-stromal tumors, including recurrent tumors. Aromatase status in granulosa cell tumors provides helpful information on whether serum estradiol could be a marker for recurrence.

  17. Expression of parafibromin in major renal cell tumors

    Directory of Open Access Journals (Sweden)

    C. Cui

    2012-10-01

    Full Text Available Parafibromin, encoded by HRPT2 gene, is a recently identified tumor suppressor. Complete and partial loss of its expression have been observed in hyperparathyroidism-jaw tumor (HPT-JT, parathyroid carcinoma, breast carcinoma, lung carcinoma, gastric and colorectal carcinoma. However, little has been known about its expression in renal tumors. In order to study the expression of parafibromin in a series of the 4 major renal cell tumors - clear cell renal cell carcinoma (ccRCC, papillary renal cell carcinoma (pRCC, chromophobe renal cell carcinoma (chRCC and oncocytoma. One hundred thirty nine renal tumors including 61 ccRCCs, 37 pRCCs, 22 chRCCs and 19 oncocytomas were retrieved and used for the construction of renal tissue microarrays (TMAs. The expression of parafibromin was detected by immunohistochemical method on the constructed TMAs. Positive parafibromin stains are seen in 4 out of 61 ccRCCs (7%, 7 out of 37 pRCCs (19%, 12 out of 23 chRCCs (52% and all 19 oncocytomas (100%. Parafibromin expression varies significantly (P< 8.8 x10-16 among the four major renal cell tumors and were correlated closely with tumor types. No correlation of parafibromin expression with tumor staging in ccRCCs, pRCCs and chRCCs, and Fuhrman nuclear grading in ccRCCs and pRCCs. In summary, parafibromin expression was strongly correlated with tumor types, which may suggest that it plays a role in the tumorigenesis in renal cell tumors.

  18. [Granular cell tumor: an infrequent cause of dysphonia in childhood].

    Science.gov (United States)

    Lassaletta Atienza, L; Alonso García, S; Villafruela, M A; Martínez Tello, F J; Alvarez Vicent, J J

    1999-01-01

    Granular cell tumors (GCT) are rare and usually benign tumors whose histogenesis is debated. The skin, subcutaneous tissues, and mucosae of the head and neck are areas of predilection for GCT. Laryngeal involvement is uncommon, but may create diagnostic and therapeutic problems when it occurs. Laryngeal GCT are decidedly uncommon in children, only 17 cases having been reported in the literature. A case of GCT of the larynx in an 11-year-old girl is reported. The presenting symptom was hoarseness. The macroscopic tumor and hoarseness disappeared after chemotherapy (EVAIA) for Ewing sarcoma of the knee.

  19. Testicular mixed germ cell tumor with polyembryoma component in brothers.

    Science.gov (United States)

    Bakaris, Sevgi; Resim, Sefa; Tunali, Nurdan

    2005-01-01

    We report the case of a 17-year-old male with a testicular tumor and high serum levels of alpha-fetoprotein. The patient was treated with surgery followed by combination chemotherapy with bleomycin, etoposide, and cisplatin. Histologic examination showed features of a mixed germ cell tumor composed of mature teratoma, immature teratoma, embryonal carcinoma, yolk sac tumor, and polyembryoma. He is currently well, and his serum levels of alpha-fetoprotein have been normal more than 5 months after treatment. His brother, aged 17 years at the time, had a similar tumor removed from the right testicle 5 years previously.

  20. Spinal fusion

    Science.gov (United States)

    ... Low back pain - fusion; Herniated disk - fusion; Spinal stenosis - fusion; Laminectomy - fusion ... be done: With other surgical procedures for spinal stenosis , such as foraminotomy or laminectomy After diskectomy in ...

  1. Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in mice.

    Science.gov (United States)

    Liu, Chang; Fan, Mingwen; Xu, Qingan; Li, Yuhong

    2008-03-01

    To study the biodistribution and expression of anti-caries DNA vaccine pGJA-P/VAX in mice models following intranasal (i.n.) and intramuscular (i.m.) immunization. pGJA-P/VAX and pVAX1 were administrated i.n. and i.m. to mice, respectively. Blood and organs were harvested and then genomic DNA was extracted. mRNA in the original tissues and draining lymph nodes was isolated. The in vivo fate of plasmid DNA in these samples was evaluated with real-time quantitative polymerase chain reaction (PCR). The ratio of the area under the curve (AUC) and maximum concentration (Cmax) after i.n. immunization were higher than that after i.m. injection. At 1 day post i.n. immunization, the localization of plasmid to the heart, spleen and lung was notable compared with that to the nasal mucosa. At 2 days, for i.n. immunization, the concentration value of plasmid in the mucosa-associated lymphoid tissues such as lung, kidney and gastrointestine had increased and was greater than that via i.m. injection. At later time points, the plasmid was primarily in the original tissues and draining lymph nodes. mRNA expression was observed in the topical tissues up to 7 days and in the draining lymph nodes for at least 3 days. These results indicate that the distribution of pGJA-P/VAX was widespread in vivo, and the expression was significant in the inoculation tissue and draining lymph nodes after i.n. immunization and i.m. injection. This data provides evidence which supports the long-term immune responses and the basis of further research on safety issues. Copyright (c) 2007 John Wiley & Sons, Ltd.

  2. Benign granular-cell tumor of the breast: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Devi Meenal Jagannathan, MD(RD, DMRD, DNB(RD, FRCR

    2015-01-01

    Full Text Available Granular-cell tumor is an uncommon cause of breast mass in premenopausal women that presents as a painless chronic lump. It mimics infiltrating carcinoma clinically and radiologically. Granular-cell tumor is usually benign, and the treatment is wide local excision. Definitive pre-operative diagnosis helps to avoid unnecessary mastectomy. We present clinical, mamographic, and sonographic characteristics of a benign granular-cell tumor of the breast in a 57-year-old woman.

  3. Benign granular-cell tumor of the breast: Case report and literature review.

    Science.gov (United States)

    Jagannathan, Devi Meenal

    2015-01-01

    Granular-cell tumor is an uncommon cause of breast mass in premenopausal women that presents as a painless chronic lump. It mimics infiltrating carcinoma clinically and radiologically. Granular-cell tumor is usually benign, and the treatment is wide local excision. Definitive pre-operative diagnosis helps to avoid unnecessary mastectomy. We present clinical, mamographic, and sonographic characteristics of a benign granular-cell tumor of the breast in a 57-year-old woman.

  4. May Lymphadenectomy be Omitted in Granulosa Cell Tumors of the Ovary?

    OpenAIRE

    Oz, Murat; Selcuk, Ilker; Ozdal, Bulent; Biberoglu, Ebru; Bas, Sevda; Meydanli, Mehmet Mutlu; Akbay, Serap; Gungor, Tayfun

    2016-01-01

    Granulosa cell tumors (GCTs) of the ovary are rare tumors and they are generally detected in early stages with a favorable prognosis. However, the controversies over the extend of surgery are still judging the surgical management. We retrospectively evaluated demographic and clinical variables of granulosa cell tumors of the ovary with probable prognostic factors to identify the clinicopathological features. Women with adult type granulosa cell tumor pathology result between March 2007 and Ap...

  5. Granulosa cell tumor of the ovary: a clinicopathological study of six cases

    OpenAIRE

    RC Adhikari; Jha, A; G Shayami

    2011-01-01

    Background: Ovarian granulosa cell tumors are rare malignant neoplasms that originate from the sexcord stromal cells of the ovary. The study aims to collate data of all granulosa cell tumors diagnosed in Tribhuvan University Teaching Hospital over the last 3 years and to describe the incidence, patient profile, ultrasonographic and histopathologic findings in our local context. Materials and Methods: A total of 6 (5%) granulosa cell tumors, diagnosed in Tribhuvan University Teaching Hospital ...

  6. Pediatric giant cell tumor of the tendon sheath of the craniocervical junction involving the occipital condyle.

    Science.gov (United States)

    Cho, Jin Mo; Chang, Jong Hee; Kim, Sun Ho; Lee, Kyu Sung

    2016-01-01

    Giant cell tumor of the tendon sheath (GCTTS), also called pigmented villonodular synovitis, is a common lesion of the synovial membrane of the hand joint, but it uncommonly involves the axial skeleton, especially in pediatric populations. Furthermore, GCTTS originating from the occipital condyle has not been reported previously. A 15-year-old girl presented with a palpable neck mass for 1 year, and imaging studies revealed a less demarcated and heterogeneously enhanced mass in the suboccipital region. The tumor was originating from the occipital condyle that eroded the skull and atlas, and it was completely resected via a far lateral transcondylar approach followed by transarticular screw fixation. After the resection, we performed occipitocervical fusion to prevent spinal instability. The patient made an uneventful recovery after surgery. Recurrence has not been observed after 5 years of follow-up. We report this rare case and briefly review the general features and unusual locations of GCTTS with recommendations for treatment modalities.

  7. Testicular germ cell tumors and related research from a historical point of view

    DEFF Research Database (Denmark)

    Damjanov, Ivan; Albrechtsen, Nicolai Jacob Wewer

    2013-01-01

    In this brief overview of the history of testicular germ cell tumors, we touch upon the key events and personalities that have contributed to our current understanding of germ cell tumors in general, and those of the testis in particular. The intricacies of human germ cell tumor pathology...... and histogenesis have been elucidated in part by contributions in the field of experimental pathology and developmental biology. Correlation between clinical oncologic findings, pathology and experimental studies of germ cell tumors and related topics ushered the era of cellular and genetic engineering that have...

  8. Expression, Purification and Characterization of GMZ2'.10C, a Complex Disulphide-Bonded Fusion Protein Vaccine Candidate against the Asexual and Sexual Life-Stages of the Malaria-Causing Plasmodium falciparum Parasite

    DEFF Research Database (Denmark)

    Mistarz, Ulrik H; Singh, Susheel K; Nguyen, Tam T T N

    2017-01-01

    PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate...... for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method. Protein purity and stability...

  9. Pathobiology of germ cell tumors - applying the gossip test!

    Science.gov (United States)

    Looijenga, Leendert H J; Oosterhuis, J Wolter

    2013-01-01

    Residual mature teratoma, a frequent finding in clinical pathology since the introduction of cisplatin-based chemotherapy, put Wolter Oosterhuis on the track of germ cell tumors (GCTs). These neoplasms in the borderland between developmental biology and oncology have fascinated him ever since. He tells the story on how GCTs brought him in contact with leading investigators in the field like Ivan Damjanov, Peter Andrews, and Niels Skakkebaek. His fruitful line of research was made possible through a longstanding collaboration with Bauke de Jong and, to this day, Leendert Looijenga who joined his group as a student in 1988. Probably their most important contribution to the field of GCTs is an integrated approach to GCTs, combining epidemiology, pathology, (cyto)genetics and molecular biology, that has resulted in a pathobiology-based classification of GCTs in five types. It has clinical relevance and stimulates further research on these intriguing neoplasms and their corresponding animal models.

  10. Primary desmoplastic small round cell tumor of the femur

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Akihiko; Garcia, Joaquin [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Edgar, Mark A. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Meyers, Paul A. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Morris, Carol D. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Surgery, Orthopaedic Service, New York, NY (United States); Panicek, David M. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2008-09-15

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  11. Nonepiphyseal Giant Cell Tumor of the Rib: A Case Report

    Science.gov (United States)

    Moschouris, Hippocrates; Marinis, Athanasios; Bouma, Evanthia; Karagiannis, Evangelos; Kiltenis, Michalis; Papadaki, Marina

    2012-01-01

    A case of a 32-year-old female patient with a giant cell tumor originating in the middle part of the left 10th rib is presented. On X-rays and CT, the tumor caused a well-defined osteolysis with nonsclerotic borders. On MRI, it exhibited intermediate signal intensity on T1 sequences and central high signal and peripheral intermediate signal on T2 sequences. On contrast-enhanced MR images both central and peripheral-periosteal enhancement was noted. Thanks to its small size (2 × 1.3 cm), the lesion was easily resected en bloc with a part of the affected rib. The patient is free of recurrence for 3 years after the operation. PMID:23119206

  12. Nonepiphyseal Giant Cell Tumor of the Rib: A Case Report

    Directory of Open Access Journals (Sweden)

    Hippocrates Moschouris

    2012-01-01

    Full Text Available A case of a 32-year-old female patient with a giant cell tumor originating in the middle part of the left 10th rib is presented. On X-rays and CT, the tumor caused a well-defined osteolysis with nonsclerotic borders. On MRI, it exhibited intermediate signal intensity on T1 sequences and central high signal and peripheral intermediate signal on T2 sequences. On contrast-enhanced MR images both central and peripheral-periosteal enhancement was noted. Thanks to its small size ( cm, the lesion was easily resected en bloc with a part of the affected rib. The patient is free of recurrence for 3 years after the operation.

  13. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-01-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  14. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-03-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  15. Early pregnancy complicated with juvenile granulosa cell tumor.

    Science.gov (United States)

    Xu, Hongmei; Shu, Chang; Li, Na; Xia, Meihui; Li, Tingting; Zhong, Yanping; Yan, Xu; Wang, Hong; Zhang, Haipeng; He, Jin

    2011-11-01

    Granulosa cell tumors (GCTs) are extremely rare tumors and are divided into 2 types: adult (AGCT) and juvenile (JGCT). The JGCTs represent only 5% of all cases. The incidence of ovarian carcinoma diagnosed during pregnancy varies about 0.0179 to 0.11 per 1000 pregnancies. A 24-year-old woman at 12 weeks and 3 days of pregnancy was admitted to the authors' hospital due to a pelvic mass. Surgical exploration revealed a smooth, solid, mobile and well-encapsulated left ovarian mass. Histological and immunohistochemical findings led to the diagnosis of a well-differentiated JGCT. Pregnancy continued uncomplicated and she delivered a healthy baby girl at 37 weeks gestation. About 9 months after the original diagnosis, the patient showed no evidence of disease. Treatment options and a review of the literature related to JGCTs are discussed.

  16. THE EPIGENETICS OF RENAL CELL TUMORS: FROM BIOLOGY TO BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Rui eHenrique

    2012-05-01

    Full Text Available Renal cell tumors (RCT collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling / histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided.

  17. Cytology of mixed germ cell tumor with mediastinal metastasis

    Directory of Open Access Journals (Sweden)

    Dagli Adile

    2009-01-01

    Full Text Available Nonseminomatous germ cell tumors of the testis are common and are very aggressive malignant tumors. Most of the cases have metastases at the time of diagnosis, and involvement of the posterior mediastinum in particular is well known. A 33 year-old male patient presented with complaints of a swelling on the right side of the neck that had been growing for the last month, as well as shortness of breath and cough. His thoracic computed tomography (CT showed a 1.5 cm lymph node on the anterior mediastinum and a mass of about 11 x 10 x 8 cm extending from the right lung apex to the right hilus, with regular contours and without contrast enhancement. The patient, who was given the preliminary diagnosis of a mixture metastatic bronchial tumor plus lymphoma, was subjected to transthoracic fine needle aspiration cytology (FNAC. His abdominal CT revealed a hypodense, heterogeneous and cystic necrotic mass of about 10 x 7 x 5 cm that was para-aortic at the infrarenal level (initially predicted as a lymphoma. The patient, who could not be typed in his cytopathological examination, was diagnosed with malignant epithelial tumor and was recommended to undergo a genitourinary system examination. Upon finding a high alpha fetoprotein (AFP value, a scrotal ultra sonography was performed which showed a mass filling the right testis. Histopathological examination of the orchiectomy material resulted in the diagnosis of mixed germ cell tumor (60% mature teratoma and 40% yolk sac tumor. Even though metastatic lesions are mostly seen in the posterior mediastinum, our findings reveal that specimens obtained with FNAC from the anterior mediastinum bear discohesive, pleomorphic, small nuclei in epithelial cells with microvacoules in the cytoplasm. These cytopathological alterations in specimens from the anterior mediastinum might promote germ cell and yolk sac tumors.

  18. Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

    Directory of Open Access Journals (Sweden)

    Andrea Hayes-Jordan

    2011-12-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a very rare disease of children, adolescents, and young adults and involves the abdominal cavity. DSRCT has characteristic fusion gene involving EWS1 and WT1 translocation, t(11;22(p13;q12. Unlike Ewing’s sarcoma of bone, DSRCT usually presents with diffuse peritoneal implants that are prone to recur. The primary organ of origin of DSRCT is mesenchyme of the peritoneum. This makes it a very unique tumor that is difficult to treat because of the infiltrative and diffuse nature of the peritoneum. The challenge of local control is to remove dozens to hundreds of tumors studding the peritoneal cavity, and then eliminate microscopic disease. We review a sequential multimodality strategy to reduce macroscopic and microscopic disease including neoadjuvant chemotherapy, aggressive surgery including an emerging new therapy to use after surgery to treat microscopic residual disease: continuous hyperthermic peritoneal chemotherapy,

  19. Spinal Fusion

    Science.gov (United States)

    ... concept of fusion is similar to that of welding in industry. Spinal fusion surgery, however, does not ... are taking for other conditions, and your overall health can affect the rate of healing and fusion, ...

  20. Nuclear Fusion

    National Research Council Canada - National Science Library

    Ghoranneviss, Mahmood; Parashar, S. K. S; Aslan, Necdet; Aslaninejad, Morteza; Salar Elahi, A

    2014-01-01

    ... in both inertial and magnetic confinement fusion, with attendees from major fusion energy research centers worldwide. It is one of the most important issues in this field. Nuclear fusion continues t...

  1. Apparent ectopic pregnancy with unexpected finding of a germ cell tumor: A case report.

    Science.gov (United States)

    Kucera, Calen; Cox-Bauer, Callie; Miller, Caela

    2017-08-01

    •Ovarian germ cell tumors can produce hCG and be confused with ectopic pregnancy.•Ovarian germ cell tumors can present with subacute pelvic pain.•Ectopic pregnancy should be the primary differential diagnosis due to its acuity.

  2. Granular Cell Tumor - a Rare Tumor of the Mons Pubis: Case Report ...

    African Journals Online (AJOL)

    Objective: Granular cell tumor of the mons pubis is rare. A case is reported with literature review. Material and Method: Study of the management and outcome of a 23 year old Nigerian woman with granular cell tumor in the mons pubis. Literature review was done utilizing a Medline search for the last ten years. Results: The ...

  3. Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood central nervous system (CNS) germ cell tumors form from germ cells (a type of cell that forms as a fetus develops and later becomes sperm in the testicles or eggs in the ovaries). Learn about the signs, tests to diagnose, and treatment of pediatric germ cell tumors in the brain in this expert-reviewed summary.

  4. Germ Cell Tumor Located in the Midline of the Anterior Neck

    OpenAIRE

    Tatyana PIRDOPSKA; Terziev, Ivan; Sv. HRISTOVA; W. MLADENOVSKY; Petkov, R.

    2011-01-01

    Primary germ cell tumors involving midline of the anterior neck are extremely rare. Here we report a 68-year-old male who was operated due to a mass lesion in the anterior neck with infiltration of the isthmus of the thyroid gland. Histopathological examination revealed a germ cell tumor with extragonadal localization in the anterior neck infiltrating the isthmus of the thyroid gland.

  5. Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand Inhibition

    Directory of Open Access Journals (Sweden)

    Martin F. Dietrich MD, PhD

    2014-11-01

    Full Text Available Lung metastases are a rare complication of giant cell tumors of bone. We herein describe an interesting case of histological regression and size reduction of lung metastases originating from a primary giant cell tumor of bone in response to the RANK ligand inhibitor denosumab.

  6. Characterization and immunogenicity of rLipL32/1-LipL21-OmpL1/2 fusion protein as a novel immunogen for a vaccine against Leptospirosis

    Directory of Open Access Journals (Sweden)

    Zhao Xin

    2015-01-01

    Full Text Available Vaccination is an effective strategy to prevent leptospirosis, a global zoonotic disease caused by infection with pathogenic Leptospira species. However, the currently used multiple-valence vaccine, which is prepared with whole cells of several Leptospira serovars, has major side effects, while its cross-immunogenicity among different Leptospira serovars is weak. LipL32, LipL21 and 2 OmpL1 have been confirmed as surface-exposed antigens in all pathogenic Leptospira strains, but their immunoprotective efficiency needs to be improved. In the present study, we generated a fusion gene lipL32/1-lipL21-ompL1/2 using primer-linking PCR and an engineered E. coli strain to express the recombinant fusion protein rLipL32/1-LipL21-OmpL1/2 (rLLO. Subsequently, the expression conditions were optimized using a central composite design that increased the fusion protein yield 2.7-fold. Western blot assays confirmed that rLLO was recognized by anti-rLipL32/1, anti-rLipL21, and anti-rOmpL1/2 sera as well as 98.5% of the sera from leptospirosis patients. The microscopic agglutination test (MAT demonstrated that rLLO antiserum had a stronger ability to agglutinate the strains of different Leptospira serovars than the rLipL32/1, rLipL21, and rOmpL1/2 antisera. More importantly, tests in hamsters showed that rLLO provided higher immunoprotective rates (91.7% than rLipL32/1, rLipL21 and rOmpL1/2 (50.0-75.0%. All the data indicate that rLLO, a recombinant fusion protein incorporating three antigens, has increased antigenicity and immunoprotective effects, and so can be used as a novel immunogen to develop a universal genetically engineered vaccine against leptospirosis.

  7. Ovarian serous cystadenoma associated with Sertoli-Leydig cell tumor--a case report.

    Science.gov (United States)

    Seo, E. J.; Kwon, H. J.; Shim, S. I.

    1996-01-01

    We Describe a case of ovarian serous cystadenoma having Sertoli-Leydig cell tumor, well differentiated, in the cystic septum. Well differentiated Sertoli-Leydig cell tumor coexisting with other tumor, including serous tumor, has not yet been described. In all cases of Sertoli-Leydig cell tumor with heterologous components or other tumors, the androblastomatous components are intermediately or poorly differentiated. The present case revealed a well differentiated Sertoli-Leydig cell tumor arising in a septum of serous cystadenoma, as a circumscribed nodule. With these findings, we discuss the possibility of this Sertoli-Leydig cell tumor, considered a mural nodule, which is well established in cystic common epithelial tumors of the ovary. PMID:8703377

  8. Stromal p16 Overexpression in Adult Granulosa Cell Tumors of the Ovary.

    Science.gov (United States)

    Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

    2017-05-01

    Adult granulosa cell tumor of the ovary is usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the stromal p16 expression of ovarian adult granulosa cell tumors are limited. The aim of this study was to analyze the immunohistochemical p16 expression in the peritumoral stroma of primary and recurrent adult granulosa cell tumors and investigate whether there were significant differences in stromal p16 expression among nonpathological ovaries, benign sex cord-stromal tumors, and adult granulosa cell tumors. This study included 13 and 11 cases of primary and recurrent adult granulosa cell tumors, respectively. Non-pathological ovaries and benign sex cord-stromal tumors showed negative or weak positive expression, whereas most of the adult granulosa cell tumors showed diffuse and moderate-to-strong immunostaining. Primary adult granulosa cell tumors had significantly higher stromal p16 expression levels than nonpathological ovaries and benign sex cord-stromal tumors (padult granulosa cell tumors showed significantly elevated levels of stromal p16 expression compared to primary adult granulosa cell tumors (p=0.032). In contrast, the difference in stromal p16 expression between non-pathological ovaries and benign sex cord-stromal tumors was not statistically significant (p=0.522). Our observations suggest that stromal p16 expression may be involved in the development and progression of ovarian adult granulosa cell tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens...... to inducing hybrid formation by expression of viral fusogenic membrane glycoproteins....

  10. The role of membrane fusion activity of a whole inactivated influenza virus vaccine in (re)activation of influenza-specific cytotoxic T lymphocytes

    NARCIS (Netherlands)

    Budimir, Natalija; Meijerhof, Tjarko; Wilschut, Jan; Huckriede, Anke; de Haan, Aalzen

    2010-01-01

    Induction of cytotoxic T lymphocyte (CTL) activity against conserved influenza antigens, e.g. nucleoprotein (NP) could be a step towards cross-protective influenza vaccine. The major challenge for non-replicating influenza vaccines aiming for activation of CTLs is targeting of antigen to the MHC

  11. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimi, Seyyed Mahmoud, E-mail: smebrahimi@shirazu.ac.ir [Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651,Tehran (Iran, Islamic Republic of); Research Center of Virus and Vaccine, Baqiyatallah University of Medical Science, P.O.Box 14155-3651, Tehran (Iran, Islamic Republic of); Dabaghian, Mehran [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of); Tebianian, Majid [Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), P.O. Box 31975/148, Karaj, Tehran (Iran, Islamic Republic of); Zabeh Jazi, Mohammad Hossein [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of)

    2012-08-15

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  12. Molecular Cytogenetic Characterization of Tenosynovial Giant Cell Tumors

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    Petter Brandal

    2004-09-01

    Full Text Available Tenosynovial giant cell tumor (TSGCT is a disease of disputed etiology and pathogenesis. Some investigations indicate a neoplastic origin of the tumors; others indicate that they are polyclonal and inflammatory. The cytogenetic and molecular genetic features of TSGCTs are largely unknown, as only some 20 localized and 30 diffuse tumors with cytogenetic aberrations have been reported. The most common karyotypic aberrations have been trisomy for chromosomes 5 and 7 and translocations involving chromosomal area 1 pi 1-13. We decided to screen the genomes of TSGCTs by comparative genomic hybridization (CGH to perform interphase fluorescence in situ hybridization (IP-FISH, looking for numerical aberrations of chromosomes 1, 5, and 7, and to analyze the tumors for microsatellite instability. Except for two diffuse TSGCTs that came fresh to us, and which, by karyotyping, exhibited t(1;22(p13;g12 and a t(1;1(g21;p11 and +7, respectively, all studies had to be performed on formalinfixed, paraffin-embedded material. DNA was extracted from 51 localized and nine diffuse TSGCTs. CGH was successful for 24 tumors, but none of them showed copy number changes. The IP-FISH studies showed trisomy 7 in 56% of the tumors (15/27, whereas chromosomes 1 and 5 seemed to be disomic in all TSGCTs. All informative tumors were wild-type by microsatellite instability analysis.

  13. Ulcerative Granular Cell Tumor: A Clinicopathological and Immunohistochemical Study

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    Mohamed El-Khalawany

    2011-01-01

    Full Text Available Granular cell tumor (GCT is uncommonly presented with cutaneous ulcer. We examined the clinicopathological and immunohistochemical features of this ulcerative form in fourteen cases that may raise the awareness of this variant. The study included 11 males and 3 females with a mean age 31.5 ± 7.42 years. All cases were presented with large solitary ulcer with indurated base, elevated border, skin colored margin, and necrotic floor. Twelve lesions were located on the extremities and two lesions on the genital region. Histologically, the lesions showed dermal infiltrate composed of large polygonal cells with granular cytoplasm and characteristic infiltration of the dermal muscles in all cases. Immunostaining showed positive reaction for S100 (14/14, NSE (14/14, CD68 (5/14, and Vimentin (7/14 while HMB45, CK, EMA, and Desmin were negative. We hope that this paper increases the awareness of ulcerative GCT and consider it in the differential diagnosis of ulcerative lesions.

  14. Canine mast cell tumors: diagnosis, treatment, and prognosis

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    Garrett LD

    2014-08-01

    Full Text Available Laura D Garrett Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Abstract: Mast cell tumors (MCTs are the most common malignant skin cancer in dogs, and significant variability exists in their biological behavior. Most MCTs are cured with appropriate local therapy, but a subset shows malignant behavior with the potential to spread to lymph nodes, liver, spleen, and other areas and to thus become a systemic cancer. Because of this variable behavior, it is difficult to predict how any individual tumor is going to behave. The variability thus creates uncertainty in deciding what a particular dog's prognosis is, whether staging tests to assess for metastasis are needed, and even what treatments will be necessary for best outcome. In addition to controversies over the potential for development of systemic disease, or diffuse metastasis, controversies also exist over what treatment is needed to best attain local control of these tumors. This article will briefly discuss the diagnosis of MCTs in dogs and will summarize the literature in regards to the controversial topics surrounding the more aggressive form of this disease, with recommendations made based on published studies. Keywords: mitotic index, mastocytosis, tyrosine kinase inhibitor, histologic grade

  15. Review of juxtaglomerular cell tumor with focus on pathobiological aspect

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    Pan Chin-Chen

    2011-08-01

    Full Text Available Abstract Juxtaglomerular cell tumor (JGCT generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

  16. Ovarian granulosa cell tumor and increased risk of breast cancer.

    Science.gov (United States)

    Hammer, Anne; Lauszus, Finn F; Petersen, Astrid C

    2013-12-01

    Granulosa cell tumor of the ovary (GCT) is a rare neoplasm. The tumor often secretes estrogens and then presents at an earlier stage due to hormone-related symptoms. GCT women are at increased risk of endometrial carcinoma, but there is only limited information about GCTs and potential association to other hormone-related neoplasms such as breast cancer. We conducted a retrospective follow-up study on 163 women with GCT. Medical records and histological sections were reviewed and a search in the pathology registry performed. Eight [95% confidence interval (CI); 3.4-15.8] GCT women were diagnosed with a breast neoplasm; one with Paget's disease of the nipple and seven with breast carcinoma. Based on calculations using incidence rates on breast cancer among Danish women, we would have expected 2.5 cases of breast cancer. The odds ratio was 3.3 (95% CI, 1.6-6.6), suggesting an increased risk of breast cancer in GCT women. © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

  17. Cryosurgery as Additional Treatment in Tenosynovial Giant Cell Tumors

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    F. G. M. Verspoor

    2016-01-01

    Full Text Available Introduction. Tenosynovial giant cell tumors (TGCT emerge from the synovium and can behave aggressively. Surgical resection is the standard treatment. However, up to half of the patients with diffuse type show recurrences. Several additional treatments have been applied to reduce recurrences; none of these treatments was proven to be superior to surgical resection solely. This article describes the results of additional cryosurgery to surgical resection. Materials and Methods. We retrospectively evaluated 141 TGCT patients, between 1999 and 2007. Twelve patients had additional cryosurgery. The knee (n=8, hip (n=2, ankle (n=1, and elbow (n=1 were affected. Primary outcome variables were treatment indications, recurrences, and complications. Results. Indications for additional cryosurgery were extended disease, bone involvement, and locations that are difficult to surgically get disease-free such as cruciate ligaments. Five patients had recurrent disease, all of which had prior treatments. None of the primary treated patients had recurrent disease. One patient had a deep infection. Discussion. Cryosurgery may serve as an additional treatment for diffuse TCGT in selected cases. However, because of the small number of patients and the heterogeneous group we could not prove an advantage of additional cryosurgery over surgical resection only. Cryosurgery should be considered for further evaluation in a prospective study. If there is any effect it would be helpful, especially in patients with multiple TGCT recurrences.

  18. Characteristic promoter hypermethylation signatures in male germ cell tumors

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    Bosl George J

    2002-11-01

    Full Text Available Abstract Background Human male germ cell tumors (GCTs arise from undifferentiated primordial germ cells (PGCs, a stage in which extensive methylation reprogramming occurs. GCTs exhibit pluripotentality and are highly sensitive to cisplatin therapy. The molecular basis of germ cell (GC transformation, differentiation, and exquisite treatment response is poorly understood. Results To assess the role and mechanism of promoter hypermethylation, we analyzed CpG islands of 21 gene promoters by methylation-specific PCR in seminomatous (SGCT and nonseminomatous (NSGCT GCTs. We found 60% of the NSGCTs demonstrating methylation in one or more gene promoters whereas SGCTs showed a near-absence of methylation, therefore identifying distinct methylation patterns in the two major histologies of GCT. DNA repair genes MGMT, RASSF1A, and BRCA1, and a transcriptional repressor gene HIC1, were frequently methylated in the NSGCTs. The promoter hypermethylation was associated with gene silencing in most methylated genes, and reactivation of gene expression occured upon treatment with 5-Aza-2' deoxycytidine in GCT cell lines. Conclusions Our results, therefore, suggest a potential role for epigenetic modification of critical tumor suppressor genes in pathways relevant to GC transformation, differentiation, and treatment response.

  19. Baculovirus-expressed virus-like particle vaccine in combination with DNA encoding the fusion protein confers protection against respiratory syncytial virus.

    Science.gov (United States)

    Lee, Jong Seok; Kwon, Young-Man; Hwang, Hye Suk; Lee, Yu-Na; Ko, Eun-Ju; Yoo, Si-Eun; Kim, Min-Chul; Kim, Ki-Hye; Cho, Min Kyoung; Lee, Young-Tae; Lee, You Ri; Quan, Fu-Shi; Kang, Sang-Moo

    2014-10-07

    Respiratory syncytial virus (RSV) is a major viral agent causing significant morbidity and mortality in young infants and the elderly. There is no licensed vaccine against RSV and it is a high priority to develop a safe RSV vaccine. We determined the immunogenicity and protective efficacy of combined virus-like particle and DNA vaccines presenting RSV glycoproteins (Fd.VLP) in comparison with formalin inactivated RSV (FI-RSV). Immunization of mice with Fd.VLP induced higher ratios of IgG2a/IgG1 antibody responses compared to those with FI-RSV. Upon live RSV challenge, Fd.VLP and FI-RSV vaccines were similarly effective in clearing lung viral loads. However, FI-RSV immunized mice showed a substantial weight loss and high levels of T helper type 2 (Th2) cytokines as well as extensive lung histopathology and eosinophil infiltration. In contrast, Fd.VLP immunized mice did not exhibit Th2 type cytokines locally and systemically, which might contribute to preventing vaccine-associated RSV lung disease. These results indicate that virus-like particles in combination with DNA vaccines represent a potential approach for developing a safe and effective RSV vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Fusion of antigen to a dendritic cell targeting chemokine combined with adjuvant yields a malaria DNA vaccine with enhanced protective capabilities.

    Science.gov (United States)

    Luo, Kun; Zhang, Hong; Zavala, Fidel; Biragyn, Arya; Espinosa, Diego A; Markham, Richard B

    2014-01-01

    Although sterilizing immunity to malaria can be elicited by irradiated sporozoite vaccination, no clinically practical subunit vaccine has been shown to be capable of preventing the approximately 600,000 annual deaths attributed to this infection. DNA vaccines offer several potential advantages for a disease that primarily affects the developing world, but new approaches are needed to improve the immunogenicity of these vaccines. By using a novel, lipid-based adjuvant, Vaxfectin, to attract immune cells to the immunization site, in combination with an antigen-chemokine DNA construct designed to target antigen to immature dendritic cells, we elicited a humoral immune response that provided sterilizing immunity to malaria challenge in a mouse model system. The chemokine, MIP3αCCL20, did not significantly enhance the cellular infiltrate or levels of cytokine or chemokine expression at the immunization site but acted with Vaxfectin to reduce liver stage malaria infection by orders of magnitude compared to vaccine constructs lacking the chemokine component. The levels of protection achieved were equivalent to those observed with irradiated sporozoites, a candidate vaccine undergoing development for further large scale clinical trial. Only vaccination with the combined regimen of adjuvant and chemokine provided 80-100% protection against the development of bloodstream infection. Treating the immunization process as requiring the independent steps of 1) attracting antigen-presenting cells to the site of immunization and 2) specifically directing vaccine antigen to the immature dendritic cells that initiate the adaptive immune response may provide a rational strategy for the development of a clinically applicable malaria DNA vaccine.

  1. Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors.

    Science.gov (United States)

    Lau, Sean K; Weiss, Lawrence M; Chu, Peiguo G

    2007-07-01

    The classification of intratubular germ cell neoplasia of the testis includes an unclassified type (IGCNU), in addition to various other intratubular lesions that show specific forms of differentiation, such as intratubular seminoma and intratubular embryonal carcinoma. Although IGCNU is recognized as a precursor lesion for testicular germ cell tumors, the relationship between differentiated types of intratubular germ cell neoplasia and invasive germ cell tumors of the testis is not well established. The aim of the present study was to examine the association between invasive testicular germ cell tumors and intratubular neoplastic lesions, with particular emphasis on differentiated types of intratubular germ cell neoplasia. The seminiferous tubules adjacent to 42 testicular germ cell tumors were evaluated for the presence of various forms of intratubular germ cell neoplasia. IGCNU was observed in 37 (88%) of 42 cases, whereas intratubular seminoma and intratubular embryonal carcinoma were seen in 19% and 7% of the cases, respectively. Intratubular seminoma was associated primarily with seminomas or mixed germ cell tumors with a seminomatous component, but was also present in a case of a nonseminomatous germ cell tumor. Intratubular embryonal carcinoma was associated exclusively with nonseminomatous germ cell tumors. All cases of intratubular embryonal carcinoma were identified morphologically and exhibited histologic features corresponding to traditional definitions of this lesion. No examples of intratubular embryonal carcinoma as defined by CD30 expression alone in the absence of an intratubular proliferation were observed. The presence of intratubular seminoma in a nonseminomatous germ cell tumor suggests that it is a true preinvasive lesion rather than a manifestation of intratubular spread of an established invasive seminoma. The low incidence of intratubular embryonal carcinoma supports the theory that most nonseminomatous germ cell tumors evolve initially as

  2. Mucosal vaccination of conserved sM2, HA2 and cholera toxin subunit A1 (CTA1) fusion protein with poly gamma-glutamate/chitosan nanoparticles (PC NPs) induces protection against divergent influenza subtypes.

    Science.gov (United States)

    Chowdhury, Mohammed Y E; Kim, Tae-Hwan; Uddin, Md Bashir; Kim, Jae-Hoon; Hewawaduge, C Y; Ferdowshi, Zannatul; Sung, Moon-Hee; Kim, Chul-Joong; Lee, Jong-Soo

    2017-03-01

    To develop a safe and effective mucosal vaccine that broad cross protection against seasonal or emerging influenza A viruses, we generated a mucosal influenza vaccine system combining the highly conserved matrix protein-2 (sM2), fusion peptide of hemagglutinin (HA 2 ), the well-known mucosal adjuvant cholera toxin subunit A1 (CTA1) and poly-γ-glutamic acid (γ-PGA)-chitosan nanoparticles (PC NPs), which are safe, natural materials that are able to target the mucosal membrane as a mucosal adjuvant. The mucosal administration of sM2HA2CTA1/PC NPs could induce a high degree of systemic immunity (IgG and IgA) at the site of inoculation as well as at remote locations and also significantly increase the levels of sM2- or HA2-specific cell-mediated immune response. In challenge tests in BALB/c mice with 10 MLD 50 of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird/Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005 (H7N3) or A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant sM2HA2CTA1/PC NPs provided cross protection against divergent lethal influenza subtypes and also the protection was maintained up to six months after vaccination. Thus, sM2HA2CTA1/PC NPs could be a promising strategy for a universal influenza vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Severe acute tumor lysis syndrome in patients with germ-cell tumors

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    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.

  4. MR imaging findings of pineal germinoma: focus on differential diagnosis from other germ cell tumors

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    Kim, Hyun Jin; Lee, Ho Kyu; Kim, Jae Kyun; Shin, Ji Hoon; Choi, Choong Gon; Lee, Myung Jun; Ham, Soo Youn; Lee, Jong Hwa; Suh, Dae Chul [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    To determine the characteristic MR imaging findings of pineal germinoma, and differential diagnosis from other germ cell tumors. MR images of patients with histopathologically proven pineal germinoma(n=3D14) and other pineal germ cell tumors(n=3D10) were retrospectively analyzed with regard to size, signal intensity and homogeneity, enhancing features, cyst formation, and multiplicity of lesions. Other pineal germ cell tumors were the mixed germ cell tumors (n=3D4), malignant teratomas (n=3D3), choriocarcinoma(n=3D1), embryonal carcinoma(n=3D1), and endodermal sinus tumor(n=3D1). Tumor markers were evaluated. On T1-weighted images, germinomas showed homogeneous(86%) or iso signal intensity (93%), while other germ cell tumors showed inhomogeneous(70%) or iso signal intensity(70%). On T2-weighted images, germinomas showed homogeneous(64%) or iso signal intensity(57%), while other germ cell tumors showed inhomogeneous(70%) or high signal intensity(80%). On Gd-DTPA enhanced images, germinomas showed homogeneous (93%) or strong enhancement (64%), while other germ cell tumors showed homogeneous(60%) or strong enhancement (70%). Cyst formation was noted in ten Patients (71%) with germinoma and in six (60%) with other germ cell tumors. Invasion on surrounding structures was seen in 11 patients (79%) with germinoma and in five (50%) with other germ cell tumors. Lesions were multiple in three patients(21%) with germinoma. Thirteen of 14 patients with germinoma had normal serum {alpha}-FP(tetoprotein) and {beta}-HCG(human chononic gonafotrophin) levels. Two of four patients with mixed germ cell tumors had elevated serum {beta}-FP and {alpha}-HCG levels; in the ther two, elevated serum {alpha}-FP or {beta}-HCG levels were noted. In the malignant teratoma and embryonal carcinoma patients, serum {alpha}-FP and {beta}-HCG levels were normal. The patient with choriocarcinoma had an elevated serum {beta}-HCG level. On T1W1, the only significant differential point (p<0.01) between

  5. Bilateral interstitial cell tumor of the testis: a report of a case in an adult.

    Science.gov (United States)

    Leotta, A; Lio, S G

    1994-10-01

    We describe a case of metachronous bilateral interstitial-cell tumor of the testis in a 54-year-old man with no evidence of endocrine symptoms. About 300 Leydig cell tumor cases have been reported in literature and only in 3% the tumor was bilateral. Rare examples have been reported in cryptorchid testis. In adult patients with Leydig cell tumor of the testis, endocrinologic signs occur in 20 per cent of cases and often precede the onset of a palpable testicular mass. Pathological aspects are discussed and a survey of the literature is reported.

  6. A late recurring and easily forgotten tumor: ovarian granulosa cell tumor

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    Chen Yi-Chan

    2012-05-01

    Full Text Available Abstract Ovarian granulosa cell tumor (GCT is a malignant tumor with slow progression. The recurrence of granulosa cell tumor often happens after 5 years, leading to a ‘forgotten tumor’ by the patient. We present the case of a 64-year-old woman with a presentation of left flank pain. An initial computed tomography scan revealed a single tumor with multiple adjacent organ invasions. Surgical intervention was prescribed and the pathological results revealed a metastatic granulosa cell tumor. We also review the literature for the follow-up and further management of this tumor.

  7. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

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    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  8. Surgical treatment for diffused-type giant cell tumor (pigmented villonodular synovitis) about the ankle joint.

    Science.gov (United States)

    Li, Xingchen; Xu, Yang; Zhu, Yuan; Xu, Xiangyang

    2017-11-14

    Diffused-type giant cell tumor(Dt-GCT) is a rare, aggressive disorder of the joint synovium, bursa and tendon sheaths. Osseous erosions and subchondral cysts may develop as the result of synovium infiltration in Dt-GCT. We present a retrospective study of a series of patients who are diagnosed with Dt-GCT about the ankle joint, there clinical outcome is evaluated in this study. Fifteen patients with radiologically and histologically confirmed Dt-GCT about the ankle joint were identified in our foot and ankle department. Patients were managed with open synovectomy for the tumor tissue and bone grafting for bony erosions. X-rays and MRI scans were used for evaluation of the tumor and bony erosions pre- and post-operatively. Pre- and post-operative ankle function was assessed using the American Orthopedic Foot and Ankle Society -Ankle and Hindfoot (AOFAS-AH) score and the Muscularskeletal Tumor Society (MSTS) score. The mean follow-up duration was 37.4 months (range 25 to 50 months). There were 6 males and 9 females, with a mean age of 35 years old (range 18 to 65 years). All patients had talar erosion with the average size of 10.1*9.1*8.2 mm, distal tibia was affected in 5 patients with the average size of 6.2*5.6*5.8 mm. 7 patients had tendon involvement, 2 patients had recurrence and progression of ankle osteoarthritis. Both of them underwent ankle fusion. At the time of last follow-up, the mean AOFAS-AH score increased from 49 to 80 points (p < 0.05), the MSTS score increased from 12 to 22 points (p < 0.05). For Dt-GCT with bony erosions, open synovectomy combined with bone grafting seems to be a safe and effective operation for the salvage of ankle joint. Fusion is recommended for failed and severe cartilage destruction of the ankle joint.

  9. Androgen Secreting Steroid Cell Tumor of the Ovary Represented with Postmenopasal Bleeding and Extensive Hirsutism

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    Jadranka Georgievska

    2013-12-01

    Conclusion: In adult patients with hirsutism and elevated serum testosterone a possibility of a presence of an ovarian steroid cell tumor should be considered. Surgery is the main treatment of such patients.

  10. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    Science.gov (United States)

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  11. Acute Carpal Tunnel Syndrome Caused by Diffuse Giant Cell Tumor of Tendon Sheath: A Case Report

    Science.gov (United States)

    Ward, Christina M; Lueck, Nathan E; Steyers, Curtis M

    2007-01-01

    A 46 year old male developed spontaneous acute carpal tunnel syndrome of the right wrist without any antecedent trauma. Surgical exploration revealed hemorrhage secondary to diffuse giant cell tumor of tendon sheath as the underlying cause. PMID:17907439

  12. Giant cell tumor of soft tissue: a case report with emphasis on MR imaging

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    Lee, Moon Young; Jee, Won-Hee [The Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seocho-gu, Seoul (Korea, Republic of); Jung, Chan Kwon [The Catholic University of Korea, Department of Pathology, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Yoo, Ie Ryung [The Catholic University of Korea, Department of Nuclear Medicine, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Chung, Yang-Guk [The Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of)

    2015-04-03

    Giant cell tumor of soft tissue is a rare neoplasm, histologically resembling giant cell tumor of bone. In this report, we describe a deep and solid giant cell tumor of soft tissue interpreted as a benign soft tissue tumor based on magnetic resonance (MR) findings with hypointense to intermediate signals on T2-weighted images and impeded diffusivity (water movement) on diffusion-weighted imaging (DWI), which could suggest a giant-cell-containing benign soft tissue tumor, despite the malignancy suggested by {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography in a 35-year-old male. To our knowledge, this report introduces the first deep, solid giant cell tumor of soft tissue with MR features of a giant-cell-containing benign soft tissue tumor, despite the malignancy-mimicking findings on {sup 18}F-FDG PET-CT. (orig.)

  13. FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development

    National Research Council Canada - National Science Library

    Liu, Zhilin; Ren, Yi A; Pangas, Stephanie A; Adams, Jaye; Zhou, Wei; Castrillon, Diego H; Wilhelm, Dagmar; Richards, JoAnne S

    2015-01-01

    .... Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation...

  14. Adult granulosa cell tumor associated with endometrial carcinoma: a case report

    National Research Council Canada - National Science Library

    Ukah, Cornelius O; Ikpeze, Okechukwu C; Eleje, George U; Eke, Ahizechukwu C

    2011-01-01

    If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5...

  15. DEFINITION OF A NEW ENTITY OF MALIGNANT EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    VANECHTEN, J; DEJONG, B; SINKE, RJ; WEGHUIS, DO; SLEIJFER, DT; OOSTERHUIS, JW

    Two malignant extragonadal germ cell tumors are reponed, histologically classified as immature teratomas, having pseudodiploid karyotypes with complex structural rearrangements but lacking isochromosome 12p or other rearrangements involving 12p. The absence of 12p material in structural

  16. Functional Genomics of Germ Cell Tumors: from balls to bytes and back again

    NARCIS (Netherlands)

    M.A. Rijlaarsdam (Martin)

    2014-01-01

    markdownabstract__Abstract__ The work discussed in this thesis explains the role of the functional genome in germ cell tumor (GCT) pathogenesis by applying newly developed and existing computational methods to (genome-wide) functional genomic datasets. Specifically, epigenetic and

  17. Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

    NARCIS (Netherlands)

    Ozturk, Cigdem; van Ginkel, Robert J.; Krol, Ruby M.; Gietema, Jourik A.; Hofker, Hendrik S.; Hoekstra, Harald J.

    Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with

  18. Cytogenetic abnormalities and clinical stage in testicular nonseminomatous germ cell tumors

    NARCIS (Netherlands)

    de Graaff, W E; van Echten-Arends, J; Oosterhuis, J W; de Jong, B; te Meerman, G J; Wiersema-Buist, J; Sleijfer, D T; Schraffordt Koops, H

    1993-01-01

    To study the impact of chromosomal abnormalities on the clinical behavior of testicular nonseminomatous germ cell tumors (TNSGCTs), we compared the chromosomal constitution of primary tumors of patients who initially presented and remained without metastases to those with metastatic disease.

  19. Epidemiological Aspects and Differential Diagnosis of the Cutaneous Round Cell Tumors in Dogs

    Directory of Open Access Journals (Sweden)

    Roxana CORA

    2017-05-01

    Full Text Available Round cell neoplasms (RCNs are frequent cutaneous lesions in dogs, with high percentages among skin tumors. In this category are included histiocytoma, mast cell tumor, plasmacytoma, lymphoma and transmissible venereal tumor. The aim of the study was to perform an epidemiological study with reference to the cutaneous round cell tumors in a period of 10 years in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania. Additionally, in the recorded cases with round cell tumors (mast cell tumor, histiocytoma and lymphoma we described the main histological and cytological features. The epidemiological data were collected from the records of Pathology Department between 2005-2014. The investigation included dogs diagnosed with cutaneous round cell neoplasms, following necropsy analysis or assessment of biopsies or cytological samples. All collected specimens were analyzed by histopathological and/or cytological techniques. The staining used for histological investigation were Hematoxylin-eosin, Masson’s trichrome and Toluidine blue, whereas Diff Quik and Wright methods were utilized in cytological specimens. The distribution of the cutaneous round cell tumors in relation to age, breed and sex was also assessed. The most frequent round cell tumor type was the mast cell tumor (19.54% followed by histiocytoma (11.33% and lymphoma (1.98%. The round cell tumors recorded were equally distributed in both males and females. Concerning the distribution of cutaneous RCNs by age (average age, histiocytoma occurred in 5 years old subjects, mast cell tumor in 11.9 years old subjects, and lymphoma in 6 years old subjects. Mast cell tumor was more frequent in stray dogs and Boxer breed, while histiocytoma occurred more commonly in stray dogs. Histological and cytological analysis was mandatory to perform the differential diagnosis between RCNs. Microscopic details concerning cytoplasm and nucleus of tumoral cells, together with the

  20. Giant cell tumor of the flexor tendon of the wrist: US and MRI evaluation. Case report

    OpenAIRE

    Bassetti, E.; Candreva, R.; Santucci, E.

    2011-01-01

    Giant cell tumor of the tendon sheath (GCTTS) is a benign proliferative lesion of synovial origin that may affect the joints, bursae and tendon sheaths. We report the case of a giant cell tumor of the tendon sheath arising from the carpal tunnel of the wrist in a 47-year-old woman. The patient underwent ultrasound (US) examination and subsequently magnetic resonance imaging (MRI).

  1. Adult granulosa cell tumor associated with endometrial carcinoma: a case report

    OpenAIRE

    Eke Ahizechukwu C; Eleje George U; Ikpeze Okechukwu C; Ukah Cornelius O

    2011-01-01

    Abstract Introduction If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early. Case presentation We report the ca...

  2. Granulosa cell tumor of ovary: A clinicopathological study of four cases with brief review of literature

    Directory of Open Access Journals (Sweden)

    B R Vani

    2014-01-01

    Full Text Available Introduction: Adult granulosa cell tumor (GCT is a rare ovarian malignancy having good prognosis in comparison with other epithelial tumors. The study aims to collect data of all granulosa cell tumors diagnosed in ESIC Medical College & PGIMSR, Rajajinagar, Bangalore over the last 3 years and to describe the patient profile, ultrasonographic and various histopathological features.Materials and Methods: A total of 4 granulosa cell tumors were diagnosed in ESIC Medical College & PGIMSR, Rajajinagar, Bangalore during the period from June 2010 to June 2013. The patient′s age, clinical manifestations, radiological and histopathological findings were evaluated.Results: All 4 patients were diagnosed as adult granulosa cell tumor, three of four cases were in premenopausal age group and one case was in perimenopausal age. The clinical manifestations were menorrhagia and abdominal pain. Ultrasonographically, 2 cases of granulosa cell tumors were both solid and cystic and one case each was either solid or cystic. Histologically, variety of patterns like diffuse, trabecular, cords, spindle and clear cells were noted. Both Call-Exner bodies and nuclear grooves were observed in all cases. All four cases showed simple hyperplasia without atypia endometrial findings. Follow up on all patients revealed no evidence of recurrence.Conclusion: Granulosa cell tumor of the ovary is a rare ovarian entity. The important prognostic factor is staging of the tumor. Staging and histopathology helps in prediction of survival. Also diligent endometrial pathology has to be sorted to rule out endometrial carcinoma.

  3. Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

    Science.gov (United States)

    Kanto, Satoru; Hiramatsu, Masayoshi; Suzuki, Kenichi; Ishidoya, Shigeto; Saito, Hideo; Yamada, Shigeyuki; Satoh, Makoto; Saito, Seiichi; Fukuzaki, Atsushi; Arai, Yoichi

    2004-08-01

    A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.

  4. Osteoclast Fusion

    DEFF Research Database (Denmark)

    Marie Julie Møller, Anaïs; Delaissé, Jean-Marie; Søe, Kent

    2017-01-01

    suggesting that fusion partners may specifically select each other and that heterogeneity between the partners seems to play a role. Therefore, we set out to directly test the hypothesis that fusion factors have a heterogenic involvement at different stages of nuclearity. Therefore, we have analyzed...... on the nuclearity of fusion partners. While CD47 promotes cell fusions involving mono-nucleated pre-osteoclasts, syncytin-1 promotes fusion of two multi-nucleated osteoclasts, but also reduces the number of fusions between mono-nucleated pre-osteoclasts. Furthermore, CD47 seems to mediate fusion mostly through......Investigations addressing the molecular keys of osteoclast fusion are primarily based on end-point analyses. No matter if investigations are performed in vivo or in vitro the impact of a given factor is predominantly analyzed by counting the number of multi-nucleated cells, the number of nuclei per...

  5. S-100 Negative Granular Cell Tumor (So-called Primitive Polypoid Non-neural Granular Cell Tumor) of the Oral Cavity.

    Science.gov (United States)

    Rawal, Yeshwant B; Dodson, Thomas B

    2017-09-01

    Four cases of cutaneous S-100 negative granular cell tumor were described in 1991. Until now, only 3 cases of oral involvement have been documented in English literature. Two additional cases of oral S-100 negative granular cell tumor are described. Immunohistochemical markers were applied to exclude other lesions that may show the presence of granular cells. The clinical findings were correlated with the histopathological and immunohistochemical features to arrive at the appropriate diagnosis. S-100 negative granular cell tumors are erythematous polypoid masses commonly mistaken for granulation tissue or a pyogenic granuloma. Any part of the oral cavity may be affected. Histopathologically, the lesions consist of sheets, nests, and fascicles of granular cells that are S-100 negative. The granular cells are non-reactive to SMA, HMB45, Melan A, and CD163. The intracytoplasmic granules are diffusely and strongly positive to NKI/C3. The cell lineage of the S-100 negative granular cell tumor is obscure. Absence of staining with CD163 excludes a histiocytic lineage. Absence of staining with S-100 excludes a neural origin. Absence of staining with S-100 and key melanoma markers HMB45 and Melan A also excludes a melanocytic origin. In this context, positive reactivity with NKI/C3 is indicative of presence of intracytoplasmic lysosomal granules only. Greater awareness of this lesion in the oral cavity will result in better characterization of its biologic potential.

  6. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  7. Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Holst, Peter J; Christensen, Jan P

    2009-01-01

    against lethal peripheral challenge. The current study questioned whether the same strategy, i.e. linkage of GP to an Ii chain, could be applied to a naked DNA vaccine. Following gene-gun immunization with the linked construct (DNA-IiGP), GP-specific CD4(+) T cells could not be detected by flow cytometry...... with the unlinked construct. In contrast, substantial protection against peripheral challenge was not observed. Additional experiments with T-cell subset-depleted or perforin-deficient mice revealed that virus control in vaccinated mice depends critically on cytotoxic CD8(+) T cells. Finally, priming with the naked...

  8. Long-term protection against human papillomavirus e7-positive tumor by a single vaccination of adeno-associated virus vectors encoding a fusion protein of inactivated e7 of human papillomavirus 16/18 and heat shock protein 70.

    Science.gov (United States)

    Zhou, Liqiao; Zhu, Tong; Ye, Xiaojing; Yang, Lin; Wang, Bing; Liang, Xiaoyan; Lu, Lina; Tsao, Yeou-Ping; Chen, Show-Li; Li, Juan; Xiao, Xiao

    2010-01-01

    We investigated a gene vaccine strategy against human papillomavirus (HPV)-induced cancer and premalignant diseases, using adeno-associated virus (AAV) vector encoding the viral E7 oncoproteins as the tumor antigens from HPV serotypes 16 (HPV16) and 18 (HPV18). Genetically inactivated E7 proteins were fused with a heat shock protein 70 (hsp70) to minimize the risk of cell transformation and enhance immune responses. The fusion protein gene was packaged in AAV serotype 1 or 2 (AAV1 or 2) for efficient in vivo gene expression. Our results showed that after a single intramuscular injection, the AAV1 vector elicited stronger HPV-specific cytotoxic T lymphocyte (CTL) responses and interferon-gamma secretion when compared with the AAV2 vector. Prophylactic immunization with AAV1 protected 100% of the mice from tumor growth for more than 1 year, whereas all the control mice immunized with either a LacZ vector or saline grew large tumors and died within 6 weeks after inoculation of E7-positive tumor cell line TC-1. In addition, this single-dose AAV1 vaccination completely protected the mice against second and third challenges with higher numbers of TC-1 cells. Despite lower CTL responses against the E7 antigens, AAV2 vector prophylactic immunization was also sufficient to protect 100% of the mice against the initial and second tumor challenges and 70% of the mice against the third challenge. In addition, therapeutic immunization with AAV1 after palpable tumor formation inhibited tumor growth and caused tumor regression in some mice. Thus, our studies support the potential of AAV vectors as a genetic vaccine for the prevention and treatment of HPV-induced malignancies.

  9. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  10. [Construction of gene vaccine of myostatin fusion with T-helper epitope and its effects on forelimb grip in immunized mice].

    Science.gov (United States)

    Tang, Liang; Liu, Chen-Tao; Wang, Yuan-Li; Luo, Kai; Wang, Xu-Dan

    2013-01-01

    To further study the therapy of wasting muscle by myostatin as a new targets, the eucaryotic expression vector coupled the foreign T-helper epitope of tetanus toxin (TT) to the N terminus of myostatin was constructed, and the effects of the gene vaccine on forelimb grip were tested in immunized mice. A DNA fragment encoding the TT epitope followed by the N terminus of mature myostatin (330bp) was synthesized. The eucaryotic expression vector of myostatin was constructed and the chinese hamster ovary (CHO) cells were infected with the recombinant plasmids pVAC-TT-Ms by liposome transfection according to routine laboratory procedure. The myostatin expression was tested by cell immunofluorescence technique in transfected CHO. The forelimbs grip were tested in immunized mice with myostatin gene vaccine. The eucaryotic expression vector of myostatin coupled TT epitope was constructed successfully through the restriction analysis and sequencing. The recombinant plasmids pVAC-TT-Ms met quality criterion as gene vaccine by analysis OD260/280 and electrophoresis. The myostatin expression was detected obviously in transfected CHO. The forelimb grip in immunized mice had an obvious increase. The average value of forelimb grip of the mice immunized with pVAC-TT-Ms was about 29.88% greater than that of control mice. The construction of eucaryotic expression vector of myostatin coupled TT epitope is successful in expression for recombinant human mature peptide of myostatin. The gene vaccine of myostatin meet quality criterion. The immunized mice has an obvious increase in forelimb grip.

  11. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum...

  12. Fusion neutronics

    CERN Document Server

    Wu, Yican

    2017-01-01

    This book provides a systematic and comprehensive introduction to fusion neutronics, covering all key topics from the fundamental theories and methodologies, as well as a wide range of fusion system designs and experiments. It is the first-ever book focusing on the subject of fusion neutronics research. Compared with other nuclear devices such as fission reactors and accelerators, fusion systems are normally characterized by their complex geometry and nuclear physics, which entail new challenges for neutronics such as complicated modeling, deep penetration, low simulation efficiency, multi-physics coupling, etc. The book focuses on the neutronics characteristics of fusion systems and introduces a series of theories and methodologies that were developed to address the challenges of fusion neutronics, and which have since been widely applied all over the world. Further, it introduces readers to neutronics design’s unique principles and procedures, experimental methodologies and technologies for fusion systems...

  13. Granulosa cell tumor of the ovary: a clinicopathological study of six cases

    Directory of Open Access Journals (Sweden)

    RC Adhikari

    2011-10-01

    Full Text Available Background: Ovarian granulosa cell tumors are rare malignant neoplasms that originate from the sexcord stromal cells of the ovary. The study aims to collate data of all granulosa cell tumors diagnosed in Tribhuvan University Teaching Hospital over the last 3 years and to describe the incidence, patient profile, ultrasonographic and histopathologic findings in our local context. Materials and Methods: A total of 6 (5% granulosa cell tumors, diagnosed in Tribhuvan University Teaching Hospital during the period from April 2008 to March 2011. The patient’s age, symptoms, radiological findings, type of surgery performed, tumor size and follow-up status were evaluated. Results: All 6 patients were diagnosed as adult granulosa cell tumor, three of which were postmenopausal (50% and remaining there was premenopausal. The symptoms recorded were uterine bleeding, abdominal pain, distention and mass. Grossly, in 3 cases granulosa cell tumors were solid and firm, in 2 cases solid and cystic and 1 case is predominantly cystic. Histologically, variety of patterns including diffuse, trabecular, cords, tubular, nesting and Call-Exner bodies were found. Nuclear grooves were observed in all cases. Follow up on 2 patients revealed no evidence of recurrence. Conclusion: This study supports the view that most granulosa cell tumors are diagnosed in stage I and there is good correlation between radiological and gross findings in terms of tumor size and solid or cystic status. Keywords: Granulosa cell tumor; Ovary; Histopathological findings DOI: http://dx.doi.org/10.3126/jpn.v1i2.5400 JPN 2011; 1(2: 96-99

  14. Reconstructive procedures for segmental resection of bone in giant cell tumors around the knee

    Directory of Open Access Journals (Sweden)

    Aggarwal Aditya

    2007-01-01

    Full Text Available Background: Segmental resection of bone in Giant Cell Tumor (GCT around the knee, in indicated cases, leaves a gap which requires a complex reconstructive procedure. The present study analyzes various reconstructive procedures in terms of morbidity and various complications encountered. Materials and Methods: Thirteen cases (M-six and F-seven; lower end femur-six and upper end tibia -seven of GCT around the knee, radiologically either Campanacci Grade II, Grade II with pathological fracture or Grade III were included. Mean age was 25.6 years (range 19-30 years. Resection arthrodesis with telescoping (shortening over intramedullary nail ( n=5, resection arthrodesis with an intercalary allograft threaded over a long intramedullary nail ( n=3 and resection arthrodesis with intercalary fibular autograft and simultaneous limb lengthening ( n=5 were the procedure performed. Results: Shortening was the major problem following resection arthrodesis with telescoping (shortening over intramedullary nail. Only two patients agreed for subsequent limb lengthening. The rest continued to walk with shortening. Infection was the major problem in all cases of resection arthrodesis with an intercalary allograft threaded over a long intramedullary nail and required multiple drainage procedures. Fusion was achieved after two years in two patients. In the third patient the allograft sequestrated. The patient underwent sequestrectomy, telescoping of fragments and ilizarov fixator application with subsequent limb lengthening. The patient was finally given an ischial weight relieving orthosis, 54 months after the index procedure. After resection arthrodesis with intercalary autograft and simultaneous lengthening the resultant gap (~15cm was partially bridged by intercalary nonvascularized dual fibular strut graft (6-7cm and additional corticocancellous bone graft from ipsilateral patella. Simultaneous limb lengthening with a distal tibial corticotomy was performed on an

  15. Adult granulosa cell tumor associated with endometrial carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Eke Ahizechukwu C

    2011-08-01

    Full Text Available Abstract Introduction If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early. Case presentation We report the case of a 65-year-old post-menopausal Nigerian woman of the Igbo tribe with an adult granulosa cell tumor that was initially treated as endometrial carcinoma. She underwent a total abdominal hysterectomy and a bilateral salpingo-oophorectomy after histopathologic confirmation of a well-differentiated granulosa cell tumor of the ovary and a nuclear grade 1 adenocarcinoma of the endometrium (International Federation of Obstetricians and Gynecologists stage 1B. She had a good post-operative recovery and was discharged 10 days after treatment. Conclusion The association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion as well as good imaging and histopathologic analyses are important in making this diagnosis.

  16. Adult granulosa cell tumor associated with endometrial carcinoma: a case report.

    Science.gov (United States)

    Ukah, Cornelius O; Ikpeze, Okechukwu C; Eleje, George U; Eke, Ahizechukwu C

    2011-08-02

    If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early. We report the case of a 65-year-old post-menopausal Nigerian woman of the Igbo tribe with an adult granulosa cell tumor that was initially treated as endometrial carcinoma. She underwent a total abdominal hysterectomy and a bilateral salpingo-oophorectomy after histopathologic confirmation of a well-differentiated granulosa cell tumor of the ovary and a nuclear grade 1 adenocarcinoma of the endometrium (International Federation of Obstetricians and Gynecologists stage 1B). She had a good post-operative recovery and was discharged 10 days after treatment. The association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion as well as good imaging and histopathologic analyses are important in making this diagnosis.

  17. Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog.

    Science.gov (United States)

    Beltran, Elsa; de Stefani, Alberta; Stewart, Jennifer; De Risio, Luisa; Johnson, Victoria

    2010-05-01

    Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6-year-old male neutered Greyhound presented with a 3-day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo-oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2-weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.

  18. Purification and Protective Efficacy of Monomeric and Modified Yersina pestis Capsular F1-V Antigen Fusion Proteins for Vaccination Against Plague

    Science.gov (United States)

    2006-12-31

    stability [9].2 Abbreviations used: , approximately; AX, absorbance at x nm; ADM, as described in Materials and methods; ALH , alhydrogel adjuvant, CL...formed to assign F1-V solution states to HPLC-SEC assay elution profiles. Based on HPLC-SEC retention Table 3 ELISA titers after vaccination with ALH ...alone negative control and with ALH -adsorbed F1-V formulations (ADM) Titer Type Treatment N Geometric Mean Lower 95% CL Upper 95% CL V ALH 10 300 300

  19. Granulosa Cell Tumor-like Variant of Endometrioid Carcinoma of the Ovary with Osseous Metaplasia: Report of a Rare Case

    OpenAIRE

    Kavita Mardi; Neelam Gupta; Shivani Sood; Manju Rao

    2015-01-01

    The sex cord-like variant of endometrioid carcinoma is a rare subtype with a close histological resemblance to the sex cord-stromal tumor of the ovaries, in particular the Sertoli cell tumor. However, very few cases of the granulosa cell tumor-like variant have been reported since it is commonly misdiagnosed as a granulose cell tumor. Immunohistochemistry is useful in the diagnosis of these tumors as they are typically negative for inhibin alpha. We herein describe the histolog...

  20. Giant cell tumor of the rib: Two cases of F-18 FDG PET/CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hye Lim; Yoo, Le Ryung; Lee, Yeong Joo; Jung, Chan Kwon [Seoul St. Mary' s Hospital, College of MedicineThe Catholic University of Korea, Seoul (Korea, Republic of); Park, Sonya Young Ju [Molecular Imaging Program, Dept. of Radiology, Stanford Hospital and Clinics, Stanford (Korea, Republic of)

    2017-06-15

    We report two cases of giant cell tumor arising from the rib and their F-18 FDG PET/CT findings. The two patients complained of chest wall pain, and large lobulated soft tissue masses with intense FDG uptake were seen on F-18 FDG PET/CT. A malignant tumor such as osteosarcoma or chondrosarcoma was suspected due to the large size of the mass, bony destruction, and intense FDG uptake. En bloc resection was performed and final pathologic results revealed giant cell tumor of the rib. Giant cell tumor of the rib is very rare, and larger lesions with high FDG uptake can be misdiagnosed as an intrathoracic malignancy arising from the rib, pleura, or chest wall.

  1. Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, Arthur B. [Children' s Hospital of Wisconsin, Department of Radiology, Milwaukee, WI (United States); Nemours Children' s Health System/Nemours Children' s Hospital, Department of Radiology, Orlando, FL (United States); Awomolo, Agboola O. [Children' s Hospital of Wisconsin, Department of Radiology, Milwaukee, WI (United States); Szabo, Sara [Medical College of Wisconsin and Children' s Hospital of Wisconsin, Department of Pathology, Milwaukee, WI (United States); Cincinnati Children' s Hospital Medical Center, Division of Pathology and Laboratory Medicine, Cincinnati, OH (United States)

    2017-03-15

    Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions. (orig.)

  2. Pathophysiological mechanism of ipsilateral cerebral and brainstem hemiatrophy in basal ganglia germ cell tumors: case report.

    Science.gov (United States)

    Wong, Sui-To; Yuen, Shing-Chau; Fong, Dawson

    2009-06-01

    The basal ganglia is an uncommon location for germ cell tumors. It has been reported that basal ganglia germinomas and mixed germ cell tumors are associated with ipsilateral cerebral and brainstem hemiatrophy on presentation. Several pathophysiological mechanisms including autoimmune process and direct tumor infiltration of the thalamus or the internal capsule have been postulated to explain this association. The authors report two boys, aged 7 and 10, with basal ganglia germ cell tumors. Both of them presented with gradual onset of hemiparesis and had features of ipsilateral cerebral and brainstem hemiatrophy on imaging studies. They underwent chemotherapy followed by reduced dose radiotherapy with good response. Pathophysiological mechanisms of the associated ipsilateral cerebral and brainstem hemiatrophy are discussed. The authors postulate that the gradual obliteration of the perforating arteries to the diencephalon especially the lenticulostriate arteries of the prebifurcation middle cerebral artery may be the major mechanism of the associated hemiatrophy.

  3. Dysregulation of Parkin-mediated mitophagy in thyroid Hürthle cell tumors.

    Science.gov (United States)

    Lee, Junguee; Ham, Sujin; Lee, Min Hee; Kim, Soung Jung; Park, Ji Hoon; Lee, Seong Eun; Chang, Joon Young; Joung, Kyong Hye; Kim, Tae Yong; Kim, Jin Man; Sul, Hae Joung; Kweon, Gi Ryang; Jo, Young Suk; Kim, Koon Soon; Shong, Young Kee; Gasparre, Giuseppe; Chung, Jong Kyeong; Porcelli, Anna Maria; Shong, Minho

    2015-11-01

    Abnormal accumulation of defective mitochondria is the hallmark of oncocytes, which are frequently observed in thyroid Hürthle cell lesions. Autophagy is an essential cellular catabolic mechanism for the degradation of dysfunctional organelles and has been implicated in several human diseases. It is yet unknown how autophagic turnover of defective mitochondria in Hürthle cell tumors is regulated. We characterized the expression patterns of molecular markers including Beclin1, LC3, PINK1 and Parkin, which are required for autophagy or mitophagy, in human oncocytic lesions of the thyroid. To undertake mechanistic studies, we investigated autophagy and mitophagy using XTC.UC1 cells, the only in vitro model of Hürthle cell tumors. Beclin1 and LC3 were highly expressed in oncocytes of Hürthle cell tumors. XTC.UC1 showed autophagic responses to starvation and rapamycin treatment, whereas they displayed ineffective activation of mitophagy, which is triggered by the coordinated action of PINK1 and Parkin in response to CCCP. This resulted in a decreased turnover of abnormal mitochondria. The mechanisms underlying defective mitophagy and mitochondrial turnover were investigated by genetic analysis of the PARK2 gene in XTC.UC1 and Hürthle cell tumor tissues. XTC.UC1 and several tumors harbored the V380L mutation, resulting in dysfunctional autoubiquitination and decreased E3 ligase activity. Consistently, oncocytes in Hürthle cell tumors displayed comparable expression of PINK1 but decreased Parkin expression in comparison to normal thyrocytes. The introduction of wild-type Parkin sensitized XTC.UC1 to death induced by CCCP. This study provides a possible etiological basis for oncocytic formation in heterogeneous Hürthle cell tumors through insufficient mitophagy leading to ineffective turnover of aberrant mitochondria caused by dysfunctional Parkin-mediated pathways of mitochondria quality control. © The Author 2015. Published by Oxford University Press. All rights

  4. Biophysical Characterization of a Vaccine Candidate against HIV-1: The Transmembrane and Membrane Proximal Domains of HIV-1 gp41 as a Maltose Binding Protein Fusion

    Science.gov (United States)

    Gong, Zhen; Martin-Garcia, Jose M.; Daskalova, Sasha M.; Craciunescu, Felicia M.; Song, Lusheng; Dörner, Katerina; Hansen, Debra T.; Yang, Jay-How; LaBaer, Joshua; Hogue, Brenda G.; Mor, Tsafrir S.; Fromme, Petra

    2015-01-01

    The membrane proximal region (MPR, residues 649–683) and transmembrane domain (TMD, residues 684–705) of the gp41 subunit of HIV-1’s envelope protein are highly conserved and are important in viral mucosal transmission, virus attachment and membrane fusion with target cells. Several structures of the trimeric membrane proximal external region (residues 662–683) of MPR have been reported at the atomic level; however, the atomic structure of the TMD still remains unknown. To elucidate the structure of both MPR and TMD, we expressed the region spanning both domains, MPR-TM (residues 649–705), in Escherichia coli as a fusion protein with maltose binding protein (MBP). MPR-TM was initially fused to the C-terminus of MBP via a 42 aa-long linker containing a TEV protease recognition site (MBP-linker-MPR-TM). Biophysical characterization indicated that the purified MBP-linker-MPR-TM protein was a monodisperse and stable candidate for crystallization. However, crystals of the MBP-linker-MPR-TM protein could not be obtained in extensive crystallization screens. It is possible that the 42 residue-long linker between MBP and MPR-TM was interfering with crystal formation. To test this hypothesis, the 42 residue-long linker was replaced with three alanine residues. The fusion protein, MBP-AAA-MPR-TM, was similarly purified and characterized. Significantly, both the MBP-linker-MPR-TM and MBP-AAA-MPR-TM proteins strongly interacted with broadly neutralizing monoclonal antibodies 2F5 and 4E10. With epitopes accessible to the broadly neutralizing antibodies, these MBP/MPR-TM recombinant proteins may be in immunologically relevant conformations that mimic a pre-hairpin intermediate of gp41. PMID:26295457

  5. Clinical activity of eribulin in advanced desmoplastic small round-cell tumor.

    Science.gov (United States)

    Emambux, Sheik; Kind, Michele; Le Loarer, Francois; Toulmonde, Maud; Stoeckle, Eberhard; Italiano, Antoine

    2017-10-01

    Desmoplastic small round-cell tumor is a rare but highly aggressive tumor occurring mainly in adolescents and young adults. Prolonged progression-free survival has been documented in patients who have undergone aggressive multimodality therapy - that is, multiagent intensive chemotherapy, debulking surgery, and radiation therapy. Eribulin is a microtubule-dynamics inhibitor, and it has recently been shown to be active in liposarcomas. In preclinical models, eribulin activities have also been shown to occur in Ewing's sarcoma cell lines, rhabdomyosarcomas and osteosarcomas. In this study, we report three cases of male patients suffering from desmoplastic small round-cell tumor and the clinical response to eribulin in two of them.

  6. Benign Pigmented Dermal Basal Cell Tumor in a Namibian Cheetah (Acinonyx jubatus

    Directory of Open Access Journals (Sweden)

    Sonja K. Heinrich

    2016-01-01

    Full Text Available A 3.5-year-old wild born cheetah (Acinonyx jubatus, living in a large enclosure on a private Namibian farm, developed a large exophytic nodular neoplasm in its skin at the height of the left shoulder blade. We describe the clinical appearance, the surgical removal, and histological examination of the tumor, which was diagnosed as a moderately pigmented benign basal cell tumor. A three-year follow-up showed no evidence of recurrence after the surgery. Although neoplasia is reported in nondomestic felids, only very few concern cheetahs. So far, no case of basal cell tumor was described in this species.

  7. A comprehensive review of diagnostic and treatment options for granulosa cell tumors of the ovary.

    Science.gov (United States)

    Stine, Jessica E; Pierce, Stuart; Soper, John T

    2014-01-01

    Granulosa cell tumors are rare and comprise approximately 2% to 8% of all ovarian malignancies. Research dedicated to these tumors is rare given the low incidence. These tumors are more difficult to diagnose than epithelial ovarian tumors, and understanding how they present may aid in appropriate referral to a gynecologic oncologist. The aim of this review was to summarize the epidemiology, risk factors, and clinical presentation of granulosa cell tumors to aid in provider recognition. We will also explore current diagnostic and treatment modalities with examination of newer, novel treatments. At the end of this review, the reader should understand how to appropriately diagnose and treat these rare malignancies.

  8. Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs

    Science.gov (United States)

    Quartuccio, Marco; Garufi, Giuseppe; Cristarella, Santo; Zanghì, Antonina

    2012-01-01

    The association of cryptorchidism, functional Sertoli cell tumors, and spermatic cord torsion has been rarely reported in the literature. Two dogs were admitted for bilateral skin alopecia and weight loss. Both animals were cryptorchid and displayed a pendulous preputial sheath, prostate hypertrophy, and increased levels of circulating oestrogen. Transabdominal palpation and ultrasonography revealed the presence of neoplastic retained gonads. During surgery, spermatic cord torsion was also detected in the enlarged neoplastic testes of both dogs. Histologic examination confirmed the presence of Sertoli cell tumors that were primarily responsible for the feminizing syndrome. Complete remission of all symptoms occurred within 3 months after orchiectomy. PMID:22705745

  9. Extra gonadal germ cell tumors. Clinico pathologic findings, staging and treatment experience in 14 patients

    Energy Technology Data Exchange (ETDEWEB)

    Berkmen, F.; Peker, F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara, Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy (Turkey)

    2000-09-01

    Extra gonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. The modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

  10. Extragonadal germ cell tumors. Clinicaopathologic findings, staging and treatment experience in 14 patients

    Energy Technology Data Exchange (ETDEWEB)

    Berkmen, F.; Peker, A.F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy, Ankara (Turkey)

    2000-09-01

    Extragonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. Our modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

  11. Controlled fusion; La fusion controlee

    Energy Technology Data Exchange (ETDEWEB)

    Bobin, J.L

    2005-07-01

    During the last fifty years the researches on controlled thermonuclear fusion reached great performance in the magnetic confinement (tokamaks) as in the inertial confinement (lasers). But the state of the art is not in favor of the apparition of the fusion in the energy market before the second half of the 21 century. To explain this opinion the author presents the fusion reactions of light nuclei and the problems bound to the magnetic confinement. (A.L.B.)

  12. The development and preliminary evaluation of a new Mycobacterium tuberculosis vaccine comprising Ag85b, HspX and CFP-10:ESAT-6 fusion protein with CpG DNA and aluminum hydroxide adjuvants.

    Science.gov (United States)

    Chen, Lei; Xu, Miao; Wang, Zhi-Yu; Chen, Bao-Wen; Du, Wei-Xin; Su, Cheng; Shen, Xiao-Bing; Zhao, Ai-Hua; Dong, Na; Wang, Ya-Jun; Wang, Guo-Zhi

    2010-06-01

    Ag85b and HspX of Mycobacterium tuberculosis (Mtb) (H37Rv) were expressed and purified in this study. These two proteins were combined with another fusion protein CFP-10:ESAT-6 (C/E) (Ag), then mixed with the adjuvants CpG DNA and aluminum hydroxide and used to vaccinate mice and guinea pigs challenged with Mtb (H37Rv). The number of spleen lymphocytes secreting Ag85b, HspX and C/E-specific interferon-gamma were significantly higher in the Ag+Al+CpG group than in the Ag and CpG groups. The combination of Ag, Al and CpG induced the highest concentrations of anti-Ag85b, anti-HspX and anti-C/E immunoglobulin G in mouse serum. Mouse peritoneal macrophages from the Ag+Al+CpG group secreted significantly higher levels of interleukin-12 compared with macrophages from the other groups. The total mean liver, lung and spleen lesion scores and bacterial loads in the spleen in guinea pigs vaccinated with Ag+Al+CpG were lower than those of the other groups, but no significant difference was found. These results show that the mixture of Ag85b, HspX and C/E with a combination of CpG and aluminum adjuvants can induce both humoral and cellular immune responses in mice, whereas it plays only a small role in the control of disease progression in guinea pigs challenged with Mtb.

  13. Fusion physics

    CERN Document Server

    Lackner, Karl; Tran, Minh Quang

    2012-01-01

    This publication is a comprehensive reference for graduate students and an invaluable guide for more experienced researchers. It provides an introduction to nuclear fusion and its status and prospects, and features specialized chapters written by leaders in the field, presenting the main research and development concepts in fusion physics. It starts with an introduction to the case for the development of fusion as an energy source. Magnetic and inertial confinement are addressed. Dedicated chapters focus on the physics of confinement, the equilibrium and stability of tokamaks, diagnostics, heating and current drive by neutral beam and radiofrequency waves, and plasma–wall interactions. While the tokamak is a leading concept for the realization of fusion, other concepts (helical confinement and, in a broader sense, other magnetic and inertial configurations) are also addressed in the book. At over 1100 pages, this publication provides an unparalleled resource for fusion physicists and engineers.

  14. Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease.

    Science.gov (United States)

    Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul; Lee, Young-Tae; Lee, Jong Seok; Moore, Martin L; Kang, Sang-Moo

    2015-03-01

    Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis in both children and the elderly. There is no vaccine available for the prevention of RSV infection. Here, we generated recombinant influenza virus (PR8/RSV.HA-F) expressing an RSV F243-294 neutralizing epitope in the hemagglutinin (HA) as a chimeric protein. Neutralizing antibodies specific for both RSV and influenza virus were induced by a single intranasal immunization of mice with PR8/RSV.HA-F. Mice that were immunized with PR8/RSV.HA-F were protected against RSV infection comparable with live RSV as evidenced by significant reduction of RSV lung viral loads, as well as the absence of lung eosinophilia and RSV-specific cellular immune responses. In contrast, formalin-inactivated RSV-immunized mice showed severe disease and high cellular immune responses in lungs after RSV infection. These findings support a concept that recombinant influenza virus carrying the RSV F243-294 neutralizing epitope can be developed as a promising RSV vaccine candidate which induces protective neutralizing antibodies but avoids lung immunopathology. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Francisella tularensis Live Vaccine Strain deficient in capB and overexpressing the fusion protein of IglA, IglB, and IglC from the bfr promoter induces improved protection against F. tularensis respiratory challenge.

    Science.gov (United States)

    Jia, Qingmei; Bowen, Richard; Lee, Bai-Yu; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

    2016-09-22

    A safer and more effective vaccine than the unlicensed Francisella tularensis Live Vaccine Strain (LVS) is needed to protect against the biowarfare agent F. tularensis. Previously, we developed an LVS ΔcapB mutant that is significantly safer than LVS and provides potent protective immunity against F. tularensis respiratory challenge when administered intranasally but limited protection when administered intradermally unless as part of a prime-boost vaccination strategy. To improve the immunogenicity and efficacy of LVS ΔcapB, we developed recombinant LVS ΔcapB (rLVS ΔcapB) strains overexpressing various F. tularensis Francisella Pathogenicity Island (FPI) proteins - IglA, IglB and IglC, and a fusion protein (IglABC) comprising immunodominant epitopes of IglA, IglB, and IglC downstream of different Francisella promoters, including the bacterioferritin (bfr) promoter. We show that rLVS ΔcapB/bfr-iglA, iglB, iglC, and iglABC express more IglA, IglB, IglC or IglABC than parental LVS ΔcapB in broth and in human macrophages, and stably express FPI proteins in macrophages and mice absent antibiotic selection. In response to IglC and heat-inactivated LVS, spleen cells from mice immunized intradermally with rLVS ΔcapB/bfr-iglC or bfr-iglABC secrete greater amounts of interferon-gamma and/or interleukin-17 than those from mice immunized with LVS ΔcapB, comparable to those from LVS-immunized mice. Mice immunized with rLVS ΔcapB/bfr-iglA, iglB, iglC or iglABC produce serum antibodies at levels similar to LVS-immunized mice. Mice immunized intradermally with rLVS ΔcapB/bfr-iglABC and challenged intranasally with virulent F. tularensis Schu S4 survive longer than sham- and LVS ΔcapB-immunized mice. Mice immunized intranasally with rLVS ΔcapB/bfr-iglABC - but not with LVS - just before or after respiratory challenge with F. tularensis Schu S4 are partially protected; protection is correlated with induction of a strong innate immune response. Thus, rLVS

  16. Parental Occupational Exposure to Organic Solvents and Testicular Germ Cell Tumors in their Offspring

    DEFF Research Database (Denmark)

    Le Cornet, Charlotte; Fervers, Béatrice; Pukkala, Eero

    2017-01-01

    BACKGROUND: Testicular germ cell tumors (TGCT) were suggested to have a prenatal environmentally related origin. The potential endocrine disrupting properties of certain solvents may interfere with the male genital development in utero. OBJECTIVES: We aimed to assess the association between mater...

  17. TRA-1-60 - A NEW SERUM MARKER IN PATIENTS WITH GERM-CELL TUMORS

    NARCIS (Netherlands)

    MARRINK, J; ANDREWS, PW; VANBRUMMEN, PJ; DEJONG, HJ; SLEIJFER, DT; KOOPS, HS; OOSTERHUIS, JW

    1991-01-01

    TRA-1-60 is a monoclonal antibody (MAb) that recognizes a mucin-like antigenic determinant expressed on the surface of embryonal carcinoma (EC) progenitor cells. In order to determine whether this antigen is released into the serum of patients with a non-seminomatous germ-cell tumor (NSGCT), we

  18. Hurthle cell tumor of the thyroid gland: Report of a rare case and ...

    African Journals Online (AJOL)

    2013-07-09

    Jul 9, 2013 ... This article presents a case of Hurthle cell adenoma (HCA) of the thyroid gland with a review of literature on Hurthle cell tumors. This case presented is that of a 57‑year‑old woman with a recurrent thyroid swelling. She previously underwent a right hemithyroidectomy for thyroid mass 10 years prior.

  19. Giant cell tumor of the tendon seath of the tendinous insertion in pes anserinus

    Directory of Open Access Journals (Sweden)

    Aikaterini Solomou, MD, PhD

    2017-06-01

    Full Text Available A 56-year-old woman with a palpable lump in the medial surface of her left knee was referred for diagnostic workup with magnetic resonance imaging. The lesion was pathogically confirmed to be a giant cell tumor of the tendon seath. The MR features of the lesion are presented.

  20. Giant cell tumor of the tendon seath of the tendinous insertion in pes anserinus

    OpenAIRE

    Solomou, Aikaterini; Kraniotis, Pantelis

    2017-01-01

    A 56-year-old woman with a palpable lump in the medial surface of her left knee was referred for diagnostic workup with magnetic resonance imaging. The lesion was pathogically confirmed to be a giant cell tumor of the tendon seath. The MR features of the lesion are presented.

  1. Hurthle cell tumor of the thyroid gland: Report of a rare case and ...

    African Journals Online (AJOL)

    This article presents a case of Hurthle cell adenoma (HCA) of the thyroid gland with a review of literature on Hurthle cell tumors. This case presented is that of a 57-year-old woman with a recurrent thyroid swelling. She previously underwent a right hemithyroidectomy for thyroid mass 10 years prior. A left lobectomy was ...

  2. Restricted 12p amplification and RAS mutation in human germ cell tumors of the adult testis

    NARCIS (Netherlands)

    H. Roelofs; J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert); C. Bokemeyer; M.C. Mostert (Marijke); K. Pompe; G. Zafarana (Gaetano); M. van Oorschot; R.J.H.L.M. van Gurp (Ruud); A.J.M. Gillis (Ad); J.A. Stoop (Hans); H.B. Beverloo (Berna)

    2000-01-01

    textabstractHuman testicular germ-cell tumors of young adults (TGCTs), both seminomas and nonseminomas, are characterized by 12p overrepresentation, mostly as isochromosomes, of which the biological and clinical significance is still unclear. A limited number of TGCTs has been

  3. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  4. Testis sparing surgery for Leydig cell tumors: New three cases and ...

    African Journals Online (AJOL)

    A. Chaabouni

    Testis sparing surgery for Leydig cell tumors: New three cases and review of the current literature. A. Chaabouni. ∗. , K. Chabchoub, N. Rebai, M. Bouacida, M.H. Slimen,. A. Bahloul, M.N. Mhiri. Department of Urology, Habib Bourguiba University Hospital, Majida Boulila Road, Sfax 3029, Tunisia. Received 25 January 2013 ...

  5. Juvenile granulosa cell tumor associated with pregnancy: Report of a case and review of the literature.

    Science.gov (United States)

    Hasiakos, Dimitris; Papakonstantinou, Katerina; Goula, Kaliroi; Karvouni, Eleni; Fotiou, Stelios

    2006-02-01

    Juvenile granulosa cell tumors account for about 5% of all granulosa cell tumors and are diagnosed in nearly 80% of cases during the first two decades of life. Only 10% of granulosa cell tumors present during pregnancy. The incidence of ovarian malignancies during pregnancy varies from 0.05 to 0.07 per 1000 pregnancies. A 31-year-old pregnant woman was admitted to our university hospital due to an adnexal mass, 9.5 cm in diameter, which was detected at 34 weeks of gestation. At 37 + 5 weeks of gestation, a cesarean section with right salpingo-oophorectomy and removal of the tumor was performed. Histopathological findings, including immunohistochemical study, led to the diagnosis of juvenile granulosa cell tumor (JGCT). The histological features and the differential diagnosis of the JGCT are discussed. The optimal management of such adnexal masses during pregnancy is also discussed. A JGCT that is confined to the ovary appears to have an excellent prognosis and can be treated by unilateral salpingo-oophorectomy.

  6. Coexistence of Granular Cell Tumor and Invasive Ductal Breast Cancer in Contralateral Breasts: A Case Report

    Directory of Open Access Journals (Sweden)

    Maurizio Di Bonito

    2014-07-01

    Full Text Available Granular cell tumor (GCT is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up.

  7. Perivascular epithelioid cell tumor of gastrointestinal tract: case report and review of the literature

    NARCIS (Netherlands)

    Lu, B.; Wang, C.; Zhang, J.; Kuiper, R.P.; Song, M.; Zhang, X.; Song, S.; Geurts van Kessel, A.; Iwamoto, A.; Wang, J; Liu, H.

    2015-01-01

    Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are exceedingly rare, with only a limited number of published reports worldwide. Given the scarcity of GI PEComas and their relatively short follow-up periods, our current knowledge of their biologic behavior, molecular

  8. Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers

    NARCIS (Netherlands)

    M.L. Cools (Martine); S.L.S. Drop (Stenvert); K.P. Wolffenbuttel (Katja); J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert)

    2006-01-01

    textabstractThe risk for the development of germ cell tumors is an important factor to deal with in the management of patients with disorders of sex development (DSD). However, this risk is often hard to predict. Recently, major progress has been made in identifying gene-products related to germ

  9. Malignant Granular Cell Tumor of the Back: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Laura Stone McGuire

    2014-01-01

    Full Text Available Malignant granular cell tumors are rare, intensely aggressive entities. This paper presents a case of a large rapidly recurrent malignant granular cell tumor with regional and distal metastases on the back of a 54-year-old Cuban man. The primary tumor recurred within six months of the original wide local excision and with satellite lesions apparent at twelve months, and the mass was diagnosed using the histological criteria established by Fanburg-Smith et al. for malignant granular cell tumors. By fifteen months, right axillary lymphadenopathy, multiple satellite lesions, pulmonary nodules, and distant metastasis in the right thigh were present. At sixteen months, wide local excision of recurrent mass and local satellite masses along with right axillary dissection and placement of Integra with subsequent split-thickness skin graft were performed by surgical oncology and plastic surgery teams. The surgical specimen measured 32.0 × 13.5 × 5.5 cm, containing multiple homogeneous masses with the largest mass 22.0 × 9.0 × 4.6 cm. Following surgery, patient was started on Pazopanib 800 mg/day based on phase III randomized trial data in the treatment of soft tissue sarcomas showing this as a potential novel therapy for malignant granular cell tumors.

  10. Saudi oncology society and Saudi urology association combined clinical management guidelines for testicular germ cell tumors.

    Science.gov (United States)

    Alotaibi, Mohammed; Bazarbashi, Shouki; Alkhateeb, Sultan; Abusamra, Ashraf; Rabah, Danny; Almansour, Mubarak; Murshid, Esam; Alsharm, Abdullah; Ahmad, Imran; Alghamdi, Khalid; Saadeddin, Ahmad; Alghamdi, Abdullah

    2014-10-01

    In this report, updated guidelines for the evaluation, medical, and surgical management of germ cell tumor of testes are resented. They are categorized according the stage of the disease using the tumor-node-metastasis staging system 7(th) edition. The recommendations are presented with supporting level of evidence.

  11. Saudi oncology society and Saudi urology association combined clinical management guidelines for testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mohammed Alotaibi

    2014-01-01

    Full Text Available In this report, updated guidelines for the evaluation, medical, and surgical management of germ cell tumor of testes are resented. They are categorized according the stage of the disease using the tumor-node-metastasis staging system 7 th edition. The recommendations are presented with supporting level of evidence.

  12. Treatment of metastatic germ cell tumor in a newly diagnised HIV ...

    African Journals Online (AJOL)

    cell tumors in men infected with the human immunodeficiency virus: natural history and results of therapy. J Clin Oncol 13: 1391–1397. Two scholarships available. Just a reminder that COPE member editors from developing countries can apply for one of two scholarships to attend the seminar and annual general meeting.

  13. Giant-cell tumor of the patella: An uncommon cause of fracture

    Directory of Open Access Journals (Sweden)

    Esther Carbó-Laso

    2017-06-01

    Full Text Available Primary patellar tumors are highly unusual. Most are benign neoplasms with giant-cell tumors being the most common, followed by chondroblastomas and aneurysmal bone cysts. Intralesional curettage and bone grafting is the treatment of choice for most giant-cell tumors in the patella. The use of adjuvants can reduce the high recurrence rate. This is a case report of a giant-cell tumor in a 61-year-old man who was diagnosed with a pathological fracture in the patella after minimal trauma. Extended curettage through an osteotomy made in the medial cortical of the patella was performed. The tumor cavity was filled with high viscosity bone cement and the medial cortical was repositioned. Histological analysis showed mononuclear cells and numerous multinucleated giant cells, confirming the diagnosis. Twenty-four months after surgery, the patient was asymptomatic and there was no evidence of local recurrence. Epidemiology, symptomatology, imagenology, histopathology, treatment options and prognoses of giant-cell tumors of the patella are discussed herein. [Arch Clin Exp Surg 2017; 6(2.000: 112-116

  14. Cathepsin K is the principal protease in giant cell tumor of bone

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Hanemaaijer, R.; Mulder, A.; Dijkstra, P.D.S.; Szuhai, K.; Bromme, D.; Verheijen, J.H.; Hogendoorn, P.C.W.

    2004-01-01

    Giant cell tumor (GCT) of bone is a neoplasm of bone characterized by a localized osteolytic lesion. The nature of GCT is an enigma and the cell type(s) and protease(s) responsible for the extensive localized clinicoradiological osteolysis remain unresolved. We evaluated protease expression and

  15. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors

    NARCIS (Netherlands)

    M.A. Rijlaarsdam (Martin); D.M.J. Tax (David); A.J.M. Gillis (Ad); L.C.J. Dorssers (Lambert); Koestler, D.C. (Devin C.); De Ridder, J. (Jeroen); L.H.J. Looijenga (Leendert)

    2015-01-01

    textabstractThe cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the

  16. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors

    NARCIS (Netherlands)

    Rijlaarsdam, M.A.; Tax, D.M.J.; Gillis, A.J.M.; Dorssers, L.C.J.; Koestler, D.C.; De Ridder, J.; Looijenga, L.H.J.

    2015-01-01

    The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to

  17. Pathogenesis of Testicular Germ Cell Tumors from a Developmental Point of View

    NARCIS (Netherlands)

    K. Biermann (Katharina)

    2010-01-01

    textabstractCurrent classification systems of human germ cell tumors (GCTs) are based on histological composition. In the group of nonseminomas, different variants of teratoma (somatic differentiation), yolk sac tumor and choriocarcinoma (extra-embryonic differentiation), are recognized, as well as

  18. L-[1-carbon-11]tyrosine imaging of metastatic testicular nonseminoma germ-cell tumors

    NARCIS (Netherlands)

    Kole, AC; Hoekstra, HJ; Sleijfer, DT; Nieweg, OE; Vaalburg, W; Schraffordt Koops, H.

    The aim of this study was to investigate whether PET with L-[1-C-11]tyrosine (TYR) can be used to visualize metastatic disease of nonseminoma testicular germ-cell tumors and to monitor the effect of systemic cisplatinum-based polychemotherapy in a noninvasive fashion to reduce the number of

  19. Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors.

    NARCIS (Netherlands)

    Spermon, J.R.; Roeleveld, T.A.; Poel, H.G. van der; Hulsbergen-van de Kaa, C.A.; Bokkel Huinink, W.W. ten; Vijver, M. van de; Witjes, J.A.; Horenblas, S.

    2002-01-01

    OBJECTIVES: To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands. METHODS: From 1982 to 1994, 90

  20. Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors

    NARCIS (Netherlands)

    Spermon, J. R.; Roeleveld, T. A.; van der Poel, H. G.; Hulsbergen-van de Kaa, C. A.; ten Bokkel Huinink, W. W.; van de Vijver, M.; Witjes, J. A.; Horenblas, S.

    2002-01-01

    OBJECTIVES: To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands. METHODS: From 1982 to 1994, 90

  1. MR imaging findings in granular cell tumor of the neurohypophysis: a difficult preoperative diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, A.; Arias, M.; Brasa, J. [Unidad de Resonancia Magnetica (MEDTEC), Hospital Xeral-Cies, Vigo (Spain); Paramo, C. [Servicio de Endocrinologia, Hospital Xeral-Cies, Vigo (Spain); Conde, C. [Servicio de Neurocirugia, Hospital Xeral-Cies, Vigo (Spain); Fernandez, R. [Servicio de Anatomia Patologica, Hospital Xeral-Cies, Vigo (Spain)

    2000-12-01

    Granular cell tumor is a rare neoplasm arising within the neurohypophysis. We describe the MR imaging findings in two symptomatic patients. In one patient with history of panhypopituitarism, MR images showed a large sellar and suprasellar mass. The other patient presented with acute loss of vision in her left eye, and MR images showed a suprasellar mass with compression of the optic chiasm. (orig.)

  2. Role of immunohistochemistry in the diagnosis of malignant small round cell tumors

    Directory of Open Access Journals (Sweden)

    R Bashyal

    2011-10-01

    Full Text Available Background: Immunohistochemistry is a key tool for the analysis of localization of target molecules within tissues. It has a significant role in the identification of tumors lacking evidence of lineage differentiation on the basis of routine light microscopic morphology alone. Approximately 90% of tumors posing diagnostic difficulties by morphology could be accurately classified by exploiting immunohistochemistry. The aim of this study is to identify the true identity of malignant small round cell tumors by immunohistochemical analysis. Materials and Methods:This was a retrospective study done in Department of Histopathology of B.P.Koirala Memorial Cancer Hospital from January 2010 to April 2011.A total of 40 cases small round cell tumors were selected for immunostaining. The immunohistochemistry technique used is the Polymer detection-EnvisionTM System, a two step staining technique based on Horse Radish Peroxidase labeled dextran polymer technology (DAKO Company. Results: Out of 40 cases of malignant small round cell tumors, there were 21 cases (52.5% of Non- Hodgkin Lymphoma , 11 cases (27.5% of Ewing’s Sarcoma/Primitive Neuroectodermal Tumor, 1 case (2.5% of Lymphoblastic Lymphoma , 1 case (2.5% of Rhabdomyosarcoma, 2 cases (5% of Low grade neuroendocrine tumor, 1 case (2.5% of Neuroblastoma, 2 cases (5% of Poorly differentiated Synovial Sarcoma (small cell variant, 1case (2.5% of Malignant Melanoma (small cell variant. Conclusion: Immunohistochemistry is a valuable adjunct to routine hematoxylin and eosin staining for adequate and accurate categorization of malignant small round cell tumors. Keywords: Immunohistochemistry; Malignant Small Round Cell Tumor; Non Hodgkin’s Lymphoma; Ewing’s Sarcoma; Rhabdomyosarcoma DOI: http://dx.doi.org/10.3126/jpn.v1i2.5398 JPN 2011; 1(2: 87-91

  3. A patient presenting with a perivascular epithelioid cell tumor in the broad ligament: a case report

    Directory of Open Access Journals (Sweden)

    Ross Claire

    2011-08-01

    Full Text Available Abstract Introduction Perivascular epithelioid cell tumors are a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. They can originate in any visceral organ or soft tissue and include a range of lesions such as angiomyolipoma, clear cell 'sugar' tumor of the lung, lymphangioleiomyomatosis and clear cell myomelanocytic tumors of the falciparum ligament/ligament teres. Due to their rarity and varied sites and presentation, management of these tumors remains highly challenging. Case Presentation A 46-year-old para 2 Caucasian woman initially presented to the general surgeons at our hospital in North West London with abdominal pain. Laparoscopy revealed a right broad ligament hematoma, which was thought to be iatrogenic in origin, from insertion of the Veress needle at the time of surgery, and was managed conservatively. Upon her re-presentation two months later with severe pain, ultrasound scanning revealed the hematoma had increased in size and she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histology results from necrotic tissue from the hematoma led to a diagnosis of perivascular epithelioid cell tumor. She was then referred to a tertiary oncology center, where she underwent several further operations in an attempt to debulk the tumor for symptomatic relief of her pain, with limited success. She is now taking the immunosuppressive drug sirolimus, which has produced a modest reduction in tumor size. She is now 47 months on from initial presentation. Conclusions A literature search has revealed only six other case reports of broad ligament perivascular epithelioid cell tumors, with varied presentations and management. The longest duration of follow-up was 21 months. Only five other cases of perivascular epithelioid cell tumor managed with sirolimus have been reported. We therefore feel that this report highlights some of the

  4. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    So called `cold fusion phenomena` are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording {sup 4}He, {sup 3}He, {sup 3}H, which are not rich in quantity basically. An experiment where plenty of {sup 4}He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author).

  5. Fusion plasmas

    Science.gov (United States)

    Engelmann, F.

    1995-09-01

    In the following, a synthetic review of the information reported at the Conference will be given. No attempt is made to summarize specific contributions; rather the material contributed will be looked at from a few different angles. All areas of fusion plasma physics were represented: there were experimental results on magnetic confinement (tokamaks; stellarators; mirrors; reversed field pinches; field reversed configurations; Z-pinches, with emphasis on the dense Z-pinch; plasma focus, ect.) and on inertial confinement; related modelling and diagnolstics development; theory, as well as some technological activities (power generators; RF sources, etc.) and component (e.g. antennae) development for smaller fusion devices. In particular, fusion-related research in Latin America was exhaustively covered. In addition, large future projects in fusion research were summarized. (AIP)

  6. The Virosome concept in influenza vaccines

    NARCIS (Netherlands)

    Wilschut, J; Huckriede, A; Bungener, L; Daemen, T; Stegmann, T; Palache, A

    2004-01-01

    Reconstituted influenza virus envelopes (virosomes) represent efficient influenza vaccines inducing high antibody titers upon intramuscular adminsitration. Virosomes are reconstituted viral envelopes which retain the cell entry and membrane fusion characteristics of native influenza virus. Here, we

  7. Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the ovary.

    Science.gov (United States)

    Abu-Rustum, Nadeem R; Restivo, Antonella; Ivy, Joseph; Soslow, Robert; Sabbatini, Paul; Sonoda, Yukio; Barakat, Richard R; Chi, Dennis S

    2006-10-01

    To describe the incidence of retroperitoneal pelvic or paraaortic lymph node metastasis in patients with primary and recurrent ovarian granulosa cell tumors. At Memorial Sloan-Kettering Cancer Center, we conducted a retrospective chart review of all patients with ovarian granulosa cell tumors managed as inpatients from January 1991 to July 2005. The initial date of diagnosis ranged from 1971 to 2005. We identified 68 patients with a median age of 49 years (mean, 47.5 years; range, 19-78 years). Sixty-four (94%) patients had adult type and 4 (6%) had juvenile granulosa cell tumors. Fifty-three (78%) patients had their initial surgery at another institution and 55 (81%) were incompletely surgically staged at diagnosis due to the absence of pelvic and/or aortic lymph node dissection. Patients were assigned an International Federation of Gynecology and Obstetrics (FIGO) stage that included IA, 39; IC, 15; IIB, 3; IIC, 3; IIIC, 1. In 7 patients, the original stage was not assigned. Only 16 (24%) patients had a pelvic lymph node sampling and 13 (19%) also had a paraaortic lymph node sampling at primary surgery or at restaging surgery performed shortly following initial diagnosis; however, in these cases, lymph nodes were negative for metastasis. The median number of pelvic lymph nodes removed was 10 (mean, 11.6 nodes; range, 0-36 nodes). The median number of paraaortic lymph nodes removed was 4 (mean, 6 nodes; range, 0-19 nodes). Nine of 15 (60%) of patients managed initially at our institution were surgically staged compared to 4 of 53 (7.5%) who were managed initially elsewhere (P granulosa cell tumors were managed during the study, 31 (91%) had adult type granulosa cell tumor, and 3 had juvenile histology. Thirty-three of 34 patients who recurred were incompletely surgically staged at the initial operation. Original "clinical" FIGO stage for patients who recurred included IA, 15; IC, 8; IIB, 1; IIC, 3; IIIC, 1; and in 6 patients, the original stage was not available

  8. Mastocytemia associated with a visceral mast cell tumor in a Sumatran tiger (Panthera tigris).

    Science.gov (United States)

    Graille, Mélanie; Huyghe, François-Pierre; Nicolier, Alexandra

    2013-03-01

    A 6-yr-old male Sumatran tiger (Panthera tigris) with no significant past clinical history was anesthetized for clinical examination after 5 days of lethargy. Clinically, the animal presented with anorexia, pale mucous membranes, and icterus. Hematologic results indicated moderate anemia and severe thrombocytopenia and showed a circulating population of atypical mast cells. The tiger died during anesthesia. On postmortem examination, abdominal hemorrhage associated with marked diffuse hepato-splenomegaly and mesenteric, hepatic, and splenic lymph node hypertrophy were observed. A visceral mast cell tumor was confirmed by histologic examination and toluidine blue staining, with splenic, hepatic, lymphoid, renal, and pulmonary infiltration. Hematologic, postmortem, and histologic findings were consistent with mastocytemia associated with the splenic form of mast cell tumor described in domestic cats.

  9. Oral Granular Cell Tumor: Report of Case Series and a Brief Review of the Literature

    Directory of Open Access Journals (Sweden)

    Karakostas Panayiotis

    2017-07-01

    Full Text Available Background/Aim: The present analysis focuses on examining a case series of eight patients diagnosed with a granular cell tumor located in the oral cavity. Case series: The patients’ clinical states were thoroughly studied, along with the histopathological and immunohistochemical examinations findings. Their surgical treatment and postoperative course are also within the scope of this analysis. Numerous histogenesis theories and the appropriate tumor treatment are mentioned within the article being always in accordance with the relative literature. Conclusions: Oral granular cell tumor is a benign oral disease of possible neural origin commonly located on the tongue. Surgical excision is the treatment of choice. In any case, histological and immunohistochemical examination confirm both the clinical diagnosis and the differential diagnosis between oral squamous cell carcinoma.

  10. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mohammed Alotaibi

    2016-01-01

    Full Text Available This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with testicular germ cell tumors. It is categorized according to the stage of the disease using the tumor-node-metastasis staging system 7th edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with testicular germ cell tumors.

  11. Gene transfection in primary stem-like cells of giant cell tumor of bone

    Directory of Open Access Journals (Sweden)

    Shalini Singh

    2010-09-01

    Full Text Available Shalini Singh1, Isabella Mak1, Patricia Power1, Melissa Cunnigham2, Robert Turcotte3, Michelle Ghert11Departments of Surgery, 2Biology, McMaster University, Hamilton, Ontario; 3Department of Orthopaedic Surgery, McGill University Medical Centre, Montreal, Quebec, CanadaAbstract: The neoplastic stem-like stromal cell of giant cell tumor of bone (GCT survives for multiple passages in primary culture with a stable phenotype, and exhibits multipotent characteristics. The pathophysiology of this tumor has been studied through the primary culture of these cells. However, successful gene transfer of these cells has not been reported to date. In this short report, we describe the development of the first reported technique that results in efficient gene transfection in primary stem-like cells of GCT.Keywords: gene, transfection, primary cells, TWIST, giant cell tumor

  12. Equine placental mixed germ cell tumor with metastasis to the foal.

    Science.gov (United States)

    Bockenstedt, M M; Fales-Williams, A; Haynes, J S

    2015-03-01

    The placenta from an embryo transfer-recipient mare and live foal was examined. The placenta was effaced by multifocal masses, which ranged from less than 1 cm to 14 cm in diameter. The foal represented at 52 days for lethargy, ataxia, and urine dribbling; due to a poor prognosis, the foal was euthanized. At necropsy, the liver was effaced by multifocal, pale, irregular nodules. The lumbar vertebrae and other skeletal sites had multifocal lytic lesions. The placenta had 4 populations of neoplastic cells, including a spindle cell population, tall columnar and transitional epithelial cell populations, and an undifferentiated polygonal cell population. The foal's liver had similar populations and patterns of cells as those in the placenta. The lesion in the placenta and the masses in the foal were diagnosed as a mixed germ cell tumor and metastatic mixed germ cell tumor, respectively. © The Author(s) 2014.

  13. Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs

    OpenAIRE

    QUARTUCCIO, Marco; MARINO*, Gabriele; Garufi, Giuseppe; Cristarella, Santo; Zanghì, Antonina

    2012-01-01

    The association of cryptorchidism, functional Sertoli cell tumors, and spermatic cord torsion has been rarely reported in the literature. Two dogs were admitted for bilateral skin alopecia and weight loss. Both animals were cryptorchid and displayed a pendulous preputial sheath, prostate hypertrophy, and increased levels of circulating oestrogen. Transabdominal palpation and ultrasonography revealed the presence of neoplastic retained gonads. During surgery, spermatic cord torsion was also de...

  14. Giant cell tumor of the capitate: an unusual case with 10 years follow-up

    Directory of Open Access Journals (Sweden)

    Duman Serda

    2015-01-01

    Full Text Available Giant cell tumor of the small bones, particularly the carpal bones of the hand, is exceedingly rare. We present a case report of giant cell tumor of the capitate in a 24 year-old female with 10 years postoperative follow-up. Although carpal bones are extremely unusual location, orthopedic surgeons should always keep in mind that differential diagnosis must include giant cell tumor of bone whenever an expansile osteolytic lesion with well-defined but nonsclerotic margins is identified in a young adult with closed physes.

  15. Giant Cell Tumor of the Thoracic Spine Presenting as a Posterior Mediastinal Tumor with Benign Pulmonary Metastases: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hun [Daegu Fatima Hospital College of Medicine, Daegu (Korea, Republic of); Rho, Byung Hak; Bahn, Young Eun; Choi, Won Il [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2010-11-15

    Giant cell tumor of bone is a benign, but potentially aggressive lesion that can show local recurrence and metastases. We report here on a case of a 29-year-old man who presented with an incidentally found mediastinal mass. Chest radiography and computed tomography showed a huge mediastinal mass with bilateral pulmonary nodules and the diagnosis of giant cell tumor with benign pulmonary metastasis was confirmed. To the best of our knowledge, this is the first reported case of primary thoracic spinal giant cell tumor manifesting as a huge mediastinal mass with pulmonary metastases

  16. Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

    Science.gov (United States)

    2017-10-31

    Adult Central Nervous System Germ Cell Tumor; Adult Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Adult Medulloblastoma; Adult Pineoblastoma; Adult Supratentorial Embryonal Tumor, Not Otherwise Specified; Atypical Teratoid/Rhabdoid Tumor; Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Medulloepithelioma; Ototoxicity; Recurrent Adult Brain Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified

  17. Absence of microsatellite instability and BRAF (V600E) mutation in testicular germ cell tumors.

    Science.gov (United States)

    Cárcano, F M; Lengert, A H; Vidal, D O; Scapulatempo Neto, C; Queiroz, L; Marques, H; Baltazar, F; Berardinelli, G N; Martinelli, C M S; da Silva, E C A; Reis, R M; Lopes, L F

    2016-09-01

    Testicular germ cell tumors (TGCT) are the most common malignant neoplasm in young men. DNA mismatch repair deficiency can lead to microsatellite instability (MSI), an important mechanism of genetic instability. A mutation of the BRAF gene has been implicated in the pathogenesis of several solid tumors and has recently become an important therapeutic target. The role of MSI and BRAF gene mutation in TGCT, particularly in refractory disease, is poorly understood and reported findings are controversial. In this study, we aimed to determine the frequency and clinical impact of MSI status and BRAF mutations in TGCT. DNA was isolated from formalin-fixed paraffin embedded (FFPE) tissue from 150 TGCT cases. The MSI phenotype was evaluated using multiplex PCR for five quasimonomorphic mononucleotide repeat markers. Exon 15 of the BRAF oncogene (V600E) was analyzed by PCR, followed by direct sequencing. Sixteen percent of cases were considered to have refractory disease. In a small subset of cases (17 for MSI and 18 for BRAF), the quantity and quality of DNA recovery were poor and therefore, were unable to be analyzed. The remaining 133 TGCT cases showed a complete absence of MSI. Of the 132 cases successfully evaluated for BRAF mutations, all were V600E wild-type. In conclusion, despite a distinct response of testicular germ cell tumors to therapy, microsatellite instability, and the BRAF V600E mutation were absent in all testicular germ cell tumors tested in this study. © 2016 American Society of Andrology and European Academy of Andrology.

  18. Tumor gigantocelular sinovial do joelho Synovial giant cell tumor of the knee

    Directory of Open Access Journals (Sweden)

    Rene Jorge Abdalla

    2009-10-01

    Full Text Available Tumor gigantocelular sinovial é uma neoplasia benigna, raramente sendo relatada na forma de metástase maligna. A localização mais comum de ocorrer um tumor gigantocelular sinovial é na mão e as mais infrequentes são tornozelo e joelho. No presente estudo os autores têm como objetivo descrever um caso raro de tumor gigantocelular sinovial localizado no joelho e o tratamento escolhido. A artroscopia demonstrou, nesse caso, ser o método ideal para o tratamento da lesão, uma vez que permitiu abordagem pouco agressiva e, ao mesmo tempo, boa visualização de todos os compartimentos da articulação do joelho e a completa ressecção do tumor.Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  19. Anxiety and depression in long-term testicular germ cell tumor survivors.

    Science.gov (United States)

    Vehling, S; Mehnert, A; Hartmann, M; Oing, C; Bokemeyer, C; Oechsle, K

    2016-01-01

    Despite a good prognosis, the typically young age at diagnosis and physical sequelae may cause psychological distress in germ cell tumor survivors. We aimed to determine the frequency of anxiety and depression and analyze the impact of demographic and disease-related factors. We enrolled N=164 testicular germ cell tumor survivors receiving routine follow-up care at the University Cancer Center Hamburg and a specialized private practice (mean, 11.6 years after diagnosis). Patients completed the Generalized Anxiety Disorder Screener-7, the Patient Health Questionnaire-9 and the Memorial Symptom Assessment Scale-Short Form. We found clinically significant anxiety present in 6.1% and depression present in 7.9% of survivors. A higher number of physical symptoms and having children were significantly associated with higher levels of both anxiety and depression in multivariate regression analyses controlling for age at diagnosis, cohabitation, socioeconomic status, time since diagnosis, metastatic disease and relapse. Younger age at diagnosis and shorter time since diagnosis were significantly associated with higher anxiety. Although rates of clinically relevant anxiety and depression were comparably low, attention toward persisting physical symptoms and psychosocial needs related to a young age at diagnosis and having children will contribute to address potential long-term psychological distress in germ cell tumor survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Ruptured Granulosa Cell Tumor of the Ovary as a Cause of Acute Abdomen in Postmenopausal Woman

    Directory of Open Access Journals (Sweden)

    Tufan Oge

    2012-01-01

    Full Text Available Acute abdomen with hemoperitoneum is a very rare entity in postmenopausal women due to gynecologic conditions. A 54-year-old, postmenopausal woman was brought to emergency department with severe abdominal pain. Physical examination revealed acute abdomen findings with 15 cm pelvic mass on the right adnexal region. Immediate exploratory laparotomy was performed. During laparotomy 1000 cc of bloodstained fluid, ruptured and actively bleeding large mass arising from right ovary was observed. Right salpingo-oopherectomy was performed in emergency conditions, and pathology report revealed an adult type of granulosa cell tumor. After this result, staging surgery was performed and patient was diagnosed as granulosa cell tumor stage 1 c. Cisplatin, etoposide, and bleomycin chemotherapy was given. Clinicians should be aware of granulosa cell tumors which may occur at any age and prone to rupture. Frozen section will be helpful in order to avoid incomplete surgeries especially in postmenopausal women presented with intra-abdominal bleeding.

  1. Primary Spinal Germ Cell Tumors: A Case Analysis and Review of Treatment Paradigms

    Directory of Open Access Journals (Sweden)

    Joshua J. Loya

    2013-01-01

    Full Text Available Objective. Primary intramedullary spinal germ cell tumors are exceedingly rare. As such, there are no established treatment paradigms. We describe our management for spinal germ cell tumors and a review of the literature. Clinical Presentation. We describe the case of a 45-year-old man with progressive lower extremity weakness and sensory deficits. He was found to have enhancing intramedullary mass lesions in the thoracic spinal cord, and pathology was consistent with an intramedullary germ cell tumor. A video presentation of the case and surgical approach is provided. Conclusion. As spinal cord germinomas are highly sensitive to radiation and chemotherapy, a patient can be spared radical surgery. Diverse treatment approaches exist across institutions. We advocate biopsy followed by local radiation, with or without adjuvant chemotherapy, as the optimal treatment for these tumors. Histological findings have prognostic value if syncytiotrophoblastic giant cells (STGCs are found, which are associated with a higher rate of recurrence. The recurrence rate in STGC-positive spinal germinomas is 33% (2/6, whereas it is only 8% in STGC-negative tumors (2/24. We advocate limited volume radiotherapy combined with systemic chemotherapy in patients with high risk of recurrence. To reduce endocrine and neurocognitive side effects, cranio-spinal radiation should be used as a last resort in patients with recurrence.

  2. Sertoli-Leydig cell tumor: a rare ovarian neoplasm. Case report and review of literature.

    Science.gov (United States)

    Sachdeva, Poonam; Arora, Raksha; Dubey, Chandan; Sukhija, Astha; Daga, Mridula; Singh, Deepak Kumar

    2008-04-01

    Sertoli-Leydig cell tumor is a gonadal tumor of the sex cord-stromal type. It is a rare tumor comprising 0.1 to 0.5% of all ovarian tumors. Management of these cases poses a difficult therapeutic challenge. A 13-year-old girl presented with acute urinary retention, excessive hair growth and deepening of the voice. A mass the size of a 28-week gravid uterus was arising from the pelvis. Serum testosterone level was raised to 145.2 ng/dl. Computed tomography revealed a heterogeneously hypoechoic, solid cystic mass arising from the left adnexa. Left salpingo-oophorectomy was done. A histopathological diagnosis of Sertoli-Leydig cell tumor (intermediate, Meyers type II) was given. Patients with Sertoli-Leydig cell tumors present with signs of defeminization followed by masculinization. Age of the patient, stage of the disease and degree of tumor differentiation based on morphology are the most important factors to consider in the management of the case.

  3. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  4. Benign giant-cell tumor of the common bile duct: a case report.

    Science.gov (United States)

    Wang, Dan-Dan; Zheng, Ya-Min; Teng, Liang-Hong; Sun, Yan-Ni; Gao, Wei; Wang, Lei-Ming; Wang, Yue-Hua; Li, Fei; Lu, De-Hong

    2014-11-07

    Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor's possible confusion with other malignant tumors.

  5. Alpha-fetoprotein secretion in a craniopharyngioma. Are craniopharyngiomas part of the germ cell tumor family?

    Science.gov (United States)

    Moschovi, Maria; Alexiou, George A; Dastamani, Anastasia; Stefanaki, Kalliopi; Prodromou, Neofytos; Hatzigiorgi, Hristiana; Karamolegou, Kalliopi; Tzortzatou-Stathopoulou, Fotini

    2010-09-01

    A 14-months-old girl was admitted to our hospital because of excessive irritability and abnormal eye movements over the last two months. Brain CT and MRI revealed a suprasellar cystic and partially solid mass with calcifications. The laboratory investigation revealed increased serum levels of AFP. These findings were suggestive for a brain germ cell tumor. Therefore, systemic chemotherapy was started. After two courses there was a reduction in the levels of AFP but the tumor size remained unchanged. Subtotal tumor excision was performed that revealed the presence of a craniopharyngioma. One month later there was enlargement of the cystic part of the tumor, while serum AFP was elevated. The child received again systemic chemotherapy and placement of a reservoir into the cystic part of the tumor. Analysis of the intracystic flouid revealed the presence of beta-HCG and AFP. Following that the patient received brachytherapy with intracavity yttrium placement. Three months later repeated MRI showed a decrease in the size of the cystic part, while the solid part remained unchanged. Thus, the solid part was treated by radiosurgery. One year later the patient was stable but with complete loss of vision. These observations support the theory of a germ cell tumor family, in which craniopharyngioma and germ cell tumor present the two sides of the same entity, while between them a wide variety of tumors, with variable type of secretion of AFP and/or beta-HCG, may exist.

  6. Fusion Machinery

    DEFF Research Database (Denmark)

    Sørensen, Jakob Balslev; Milosevic, Ira

    2015-01-01

    the vesicular SNARE VAMP2/synaptobrevin-2 and the target (plasma membrane) SNAREs SNAP25 and syntaxin-1 results in fusion and release of neurotransmitter, synchronized to the electrical activity of the cell by calcium influx and binding to synaptotagmin. Formation of the SNARE complex is tightly regulated...... and appears to start with syntaxin-1 bound to an SM (Sec1/Munc18-like) protein. Proteins of the Munc13-family are responsible for opening up syntaxin and allowing sequential binding of SNAP-25 and VAMP2/synaptobrevin-2. N- to C-terminal “zippering” of the SNARE domains leads to membrane fusion...

  7. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  8. Failure pattern of pineal and ectopic pineal germ cell tumor after gamma knife radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Heung Lae; Sohn, Seung Chang [College of Medicine, Inje Univ., Pusan (Korea, Republic of)

    2000-06-01

    This study was performed to determine the optimal treatment volume of patients treating with radiation therapy for intracranial germ cell tumor. From 1993 to 1998, 19 patients with intracranial germ cell tumors treated by gamma knife radiosurgery were analyzed. The location of tumor was as follows; 9 cases on pineal region, 1 case on suprasellar region, and 9 cases of multiple lesion. 7 patients were pathologically verified; 5 cases of germ cell tumor and 2 cases of non germinomatous germ cell tumor. Tumor volume was ranged from 2.4 cm{sup 3} to 74 cm{sup 3}. Irradiation dose was 10 Gy to 20 Gy with 50% isodose curve. Follow up period was 10 months to 54 months. Recurrences were observed in 14 cases among 19 (74%) patients. Complete remission and partial remission were achieved in 2 (11%) and 10 (53%) respectively. No response was observed in 7 (36%). 2 cases were recurred within original tumor bed. 6 cases were recurred beyond but contiguous with tumor bed. Bentricular relapses separated from pretreatment tumor bed were 3. Spinal recurrences were 4. Among 8 recurred cases of which tumor volume is smaller than 20 cm{sup 3}, 2 were recurred within original tumor bed, 4 were recurred beyond but contiguous with tumor bed, and 1 spinal recurrence. Meanwhile, 6 cases of which tumor volume larger than 20 cm{sup 3}, 1 case was recurred beyond but contiguous with tumor bed, 2 ventricular recurrences separated with original tumor bed, and 3 spinal recurrences. 5 cases which did not show any recurrence sign show any recurrence sign showed characteristics of single lesion, tumor volume smaller than 20 cm{sup 3} and normal tumor marker. All of 4 cases of spinal recurrences happened in the case having ventricular invasion or lesion. Among 9 cases having multiple lesion, only 3 cases recurred within original tumor bed or around tumor bed, the other 6 cases recurred separated from pretreatment tumor bed. Gamma knife radiosurgery is not recommended for the treatment of

  9. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  10. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Suk Yong; You, Jae Jun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-01-01

    Nearly every technical information is chased in the world. All of them are reviewed and analyzed. Some of them are chosen to study further more to review every related documents. And a probable suggestion about the excitonic process in deuteron absorbed condensed matter is proposed a way to cold fusion. 8 refs. (Author).

  11. Fusion systems

    OpenAIRE

    Aschbacher, Michael; Oliver, Bob

    2016-01-01

    This is a survey article on the theory of fusion systems, a relatively new area of mathematics with connections to local finite group theory, algebraic topology, and modular representation theory. We first describe the general theory and then look separately at these connections.

  12. Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

    Science.gov (United States)

    2017-06-02

    Adult Germ Cell Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Germ Cell Tumor; Extragonadal Embryonal Carcinoma; Grade 2 Immature Ovarian Teratoma; Grade 3 Immature Ovarian Teratoma; Malignant Germ Cell Tumor; Stage I Ovarian Choriocarcinoma; Stage I Ovarian Embryonal Carcinoma; Stage I Ovarian Teratoma; Stage I Ovarian Yolk Sac Tumor; Stage I Testicular Choriocarcinoma; Stage I Testicular Embryonal Carcinoma; Stage I Testicular Yolk Sac Tumor; Stage II Ovarian Choriocarcinoma; Stage II Ovarian Embryonal Carcinoma; Stage II Ovarian Yolk Sac Tumor; Stage II Testicular Choriocarcinoma; Stage II Testicular Embryonal Carcinoma; Stage II Testicular Yolk Sac Tumor; Stage III Ovarian Choriocarcinoma; Stage III Ovarian Embryonal Carcinoma; Stage III Ovarian Yolk Sac Tumor; Stage III Testicular Choriocarcinoma; Stage III Testicular Embryonal Carcinoma; Stage III Testicular Yolk Sac Tumor; Stage IV Ovarian Choriocarcinoma; Stage IV Ovarian Embryonal Carcinoma; Stage IV Ovarian Yolk Sac Tumor; Testicular Mixed Choriocarcinoma and Embryonal Carcinoma; Testicular Mixed Choriocarcinoma and Teratoma; Testicular Mixed Choriocarcinoma and Yolk Sac Tumor

  13. Granulosa Cell Tumor-like Variant of Endometrioid Carcinoma of the Ovary with Osseous Metaplasia: Report of a Rare Case

    Directory of Open Access Journals (Sweden)

    Kavita Mardi

    2015-04-01

    Full Text Available The sex cord-like variant of endometrioid carcinoma is a rare subtype with a close histological resemblance to the sex cord-stromal tumor of the ovaries, in particular the Sertoli cell tumor. However, very few cases of the granulosa cell tumor-like variant have been reported since it is commonly misdiagnosed as a granulose cell tumor. Immunohistochemistry is useful in the diagnosis of these tumors as they are typically negative for inhibin alpha. We herein describe the histological and immunohistochemical features of a rare case of granulosa cell tumor-like variant of endometrioid carcinoma of the ovary with extensive areas of hyalinization, calcification and osseous metaplasia in a 45-year-old female patient.

  14. [The diffuse giant cell tumor of tendon sheath with chondroid metaplasia in right temporomandibular joint: a case report].

    Science.gov (United States)

    Xiao, Yang; Qian, Zhang; Ning, Geng; Junyu, Liu; Haoman, Niu; Yu, Chen

    2017-04-01

    A case diagnosed as diffuse giant cell tumor of tendon sheath with chondroid metaplasia in right temporomandibular joint was reported. The clinicopathological features, diagnosis, and treatment were discussed with the literature review.

  15. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases.

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; McCue, Peter A; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-03-01

    The SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non-germ cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10-week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, in which it was selectively expressed in intestinal-like and some squamous epithelia. In non-germ cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of the ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤ 5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4-positive carcinomas showed poorly differentiated patterns, and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of nonteratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem cell-like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful.

  16. SALL4 EXPRESSION IN GERM CELL AND NON GERM-CELL TUMORS – A SYSTEMATIC IMMUNOHISTOCHEMICAL STUDY OF 3215 CASES

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; Mc. Cue, Peter A.; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-01-01

    SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non germ-cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10th week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, where it was selectively expressed in intestinal-like and some squamous epithelia. In non germ-cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4 positive carcinomas showed poorly differentiated patterns and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of kidney and extrarenal sites, and in Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of non-teratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem-cell like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

  17. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults.

    Directory of Open Access Journals (Sweden)

    Gloria Omosa-Manyonyi

    Full Text Available Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01 plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN may lead to a unique immune profile, inducing both strong T-cell and antibody responses.In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured.The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration.Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.ClinicalTrials.gov NCT01264445.

  18. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  19. Magnetic fusion; La fusion magnetique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project.

  20. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  1. Splenogonadal Fusion

    Directory of Open Access Journals (Sweden)

    Sung-Lang Chen

    2008-11-01

    Full Text Available Splenogonadal fusion (SGF is a rare congenital non-malignant anomaly characterized by fusion of splenic tissue to the gonad, and can be continuous or discontinuous. Very few cases have been diagnosed preoperatively, and many patients who present with testicular swelling undergo unnecessary orchiectomy under the suspicion of testicular neoplasm. A 16-year-old boy presented with a left scrotal mass and underwent total excision of a 1.6-cm tumor without damaging the testis, epididymis or its accompanying vessels. Pathologic examination revealed SFG (discontinuous type. If clinically suspected before surgery, the diagnosis may be confirmed by Tc-99m sulfur colloid imaging, which shows uptake in both the spleen and accessory splenic tissue within the scrotum. Frozen section should be considered if there remains any doubt regarding the diagnosis during operation.

  2. Fusion ambassador

    Science.gov (United States)

    Smith, Chris Llewellyn

    2009-02-01

    With his glasses and shock of thick, white hair, Chris Llewellyn Smith does not look like a superhero saving the world from peril. Yet the slim, 66-year-old physicist is seemingly becoming a potential saviour in the public eye. At least that is the reaction he says he got while recently moving house in Oxford. "I was quite surprised by my new neighbours' knowledge of energy issues when they said 'The world is relying on you to develop fusion!'."

  3. Platinum-refractory germ cell tumors: an update on current treatment options and developments.

    Science.gov (United States)

    Oing, Christoph; Alsdorf, Winfried H; von Amsberg, Gunhild; Oechsle, Karin; Bokemeyer, Carsten

    2017-08-01

    In general, 50 % up to 80 % of metastasized germ cell tumor patients can be cured by platinum-based chemotherapy. However, 3-5 % of patients will still die of platinum-refractory disease and new systemic treatment options are needed to improve treatment success in this difficult setting. This review aims to give an overview on treatment options and current developments in the field of platinum-refractory male germ cell tumors. A comprehensive literature search was conducted searching PubMed, Medline, Cochrane and Embase to identify clinical trials regarding the treatment of platinum-refractory disease. ASCO, EAU and ESMO conference proceedings were searched to identify unpublished results of relevant trials. Comprehensive review papers were hand searched for additional references. Clinicaltrials.gov was checked for ongoing clinical trials in the field of platinum-refractory germ cell tumors. Outcome of platinum-refractory disease remains poor. Single-agents with reasonable activity are gemcitabine, oxaliplatin and paclitaxel, but complete remissions resulting in long-term survival could not be achieved. The triple-combination of gemcitabine, oxaliplatin and paclitaxel followed by resection of residual masses provides the best outcomes with objective responses in 51 % of patients and long-term survival in approximately 10-15 %. To date, no molecularly targeted agent has shown reasonable activity. Treatment options for platinum-refractory disease are limited, but a small subset of patients may achieve long-term disease-free survival by multimodal treatment. The potential of novel targeted agents, i.e. by immune-checkpoint-inhibition remains to be defined.

  4. CT restaging of testicular germ cell tumors: The incidence of isolated pelvic metastases.

    Science.gov (United States)

    Sadow, Cheryl A; Maurer, Amma N; Prevedello, Luciano M; Sweeney, Christopher J; Silverman, Stuart G

    2016-08-01

    We determined the incidence of isolated pelvic metastases at restaging computed tomography (CT) in patients with testicular germ cell tumors to consider if imaging the pelvis could be omitted. After receiving IRB approval for this HIPAA-compliant retrospective study, medical records of 560 men (mean age 32.8) with 583 testicular germ cell tumors who underwent 3683 restaging CT scans of the abdomen and pelvis were reviewed to determine the proportion of patients with metastatic disease in the pelvis alone, as verified by histology or by resolution after therapy. Chi-square statistical analysis tested the association between factors currently thought to predispose patients to pelvic metastases. Patients were also categorized by clinical stage, tumor histology, and initial treatment. Isolated pelvic metastases were detected in nine (1.6%) of 560 men. Neither bulky abdominal disease (p=0.85) nor extratesticular invasion by the primary tumor (p=0.37) were statistically significant in predicting which patients were more likely to have isolated pelvic metastases. Among the nine patients with isolated pelvic recurrence, only three (0.7%) of 408 men with no known pelvic disease at initial staging and no tumor marker elevation at restaging had isolated pelvic metastases. Isolated pelvic recurrence was not statistically different when analyzed by initial stage and treatment. The incidence of isolated pelvic metastases in testicular germ cell tumors at restaging CT is low, but no group of patients was found to be without risk. Therefore, given the small, if any, risk of radiation-induced harm, the decision about whether to include routine pelvic CT in surveillance protocols should be individualized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Lymph Node Yield in Primary Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumors.

    Science.gov (United States)

    Nayan, Madhur; Jewett, Michael A S; Sweet, Joan; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Chung, Peter; Warde, Padraig; Hamilton, Robert J

    2015-08-01

    The number of lymph nodes removed at surgery for various malignancies has diagnostic and prognostic value. However, there are limited data on the significance of the number of nodes removed at retroperitoneal lymph node dissection performed for testicular nonseminoma germ cell tumors. From 1979 to 2012 primary open retroperitoneal lymph node dissection was performed by a single experienced surgeon for clinical stage I/II testicular nonseminoma germ cell tumor in 157 patients. Node count was available in 111 cases (71%). Factors associated with total node count and nodes with viable cancer were assessed by linear regression. The association between node count and time to relapse was assessed by multivariate Cox proportional hazards models controlled for adjuvant chemotherapy. The median total lymph node count was 28 (IQR 19-38). Patient age, cancer laterality, body mass index, clinical stage, time from orchiectomy to retroperitoneal lymph node dissection, pathologist and lymph node dissection year were not associated with total lymph node count. A viable germ cell tumor was found in 70 patients (63%). Total node yield was not associated with nodal cancer metastasis. After lymph node dissection 17 patients (16%) received adjuvant chemotherapy. At a median 57-month followup 18 cases (17%) relapsed after primary retroperitoneal lymph node dissection. Increasing total node count was associated with a decreased risk of relapse on univariate and multivariate analysis (HR 0.96, 95% CI 0.92-0.99, p = 0.03 and HR 0.94, 95% CI 0.89-0.99, p = 0.017, respectively). No analyzed clinical or pathological variable was associated with the node yield of primary retroperitoneal lymph node dissection. However, there may be a relationship between the total node yield at retroperitoneal lymph node dissection and the risk of relapse. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Report of two cases of granular cell tumor, a rare tumor in children

    Directory of Open Access Journals (Sweden)

    Tuğçe Yasak

    2016-11-01

    Full Text Available Granular cell tumor (GCT is a rare soft tissue neoplasm. It was first named as “granular cell myoblastoma” in 1926 by Abrikossof. GCT often manifests as a single, painless nodule that shows a slow enlargement in the cutaneous, subcutaneous, or submucosal tissues. It mostly affects adults between ages 30 and 60 years, and is very rare in children. We herein report two children with GCT; the first patient with a tumor in the neck is presented due to the rare occurrence of the tumor in children. The other patient with a tumor in the leg is presented both due to the rare occurrence of the tumor in children and the relatively less common site of occurrence. Both of the patients were female. The mean tumor size was 2.5 × 2 cm. Histopathological examination of the specimens revealed benign granular cell tumor. One of the patients who had positive margin did not follow-up after the first excision of the tumor and she presented with a local recurrence in a year. Then a wide excision was performed and the defect was closed primarily. The second patient had negative margin and had no recurrence during the follow-up period. Granular cell tumor is rare in children. Although it is mostly benign, it may be malignant in approximately 2% of the cases and metastasize. The local recurrence in a year is characteristic for malignant GCT before metastasis. Positive surgical margins are associated with high recurrence rates, therefore total excision of the tumor is crucial for local recurrence. GCT should be included in the differential diagnosis of head and neck masses. It should be remembered that the tumor may arise in atypical locations and there is a possibility of malignancy.

  7. MAST CELL TUMOR IN DOGS: RETROSPECTIVE STUDY MASTOCITOMA CANINO: ESTUDO RETROSPECTIVO

    OpenAIRE

    Duvaldo Eurides; Áureo Evangelista Santana; Gener Tadeu Pereira; Andrigo Barboza De Nardi; Felipe Antonio Mendes Vicenti; Carlos Roberto Daleck; Juliana Maziero Furlani; Luiz Antônio Franco da Silva

    2008-01-01

    This retrospective study included 49 dogs, 28 males and 21 females, of several breeds, between two and 17 years old. The majority of dogs were mixed breed or Boxers and Teckels, six to nine years old. Eleven animals showed grade I mast cell tumor, 10 grade II and nine grade III. Surgery alone or associated with chemotherapy were performed in the most of cases. The results from our study indicate that surgery alone promotes the highest survival time because surgery procedure is indicated in ca...

  8. Primary hyperparathyroidism associated with a giant cell tumor: One case in the distal radius.

    Science.gov (United States)

    Ouzaa, M R; Bennis, A; Iken, M; Abouzzahir, A; Boussouga, M; Jaafar, A

    2015-10-01

    Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive lesions) that usually disappear after normalization of calcium and phosphate levels. It rarely occurs simultaneously with a giant cell tumor. The authors report one case of a localized form at the distal radius in a patient being followed for primary hyperparathyroidism. The diagnostic challenges related to the clinical and radiological similarities of these two pathological entities are discussed, as they can lead to delays in therapeutic management. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

    Directory of Open Access Journals (Sweden)

    Se Won Kim

    2016-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

  10. Hernia uterine inguinale with transverse testicular ectopia and mixed germ cell tumor

    Directory of Open Access Journals (Sweden)

    Rajshekhar C Jaka

    2007-01-01

    Full Text Available Persistent mullerian duct syndrome is a rare disorder characterized by the presence of uterus and fallopian tube in 46XY phenotypic males and is ascribed to defects in the synthesis or action of anti-mullerian hormone. We report a rare case of hernia uterine inguinale, transverse testicular ectopia associated with mixed germ cell tumor of the testis with metastasis. Transverse testicular ectopia should be suspected preoperatively in patients who have unilateral inguinal hernia associated with contralateral nonpalpable testis. In such cases ultrasonography should be done prior to repair of hernia to evaluate the possible presence of mullerian structures and testicular malignancy, for better management.

  11. The role of systemic chemotherapy in the management of granulosa cell tumors.

    Science.gov (United States)

    Meisel, Jane L; Hyman, David M; Jotwani, Anjali; Zhou, Qin; Abu-Rustum, Nadeem R; Iasonos, Alexia; Pike, Malcolm C; Aghajanian, Carol

    2015-03-01

    Granulosa cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined. We performed a retrospective cohort study of GCT patients diagnosed from January 1996 through June 2013 at the Memorial Sloan Kettering Cancer Center, comparing those who received adjuvant chemotherapy to those who did not. Differences between groups were assessed using the log-rank test. Statistical significance was set at pincidence rate 3.22 times higher than Surveillance, Epidemiology, and End Results (SEER) data predicts (pincidence of antecedent breast cancer in this population, an association that deserves further exploration. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The value of recognizing suspect diagnoses in the triple diagnosis of giant cell tumor of bone

    Directory of Open Access Journals (Sweden)

    Kotru Mrinalini

    2007-01-01

    Full Text Available Giant cell tumor (GCT of bone is the most frequently over-diagnosed neoplasm in orthopedic pathology because giant cells are a common component of many neoplastic and nonneoplastic conditions of bone. Triple diagnosis, requiring substantial individual and collective inputs by orthopedic surgeons, radiologists and pathologists, is the preferred method for the workup of patients with suspected bone neoplasms. At each stage in triple diagnosis, deviations from the typical must be regarded as clues to alternate diagnoses: the greater the deviation, the more a diagnosis of GCT must be considered suspect. A suspect diagnosis must trigger renewed analysis of the available data and a diligent search to exclude alternate diagnoses.

  13. Ovarian Sertoli-Leydig Cell Tumor with High Serum Level of alpha-Fetoprotein

    OpenAIRE

    Iwaki, Hiroyuki; Jie, Ma; Satoh, Masaaki

    1996-01-01

    A case of an ovarian Sertoli Leydig cell tumor (SLCT) associated with ele-vated serum alpha-fetoprotein (AFP) levels occurred in a 16-year-old girl. She had no signs of virilization or defeminization at the operation. In the abdominal cavity, a large and well demarcated tumor had replaced the right ovary. After the surgical removal of the tumor, the serum level of AFP decreased to within the normal limits. Microscopic examination of the tumor revealed intermediately differentiated SLCT with a...

  14. Complicated pediatric subglottic granular cell tumor with extensive intraluminal and extraluminal invasion.

    Science.gov (United States)

    Gonik, Nathan J; Zeltsman, David; Smith, Lee P

    2014-09-01

    Subglottic granular cell tumors (GCT) are rare, potentially life threatening benign tumors. Complete resection is necessary, yet care must be taken to preserve laryngeal function. We present the first description of a pediatric subglottic GCT with extensive invasion beyond the confines of the subglottis to include the vocal folds and central neck. Urgent endoscopic debulking avoided tracheotomy and facilitated extubation. Later, complete resection required hemithyroidectomy, laryngofissure and partial cricotracheal resection. We conclude that endoscopic debulking is an appropriate initial treatment. Transmural extension should be suspected in tumors larger than 1cm and warn of the need for tracheal resection. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Unusual morphology of desmoplastic small round cell tumor from an ascitic fluid in the postchemotherapy setting

    Directory of Open Access Journals (Sweden)

    Ricardo González-Arango

    2015-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a malignant neoplasm that most often presents in male adolescents as an abdominal mass. Cytological features have been previously described, but only two reports noted post chemotherapy changes on effusions. We report a case of a 15-year-old male with DSRCT status postchemotherapy that presented with ascitis. Unusual morphology was seen: Numerous malignant large and single cells with prominent nucleoli and abundant cytoplasm in a background without the stroma, occasional mitosis, and the abundant apoptosis. Cell block immunocytochemistry was confirmatory. Awareness of the postchemotherapy changes in this tumor will allow us to diagnose recurrence.

  16. Imaging findings of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen.

    Science.gov (United States)

    Rao, Liangjun; Yang, Zhiyun; Wang, Xiaoyan; Zhang, Xiangsong; Shen, Bingqi

    2014-04-01

    Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) histology is similar to that of the classical follicular dendritic cell (FDC) tumor, but, in addition, the inflammatory component is quite prominent. We report a case of IPT-like FDCT of the spleen by abdominal CT and 18F-FDG PET/CT. Abdominal CT showed a low-density, round, well-circumscribed defined mass in spleen, and the mass showed a high metabolism rate on 18F-FDG PET/CT.

  17. Interferon alfa-2b for recurrent and metastatic giant cell tumor of the spine: report of two cases.

    Science.gov (United States)

    Wei, Feng; Liu, Xiaoguang; Liu, Zhongjun; Jiang, Liang; Dang, Gengting; Ma, Qingjun; Dang, Lei

    2010-11-15

    Case report. To demonstrate that interferon alfa-2b is a therapeutic option for obtaining long-term control of recurrent and metastatic giant cell tumor of spine. Interferon alfa served as angiogenesis inhibitor and has been successfully used to treat giant cell tumor of long bones and facial bones. Up to date, no report is found with regard to the use of interferon as a stand-alone treatment for unresectable, recurrent, and metastatic giant cell tumor originated from the spine. A 29-year-old woman with C1 and C2 giant cell tumor was treated by radiotherapy, intralesional curet, and chemotherapy orderly. Tumor recurred after 2 years. A second curet was undertaken. Tumor recurred second time and caused severe spinal cord compression. Lung metastasis was diagnosed simultaneously. A 24-year-old man with recurrent giant cell tumor of T5 and T6 was treated by spondylectomy of T5 and T6. Six months later, a giant metastatic lesion was found in sacrococcygeal region, which was excised and proved to be giant cell tumor of bone. Four months later, 2 recurrent lesions were found beside the rectum. Interferon alfa-2b at a dose of 3,000,000 U/m was then administered subcutaneously everyday for both patients for 3.5 and 3 years, respectively. No major complications related to the use of interferon occurred. The lesion in C1-C2 of the first patient regressed steadily and was restricted and encircled within the lateral mass. The metastatic lesions in the lungs also significantly reduced. The pararectal lesions of the second patient disappeared completely. Interferon therapy may be an effective and safe treatment for spine giant cell tumor recurrence and metastasis in soft tissue. The effectiveness may be time and dosage dependent.

  18. Does Wrist Arthrodesis With Structural Iliac Crest Bone Graft After Wide Resection of Distal Radius Giant Cell Tumor Result in Satisfactory Function and Local Control?

    Science.gov (United States)

    Wang, Tao; Chan, Chung Ming; Yu, Feng; Li, Yuan; Niu, Xiaohui

    2017-03-01

    Many techniques have been described for reconstruction after distal radius resection for giant cell tumor with none being clearly superior. The favored technique at our institution is total wrist fusion with autogenous nonvascularized structural iliac crest bone graft because it is structurally robust, avoids the complications associated with obtaining autologous fibula graft, and is useful in areas where bone banks are not available. However, the success of arthrodesis and the functional outcomes with this approach, to our knowledge, have only been limitedly reported. (1) What is the success of union of these grafts and how long does it take? (2) How effective is the technique in achieving tumor control? (3) What complications occur with this type of arthrodesis? (4) What are the functional results of wrist arthrodesis by this technique for treating giant cell tumor of the distal radius? Between 2005 and 2013, 48 patients were treated for biopsy-confirmed Campanacci Grade III giant cell tumor of the distal radius. Of those, 39 (81% [39 of 48]) were treated with wrist arthrodesis using autogenous nonvascularized iliac crest bone graft. Of those, 27 (69% [27 of 39]) were available for followup at a minimum of 24 months (mean, 45 months; range, 24-103 months). During that period, the general indications for this approach were Campanacci Grade III and estimated resection length of 8 cm or less. Followup included clinical and radiographic assessment and functional assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Musculoskeletal Tumor Society (MSTS) score, grip strength, and range of motion at every followup by the treating surgeon and his team. All functional results were from the latest followup of each patient. Union of the distal junction occurred at a mean of 4 months (± 2 months) and union of the proximal junction occurred at a mean of 9 months (± 5 months). Accounting for competing events, at 12 months, the rate of proximal

  19. Custom-made wrist prosthesis in a patient with giant cell tumor of the distal radius.

    Science.gov (United States)

    Damert, Hans-Georg; Altmann, Silke; Kraus, Armin

    2013-05-01

    Treatment for giant cell tumors of the distal radius is challenging when motion is to be preserved. As standard wrist prostheses typically do not achieve favorable results, we treated a 36-year-old man with giant cell tumor of the distal radius with a new, custom-made implant. A custom-made wrist prosthesis with a long shaft was designed according to the patient's X-ray findings. After complete tumor resection, the prosthesis was subsequently implanted into the distal radius without complications. Two months after surgery, range of motion was 30°-0-25° for extension/flexion, 10°-0-5° for ulnar/radial abduction, 80°-0-0 for pronation/supination, complete range of motion for the fingers, and a grip strength of 6 kg. Two years after surgery, implant position was still correct and range of motion was 45°-0-10° for extension/flexion, 10°-0-20° for ulnar/radial abduction, and 80°-0-10° for pronation/supination. Grip strength was 16 kg, and DASH score was 25 compared to 39 before surgery. The patient returned to work as a craftsman. Custom-made wrist prostheses could become a practical option in patients with large defects of the distal radius who desire to preserve wrist motion.

  20. Giant cell tumor expanded into the thoracic cavity with spinal involvement.

    Science.gov (United States)

    Demura, Satoru; Kawahara, Norio; Murakami, Hideki; Akamaru, Tomoyuki; Kato, Satoshi; Oda, Makoto; Tomita, Katsuro; Tsuchiya, Hiroyuki

    2012-03-07

    This article describes a case of a giant cell tumor that expanded into the thoracic cavity and through the spinal canal into the vertebrae. A 36-year-old man presented with a 6-month history of back pain and dyspnea. Plain chest radiographs showed a huge mass accompanied by right pleural effusion. The mass involved the 12th thoracic spine, and the spinal cord was severely compressed. The tumor was resected with a 2-stage procedure. As a first stage to separate the tumor from the anterior vital structures under direct vision, thoracic surgeons performed a right thoracotomy with chest wall reconstruction from the 8th to 11th ribs. The right lung and inferior vena cava were gently retracted, and the tumor was carefully detached from these structures. We were not able to separate the tumor from the right diaphragm due to severe invasion; therefore, we performed partial resection of the right diaphragm with the tumor. After excision of the anterior part of the tumor, the thoracic wall was reconstructed with the right eighth rib and Marlex mesh. When the patient's general condition improved 2 weeks later, spondylectomy by posterior approach was performed. We achieved excision of a giant cell tumor that had expanded into the thoracic cavity and through the spinal canal into the vertebrae. The patient had achieved full rehabilitation with no neurological or respiratory abnormalities at 7 years postoperatively. Copyright 2012, SLACK Incorporated.

  1. [Primary mediastinal germs cells tumors: a twenty years experience in a comprehensive cancer center].

    Science.gov (United States)

    Joly, Charlotte; Deblock, Mathilde; Desandes, Emmanuel; Geoffrois, Lionnel

    2014-12-01

    The aim of this study is to report treatments results of patients with primary germ cell tumors (GCTs) of mediastinum. A retrospective review was done of 19 consecutive patients with mediastinal GCTs treated in "Institut de cancérologie de Lorraine" between 1990 and 2012. A total of 19 patients were enrolled in this study. Three patients had pure seminoma and 16 patients had non-seminomatous germ cell tumors. All patients were treated with cisplatinum based chemotherapy at a dose of 33.48 mg/m(2)/week. At the end of chemotherapy, three patients (15.8%) had complete response and negative marker, seven of them (36.8%) had partial response and negative marker, five of them (26.32%) had partial response and positive marker, three of them (15.8%) had progressive disease (refractory disease) and one patient died because of the disease during treatment. The 1-year and 5-year overall survival rates were respectively 78 and 36% and the progression-free survival rate was 43%. When relapse occurred, this happened within a 13 month period. Our study confirmed the good management of mediastinal GCTs in our institute with similar results compared to literature.

  2. Fibroma and giant-cell tumor of tendon sheath: a case report

    Directory of Open Access Journals (Sweden)

    Batista KT

    2014-04-01

    Full Text Available Kátia Tôrres Batista,1 Heveline Becker de Moura,1 Maria Isabel Lima,2 Kikue Terada Abe3 1Department of Plastic Surgery and Pathology, 2Electron Microscopy Laboratory, 3Cytogenetic Laboratory, Sarah Hospital Brasilia, Brazil Abstract: A 53-year-old man presented in 2009 with a tumor over the dorsum of his hand and wrist. Magnetic resonance imaging was performed before surgery and histopathological and immunohistochemical studies were performed after surgery. This demonstrated an ill-defined lesion measuring 46 mm × 31 mm confined to the subcutaneous tissues, extensor tendons, and articular capsule on the dorsum of the hand and wrist with heterogeneous intermediate and high T1 and T2 signal suggesting a complex mixture of fat and fibrous elements. A histopathological differential diagnosis of hemosiderotic fibrohistiocytic lipomatous lesion/tumor (HFLL/T and giant-cell tumor of tendon sheath and fibroma of tendon sheath was made. We describe this rare lesion and call attention to important points in diagnosis. Keywords: giant cell tumor, fibroma tumor, sheath tendon tumor

  3. Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus).

    Science.gov (United States)

    Fortin, Jessica S; Benoit-Biancamano, Marie-Odile

    2014-01-01

    Herein, we report a 25-year-old male polar bear suffering from a pancreatic islet cell tumor. The aim of this report is to present a case of this rare tumor in a captive polar bear. The implication of potential risk factors such as high carbohydrate diet or the presence of amyloid fibril deposits was assessed. Necropsy examination revealed several other changes, including nodules observed in the liver, spleen, pancreas, intestine, and thyroid glands that were submitted for histopathologic analysis. Interestingly, the multiple neoplastic nodules were unrelated and included a pancreatic islet cell tumor. Immunohistochemistry of the pancreas confirmed the presence of insulin and islet amyloid polypeptide (IAPP) within the pancreatic islet cells. The IAPP gene was extracted from the paraffin-embedded liver tissue and sequenced. IAPP cDNA from the polar bear exhibits some differences as compared to the sequence published for several other species. Different factors responsible for neoplasms in bears such as diet, infectious agents, and industrial chemical exposure are reviewed. This case report raised several issues that further studies may address by evaluating the prevalence of cancers in captive or wild animals. © 2014 Wiley Periodicals, Inc.

  4. [Growing teratoma syndrome in a patient with intracranial germ cell tumor].

    Science.gov (United States)

    Zheludkova, O G; Shishkina, L V; Konovalov, A N; Ryzhova, M V; Kislyakov, A N; Ozerov, S S; Trunin, Yu Yu; Mazerkina, N A; Klimchuk, O V; Tarasova, E M

    2015-01-01

    A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

  5. Coexistence of Granular Cell Tumor with Squamous Cell Carcinoma on the Tongue: A Case Report

    Directory of Open Access Journals (Sweden)

    Recep Bedir

    2015-01-01

    Full Text Available Introduction: Granular cell tumors (GCTs are rare and mostly benign soft tissue tumors. Though they have been reported in all parts of body, they are generally located in the head and neck region, especially on the tongue. Some malign forms exist, but these have been rarely reported. Granular cell tumors have a neural origin and, in immunohistochemical evaluations, they express S-100 and neuron specific enolase (NSE. The treatment of these tumors is bulky surgical excision.   Case Report:   In this case, a cauliflower shaped lesion with a 1 cm diameter was excised from the midline tongue of a 65 year old woman. The histopathological evaluation indicated that it was squamous cell carcinoma (SCC covering GCT. Herein, the coexistence of GCT and SCC we describe on the same region of the tongue, in accordance with literature review, since this is a very rare condition.   Conclusion: Pseudoepitheliomatous hyperplasia may accompany GCTs on the tongue and this condition may mimic well-differentiated SCC. For this reason, with the help of Ki-67 and p63 expression, in addition to immunohistochemical markers, well-differentiated SCC should be differentiated from pseudoepitheliomatous hyperplasia through careful investigation.

  6. Recent advances in molecular and cell biology of testicular germ-cell tumors.

    Science.gov (United States)

    Chieffi, Paolo

    2014-01-01

    Testicular germ-cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20-40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs comprise two major histologic groups: seminomas and nonseminomas germ-cell tumors (NSGCTs). NSGCTs can be further divided into embryonal, carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the primordial germ cells. Many discovered biomarkers including OCT3/4, SOX2, SOX17, HMGA1, Nek2, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful novel molecular targets for antineoplastic strategies. More insight into the pathogenesis of TGCTs is likely to improve disease management not only to better treatment of these tumors but also to a better understanding of stem cells and oncogenesis. © 2014 Elsevier Inc. All rights reserved.

  7. Giant cell tumor of bone: current review of morphological, clinical, radiological, and therapeutic characteristics

    Directory of Open Access Journals (Sweden)

    Georgi P. Georgiev

    2014-09-01

    Full Text Available Giant cell tumor of bone accounts for about 5% of all primary bone tumors in adults and is still one of the most obscure and intensively examined tumors of bone. This largely results from the lack of uniform clinical, radiographic, histological or morphological aspects that allow prediction of recurrence. Classified by the World Health Organization as “an aggressive, potentially malignant lesion”, the giant cell tumor of bone could give lung metastases, could undergo malignant degeneration or could have multicentric localization. It usually develops in long bones but can also occur in unusual locations. The common presenting symptom is increasing pain at the tumor site. Standard treatment ranges from curettage to wide resection, with reports of varying oncological and functional results. The recurrence rate is high during the first 2-3 years after surgery regardless of pre-operative tumor stage. Herein, we discuss the morphological, clinical, radiological, and therapeutic characteristics of this pathologic entity as well as its differential diagnosis. J Clin Exp Invest 2014; 5 (3: 475-485

  8. Symptomatic ovarian steroid cell tumor not otherwise specified in a post-menopausal woman

    Directory of Open Access Journals (Sweden)

    Neha Sood

    2016-06-01

    Full Text Available Steroid cell tumor not otherwise specified (NOS is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years, in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL. Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingooophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging.

  9. Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: Two Interesting Entities Identified in the Same Patient

    Directory of Open Access Journals (Sweden)

    Alfredo J. Lucendo

    2008-02-01

    Full Text Available We illustrate the case of a 41-year-old male with allergic manifestations since childhood. He sought medical attention for intermittent, progressive dysphagia from which he had been suffering for a number of years, having felt the sensation of a retrosternal lump and a self-limited obstruction to the passage of food. Endoscopy detected a submucosal tumor in the upper third of the esophagus, which was typified, via biopsy, as a granular cell tumor with benign characteristics and probably responsible for the symptoms. Two years later, the patient sought medical attention once again as these symptoms had not abated, hence digestive endoscopy was repeated. This revealed stenosis of the junction between the middle and lower thirds of the organ which had not been detected previously but was passable under gentle pressure. Eosinophilic esophagitis was detected after biopsies were taken. Esophageal manometry identified a motor disorder affecting the esophageal body. Following three months of treatment using fluticasone propionate applied topically, the symptoms went into remission, esophageal stenosis disappeared and the esophageal biopsies returned to normal. This is the first documented case of the link between granular cell tumors and Eosinophilic esophagitis, two different disorders which could cause dysphagia in young patients.

  10. The cytogenetic theory of the pathogenesis of human adult male germ cell tumors. Review article.

    Science.gov (United States)

    Chaganti, R S; Houldsworth, J

    1998-01-01

    Human male germ cell tumors (GCTs) represent a biological paradox because, in order to develop into a pluripotential tumor, a germ cell destined to a path of limited or no proliferation must acquire the potential for unlimited proliferation. In addition, it must acquire the ability to elicit embryonal differentiation patterns without the reciprocal inputs from fertilization and the imprinting-associated genomic changes which are a part of normal embryonal development. Although much speculated about, the genetic mechanisms underlying these properties of male GCTs remain enigmatic. Recent cytogenetic and molecular genetic analyses of these tumors are providing new insights and new testable hypotheses. Based on our recent work, we propose two such hypotheses. One relates to the mechanism of germ cell transformation and germ cell tumor development. We suggest that the invariable 12p amplification noted as early as in carcinoma in situ/intratubular germ cell neoplasia (CIS/ITGCN) lesions leads to deregulated overexpression of cyclin D2, a cell cycle G1/S checkpoint regulator with oncogeneic potential. Such overexpression reinitiates the cell cycle. We visualize this happening during the pachytene stage of meiosis through aberrant recombinational events which lead to 12p amplification. The other hypothesis relates to the origin of primary extragonadal GCTs. By comparing cytogenetic changes in primary mediastinal versus gonadal lesions, we propose that, in contrast to long-standing speculation that primary extra-gonadal tumors arise from embryonally misplaced primordial germ cells, these lesions arise from migration of transformed gonadal germ cells.

  11. Improved cellular immune response elicited by a ubiquitin-fused ESAT-6 DNA vaccine against Mycobacterium tuberculosis.

    Science.gov (United States)

    Wang, Qing-min; Kang, Lin; Wang, Xiao-hua

    2009-07-01

    The present study evaluated the immune response elicited by a ubiquitin-fused ESAT-6 DNA vaccine against Mycobacterium tuberculosis. BALB/c mice were vaccinated with plasmid DNA encoding ESAT-6 protein, ubiquitin-fused ESAT-6 DNA vaccine (UbGR-ESAT-6), pcDNA3-ubiquitin and blank vector, respectively. ESAT-6 DNA vaccine immunization induced a Thl-polarized immune response. The production of Thl-type cytokine (IFN-gamma) and proliferative T-cell responses was enhanced significantly in mice immunized with UbGR-ESAT-6 fusion DNA vaccine, compared to non-fusion DNA vaccine. This fusion DNA vaccine also resulted in an increased relative ratio of IgG(2a) to IgG(l) and the cytotoxicity of T cells. Thus, the present study demonstrated that the UbGR-ESAT-6 fusion DNA vaccine inoculation improved antigen-specific cellular immune responses, which is helpful for protection against tuberculosis infection.

  12. Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Maryam Yazdanian

    2015-01-01

    Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.

  13. The histogenic origin of melanoma arising in respiratory epithelium of a teratomatous germ cell tumor of the mediastinum: an enigma unraveled from an unlikely source

    OpenAIRE

    McNab¹, Patricia; Quigley, Brian; Mendoza, Tania; Hakam, Ardeshir; Khalil, Farah; Fishman, Mayer; Altiok, Soner

    2012-01-01

    Mixed germ cell tumors are rare neoplasms that are known to occur in the anterior mediastinum. Characterized by two or more types of germ cell components, these tumors comprise upwards of 25% of mediastinal germ cell tumors. Even rarer are those harboring somatic-type malignancies such as carcinoma, sarcoma, and hematopoietic malignancies. To date, however, there are no known cases of melanoma arising in a malignant mixed germ cell tumor of the anterior mediastinum. We describe the first case...

  14. Giant cell tumor of the lumbar spine: operative management via spondylectomy and short-segment, 3-column reconstruction with pedicle recreation.

    Science.gov (United States)

    Samartzis, Dino; Foster, William C; Padgett, Diana; Shen, Francis H

    2008-02-01

    Giant cell tumors of the lumbar spine are uncommon lesions. Aggressive management of such lesions via spondylectomy to obtain local control and prevent recurrence is often necessary. Spinal reconstruction after total spondylectomy can be challenging. Traditional reconstructions typically require multisegment fixation with an association loss of segmental motion and limited 3-column reconstruction. The authors report a case of a GCT of the lumbar spine occurring in a 49-year-old woman. The authors describe the surgical management of such a lesion via a 1-stage posterior-anterior-posterior procedure that entails a lumbar spondylectomy and short-segment posterior fixation with 3-column reconstruction using a stackable carbon-fiber-reinforced cage device with direct posterior rod connection for pedicle reconstruction. At 33 months postoperative follow-up, neither tumor recurrence nor instrumentation-related complications were noted, bone fusion was prevalent, and sagittal alignment was well maintained. The patient reported no loss of functions, was neurologically intact, and remained active. Aggressive operative management via spondylectomy of a lumbar GCT provides local tumor control. In select patients, spinal reconstruction after a spondylectomy via a 1-stage posterior-anterior-posterior approach to establish short-segment, 3-column reconstruction with recreation of the pedicles is a promising procedure that provides immediate spinal stabilization without evidence of early instrumentation-related complications, maintains spinal alignment, promotes a quick return to daily activities, and avoids sacrificing excessive motion segments and biomechanical function associated with more traditional procedures.

  15. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Hoei-Hansen, Christina E; Krizova, Katerina

    2014-01-01

    The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier...... cell tumors (PIGCTs), to address the roles of cell-intrinsic factors including cell of origin, versus local tissue environment, in the constitutive DDR activation in vivo. Immunohistochemical analysis of 7 biomarkers on a series of 21 PIGCTs (germinomas and other subtypes), 20 normal brain specimens......, there were no clear aberrations in the ATM-Chk2-p53 pathway components among the PIGCT cohort; iii) Subsets of PIGCTs showed unusual cytosolic localization of Chk2 and/or ATM. Collectively, these results show that PIGCTs mimic the DDR activation patterns of their gonadal germ cell tumor counterparts, rather...

  16. Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor

    Directory of Open Access Journals (Sweden)

    Hongwei Cheng

    2010-01-01

    Full Text Available Tenosynovial giant cell tumor is a neoplastic disease of joints that can cause severe morbidity. Recurrences are common following local therapy, and no effective medical therapy currently exists. Recent work has demonstrated that all cases overexpress macrophage colony-stimulating factor (CSF1, usually as a consequence of an activating gene translocation, resulting in an influx of macrophages that form the bulk of the tumor. New anti-CSF1 drugs have been developed; however there are no preclinical models suitable for evaluation of drug benefits in this disease. In this paper, we describe a novel renal subcapsular xenograft model of tenosynovial giant cell tumor. Using this model, we demonstrate that an anti-CSF1 monoclonal antibody significantly inhibits host macrophage infiltration into this tumor. The results from this model support clinical trials of equivalent humanized agents and anti-CSF1R small molecule drugs in cases of tenosynovial giant cell tumor refractory to conventional local therapy.

  17. Polio Vaccine

    Science.gov (United States)

    ... doctorMost kids have no problems with the polio vaccine. However, call your doctor if your child has any reaction after getting the vaccine. Call ... Tell the doctor when (day and time) your child received the vaccine. You also should file a Vaccine Adverse Event ...

  18. MAST CELL TUMOR IN DOGS: RETROSPECTIVE STUDY MASTOCITOMA CANINO: ESTUDO RETROSPECTIVO

    Directory of Open Access Journals (Sweden)

    Duvaldo Eurides

    2008-04-01

    Full Text Available This retrospective study included 49 dogs, 28 males and 21 females, of several breeds, between two and 17 years old. The majority of dogs were mixed breed or Boxers and Teckels, six to nine years old. Eleven animals showed grade I mast cell tumor, 10 grade II and nine grade III. Surgery alone or associated with chemotherapy were performed in the most of cases. The results from our study indicate that surgery alone promotes the highest survival time because surgery procedure is indicated in cases with better prognosis. Teckels and Boxers show highest survival time. Dogs with multiple lesions have lowest survival time. The histologic grades of mast cell tumors have similar incidence, however the incidence tends to decrease from grade I to III. High-grade tumors promote lowest survival time. Fine needle aspiration cytology allow accurate diagnosis of canine mast cell tumors, although the histopathology is required to determine the histologic grade allowing an adequate treatment and so a highest survival time. Both incomplete chemotherapy and untreated groups have poor prognosis. In the most of cases the survival time is low. Este estudo retrospectivo incluiu um total de 49 cães, 28 machos e 21 fêmeas, de diversas raças, entre dois e 17 anos de idade. A maioria dos cães acometidos era mestiça ou da raça Boxer e Teckel, apresentavam idade entre seis e nove anos. Onze animais apresentaram mastocitoma grau I, 10 grau II e nove grau III. Na maioria dos casos, empreitou-se apenas a intervenção cirúrgica ou esta associada à quimioterapia. Conclui-se que a intervenção cirúrgica isolada, utilizada em casos de prognóstico favorável, proporciona maior sobrevida. Cães das raças Teckel e Boxer apresentam sobrevida maior. Cães acometidos em múltiplas regiões do corpo apresentam menor sobrevida. A incidência dos graus histológicos do mastocitoma canino se dá de forma semelhante, porém tende a decrescer do grau I ao III. Mastocitomas de

  19. [Wrist joint reconstruction with vascularized fibular head graft after resection of distal radius giant cell tumor].

    Science.gov (United States)

    Bi, Zhenggang; Pan, Qi; Fu, Chunjiang; Han, Xinguang

    2010-12-01

    To observe the effectiveness of wrist joint reconstruction with vascularized fibular head graft after resection of distal radius giant cell tumor. Between March 2000 and March 2009, 31 cases of distal radius giant cell tumor were treated with extended resection and vascularized fibular head graft for repairing defects of the distal radius, and reconstructing wrist joint. There were 14 males and 17 females with an average age of 37.2 years (range, 15-42 years). The disease duration ranged from 1 month to 2 years and 3 months with an average of 8 months. The size of tumor was 6.5 cm x 3.5 cm-8.0 cm x 4.5 cm. The range of motion (ROM) of wrist joint was as follows: extension 5-15 degrees (mean, 10.7 degrees), flexion 9-21 degrees (mean, 14.2 degrees), radial inclination 0-10 degrees (mean, 8.6 degrees), and ulnar inclination 0-15 degrees (mean, 7.9 degrees). The ROM of forearm was as follows: pronation 15-50 degrees (mean, 28.7 degrees) and supination 10-25 degrees (mean, 16.5 degrees). The histopathological examination revealed that there were 5 cases of stage I, 17 of stage II, and 9 of stage III. All patients achieved primary healing of incision and were followed up 1-9 years with an average of 4.5 years. The X-ray films showed that bone healing time was 12-16 weeks with an average of 13 weeks. No tumors recurrence was observed. The ROM of wrist joint was as follows at 1 year after operation: extension 20-50 degrees (mean, 29.0 degrees), flexion 30-50 degrees (mean, 35.0 degrees), radial inclination 10-20 degrees (mean, 16.5 degrees), and ulnar inclination 20-25 degrees (mean, 23.5 degrees). The ROM of forearm was as follows: pronation 40-90 degrees (mean, 68.3 degrees) and supination 30-80 degrees (mean, 59.6 degrees). There were significant differences in the ROM between before operation and after operation (P wrist score, the results were excellent in 17 cases, good in 12, and fair in 2. Wrist joint reconstruction with vascularized fibular head graft can restore

  20. Osteoarticular Allograft Reconstruction of the Distal Radius After Giant Cell Tumor Resection

    Directory of Open Access Journals (Sweden)

    Hamid Modaresnejad

    2008-05-01

    Full Text Available Background:Resection of the distal end of the radius is indicated in the treatment of locally aggressive primary benign and malignant bone tumors.The aim of this study  was to evaluate the technique of osteoarticular allograft reconstruction of the distal radius after wide excision of a giant-cell tumor.Methods: We analyzed 15 patients retrospectively who had reconstruction of the  distal aspect of the radius with use of an osteoarticular allograft, between 1981 and   2005 after excision of a giant-cell tumor with a minimum follow-up of 2 years (range:   26–125 months, median: 45 months.  Results: 15 consecutive patients with a Campanacci grade 3 giant-cell tumor of the  distal radius formed the study population. Three patients had a local recurrence at 8, 14  and 18 months. Non-union of the osteotomy line was diagnosed 6 months after surgery  in one case and needed bone grafting. Distal radio–ulnar joint instability was observed  in nine cases. Subchondral bone alterations and joint narrowing were present in all cases but were painful in only one patient. Five patients needed a revision of the osteoarticular allograft, at an average of 5.4 years (range: 0.8 to 12 years after the initial reconstruction. The reason for the revision was a fracture of the allograft in four patients and recurrence of the tumor in one. Of the fifteen patients in whom the osteoarticular allograft survived, five patients reported no functional limitation, eight had limitation in  the ability to perform strenuous activities, and two had limitation in the ability to perform  moderate activities. The average range of motion of the wrist was 35 degrees of dorsiflexion, 30 degrees of volar flexion, 10 degrees of radial deviation, 14 degrees of ulnar deviation, 55 degrees of supination, and 70 degrees of pronation.Conclusion: Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft was associated with a low rate of recurrence

  1. Lymph node staging in malignant testicular germ cell tumors; Lymphknotenstaging maligner testikulaerer Keimzelltumoren

    Energy Technology Data Exchange (ETDEWEB)

    Krug, B.; Lackner, K. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Radiologische Diagnostik; Heidenreich, A. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Urologie; Dietlein, M. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    1999-08-01

    Imaging procedures are important in the initial staging and subsequent management of testicular germ cell tumors on account of the differing stage-dependent options for therapy. While the diagnosis of advanced tumors gives no cause for controversial discussion the situation in the clinical stage 1 of germ cell tumors is more ambiguous. The lymph node status is only assessed correctly in about 70% of the patients using the currently available methods since metastases in normally large lymph nodes are not detected on slice images. Although most clinical experience has been gained with computed tomography (CT), magnetic resonance imaging (MRI) offers an equally efficient diagnostic procedure. The significance of positron emission tomography with 18-fluorodoxyglucose (FDG-PET) appears to be limited on account of the absence of accumulation in lymph node metastases of the differentiating teratoma. Sonography and lymphography have not proved to be useful for retroperitoneal lymph node diagnosis. The present review presents and discusses the current value of the available imaging procedures for staging and follow-up of malignant testicular germ cell tumors in relation to modern therapy regimens. (orig.) [German] Aus den unterschiedlichen, stadienabhaengigen Therapieoptionen ergibt sich die Bedeutung bildgebende Verfahren beim initialen Staging und bei der Nachsorge von malignen testikulaeren Keimzelltumoren. Waehrend die Diagnostik fortgeschrittener Tumoren kaum Anlass zu kontroversen Diskussionen bietet, stellt sich die Situation bei Keimzelltumoren im klinischen Stadium I weniger zufriedenstellend dar: Der Lymphknotenstatus laesst sich mit den heute zur Verfuegung stehenden Methoden nur bei etwa 70% der Patienten korrekt erheben, da Metastasen in normal grossen Lymphknoten dem schichtbilddiagnostischen Nachweis entgehen. Obwohl fuer die Computertomographie (CT) derzeit die meisten klinischen Erfahrungen beim Staging testikulaerer Keimzelltumoren vorliegen, steht mit der

  2. Aneurysmal bone cyst secondary to giant cell tumor of the mobile spine: a report of 11 cases.

    Science.gov (United States)

    Wu, Zhipeng; Yang, Xinghai; Xiao, Jianru; Feng, Dapeng; Huang, Quan; Zheng, Wei; Huang, Wending; Zhou, Zhenhua

    2011-10-01

    A retrospective analysis was performed. To analyze the characteristics of aneurysmal bone cyst arising from giant cell tumor of the mobile spine and to discuss the outcome of corresponding surgical and nonsurgical treatment. Giant cell tumors are generally benign neoplasms that exhibit aggressive behavior with a tendency to recur locally. Aneurysmal bone cysts are benign, highly vascular osseous lesions. Although both of them have been described separately in previous literatures, few reports have described aneurysmal bone cyst secondary to giant cell tumor of the mobile spine. Between January 2004 and December 2009, 11 patients were identified with an aneurysmal bone cyst arising from giant cell tumor of the mobile spine. Four patients underwent subtotal tumor resection followed by radiotherapy, and the other 7 patients underwent total tumor resection. Patients with lesions located below T6 were treated with selective arterial embolization before surgery. Clinical data and the efficacy of surgery were analyzed via chart review Of the eleven patients identified for inclusion in this study, the average age was 33 months (range ∇ 14-65 months). The mean length of follow-up was 31 months. Seven patients kept disease-free during the follow-ups. The remaining four patients recurred and one died of local re-recurrence and lung metastasis. Unlike primary aneurysmal bone cyst, secondary aneurysmal bone cyst arising from giant cell tumor of the mobile spine has a more aggressive tendency to recurrence locally. Complete resection with systematic radiotherapy should be undertaken for the treatment of aneurysmal bone cyst secondary to giant cell tumor of the mobile spine, which is associated with a good prognosis for local tumor control. As complete or as radical an operation as possible should be performed at first presentation. The best chance for the patient is the first chance. Selective preoperative embolization is advised to minimize intraoperative blood loss.

  3. Catalysed fusion

    CERN Document Server

    Farley, Francis

    2012-01-01

    A sizzling romance and a romp with subatomic particles at CERN. Love, discovery and adventure in the city where nations meet and beams collide. Life in a large laboratory. As always, the challenges are the same. Who leads? Who follows? Who succeeds? Who gets the credit? Who gets the women or the men? Young Jeremy arrives in CERN and joins the quest for green energy. Coping with baffling jargon and manifold dangers, he is distracted by radioactive rats, lovely ladies and an unscrupulous rival. Full of doubts and hesitations, he falls for a dazzling Danish girl, who leads him astray. His brilliant idea leads to a discovery and a new route to cold fusion. But his personal life is scrambled. Does it bring fame or failure? Tragedy or triumph?

  4. Fusion cuisine

    DEFF Research Database (Denmark)

    Peters, Chris; Broersma, Marcel

    2018-01-01

    the challenge of multiplicity in journalism studies by proposing an audience-centred, functional approach to scholarship. We argue this approach encourages the creative intellectual advancements afforded by interdisciplinary experimental cooking while respecting the classical intellectual questions that helped......Journalism studies as an academic field is characterized by multidisciplinarity. Focusing on one object of study, journalism and the news, it established itself by integrating and synthesizing approaches from established disciplines – a tendency that lives on today. This constant gaze...... to the outside for conceptual inspiration and methodological tools lends itself to a journalism studies that is a fusion cuisine of media, communication and related scholarship. However, what happens when this object becomes as fragmented and multifaceted as the ways we study it? This essay addresses...

  5. Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis.

    Science.gov (United States)

    Spiller, Cassy M; Bowles, Josephine

    2017-05-01

    Germ cell neoplasia in situ is the non-invasive precursor cell of origin for type II testicular germ cell tumors. It has long been postulated that germ cell neoplasia in situ is derived from defective germ cell development during embryonic life, and although it is impossible to trace in vivo the progression from fetal germ cell to germ cell neoplasia in situ to tumor, there is a large volume of evidence supporting this theory. Current studies focus on understanding how germ cell neoplasia in situ forms, how these cells are activated at puberty and how they transform to invasive tumors of various subtypes. Such information is informing novel diagnostic and therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Role of lipopolysaccharide in the production of plasma cell tumors in mice given mineral oil injections.

    Science.gov (United States)

    Platica, M; Hollander, V P

    1978-03-01

    The lipopolysaccharide (LPS) content of peritoneal fluids of BALB/c mice given mineral oil injections and of normal mice was measured. Peritoneal fluids were passed through DEAE-Bio-Gel columns to remove an inhibitor to the Limulus amebocyte lysate reaction and then were assayed for LPS by a spectrophotometric Limulus amebocyte lysate test. A highly significant difference between control animals and animals given mineral oil injections was found. A clear correlation between LPS concentration and time after first oil injection was shown. P-200 gel chromatography and heat stability of the active material were consistent with the behavior of LPS. The possible role of LPS in the pathogenesis of plasma cell tumor is discussed.

  7. Giant cell tumor of the tendon sheath mimicking a plexiform neurofibroma

    Directory of Open Access Journals (Sweden)

    Swagata Arvind Tambe

    2015-01-01

    Full Text Available Giant-cell tumor of the tendon sheath (GCTTS is a benign soft tissue tumor of the limbs arising from the complex of the tendon sheath and periarticular soft tissues of small joints. It is the second most common benign space occupying lesion in the hand and usually presents as a painless soft tissue mass, which grows slowly in size for many years. We present an interesting case of an enormous GCTTS presenting as a slowly growing mass over left sole of a 52-year-old woman. The duration of GCTTS may range from a few weeks to 30 years but in our case the duration of tumor was almost 48 years, which could be the longest reported duration of GCTTS.

  8. Giant cell tumor of tendon sheath in palmar region-cytological aspect of an uncommon tumor

    Directory of Open Access Journals (Sweden)

    Yeddula Chakrapani Spoorthy Rekha

    2017-01-01

    Full Text Available Giant cell tumor of tendon sheath (GCTTS is a benign soft tissue neoplasm. It is the second most common tumor of the hand after ganglion. The pathogenesis of GCTTS is not known. This tumor is known to recur after excision. We present a case of GCTTS in the palmar aspect of the right hand of a 41-year-old female. Ultrasonography of hand revealed a well-defined hypoechoic lesion in the subcutaneous plane with focal areas of calcification. She underwent fine-needle aspiration (FNA. The FNA smears showed the characteristic presence of stromal cells and multinucleated osteoclast-like giant cells. This is an uncommon case of GCTTS present in the palmar aspect of hand diagnosed by FNA.

  9. An up-date on epigenetic and molecular markers in testicular germ cell tumors.

    Science.gov (United States)

    Chieffi, Paolo

    2017-11-01

    Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. Clinically several types of immunohistochemical markers are useful and sensitive. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include OCT3/4, HMGA1 and 2, NANOG, SOX2, and LIN28. Gene expression in TGCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TGCT subtypes that reflect the normal developmental switch in primordial germ cells from an under to normally methylated genome.

  10. Expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors.

    Science.gov (United States)

    Sukhikh, G T; Becker-Kojić, Z; Kogan, E A; Demura, T A; Faizullina, N M; Nizyaeva, N V; Schott, A; Ureña-Peralta, J J; Askol'skaya, S I; Popov, Yu V

    2013-08-01

    We studied the expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors. The study was performed on tissue specimens obtained during surgery from patients with uterine leiomyoma and leiomyosarcoma (mean age 34 and 51 years, respectively). ACA was present in leiomyoma, leiomyosarcoma, and control myometrium. Intracellular expression of ACA varied in different types of tumors and was minimum in normal myometrium and maximum in leiomyosarcoma. Membrane localization of the protein is typical of common and cellular leiomyoma, while in the growth zones of mitotically active leiomyoma and leiomyosarcoma the reaction product was primarily located in tumor cell cytoplasm. TRA was detected in some leiomyosarcoma cells. Thus, ACA dysregulation was revealed in the growth zones of leiomyomas and in leiomyosarcomas, which manifested in enhanced expression of this protein and its detachment from the plasma membrane, which leads ACA translocation into the cytoplasm and nucleus of tumor cells and potentiates their proliferative activity.

  11. Bilateral presentation of pleural desmoplastic small round cell tumors: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Won, You Sun; Park, Jai Soung; Jeong, Sun Hye; Paik, Sang Hyun; Lee, Heon; Cha, Jang Gyu; Koh, Eun Suk [Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-04-15

    Desmoplastic small round cell tumor (DSRCT) is a highly aggressive malignant small cell neoplasm occurring mainly in the abdominal cavity, but it is extremely rare in the pleura. In this case, a 15-year-old male presented with a 1-month history of left chest pain. Chest radiographs revealed pleural thickening in the left hemithorax and chest computed tomography showed multifocal pleural thickening with enhancement in both hemithoraces. A needle biopsy of the left pleural lesion was performed and the final diagnosis was DSRCT of the pleura. We report this unusual case arising from the pleura bilaterally. The pleural involvement of this tumor supports the hypothesis that it typically occurs in mesothelial-lined surfaces.

  12. Cytogenetic analyses of 85 testicular germ cell tumors: comparison of postchemotherapy and untreated tumors.

    Science.gov (United States)

    Smolarek, T A; Blough, R I; Foster, R S; Ulbright, T M; Palmer, C G; Heerema, N A

    1999-01-01

    Cytogenetic analyses of 85 testicular germ cell tumors, of which 54 were karyotypically abnormal, showed recurrent breakpoints at chromosome bands 1p36, 1p13-1qh, 11q23, 19q13, and the pericentromeric regions of the acrocentric chromosomes. Postchemotherapy tumors had significantly more rearrangements of bands 3p25-p26, 6q16-q21, 8p22-p23 when compared with untreated tumors, while untreated tumors had more rearrangements of 9p22-p24 when compared with postchemotherapy tumors. Frequent breakpoints also were identified at 15q15 and 9qh in untreated tumors. Tumors of different histopathology, clinical stage, and treatment status showed no significant differences in the frequencies of i(12p)-positive and i(12p)-negative tumors.

  13. INTRAOSSEOUS AND EXTRAOSSEOUS VARIANTS OF DENTINOGENIC GHOST CELL TUMOR: TWO CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Merva SOLUK TEKKESIN

    2015-01-01

    Full Text Available This paper aims to present both intraosseous and extraosseous variant of dentinogenic ghost cell tumor as well as a review of the literature. An 11-year old female patient presented a swelling and pain in the molar area of the mandible and a 15-year-old female patient reported a complaint of swelling in the right vestibular region of teeth 12 and 13(FDI 2-digit classification system. Microscopic examinations showed similar features which characterized by ameloblastoma-like islands of epithelial cells, containing numerous ghost cells. The patients have been disease-free for one year. This paper aims to describe this rare tumor and to increase the number of cases in the literature to better understand its biologic behavior and treatment options.

  14. Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Rechnitzer, Catherine; Brok, Jesper S

    2014-01-01

    is the absence of a progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in adult/adolescent GCTs, except spermatocytic seminoma. The primordial germ cell (PGC) is the suggested origin of all GCTs, with variations in histology reflecting differentiation stage. Expression of pluripotency......Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature...... transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from...

  15. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    2013-01-01

    their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.......This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome...... profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development...

  16. Moh's micrographic surgery for the management of a periocular mast cell tumor in a dog.

    Science.gov (United States)

    Bernstein, Joseph A; Storey, Eric S; Bauer, Rudy W

    2013-05-01

    A 3-year-old neutered male boxer dog presented with a 6-month history of a waxing and waning mass of the left dorsotemporal eyelid margin. Cytology and biopsy confirmed a diagnosis of mast cell neoplasia. Systemic staging of the dog failed to reveal any evidence of metastatic neoplasia. Owing to the location of the tumor within the eyelid margin and the wide surgical margins recommended for excision of mast cell tumors, Mohs micrographic surgery (MMS) was chosen for its potential to conserve tissues while providing intraoperative confirmation the tumor was completely excised. Utilizing MMS horizontal sectioning technique, 100% of the surgical margins were assessed prior to closure of the surgical wound. This represents the first time a comprehensive MMS protocol was used in a veterinary patient under general anesthesia. © 2012 American College of Veterinary Ophthalmologists.

  17. A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases

    Directory of Open Access Journals (Sweden)

    Gray Robert

    2010-09-01

    Full Text Available Abstract Giant cell tumor (GCT of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.

  18. Pitfalls in the cytological diagnosis of tenosynovial giant cell tumor: An illustration of eight discordant cases.

    Science.gov (United States)

    Mondal, Krishnendu; Mandal, Rupali; Khan, Kalyan; Chakraborty, Jasashwi

    2017-09-23

    Tenosynovial giant cell tumor (TSGCT) is a highly recurrent benign tumor of the extremities. Wide local excision is usually sufficient to achieve its recurrence-free outcome. However, that needs a confident pre-operative cytological diagnosis as TSGCT. Aspirates from this tumor express the characteristic polymorphic cytological pattern, enough to impose a definite diagnosis. However rarely so, inadequate sampling from smaller tumors or due to faulty techniques, and selective sampling from topographic clusters of any individual component may lead to wrong interpretation. An unorthodox location near the larger limb joints further complicates the diagnostic misery on occasions. Such tumors are amenable to incomplete removal and risk for future recurrence. In this report, we describe eight cases of TSGCTs that were cytologically diagnosed otherwise. The cytological features of these discrepant tumors and the factors attributable to such dilemma are elaborated. Finally, a possible remedy has been proposed at conclusion in order to avoid future inconveniences. © 2017 Wiley Periodicals, Inc.

  19. Clinical, ultrasonographic, and laboratory findings in 12 llamas and 12 alpacas with malignant round cell tumors

    Science.gov (United States)

    Martin, Jeanne M.; Valentine, Beth A.; Cebra, Christopher K.

    2010-01-01

    Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings were evaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or was euthanized. Common clinical findings were anorexia, recumbency or weakness, and weight loss or poor growth. Peripheral lymphadenomegaly occurred in only 7 animals and was detected more often at necropsy than during physical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia, hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluid or tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or less prior to death or euthanasia was more common in animals ≤ 2 y of age (9/11) than in older animals (6/13). Regular examination of camelids to include clinical pathology and evaluation of peripheral lymph nodes may result in early detection of MCRT. PMID:21358931

  20. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...... with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small...... incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously...

  1. Management options for stage 1 nonseminomatous germ cell tumors of the testis

    Directory of Open Access Journals (Sweden)

    Stephen D.W Beck

    2010-01-01

    Full Text Available Management of clinical stage I non seminomatous germ cell tumor includes surveillance, primary chemotherapy and retroperitoneal lymph node dissection. Stratifying clinical stage I disease to high- and low-risk groups for harboring micrometastic retroperitoneal disease (pathologic stage B is based on pathologic characteristics of the primary tumor. The presence of embryonal dominant histology and lymphovascular invasion (high-risk group predicts for a 50% incidence of retroperitoneal disease. Low-risk group, the absence of either factor, predicts a 20% chance of retroperitoneal disease. Irrespective of risk classification, all treatment modalities have equal survival rates of 99% to 100%, and differ only in their unique short and long-term modalities. The mode of treatment in clinical stage I disease should remain patient driven and is guided by the perceived morbidities of each therapy.

  2. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

    Science.gov (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  3. Is the endometrial evaluation routinely required in patients with adult granulosa cell tumors of the ovary?

    Science.gov (United States)

    Ottolina, Jessica; Ferrandina, Gabriella; Gadducci, Angiolo; Scollo, Paolo; Lorusso, Domenica; Giorda, Giorgio; Breda, Enrico; Savarese, Antonella; Candiani, Massimo; Zullo, Fulvio; Mangili, Giorgia

    2015-02-01

    Granulosa cell tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCT patients treated in MITO centers. A retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities. A total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40years. All patients with endometrial cancer were older than 40years and postmenopausal. Endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients >40years; based on these data, endometrial sampling should be performed in symptomatic women at least 40years of age. In asymptomatic women <40years, endometrial sampling is of low yield. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy.

    Science.gov (United States)

    Lee, Junguee; Yi, Shinae; Kang, Yea Eun; Chang, Joon Young; Kim, Jung Tae; Sul, Hae Joung; Kim, Jong Ok; Kim, Jin Man; Kim, Joon; Porcelli, Anna Maria; Kim, Koon Soon; Shong, Minho

    2016-11-29

    Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy.

  5. Therapeutic radiotherapy for giant cell tumor of the spine: a systemic review.

    Science.gov (United States)

    Ma, Yifei; Xu, Wei; Yin, Huabin; Huang, Quan; Liu, Tielong; Yang, Xinghai; Wei, Haifeng; Xiao, Jianru

    2015-08-01

    Giant cell tumor of the bone (GCTB) is a benign but locally aggressive tumor. Giant cell tumor of the spine (GCTS) accounts for 3-6 % of GCTB. Surgery remains the treatment of choice. For those not suitable for surgery, therapeutic radiotherapy (RT) is one classic modality. Although there are several articles on therapeutic RT for GCTS therapy, few systemic reviews have been performed on effects of therapeutic RT on GCTS. We searched EMBASE and Medline databases for papers reporting therapeutic radiotherapy for GCTS patients not suitable for surgical resection. The inclusion criteria and prognosis indicators have been defined prior to data extraction. Information of the included patients has been discreetly recorded. We analyzed the prognosis of therapeutic RT and multiple data concerning the GCTS patients. The indicators for prognosis were computed by SPSS software. The local control (LC) and overall survival (OS) rate was estimated by the Kaplan-Meier method. p values ≤0.5 were considered statistically significant. We included 13 studies comprising 42 patients who received therapeutic radiotherapy with doses ranging from 21 to 80 Gy. The results suggested a response rate of 100 %, OS of 97.6 %, 1-year local control rate (LC) of 85.4 %, 2-year LC rate of 80.2 %, and overall LC of 79 %. No patient reported malignant transformation albeit four had post-RT neurological complications. Four had distant metastasis of the tumor. Patients with previously repeated recurrence had worse prognosis after RT (p = 0.028). No association between dosage and prognosis was found. Therapeutic RT could provide a satisfactory prognosis for GCTS patients according to this study, and can be an alternative treatment modality for GCTS patients not suitable for surgery.

  6. Intra-abdominal desmoplastic small round cell tumors: CT findings and clinicopathological correlations in 13 cases

    Energy Technology Data Exchange (ETDEWEB)

    Chouli, Malik [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Viala, Juliette [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Dromain, Clarisse [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Fizazi, Karim [Department of Medicine, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Duvillard, Pierre [Department of Histopathology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Vanel, Daniel [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France)]. E-mail: vanel@igr.fr

    2005-06-01

    Purpose: We report computed tomography (CT) findings in 13 patients with a primary abdominal desmoplastic small round cell tumor. Materials and methods: 13 cases (12 men, 1 woman, mean age = 24.8 years) were found in our hospital database between 1991 and 2003. Clinical, CT and histopathological features were studied retrospectively. Results: Peritoneal involvement was the most common feature. In 10 cases, several lobulated peritoneal soft tissue masses (with a mean of four masses per patient) were seen. Two patients had diffused irregular peritoneal carcinomatosis without any distinct peritoneal masses. One patient had a solitary mass in the pelvic space. The main sites of peritoneal involvement were the pelvic space (n 7), omentum (n = 5), retroperitoneal space (n = 4), small bowel mesentery (n = 3), paracolic gutter (n = 2 on the right and n = 1 on the left), transverse colon mesentery (n = 1), peri-splenic space (n = 1), peri-hepatic space (n 1). The soft tissue masses were often bulky (mean 6 cm, range 1-28 cm), lobulated and heterogeneous with hypodense areas (in 73% of cases). In six cases, moderate ascites was seen. In one case of pelvic involvement, unilateral hydronephrosis was seen. Adenopathies were present in seven cases at the time of the diagnosis (at intraperitoneal, retroperitoneal and pelvic sites in six patients and in the groin in one patient). Five patients had liver metastases (four lesions per case excepted one patient with 30 metastases). Associated thoracic metastases were seen in three patients. The diagnosis was confirmed with four CT-guided percutaneous biopsies. Conclusion: Although CT features are nonspecific, the diagnosis of desmoplastic small round cell tumor may be suspected in young men with multiple bulky heterogeneous peritoneal soft tissue masses. Imaging is useful for staging and also to guide biopsies.

  7. Next generation prophylactic human papillomavirus vaccines.

    Science.gov (United States)

    Schiller, John T; Müller, Martin

    2015-05-01

    The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the major papillomavirus virion protein) virus-like particle (VLP) vaccines are regarded as safe, effective, and well established prophylactic vaccines. However, they have some inherent limitations, including a fairly high production and delivery cost, virus-type restricted protection, and no reported therapeutic activity, which might be addressed with the development of alternative dosing schedules and vaccine products. A change from a three-dose to a two-dose protocol for the licensed HPV vaccines, especially in younger adolescents (aged 9-13 years), is underway in several countries and is likely to become the future norm. Preliminary evidence suggests that recipients of HPV vaccines might derive prophylactic benefits from one dose of the bivalent vaccine. Substantial interest exists in both the academic and industrial sectors in the development of second-generation L1 VLP vaccines in terms of cost reduction-eg, by production in Escherichia coli or alternative types of yeast. However, Merck's nonavalent vaccine, produced via the Saccharomyces cerevisiae production system that is also used for their quadrivalent vaccine, is the first second-generation HPV VLP vaccine to be available on the market. By contrast, other pharmaceutical companies are developing microbial vectors that deliver L1 genes. These two approaches would add an HPV component to existing live attenuated vaccines for measles and typhoid fever. Prophylactic vaccines that are based on induction of broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are also being developed both as simple monomeric fusion proteins and as virus-like display vaccines. The strong interest in developing the next generation of vaccines, particularly by manufacturers in middle-to-high income countries, increases the likelihood that vaccine production will become decentralised with the hope that effective HPV vaccines will be

  8. Role of fused Mycobacterium tuberculosis immunogens and adjuvants in modern tuberculosis vaccines

    Directory of Open Access Journals (Sweden)

    Ana Paula eJunqueira-Kipnis

    2014-04-01

    Full Text Available Several approaches have been developed to improve or replace the only available vaccine for tuberculosis (TB, BCG (Bacille Calmette Guerin. The development of subunit protein vaccines is a promising strategy because it combines specificity and safety. In addition, subunit protein vaccines can be designed to have selected immune epitopes associated with immunomodulating components to drive the appropriate immune response. However, the limited antigens present in subunit vaccines reduce their capacity to stimulate a complete immune response compared with vaccines composed of live attenuated or killed microorganisms. This deficiency can be compensated by the incorporation of adjuvants in the vaccine formulation. The fusion of adjuvants with Mycobacterium tuberculosis (Mtb proteins or immune epitopes has the potential to become the new frontier in the TB vaccine development field. Researchers have addressed this approach by fusing the immune epitopes of their vaccines with molecules such as interleukins, lipids, lipoproteins, and immune stimulatory peptides, which have the potential to enhance the immune response. The fused molecules are being tested as subunit vaccines alone or within live attenuated vector contexts. Therefore, the objectives of this review are to discuss the association of Mtb fusion proteins with adjuvants; Mtb immunogens fused with adjuvants; and cytokine fusion with Mtb proteins and live recombinant vectors expressing cytokines. The incorporation of adjuvant molecules in a vaccine can be complex, and developing a stable fusion with proteins is a challenging task. Overall, the fusion of adjuvants with Mtb epitopes, despite the limited number of studies, is a promising field in vaccine development.

  9. [Vaccines, immunization and technological innovation: an update].

    Science.gov (United States)

    Homma, Akira; Martins, Reinaldo de Menezes; Leal, Maria da Luz Fernandes; Freire, Marcos da Silva; Couto, Artur Roberto

    2011-02-01

    The smallpox worldwide eradication was the major world public health achievement. The binomial - vaccines and immunization - continues to demonstrate very high performance in the prevention and control of other diseases preventable by vaccination. The new global initiatives on vaccination, such as GAVI, have made possible the introduction of new and important vaccines preventing million of children deaths in the poorest countries in the world. The National Immunization Program of Brazil is also being strengthened, with the introduction of several new vaccines into the basic calendar as rotavirus, pneumococcal and meningococcal conjugated and H1N1 in national campaign, covering the population at risk. With the discovery of high valued vaccines, the big pharmaceutical companies became interested in this area, investing heavily in technological innovation, making fusions, acquisitions and technological partnerships. Brazil has also established a new innovation policy, creating new laws as well as subsidizing projects in technological innovation and modernization of production infra-structure.

  10. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    NARCIS (Netherlands)

    Wang, Z.; McGlynn, K.A.; Rajpert- de Meyts, E.; Bishop, D.T.; Chung, C.C.; Dalgaard, M.D.; Greene, M.H.; Gupta, R; Grotmol, T.; Haugen, T.B.; Karlsson, R.; Litchfield, K.; Mitra, N.; Nielsen, K.; Pyle, L.C.; Schwartz, S.M.; Thorsson, V.; Vardhanabhuti, S.; Wiklund, F.; Turnbull, C.; Chanock, S.J.; Kanetsky, P.A.; Nathanson, K.L.; Kiemeney, B.; Skotheim, R.I.; Zheng, T.

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first

  11. Serum lactate dehydrogenase isoenzyme 1 and relapse in patients with nonseminomatous testicular germ cell tumors clinical stage I

    DEFF Research Database (Denmark)

    von Eyben, F E; Madsen, E L; Blaabjerg, O

    2001-01-01

    Serum lactate dehydrogenase isoenzyme 1 catalytic concentration (S-LD-1) was measured at the time of orchiectomy in 104 patients with nonseminomatous testicular germ cell tumors (NSTGCT) clinical stage I who participated in a randomized study comparing surveillance after orchiectomy (group I...

  12. Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis

    DEFF Research Database (Denmark)

    Giwercman, Alexander; Andrews, P W; Jørgensen, N

    1993-01-01

    Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic...... similarity between fetal germ cells, CIS cells, and invasive testicular germ cell tumors....

  13. Germ Cell Tumor Targeting Chemotherapy in Gastric Adenocarcinoma with an Endodermal Sinus Tumor Component: A Case Report.

    Science.gov (United States)

    Choi, Jung Eun; Choe, A Reum; Yoon, Sang Eun; Nam, Eun Mi; Park, Heejung; Lee, Kyoung Eun

    2017-01-01

    The most common sites for extragonadal germ cell tumors are the midline mediastinum, retroperitoneum and, much less frequently, the stomach. The stomach-originated primary germ cell tumor carries a poor prognosis, especially when metastasis occurs to the liver, with a mean survival time of 1 month. We describe the case of a 77-year-old male who presented with usual symptoms of gastric malignancy. Gastrectomy was performed. Histopathology of surgically resected tissue revealed a mixture of adenocarcinoma and endodermal sinus tumor components with α-fetoprotein production. After liver metastasis was identified, oxaliplatin and capecitabine were administered as palliative chemotherapy. The response was poor. For the second-line therapy, bleomycin, etoposide, and cisplatin (BEP) therapy was initiated. The overall response to these drugs was a partial response and the residual liver lesion was considered to be resectable. The patient died of pneumonia 11 months following the BEP session, representing an overall survival time of 22 months. Gastric adenocarcinoma with a germ cell tumor component is uncommon and an effective combination of chemotherapeutic agents is not yet clear. In this case, the patient received germ cell tumor-targeting chemotherapy and showed a durable response. Hence, germ cell-targeting cytotoxic agents have potential as the 'front-line regimen'. © 2016 S. Karger AG, Basel.

  14. Giant cell tumors of the sacrum-a nationwide study on midterm results in 26 patients after intralesional excision

    NARCIS (Netherlands)

    Heijden, L. van der; Sande, M.A.B. van der; Geest, I.C.M. van der; Schreuder, H.W.B.; Royen, B.J. van; Jutte, P.C.; Bramer, J.A.; Oner, F.C.; Noort-Suijdendorp, A.P. van; Kroon, H.M.; Dijkstra, P.D.

    2014-01-01

    PURPOSE: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). METHODS: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All

  15. Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex

    NARCIS (Netherlands)

    Boer, K. [=Karin; Troost, D.; Timmermans, W.; Gorter, J. A.; Spliet, W. G. M.; Nellist, M.; Jansen, F.; Aronica, E.

    2008-01-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and

  16. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  17. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors

    NARCIS (Netherlands)

    L.H.J. Looijenga (Leendert); C.A. de Gouveia Brazao; J. Kononen; A.J.M. Gillis (Ad); K.E. van Roozendaal (Kees); E.J.J. van Zoelen (Everardus); D.T. Schneider (Dominik); J.W. Oosterhuis (Wolter); R.F.A. Weber (Robert); K.P. Wolffenbuttel (Katja); E.J. Perlman; H. van Dekken (Herman); C. Bokemeyer; G. Sauter; J.A. Stoop (Hans); H.P. de Leeuw; F.U. Honecker (Friedemann)

    2003-01-01

    textabstractHuman germ cell tumors (GCTs) may have variable histology and clinical behavior, depending on factors such as sex of the patient, age at clinical diagnosis, and anatomical site of the tumor. Some types of GCT, i.e., the seminomas/germinomas/dysgerminomas and

  18. Giant cell tumors of the sacrum-a nationwide study on midterm results in 26 patients after intralesional excision

    NARCIS (Netherlands)

    van der Heijden, L.; van de Sande, M. A. J.; van der Geest, I. C. M.; Schreuder, H. W. B.; van Royen, B. J.; Jutte, P. C.; Bramer, J. A. M.; Oner, F. C.; van Noort-Suijdendorp, A. P.; Kroon, H. M.; Dijkstra, P. D. S.

    Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent

  19. Evaluation of response to hormone therapy in patients with measurable adult granulosa cell tumors of the ovary

    NARCIS (Netherlands)

    van Meurs, Hannah S.; van der Velden, Jacobus; Buist, Marrije R.; van Driel, Willemien J.; Kenter, Gemma G.; van Lonkhuijzen, Luc R. C. W.

    2015-01-01

    The aim of this study was to retrospectively determine the objective response rate to hormone therapy (HT) for patients with a measurable adult granulosa cell tumor (GCT) of the ovary in a consecutive series of patients. All patients with an adult GCT who were treated with HT [steroidal progestins,

  20. Giant cell tumors of the sacrum-a nationwide study on midterm results in 26 patients after intralesional excision

    NARCIS (Netherlands)

    van der Heijden, L.; van der Sande, M.; van der Geest, I.; Schreuder, H.; van Royen, B.; Jutte, P.; Bramer, J.; Oner, F.; van Noort-Suijdendorp, A.; Kroon, H.; Dijkstra, P.

    2014-01-01

    Purpose: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). Methods: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All

  1. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

  2. Giant-Cell Tumor of the Distal Ulna Treated by Wide Resection and Ulnar Support Reconstruction: A Case Report

    Directory of Open Access Journals (Sweden)

    Akio Minami

    2010-01-01

    Full Text Available Giant-cell tumor of bone occurred in the distal end of the ulna is extremely uncommon. A 23-year-old male had a giant-cell tumor occurred in the distal end of the ulna. After wide resection of the distal segment of the ulna including giant-cell tumor, ulnar components of the wrist joint were reconstructed with modified Sauvé-Kapandji procedure using the iliac bone graft, preserving the triangular fibrocartilage complex and ulnar collateral ligament in order to maintain ulnar support of the wrist, and the proximal stump of the resected ulna was stabilized by tenodesis using the extensor carpi ulnaris tendon. One year after operation, the patient's wrist was pain-free and had a full range of motion. Postoperative X-rays showed no abnormal findings including recurrence of the giant-cell tumor and ulnar translation of the entire carpus. The stability of the proximal stump of the distal ulna was also maintained.

  3. Giant-Cell Tumor of the Distal Ulna Treated by Wide Resection and Ulnar Support Reconstruction: A Case Report

    Science.gov (United States)

    Minami, Akio; Iwasaki, Norimasa; Nishida, Kinya; Motomiya, Makoto; Yamada, Katsuhisa; Momma, Daisuke

    2010-01-01

    Giant-cell tumor of bone occurred in the distal end of the ulna is extremely uncommon. A 23-year-old male had a giant-cell tumor occurred in the distal end of the ulna. After wide resection of the distal segment of the ulna including giant-cell tumor, ulnar components of the wrist joint were reconstructed with modified Sauvé-Kapandji procedure using the iliac bone graft, preserving the triangular fibrocartilage complex and ulnar collateral ligament in order to maintain ulnar support of the wrist, and the proximal stump of the resected ulna was stabilized by tenodesis using the extensor carpi ulnaris tendon. One year after operation, the patient's wrist was pain-free and had a full range of motion. Postoperative X-rays showed no abnormal findings including recurrence of the giant-cell tumor and ulnar translation of the entire carpus. The stability of the proximal stump of the distal ulna was also maintained. PMID:20592994

  4. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, C.W.; Hasle, H.; Grønbæk, Kirsten

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

  5. Surgical management of giant cell tumor of axis vertebra: review of fourteen cases in literature with a case illustration

    Directory of Open Access Journals (Sweden)

    Satyarthee Guru Dutta

    2017-09-01

    Full Text Available Primary spinal giant cell tumor (PSGCT considered as rare primary neoplasm, with predilection for subarticular location and commonly located at knee joint region, sacrum or distal radius, however, spinal involvent is uncommon and comparatively much rarer in the cervical spine. Further occurrence of giant cell tumor in the Axis vertebra is extremely uncommon and easily misdiagnosed and, thus, treatment is still debated and various treatment modalities and different surgical approaches were utilized during evolution of surgical management. Authors could collect only 14 cases of primary giant cell tumor affecting Axis vertebra in a detailed Pubmed and Medline search, out of which 12 cases were primary and rest two case was recurrent. So authors reviewed in total thirteen cases primary giant cell tumor of Axis managed surgically, including our case. Out of 13 PSGCT, twelve cases were managed with surgical resection and the rest one case was managed with monoclonal antibody using Denosomab monotherapy without any surgical intervention. In the surgical group (n=12, nine cases had two staged surgical procedure, first being posterior fixation followed by anterior approach with resection of tumor while, the rest three had one stage surgical resection including current case. Authors reports a unique case of spinal giant cell tumor developing in a- 38 - year male with history of renal transplant, presented with neck pain and difficulty in walking, neuroimaging revealed a osteolytic mass lesion involving body of axis vertebra with extension into right sided lamina, underwent two stage complete surgical intervention. Authors describes management of such rare locally recurring primary bony pathology affecting axis vertebra as it is not only interesting and challenging and different management modalities, various, surgical approaches and issue of renal osteodystrophy along with pertinent literature is also reviewed briefly.

  6. Micro-RNA expression in cisplatin resistant germ cell tumor cell lines

    Directory of Open Access Journals (Sweden)

    Meineke Viktor

    2011-05-01

    Full Text Available Abstract Background We compared microRNA expression patterns in three cisplatin resistant sublines derived from paternal cisplatin sensitive germ cell tumor cell lines in order to improve our understanding of the mechanisms of cisplatin resistance. Methods Three cisplatin resistant sublines (NTERA-2-R, NCCIT-R, 2102EP-R showing 2.7-11.3-fold increase in drug resistance after intermittent exposure to increasing doses of cisplatin were compared to their parental counterparts, three well established relatively cisplatin sensitive germ cell tumor cell lines (NTERA-2, NCCIT, 2102EP. Cells were cultured and total RNA was isolated from all 6 cell lines in three independent experiments. RNA was converted into cDNA and quantitative RT-PCR was run using 384 well low density arrays covering almost all (738 known microRNA species of human origin. Results Altogether 72 of 738 (9.8% microRNAs appeared differentially expressed between sensitive and resistant cell line pairs (NTERA-2R/NTERA-2 = 43, NCCIT-R/NCCIT = 53, 2102EP-R/2102EP = 15 of which 46.7-95.3% were up-regulated (NTERA-2R/NTERA-2 = 95.3%, NCCIT-R/NCCIT = 62.3%, 2102EP-R/2102EP = 46.7%. The number of genes showing differential expression in more than one of the cell line pairs was 34 between NTERA-2R/NTERA-2 (79% and NCCIT-R/NCCIT (64%, and 3 and 4, respectively, between these two cell lines and 2102EP-R/2102EP (about 27%. Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold in all three cell lines. The hsa-miR-371-373 cluster (counteracting cellular senescence and linked with differentiation potency, as well as hsa-miR-520c/-520h (inhibiting the tumor suppressor p21 were 3.9-16.3 fold up-regulated in two of the three cisplatin resistant cell lines. Several new micro-RNA species missing an annotation towards cisplatin resistance could be identified. These were hsa-miR-512-3p/-515/-517/-518/-525 (up to 8.1-fold up

  7. Micro-RNA expression in cisplatin resistant germ cell tumor cell lines.

    Science.gov (United States)

    Port, Matthias; Glaesener, Stephanie; Ruf, Christian; Riecke, Armin; Bokemeyer, Carsten; Meineke, Viktor; Honecker, Friedemann; Abend, Michael

    2011-05-15

    We compared microRNA expression patterns in three cisplatin resistant sublines derived from paternal cisplatin sensitive germ cell tumor cell lines in order to improve our understanding of the mechanisms of cisplatin resistance. Three cisplatin resistant sublines (NTERA-2-R, NCCIT-R, 2102EP-R) showing 2.7-11.3-fold increase in drug resistance after intermittent exposure to increasing doses of cisplatin were compared to their parental counterparts, three well established relatively cisplatin sensitive germ cell tumor cell lines (NTERA-2, NCCIT, 2102EP). Cells were cultured and total RNA was isolated from all 6 cell lines in three independent experiments. RNA was converted into cDNA and quantitative RT-PCR was run using 384 well low density arrays covering almost all (738) known microRNA species of human origin. Altogether 72 of 738 (9.8%) microRNAs appeared differentially expressed between sensitive and resistant cell line pairs (NTERA-2R/NTERA-2 = 43, NCCIT-R/NCCIT = 53, 2102EP-R/2102EP = 15) of which 46.7-95.3% were up-regulated (NTERA-2R/NTERA-2 = 95.3%, NCCIT-R/NCCIT = 62.3%, 2102EP-R/2102EP = 46.7%). The number of genes showing differential expression in more than one of the cell line pairs was 34 between NTERA-2R/NTERA-2 (79%) and NCCIT-R/NCCIT (64%), and 3 and 4, respectively, between these two cell lines and 2102EP-R/2102EP (about 27%). Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines. The hsa-miR-371-373 cluster (counteracting cellular senescence and linked with differentiation potency), as well as hsa-miR-520c/-520h (inhibiting the tumor suppressor p21) were 3.9-16.3 fold up-regulated in two of the three cisplatin resistant cell lines. Several new micro-RNA species missing an annotation towards cisplatin resistance could be identified. These were hsa-miR-512-3p/-515/-517/-518/-525 (up to 8.1-fold up-regulated) and hsa-miR-99a/-100/-145 (up to 10-fold

  8. Composition of extracellular matrix and distribution of cell adhesion molecules in renal cell tumors.

    Science.gov (United States)

    Droz, D; Patey, N; Paraf, F; Chrétien, Y; Gogusev, J

    1994-11-01

    Cell to cell and cell to matrix interactions play a major role in tumor growth and invasion. Therefore, we studied the composition of extracellular matrices and the distribution of cell adhesion molecules in 50 renal cell tumors of various types and various grades of malignancy as compared with nontumoral kidney. In the present study, we used immunolabeling with specific antibodies directed against the alpha 1, alpha 2, and alpha 3 chains of collagen type IV; laminin; heparan sulfate proteoglycan; fibronectin; collagen I; collagen III; the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1, and beta 3 subunits of integrins; and ICAM-1, VCAM-1, and ELAM-1 molecules. In clear cell type carcinomas (24 cases) the basal laminae surrounding the tumor islets contained the alpha 1 and alpha 2 chains of collagen type IV and heparan sulfate proteoglycan in all cases, and laminin in 96% of the cases. The alpha 3 chain of collagen IV was present in only one case, whereas fibronectin, collagen I, and collagen III were detected in nearly 50% of the cases. The tumor cells expressed alpha 3, alpha 6, and beta 1 integrin subunits in all cases, alpha 5 in 25%, alpha v beta 3 in 54%, and alpha 2 in none. ICAM-1 was detected in all cases, and VCAM-1 in 58%. The expression of the alpha 6 subunit was weak in 2 tumors of high grade, whereas the alpha v subunit was expressed in 7 of 14 low grade and in 7 of 10 intermediate and high grade tumors. In tubulopapillary carcinomas with chromophilic cells (12 cases), the most prominent findings were the presence of the alpha 3 chain of collagen IV in tumor basal laminae in 66% and the expression of the alpha 2 integrin subunit by the tumor cells in 58% of the cases, both features characterizing distal renal tubules. In chromophobic carcinomas (4 cases), the tumor basement membranes were tenuous and contained no fibronectin or interstitial collagens. The tumor cells expressed the alpha 6, alpha 2, alpha 3, beta 1, and alpha nu beta 3

  9. Vaccine Finder

    Science.gov (United States)

    ... list . Showing availability for 25,354 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  10. Vaccine Safety

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  11. Rotavirus Vaccine

    Science.gov (United States)

    ... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...

  12. Soft tissue recurrence of giant cell tumor of the bone: Prevalence and radiographic features

    Directory of Open Access Journals (Sweden)

    Leilei Xu

    2017-11-01

    Full Text Available Aim: Recurrence of giant cell tumor of bone (GCTB in the soft tissue is rarely seen in the clinical practice. This study aims to determine the prevalence of soft tissue recurrence of GCTB, and to characterize its radiographic features. Methods: A total of 291 patients treated by intralesional curettage for histologically diagnosed GCTB were reviewed. 6 patients were identified to have the recurrence of GCTB in the soft tissue, all of whom had undergone marginal resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic features of soft tissue recurrence were classified into 3 types. Type I was defined as soft tissue recurrence with peripheral ossification, type II was defined as soft tissue recurrence with central ossification, and type III was defined as pure soft tissue recurrence without ossification. Demographic data including period of recurrence and follow-up duration after the second surgery were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS scoring system was used to evaluate functional outcomes. Results: The overall recurrence rate was 2.1% (6/291. The mean interval between initial surgery and recurrence was 11.3 ± 4.1 months (range, 5–17. The recurrence lesions were located in the thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2 patients. According to the classification system mentioned above, 2 patients were classified with type I, 1 as type II and 3 as type III. After the marginal excision surgery, all patients were consistently followed up for a mean period of 13.4 ± 5.3 months (range, 6–19, with no recurrence observed at the final visit. All the patients were satisfied with the surgical outcome. According to the MSTS scale, the mean postoperative functional score was 28.0 ± 1.2 (range, 26–29. Conclusions: The classification of soft tissue recurrence of GCTB may be helpful for the surgeon to select the appropriate imaging procedure to

  13. [Analysis of the diagnosis and treatment of desmoplastic small round cell tumor].

    Science.gov (United States)

    Lu, Baojian; Zhang, Wei; Shang, Zhiqun; Sun, Erlin; Nian, Xuewu; Gao, Jingda; Ma, Chengquan; Han, Ruifa

    2015-09-01

    To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor. The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed. Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one

  14. Advantages of Pressurized-Spray Cryosurgery in Giant Cell Tumors of the Bone

    Directory of Open Access Journals (Sweden)

    Nevzat Dabak

    2016-10-01

    Full Text Available Background: Giant Cell Tumor is considered a benign, local and aggressive tumor. Although considered a benign bone tumor, it is still the subject of discussion and research because of the associated local bone destruction, as well as high rates of recurrence and distant metastases. Options are being developed for both surgical techniques and adjuvant therapies. Aims: The present study evaluated the administration of cryotherapy via a pressurized-spray technique in giant cell tumors of the bone. Study Design: Cross-sectional study. Methods: The study included 40 patients who were treated with extensive curettage and cryotherapy at various locations during the period from February 2006 to December 2013. Informed consent forms were obtained from the participants and ethics committee approval was taken from the local ethics committee of Ondokuz Mayıs University. The pressurized-spray technique was performed using liquid nitrogen. The patients were evaluated with respect to age, gender, radiological appearance, treatment modality, duration of follow-up, skin problems and recurrence. Results: Twenty-one patients were female; 19 were male. The average age of the patients was 33 years (range: 16–72 years, and the average duration of follow-up was 43 months (range: 12–80 months. The average time from the onset of the complaints to the diagnosis was 6 months (range: 2–12 months. Based on the Campanacci classification: 9 patients were Grade I; 25 patients were Grade II; six patients were Grade III. The lesion was located in the femur in 14 patients, in the tibia in 11 patients, in the radius in 5 patients, in the pelvis in 4 patients, in the fibula in 3 patients, in the metatarsal in 2 patients and in the phalanges of the hand in one patient. One patient had postoperative early fracture. None of the patients had skin problems and infection. Three (7.5% of the patients had recurrence. Conclusion: It was found that cryotherapy was highly effective in

  15. Expression, Purification and Characterization of GMZ2'.10C, a Complex Disulphide-Bonded Fusion Protein Vaccine Candidate against the Asexual and Sexual Life-Stages of the Malaria-Causing Plasmodium falciparum Parasite

    NARCIS (Netherlands)

    Mistarz, U.H.; Singh, S.K; Nguyen, T.; Roeffen, W.; Lissau, C.; Madsen, S.M.; Vrang, A.; Tiendrebeogo, R.W.; Kana, I.H.; Sauerwein, R.W.; Theisen, M.; Rand, K.D.

    2017-01-01

    PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a

  16. Contraceptive Vaccines

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    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  17. Correlation between retroperitoneal lymph node size and presence of metastases in nonseminomatous germ cell tumors.

    Science.gov (United States)

    Hudolin, Tvrtko; Kastelan, Zeljko; Knezevic, Nikola; Goluza, Eleonora; Tomas, Davor; Coric, Marijana

    2012-02-01

    Eighty-five patients had staging laparoscopic retroperitoneal lymph node dissection (L-RPLND) for nonseminomatous germ cell tumors at our institution. The largest lymph node size was measured and presence or absence of metastatic disease was determined. A total of 1139 lymph nodes have been removed and in 27 (31.8%) patients, metastases in one or more lymph nodes were detected. There were 338 (29.7%) hilar, 259 (22.7%) paraaortic, 221 (19.4%) interaortocaval, 171 (15%) paracaval, 133 (11.7%) preaortic and 17 (1.5%) precaval lymph nodes. The total number of lymph nodes with metastases was 74 (6.5%), and 1065 (93.5%) nodes did not have any metastases. The average size of a lymph node with metastases was 1.05 (0.3-3), and without metastases it was 0.55 (0.1-2.5) cm, (p 1 cm size of a lymph node as a "cut-off" value for enlargement and presence of metastases, 60% of metastatic lymph nodes would be missed since they were all ≤ 1 cm. Our results have shown that decreasing size of lymph nodes which are considered positive from > 1 cm to 0.7 -0.8 cm can be recommended, with specificity and sensitivity equal 70%.

  18. Differential expression of SOX2 and SOX17 in testicular germ cell tumors.

    Science.gov (United States)

    Nonaka, Daisuke

    2009-05-01

    Testicular germ cell tumors (GCTs) are subclassified to seminoma and nonseminomatous GCT for the purpose of treatment and prognostication. This study examined SOX2 and SOX17 expression patterns in a total of 67 cases, including 41 pure GCTs (32 seminomas and 9 embryonal carcinomas) and 26 mixed GCTs (9 foci of seminoma, 21 of embryonal carcinoma, 17 of yolk sac tumor, 19 of teratoma, and 5 of choriocarcinoma). All seminoma components showed diffuse SOX17 nuclear expression and were negative for SOX2. All but one of the embryonal carcinomas showed diffuse SOX2 nuclear expression with the one showing a focal reaction, whereas all were negative for SOX17. SOX17 was variably expressed in all yolk sac tumor components, but SOX2 was negative. Teratomas showed variable SOX2 and SOX17 expressions in the epithelial elements. Choriocarcinomas were negative for SOX2 and SOX17. SOX2 and SOX17 expression patterns can distinguish between seminoma and embryonal carcinoma, and this distinction may be diagnostically useful.

  19. Outpatient and Home Chemotherapy with Novel Local Control Strategies in Desmoplastic Small Round Cell Tumor

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    Dolly Aguilera

    2008-01-01

    Full Text Available Desmoplastic Small Round Cell Tumor (DSRCT has a very poor prognosis. This report illustrates novel chemotherapy and local control interventions in a 5-year old patient. The patient was treated in the outpatient setting, achieved remission, with excellent quality of life. The patient presented with massive ascites and >1000 abdominal tumors. Neoadjuvant chemotherapy included vincristine (1.5mg/m2, ifosfamide (3g/m2/day×3, dexrazoxane/doxorubicin (750/75mg/m2, and etoposide (150mg/m2. Continuous hyperthermic peritoneal perfusion (CHPP with cisplatin (100mg/m2 was given after extensive cytoreductive surgery. This was followed by irinotecan (10mg/m2/day×5×2weeks + temozolomide monthly × 2, then abdominal radiation 30 Gy with simultaneous temozolomide (100mg/m2/day×5. A total of 12 cycles of irinotecan and temozolamide were given. Except for initial chemotherapy, subsequent courses were in the outpatient setting. Focal retroperitoneal relapse at 18 months was treated with IMRT with bevacizumab (5 mg/kg and 2 perihepatic metastases with radio frequency ablation/cryoablation followed by chronic outpatient maintenance chemotherapy (valproic acid, cyclophosphamide, and rapamycin. Almost 2 years from diagnosis, the patient maintained an excellent quality of life. This is a novel approach to the treatment of children with massive abdomino-pelvic DSRCT.

  20. MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients.

    Science.gov (United States)

    Martinelli, Camila Maria da Silva; Lengert, André van Helvoort; Cárcano, Flavio Mavignier; Silva, Eduardo Caetano Albino; Brait, Mariana; Lopes, Luiz Fernando; Vidal, Daniel Onofre

    2017-08-01

    Testicular germ cell tumors (TGCT) represent the second main cause of cancer-related death in young men. Despite high cure rates, refractory disease results in poor prognosis. Epigenetic reprogramming occurs during the development of seminomas and non-seminomas. Understanding the molecular and genetic basis of these tumors would represent an important advance in the search for new TGCT molecular markers. Hence the frequency of methylation of a gene panel (VGF, MGMT, ADAMTS1, CALCA, HOXA9, CDKN2B, CDO1 and NANOG) was evaluated in 72 primary TGCT by quantitative methylation specific PCR. A high frequency of MGMT (90.9%, 20/22; p=0.019) and CALCA (90.5%, 19/21; p<0.026) methylation was associated with non-seminomatous tumors while CALCA methylation was also associated with refractory disease (47.4%, 09/19; p=0.005). Moreover, promoter methylation of both genes predicts poor clinical outcome for TGCT patients (5-year EFS: 50.5% vs 77.1%; p=0.032 for MGMT and 51.3% vs 77.0%; p=0.029 for CALCA). The findings of this study indicate that methylation of MGMT and CALCA are frequent and could be used as new molecular markers of prognosis in TGCT.

  1. A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy

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    Yutaro Tanaka

    2017-01-01

    Full Text Available Objectives. Primary mediastinal germ cell tumors (PMGCTs are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. Methods. We examined 6 patients (median age: 25 years, range: 19–27 years with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8–84 months. Results. Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP or etoposide and cisplatin (EP. One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. Conclusions. Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

  2. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

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    Christopher J. Forlenza

    2015-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT, a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days + thiotepa (300 mg/m2/day for 3 days ± topotecan (2 mg/m2/day for 5 days. All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant. 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.

  3. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

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    Schumacher, Fredrick R; Wang, Zhaoming; Skotheim, Rolf I; Koster, Roelof; Chung, Charles C; Hildebrandt, Michelle A T; Kratz, Christian P; Bakken, Anne C; Bishop, D Timothy; Cook, Michael B; Erickson, R Loren; Fosså, Sophie D; Greene, Mark H; Jacobs, Kevin B; Kanetsky, Peter A; Kolonel, Laurence N; Loud, Jennifer T; Korde, Larissa A; Le Marchand, Loic; Lewinger, Juan Pablo; Lothe, Ragnhild A; Pike, Malcolm C; Rahman, Nazneen; Rubertone, Mark V; Schwartz, Stephen M; Siegmund, Kimberly D; Skinner, Eila C; Turnbull, Clare; Van Den Berg, David J; Wu, Xifeng; Yeager, Meredith; Nathanson, Katherine L; Chanock, Stephen J; Cortessis, Victoria K; McGlynn, Katherine A

    2013-07-01

    Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

  4. Meta-analysis identifies four new loci associated with testicular germ cell tumor.

    Science.gov (United States)

    Chung, Charles C; Kanetsky, Peter A; Wang, Zhaoming; Hildebrandt, Michelle A T; Koster, Roelof; Skotheim, Rolf I; Kratz, Christian P; Turnbull, Clare; Cortessis, Victoria K; Bakken, Anne C; Bishop, D Timothy; Cook, Michael B; Erickson, R Loren; Fosså, Sophie D; Jacobs, Kevin B; Korde, Larissa A; Kraggerud, Sigrid M; Lothe, Ragnhild A; Loud, Jennifer T; Rahman, Nazneen; Skinner, Eila C; Thomas, Duncan C; Wu, Xifeng; Yeager, Meredith; Schumacher, Fredrick R; Greene, Mark H; Schwartz, Stephen M; McGlynn, Katherine A; Chanock, Stephen J; Nathanson, Katherine L

    2013-06-01

    We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

  5. NKX3.1 expression is lost in testicular germ cell tumors.

    Science.gov (United States)

    Skotheim, Rolf I; Korkmaz, Kemal S; Klokk, Tove I; Abeler, Vera M; Korkmaz, Ceren G; Nesland, Jahn M; Fosså, Sophie D; Lothe, Ragnhild A; Saatcioglu, Fahri

    2003-12-01

    NKX3.1 is a homeobox gene which exhibits prostate and testis specific expression. Loss of NKX3.1 expression has been implicated in prostate development and tumorigenesis, but the role of NKX3.1 in testis biology is not known. Here we show that NKX3.1 expression is dramatically down-regulated in testicular cancer of germ cell origin. Immunohistochemical analysis on a tissue microarray containing 510 testicular tissue samples indicate that NKX3.1 is expressed at high levels in normal germ cells and in carcinoma in situ, but is sharply decreased or absent in most seminomas and all embryonal carcinomas. However, NKX3.1 is expressed in a subset of the more differentiated nonseminomas. We provide evidence that these changes in NKX3.1 protein levels are mainly due to transcriptional effects. These results suggest that NKX3.1 is essential for normal testis function and that its loss of expression is highly associated with the invasive phenotype of testicular germ cell tumors.

  6. Intranuclear Reinke's crystals in a testicular Leydig cell tumor diagnosed by aspiration cytology. A case report.

    Science.gov (United States)

    Gupta, S K; Francis, I M; Sheikh, Z A; al-Rubah, N A; Das, D K

    1994-01-01

    Fine needle aspiration cytologic findings in a Leydig cell tumor of the testis are described. Besides the rarity of case reports on fine needle aspiration cytologic diagnosis of this tumor, the present case was of interest because of the finding of numerous intranuclear and intracytoplasmic Reinke's crystals as well as some lying free between the cells. In a few cells the intranuclear crystals were seen to orient themselves in a row, with a nipplelike protrusion of the nuclear membrane as if being pushed by the crystals. Besides the well-formed crystals, many nuclei showed irregular, thin, groovelike spaces that may have been earlier stages of crystal formation. These findings suggested the intranuclear formation of Reinke's crystals. Extranuclear crystals were seen to fuse in pairs and hence to appear thicker than the intranuclear crystals. The crystals lying free between the cells also showed a linear arrangement in places. The crystals were more numerous with May-Grünwald-Giemsa (MGG) staining. Intranuclear crystals were seen only in MGG-stained smears.

  7. Epithelial-mesenchymal transition markers in malignant ovarian germ cell tumors.

    Science.gov (United States)

    Solheim, Olesya; Førsund, Mette; Tropé, Claes G; Kraggerud, Sigrid Marie; Nesland, Jahn M; Davidson, Ben

    2017-09-01

    The purpose of this study was to determine the expression and potential clinical role of epithelial-to-mesenchymal transition (EMT)-related factors in malignant ovarian germ cell tumors (MOGCT). Protein expression of E-cadherin, N-cadherin, P-cadherin, Zeb1, HMGA2, and vimentin by immunohistochemistry was analyzed in 42 MOGCT from patients treated in Norway during the period 1981-2001. Expression was analyzed for association with clinicopathologic parameters. E-cadherin (p = 0.016) and HMGA2 (p = 0.002) expression was significantly higher in immature teratomas and yolk sac tumors compared with dysgerminomas. Vimentin (p cadherin and P-cadherin. EMT-associated markers were not significantly related to clinicopathologic parameters including age, tumor diameter, and FIGO stage. In conclusion, based on this limited series, EMT-associated markers are not associated with clinical parameters in MOGCT, in contrast to ovarian carcinoma. EMT-related proteins are differentially expressed among various MOGCT subtypes, suggesting differences in biological characteristics associated with invasion and metastasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  8. Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

    Science.gov (United States)

    Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

    2011-03-01

    To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  9. Metastasis of the liver with a granulosa cell tumor of the ovary: A case report.

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    Yu, Shuiping; Zhou, Xueling; Hou, Binzong; Tang, Bo; Hu, Jie; He, Songqing

    2015-02-01

    The present study describes the case of a 62 year-old female patient with a metastatic tumor in the right hemi-liver of >25 cm in diameter, who presented to The Affiliated Hospital of Guilin Medical University (Guangxi, China) with acute abdominal pain and severe malnutrition. Radical surgery was performed to remove the tumor by open surgery. A biopsy was not performed prior to the surgery, so the tumor was diagnosed as end-stage primary liver cancer (PLC) based solely on the character and appearance of the tumor on computed tomography prior to surgery. However, subsequent to the surgery, upon analysis by the Department of Pathology, the mass was identified as an ovarian granulosa cell tumor (GCT). These tumors occur rarely, representing only 2-3% of all ovarian tumors, and are well known for late recurrences, with an incidence of 25-30%. As metastasis of the liver with GCT is extremely rare and the data available on the subject is limited by the small number of studies, and due to the absence of a biopsy report prior to surgery, the patient was initially misdiagnosed with PLC. However, despite this misdiagnosis, a good result was obtained, as the patient was later diagnosed with GCT following a detailed pathological examination and was treated with rational therapy. The performance status and quality of life were significantly improved, and the patient remains disease-free at one year post-surgery.

  10. Giant Cell Tumor Of The Long Bones: Results With Combination Of Cryosurgery, Curettage, And Cementation

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    Mortazavi S.M.J

    2005-07-01

    Full Text Available Background: In this study we evaluated the treatment of giant cell tumor (GCT of long bones using cryosurgery combined with curettage and polymethylmetacrylate (PMMA cementing. Material and methods: From January 1999 to December 2004, twenty patients (mean age at the time of surgery 29.2 years; 13 females and 7 males; were included in the study. Cortical disruption were presented in 7 patients; 4 with soft tissue extension, but none of them had intra-articular extension of tumor, 3 patients presented with pathologic fracture of distal femoral lesions. These tumors were located in distal femur in 6 patients, proximal tibia in 7, distal radius in 3, proximal femur in 2, and each of proximal humerus and distal ulna in one patient. In each case diagnostic biopsy was done and surgical procedure performed including curettage, power burr of the wall, cryosurgery with liquid nitrogen and finally filling the space with PMMA cementing. The mean follow-up was 34 months (7 to 61 . Results: During follow-up, we observed one recurrence of GCT of proximal tibia. Secondary Aneurysmal bone cyst was reported at the site of one primary distal femoral lesion, without any finding in favor of a recurrence. Neurapraxia of the proneal nerve was occurred in one patient with proximal tibia tumor improved after 8 months. Conclusion: Cryosurgery combined with power burr and PMMA cementing in the treatment of GCT could be an effective approach in tumor eradication. This method obviates the need for extensive resections and reconstructive procedure.

  11. Desmoplastic small round cell tumor of the stomach mimicking a gastric cancer in a child

    Science.gov (United States)

    Moon, Suk-Bae; Hur, Jung-Min; Koo, Hong-Hoe; Suh, Yeon-Lim; Shin, Hyun-Baek; Seo, Jeong-Meen

    2011-01-01

    Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a highly malignant tumor of uncertain histogenesis. Here we report a case of DSRCT involving the stomach, initially misdiagnosed as gastric cancer. A 12-year-old boy presented with upper abdominal pain developed 1 month prior. On gastroscopy, a 7-cm mass was noted involving the esophago-gastric junction to the fundus, and positron emission tomography showed multiple hot uptakes suggesting distant metastasis. Gastroscopic biopsy showed poorly differentiated malignant cells. We diagnosed as stage IV gastric cancer and treated with 6 cycles of chemotherapy. Laparotomy revealed a huge gastric mass along with peritoneal disseminations. Palliative proximal gastrectomy was performed. Pathological examination revealed transmural involvement of DSRCT, and t(11;22)(p12;q12) was demonstrated on fluorescence in situ hybridization test. The chemotherapeutic regimen was changed and the patient underwent 8 additional cycles of post-operative chemotherapy. The patient is now alive and the residual tumor shows no significant changes after chemotherapy. PMID:22066092

  12. Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases

    Science.gov (United States)

    Zhang, Guangzhao; Liu, Guangjun; Zhao, Dahua; Cui, Xijun; Li, Gang

    2014-01-01

    Purpose. To study the clinical, radiological, and pathological characteristics of abdominal desmoplastic small round cell tumor (DSRCT) and investigate the optimal therapy modalities. Patients and Methods. A retrospective cohort study was performed on 12 abdominal DSRCT patients; all pathological, radiological, and prognostic data were analyzed. There were 3 patients (25%) with metastatic disease at presentation. In all 12 cases, 6 cases underwent operation and adjuvant chemotherapy (group 1, 6/12, 50%). The other 6 cases were diagnosed by fine needle aspiration or exploratory laparotomy biopsy (group 2, 6/12, 50%); all cases received four to six courses of multiple agents chemotherapy, respectively. Results. All cases were finally diagnosed as DSRCT pathologically. Among group 1, all cases underwent en bloc resection (2/6, 33%) or tumor debulking (4/6, 67%) and, following four courses of multiple agents chemotherapy, Kaplan-Meier analysis revealed that 3-year survival was 50% in group 1 versus 16.7% in group 2 (P < 0.05). Gross tumor resection was highly significant in prolonging overall survival; patients with localized solitary lesion have a better prognosis, most likely due to increased feasibility of resection. Conclusions. DSRCT is a rare malignant tumor with poor prognosis. Surgical excision with combination chemotherapy as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact. PMID:24987737

  13. Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases

    Directory of Open Access Journals (Sweden)

    Guangzhao Zhang

    2014-01-01

    Full Text Available Purpose. To study the clinical, radiological, and pathological characteristics of abdominal desmoplastic small round cell tumor (DSRCT and investigate the optimal therapy modalities. Patients and Methods. A retrospective cohort study was performed on 12 abdominal DSRCT patients; all pathological, radiological, and prognostic data were analyzed. There were 3 patients (25% with metastatic disease at presentation. In all 12 cases, 6 cases underwent operation and adjuvant chemotherapy (group 1, 6/12, 50%. The other 6 cases were diagnosed by fine needle aspiration or exploratory laparotomy biopsy (group 2, 6/12, 50%; all cases received four to six courses of multiple agents chemotherapy, respectively. Results. All cases were finally diagnosed as DSRCT pathologically. Among group 1, all cases underwent en bloc resection (2/6, 33% or tumor debulking (4/6, 67% and, following four courses of multiple agents chemotherapy, Kaplan-Meier analysis revealed that 3-year survival was 50% in group 1 versus 16.7% in group 2 (P<0.05. Gross tumor resection was highly significant in prolonging overall survival; patients with localized solitary lesion have a better prognosis, most likely due to increased feasibility of resection. Conclusions. DSRCT is a rare malignant tumor with poor prognosis. Surgical excision with combination chemotherapy as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact.

  14. Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine.

    Science.gov (United States)

    Albany, Costantine; Hever-Jardine, Mary P; von Herrmann, Katherine M; Yim, Christina Y; Tam, Janice; Warzecha, Joshua M; Shin, Leah; Bock, Sarah E; Curran, Brian S; Chaudhry, Aneeq S; Kim, Fred; Sandusky, George E; Taverna, Pietro; Freemantle, Sarah J; Christensen, Brock C; Einhorn, Lawrence H; Spinella, Michael J

    2017-01-10

    Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients.

  15. [Funcion sparing surgery in uro-oncology: germ cell tumors of the testis].

    Science.gov (United States)

    Catanzaro, Mario; Piva, Luigi; Torelli, Tullio; Biasoni, Davide; Stagni, Silvia; Milani, Angelo; Necchi, Andrea; Giannatempo, Patrizia; Nicolai, A; Salvioni, Roberto

    2012-12-30

    Surgery in germ cell tumors of the testis (TGT) may result in andrological disorders, both after orchiectomy and after retroperitoneal lymphadenectomy (RPLND). Bilateral orchiectomy suppresses both testicular functions: exocrine and endocrine. In selected cases with bilateral TGT (metachronous/synchronous), or in the case of TGT in monorchid patients, partial orchiectomy (enucleation of the tumor) can preserve both functions with a low risk of relapse in residual testicular parenchyma, in the absence of intraepithelial neoplasia (TIN). In cases of TIN and normal testosterone levels (80%), the fertility is maintained in 50% of patients. In these cases the use of radiotherapy on the residual testicular parenchyma can prevent the future development of invasive cancer, though compromising the hormonal function. The RPLND (open or laparoscopic) can produce major side effects, such as retrograde ejaculation. Knowledge of the adrenergic fiber retroperitoneal neuroanatomy enables to implement a "nerve sparing" surgery with an almost total reduction of this serious side effect, but that option is only available in few centers of excellence. Semen cryopreservation has become a common practice performed before any treatment that might impact on the andrological function of patients.

  16. Extranodal follicular dendritic cell tumor of the tonsil: report of a diagnostic pitfall and literature review.

    Science.gov (United States)

    Idrees, Muhammad T; Brandwein-Gensler, Margaret; Strauchen, James A; Gil, Joan; Wang, Beverly Y

    2004-09-01

    Follicular dendritic cell tumor (FDCT) usually arises in the dendritic reticulum cells of the lymph nodes. Extranodal cases are rare; only 24 cases have been reported in the head and neck region, and most are in the oropharynx. Nine cases of primary FDCT of the tonsil have been reported in English-language literature, to which we add the 10th case. This 77-year-old white woman presented with a tonsillar mass that was misdiagnosed as squamous cell carcinoma. She underwent neoadjuvant radiotherapy plus combined oropharyngeal and mandibular resection with radical neck dissection. Eight years later, she presented with dyspnea and was found to have a lung mass with hilar lymphadenopathy. A biopsy specimen was taken from the hilar lymph nodes, and histologic analysis yielded results similar to those found in the original tumor. Immunohistochemical analysis confirmed that FDCT was present at both sites. We wish to highlight this potential diagnostic pitfall because the treatment and prognosis for FDCT are vastly different from the treatment and prognosis for squamous cell carcinoma of the tonsil.

  17. Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors.

    Science.gov (United States)

    Spiller, Cassy M; Bowles, Josephine; Koopman, Peter

    2013-01-01

    Testicular cancer is the most frequent cancer in young men aged 15-40 years and accounts for 1% of all cancer diagnosed in males. Testicular germ cell tumors (TGCT) encompass a broad group of cancers, each displaying different levels of pluripotency and differentiation as well as malignancy potential. The TGCT cell of origin is thought to be a fetal germ cell that failed to correctly differentiate during development: this is known as the ‘fetal origins hypothesis’. This theory predicts that developmental pathways that control germ cell pluripotency or differentiation may be involved in the malignant transformation of these cells. Recently the Nodal/Cripto signaling pathway, known to control pluripotency and differentiation in embryonic stem (ES) cells, was implicated in regulating normal male fetal germ cell pluripotency. Although genes of this pathway are not normally expressed in germ cells during adult life, ectopic expression of this pathway was detected in several sub-groups of TGCTs. In this review, we consider the evidence for the fetal origins of TGCT and discuss the implications of Nodal/Cripto signaling in various aspects of germ cell development and cancer progression.

  18. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  19. Rotavirus vaccines.

    Science.gov (United States)

    Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.

    2000-10-01

    The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.

  20. Preoperative diagnosis of a mediastinal granular cell tumor by EUS-FNA: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Bean Sarah M

    2005-06-01

    Full Text Available Abstract We report the first case of a posterior mediastinal granular cell tumor initially diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA in a 51-year-old male with a prior history of colon cancer. Aspirates obtained were cellular and composed of polygonal cells with abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase stain performed on the cell block for antibodies to S-100 protein showed strong, diffuse staining of the cytoplasmic granules. Electron microscopy performed on the cell block revealed numerous cytoplasmic lysosomes. This is the first case report in the English literature of a definitive preoperative diagnosis of a mediastinal granular cell tumor utilizing material obtained via EUS-FNA.

  1. Atypical presentation of a desmoplastic small round cell tumor in the orbit: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sojitra P

    2016-08-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare malignant neoplasm. Typically it occurs in young adult males and involves the abdomen or pelvis. Other primary sites are uncommon. Only one other case of orbital DSRCT has been reported in the literature. The diagnosis of DSRCTs can be extremely challenging since they often have overlapping histologic and immunohistochemical profile with other small round blue cell tumors. This is particularly true when the tumor occurs in an unusual location, and especially when it lacks the classic histologic pattern. Molecular confirmation is critical when the biopsy sample is limited. Herein, we report a case of DSRCT involving the right orbit of a 3-year-old male with immunohistological and molecular confirmation for DSRCT.

  2. Frequency of argyrophilic nucleolar organizer regions in fine-needle aspirates and biopsy specimens from mast cell tumors in dogs.

    Science.gov (United States)

    Kravis, L D; Vail, D M; Kisseberth, W C; Ogilvie, G K; Volk, L M

    1996-10-15

    To determine for mast cell tumors in dogs whether frequency of argyrophilic nucleolar organizer regions (AgNOR) determined by examining fine-needle aspirates (FNA) correlated with frequencies determined by examining biopsy specimens or with histologic grade. Case series. 25 dogs with 32 histologically confirmed tumors. Biopsy specimens and FNA were collected from each tumor. Histologic grade and AgNOR frequency were determined. Frequency of AgNOR in FNA was significantly correlated with frequency in biopsy specimens and was significantly associated with histologic grade of the tumor. Determining AgNOR frequency in FNA of mast cell tumors in dogs is a rapid, minimally invasive means of obtaining information that potentially could be used to help predict biological behavior of the tumor and to guide clinicians and owners in making decisions about further diagnostic tests and treatment.

  3. [Diffuse tenosenovial giant cell tumor of the wrist revealed by carpal tunnel syndrome: report of a case].

    Science.gov (United States)

    Ait Essi, F; Younsi, A; Abkari, I; Benhima, M A; Najeb, Y; Latifi, M; Fakhri, A; Belaabidia, B

    2012-10-01

    Giant cell tumour of tendon sheath is a benign proliferative lesion of synovial origin that may affect the joints, bursae and tendon sheaths. It is the second most common soft tissue tumor of the hand after ganglion cyst. The localised (nodular) form is the most common. However, the less-common diffuse-type giant cell tumour is usually located in the peri-articular soft tissue. The authors report the case of a giant cell tumor of the tendon sheath arising from the carpal tunnel of the wrist in a 42-year-old woman. The patient presented a mild carpal tunnel syndrome and a mid-palmar swelling. We present an unusual localization of giant cell tumor of the tendon sheath, causing carpal tunnel syndrome. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Williams Fernandes Barra

    2010-01-01

    Full Text Available A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH. He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.

  5. Giant cell tumor of the tendon sheath restricting joint movement in the thumb: A case study and review of literature

    Directory of Open Access Journals (Sweden)

    Muzaffer Durmus

    2015-04-01

    Full Text Available Giant cell tumors of the tendon sheath are the second most common type of subcutaneous benign tumors found in the hand. These tumors are slow growing soft tissue mases that develop over a long period of time and can occur at any age. Although such lesions are usually painless, there is a possibility of recurrence of the tumor. Patients should seek postoperative management in order to prevent any possibility of recurrence. In view of the current literature, we present a case involving a patient suffering from a multifocal giant cell tumor of the tendon sheath that restricted movement of the interphalangeal joints of the thumb. [Hand Microsurg 2015; 4(1.000: 16-19

  6. Concomitant granular cell tumor and balanitis xerotica obliterans of the foreskin: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Shaun AC Medlicott, MD, FRCPC

    2017-09-01

    Full Text Available Balanitis xerotica obliterans is a chronic dermatosis that frequently involves the glans penis and the foreskin. Granular cell tumor is a benign tumor that may rarely involve the penis, but involvement of the foreskin is exceedingly rare. It may result in thickening and ulceration of the overlying epidermis, which can mimic squamous cell carcinoma. An association of these two lesions, one very common and one extremely uncommon, arising concomitantly in the penile foreskin has not been previously documented. A 23-year-old patient with phimosis and a subcutaneous foreskin nodule presented for a medical circumcision. The microscopic examination demonstrated balanitis xerotica obliterans and granular cell tumor, occurring in continuity in the foreskin. To our knowledge, this is the first reported example of these two lesions arising simultaneously in the male genitalia.

  7. A Desmoplastic Small Round Cell Tumor in a Twenty-Eight Year-old Adult Male Presenting with Urological Symptoms

    Directory of Open Access Journals (Sweden)

    Amr Idris

    2015-01-01

    Full Text Available A desmoplastic small round cell tumor is a malignant tumor of the abdominal and pelvic cavities. This tumor involves serosal surfaces such as the peritoneum, pleura, and scrotum. In this case report a 28-year old male presented with a desmoplastic small round cell tumor located in the abdomen along with urological symptoms. When the diagnosis was completed, the patient’s tumor had metastasized to the liver and retroperitoneal lymph nodes. This case not only has exemplified that this tumor is rare and fatal but its prompt diagnosis is critical. However it is most likely that the diagnosis of this tumor is found when it has metastasized and this is unfortunately very late.

  8. Towards cognitive image fusion

    NARCIS (Netherlands)

    Toet, A.; Hogervorst, M.A.; Nikolov, S.G.; Lewis, J.; Dixon, T.; Bull, D.; Canagarajah, N.

    2007-01-01

    The increasing availability and deployment of imaging sensors operating in multiple spectral bands has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, the cognitive aspects of multisensor image fusion have not received much

  9. Towards cognitive image fusion

    NARCIS (Netherlands)

    Toet, A.; Hogervorst, M.A.; Nikolov, S.G.; Lewis, J.J.; Dixon, T.D.; Bull, D.R.; Canagarajah, C.N.

    2010-01-01

    The increasing availability and deployment of imaging sensors operating in multiple spectral bands has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, the cognitive aspects of multisensor image fusion have not received much

  10. Vaccine allergies.

    Science.gov (United States)

    Chung, Eun Hee

    2014-01-01

    Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered.

  11. An inguinal hernia with cryptorchidism with a Leydig cell tumor in an elderly man: A case report

    OpenAIRE

    Zuiki, Toru; Ohki, Jun; Komatsubara, Toshihide; Lefor, Alan Kawarai; Miyahara, Yuzo; Ochi, Masanori; Hirota, Norio

    2017-01-01

    ?Abstract Introduction Cryptorchidism is common in children but is rare in the elderly. It often presents with a constellation of signs and symptoms similar to routine inguinal hernias. We present the case of an elderly man with cryptorchidism containing a Leydig cell tumor and provide clinical insights. Presentation of case An-84-year old man was admitted with an incarcerated right lower quadrant hernia. Both testes were absent on palpation of the scrotum. After reduction of the hernia, comp...

  12. MR imaging findings of giant cell tumor of the tendon sheath involving the foot : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik; Chung, Soo Young; Park, Hai Jung; Lee, Yul; Park, Young Wook; Shim, Jeong Won [Hallym Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-05-01

    Giant cell tumor of the tendon sheath(GCTTS) is a benign condition which involves the synovium of the tendon sheaths, and usually occurs around the small joints, e. g. the ankle, knee, and wrist. Histologically, GCTTS is similar to pigmented villonodular synovitis(PVNS). The authors report MRI findings of a GCTTS. This showed lower signal-intensity lesions than adjacent muscles on T1-weighted, proton density weighted, and T2-weighted images.

  13. 18F-FDG PET/CT Finding of Drop Metastases from Germ Cell Tumor of Pineal Gland.

    Science.gov (United States)

    Jain, Tarun K; Basher, Rajender K; Sood, Ashwani; Mittal, Bhagwant R; Prakash, Gaurav; Bhatia, Anmol

    2017-06-01

    Tumors of the pineal region are rare, accounting for fewer than 1% of all intracranial neoplasms. Fifty percent of pineal region tumors are germ cell tumors (GCTs). However, spinal seeding and extracranial metastases from intracranial GCTs are uncommon. We present a case of pineal gland GCT in which 18F-FDG PET/CT imaging demonstrated drop metastases to the spinal cord in addition to tracer uptake in the primary lesion. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  14. Retiform Sertoli-Leydig Cell Tumor in a 38-Year-Old Woman: A Case Report, Retrospective Review, and Review of Current Literature

    Directory of Open Access Journals (Sweden)

    Laura C. Nwogu

    2017-01-01

    Full Text Available Ovarian sex cord-stromal tumors arise from the stromal cells that surround and support the oocytes. Sertoli-Leydig cell tumors belong to this category of ovarian neoplasms. We present the case of a 38-year-old woman who was found to have a right ovarian mass. The mass was resected and diagnosed as Stage I Sertoli-Leydig cell tumor, retiform variant, following histopathologic and immunohistochemical examination. This case is unusual given the rarity of the retiform variant of Sertoli-Leydig cell tumor and the atypically older age of 38 years at presentation.

  15. Measles Virus Fusion Protein: Structure, Function and Inhibition

    Directory of Open Access Journals (Sweden)

    Philippe Plattet

    2016-04-01

    Full Text Available Measles virus (MeV, a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.

  16. Measles Virus Fusion Protein: Structure, Function and Inhibition

    Science.gov (United States)

    Plattet, Philippe; Alves, Lisa; Herren, Michael; Aguilar, Hector C.

    2016-01-01

    Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options. PMID:27110811

  17. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    Science.gov (United States)

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

    2015-02-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  18. Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages12

    Science.gov (United States)

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M.; Berg, Kaja G.; Bakken, Anne C.; Bruun, Jarle; Fosså, Sophie D.; Lothe, Ragnhild A.; Lehne, Gustav; Skotheim, Rolf I.

    2015-01-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. PMID:25748235

  19. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.

    Science.gov (United States)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Abeler, Vera M; Rajpert-De Meyts, Ewa; Lothe, Ragnhild A

    2013-06-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.

  20. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Hideaki; Minowa, Osamu; Inoue, Maki; Motegi, Hiromi; Karashima, Yuko; Ikeda, Ami [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Kaneda, Hideki [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Sakuraba, Yoshiyuki [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Saiki, Yuriko [Department of Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi (Japan); Wakana, Shigeharu [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Suzuki, Hiroshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Gondo, Yoichi [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Shiroishi, Toshihiko [Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka (Japan); Noda, Tetsuo, E-mail: tnoda@jfcr.or.jp [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo (Japan)

    2016-08-05

    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.

  1. Tenosynovial giant cell tumors of the temporomandibular joint and lateral skull base: Review of 11 cases.

    Science.gov (United States)

    Carlson, Matthew L; Osetinsky, L Mariel; Alon, Eran E; Inwards, Carrie Y; Lane, John I; Moore, Eric J

    2017-10-01

    To elucidate the clinical behavior, treatment, and outcomes of tenosynovial giant cell tumors (TGCT) involving the temporomandibular joint (TMJ) and adjacent temporal bone. Retrospective case series with histopathologic review. A retrospective chart review was performed identifying and collecting data from all cases of TGCT involving the TMJ and adjacent temporal bone that were treated at the authors' center between January 1960 and December 2015. Eleven histopathologically confirmed cases met inclusion criteria. The median age at diagnosis was 49 years, eight patients were men, and the median follow-up was 116 months. Computed tomographic (CT) imaging revealed a lytic expansile mass centered on the TMJ. Magnetic resonance imaging (MRI) most commonly exhibited hypointense signal on precontrast T1- and T2-weighted sequences and variable postcontrast enhancement. The median delay in diagnosis was 24 months, and the most common presenting symptoms were hearing loss and pain. All patients underwent surgical resection, eight receiving gross total removal, one receiving near total removal, and two patients from early in the series receiving subtotal resection with neoadjuvant or adjuvant radiation. Histopathological review of surgical specimens revealed chondroid metaplasia in seven tumors. Eight of nine cases receiving gross total or near total resection have no evidence of recurrence to date. TGCT of the TMJ and temporal bone are rare and locally aggressive tumors that commonly present with nonspecific symptoms. A careful review of CT and MRI followed by early biopsy is critical in establishing an accurate diagnosis and facilitating appropriate treatment. TGCT of the TMJ more commonly contain chondroid metaplasia when compared to TGCT at other anatomic locations. Gross total resection is achievable in most cases and offers long-term cure. Radiation may be considered for recurrent disease or adjuvant therapy following subtotal resection. 4. Laryngoscope, 127

  2. Giant cell tumor of the tendon sheath composed largely of epithelioid histiocytes.

    Science.gov (United States)

    Terada, Tadashi

    2012-01-01

    Giant cell tumor of the tendon sheath (GCTTS) is a relatively uncommon lesion. GCTTS composed largely epithelioid histiocytes are very rare. In the literature, the author could not find such cases. A 73-year-old man presented with a mass of right thumb, and resection of the mass was performed. Grossly, the mass was encapsulated and yellowish, and measured 1.5 x 2 x 2 cm. Microscopically, the mass was composed of cellular and hypocellular zones. The former was composed of spindle cells and osteoclast-like giant cells, while the latter of epithelioid clear histiocytes. The area of the former was 20%, and the latter 80%. Pigment was seen in the former elements. Mitotic figures were seen in 3/per 30 high power fields (HPFs) in the former element and 2/per 30 HPFs in the latter element. Histochemically, the pigment was hemosiderin positive with Prussian blue staining. Immunohistochemically, both the elements were negative for cytokeratin (CK) CE1/3, CK CAM5.2, CEA, HMB45, alpha-smooth muscle antigen, p53, CD10, TTF-1, and CDX2. Both the elements were positive for CD68 and Ki-67 (cellular element 30% and hypocellular element 20%). The histiocytes of the hypocellular element and osteoclast-like giant cell of the cellular element were positive for CD45. S100-protein positive Langerhans cells and CD45-positive lymphocytes were scattered. The pathological diagnosis was GCTTS. In the author's experience, GCTTS composed largely epithelioid histiocytes are very rare. In the literature, the author could not find such cases. Thus, the author reports herein this case.

  3. Future of testicular germ cell tumor incidence in the United States: Forecast through 2026.

    Science.gov (United States)

    Ghazarian, Armen A; Kelly, Scott P; Altekruse, Sean F; Rosenberg, Philip S; McGlynn, Katherine A

    2017-06-15

    Testicular germ cell tumors (TGCTs) are rare tumors in the general population but are the most commonly occurring malignancy among males between ages 15 and 44 years in the United States (US). Although non-Hispanic whites (NHWs) have the highest incidence in the US, rates among Hispanics have increased the most in recent years. To forecast what these incidence rates may be in the future, an analysis of TGCT incidence in the Surveillance, Epidemiology, and End Results program and the National Program of Cancer Registries was conducted. TGCT incidence data among males ages 15 to 59 years for the years 1999 to 2012 were obtained from 39 US cancer registries. Incidence rates through 2026 were forecast using age-period-cohort models stratified by race/ethnicity, histology (seminoma, nonseminoma), and age. Between 1999 and 2012, TGCT incidence rates, both overall and by histology, were highest among NHWs, followed by Hispanics, Asian/Pacific Islanders, and non-Hispanic blacks. Between 2013 and 2026, rates among Hispanics were forecast to increase annually by 3.96% (95% confidence interval, 3.88%-4.03%), resulting in the highest rate of increase of any racial/ethnic group. By 2026, the highest TGCT rates in the US will be among Hispanics because of increases in both seminomas and nonseminomas. Rates among NHWs will slightly increase, whereas rates among other groups will slightly decrease. By 2026, Hispanics will have the highest rate of TGCT of any racial/ethnic group in the US because of the rising incidence among recent birth cohorts. Reasons for the increase in younger Hispanics merit further exploration. Cancer 2017;123:2320-2328. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  4. Granulosa cell tumor associated with secondary amenorrhea and serum luteinizing hormone elevation.

    Science.gov (United States)

    Nasu, Kaei; Fukuda, Junichiro; Yoshimatsu, Jun; Takai, Noriyuki; Kashima, Kenji; Narahara, Hisashi

    2007-06-01

    Adult granulosa cell tumors (GCTs) are the most common type of ovarian sex cord tumors. Menstrual irregularity, menorrhagia, or even secondary amenorrhea is frequently observed in premenopausal women bearing GCTs with hormonal activity. We report herein a case of GCT in a patient presenting with secondary amenorrhea and serum luteinizing hormone elevation. A 28-year-old primigravid Japanese woman was admitted complaining of secondary amenorrhea of 2 years' duration. Pelvic examination, transvaginal ultrasonography, and magnetic resonance imaging demonstrated a left ovarian tumor 4 cm in diameter. Serum hormone assays revealed a follicle-stimulating hormone level of 4.8 mIU/ml, luteinizing hormone (LH) of 35.8 mIU/ml, estradiol of 24 pg/ml, progesterone of 1.6 ng/ml, and testosterone of 40 ng/dl. A left salpingo-oophorectomy was performed. The tumor was diagnosed as an adult-type GCT stage IIb (FIGO [International Federation of Obstetricians and Gynecologists], 1988). Spontaneous menstruation occurred soon after the surgery. Serum levels of LH also decreased to normal levels and showed cyclic changes during the menstrual cycle. Subsequently, the patient conceived and delivered a healthy female baby. The tumor recurred in the pelvis 50 months after the initial conservative surgery, with elevated serum LH levels of 36.0 mIU/ml and amenorrhea. The patient was treated by hysterectomy, right salpingo-oophorectomy, omentectomy, paraaortic and pelvic lymphadenectomy, and low anterior resection of the recto-sigmoid colon. Her hormone levels progressed to the postmenopausal state after this surgery. Although LH elevation in patients with GCT is rare and its mechanism is unknown, monitoring of serum LH may provide an additional tumor marker after conservative surgery in such patients.

  5. Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

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    Burton, J H; Venable, R O; Vail, D M; Williams, L E; Clifford, C A; Axiak-Bechtel, S M; Avery, A C; Thamm, D H

    2015-01-01

    Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy. The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine. Forty-seven client-owned dogs with measurable MCT. Toceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone. The MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy. Combined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. IMPACT OF CENTRAL SURGICAL REVIEW IN A STUDY OF MALIGNANT GERM CELL TUMORS

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    Billmire, Deborah F.; Rescorla, Frederick J.; Ross, Jonathan H.; Schlatter, Marc G.; Dicken, Bryan J.; Krailo, Mark D.; Rodriguez-Galindo, Carlos; Olson, Thomas A.; Cullen, John W.; Frazier, A. Lindsay

    2016-01-01

    BACKGROUND Verification of surgical staging has received little attention in clinical oncology trials for both children and adults. Central surgical review in a study of malignant pediatric germ cell tumors provided an opportunity to assess the impact of this process. METHODS Children’s Oncology Group study AGCT0132 data submission at study entry required operative note, surgical checklist, pathology and imaging reports. Central surgical review during the study included assessment for completeness of submitted data and confirmation of assigned stage. Review resulted in one of three conclusions: assigned status confirmed, assignment withheld pending review of additional information requested, or institutional assignment of stage disputed with reasons for recommended stage assignment explained. Changes in stage assignment based on central surgical review were left at the discretion of the enrolling institution. RESULTS 206 patients underwent central review. Failure to submit required data elements or need for clarification was noted in 40%. Disagreement with stage assignment occurred in 10%; the highest rate of discordance was in ovarian tumors submitted as stage I (34%). 17 of 21 discordant patients were reassigned to the stage recommended by central review. 4 patients with ovarian tumors not meeting central review criteria for Stage I remained in that stratum by institutional decision. Two-year event free survival (EFS) in Stage I ovarian tumor patients was 25% (1/4) for discordant patients compared to 57% (9/21) in patients who met Stage I criteria by central review. CONCLUSIONS Central review of stage assignment by a dedicated study surgeon improved collection of complete data and assignment of correct tumor stage at study entry, and allowed for prompt initiation of chemotherapy in patients determined not to have Stage I disease. PMID:25783295

  7. The Role of Systemic Chemotherapy in the Management of Granulosa Cell Tumors

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    Meisel, Jane L.; Hyman, David; Jotwani, Anjali; Zhou, Qin; Abu-Rustum, Nadeem R.; Iasonos, Alexia; Pike, Malcolm C.; Aghajanian, Carol

    2015-01-01

    Objective Granulosa cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined. Methods We performed a retrospective cohort study of GCT patients diagnosed from January 1996 through June 2013 at Memorial Sloan Kettering Cancer Center, comparing those who received adjuvant chemotherapy to those who did not. Differences between groups were assessed using the log-rank test. Statistical significance was set at p<0.05. Results Of 118 patients, 10 (8%) received adjuvant chemotherapy (1 [1%] of 103 stage I and 9 [60%] of 15 stage II–IV patients). Thirty-two patients (27%) experienced disease recurrence. Four patients had residual disease after initial surgery, and all received adjuvant chemotherapy; each recurred within 24.3 months (median PFS, 8.2 months). The time to first recurrence was longer in patients who did not receive adjuvant chemotherapy. For patients with recurrent disease, receiving chemotherapy after surgery for first recurrence did not seem to improve time to second recurrence versus surgery alone (HR 0.98; p=0.965). Additionally, 12 patients (10%) had a previous diagnosis of breast cancer—an incidence rate 3.22 times higher than Surveillance, Epidemiology, and End Results (SEER) data predicts (p<0.001). Conclusions Although the numbers were small, in this analysis chemotherapy was not found to improve the recurrence-free interval of patients with GCTs, a finding that requires prospective validation. Residual disease after surgery was associated with poor prognosis. Finally, there was a significantly higher than expected incidence of antecedent breast cancer in this population, an association that deserves further exploration. PMID:25546114

  8. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

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    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  9. Giant cell tumor of the mobile spine: a review of 49 cases.

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    Boriani, Stefano; Bandiera, Stefano; Casadei, Roberto; Boriani, Luca; Donthineni, Rakesh; Gasbarrini, Alessandro; Pignotti, Elettra; Biagini, Roberto; Schwab, Joseph H

    2012-01-01

    This is a retrospective review of 49 cases of giant cell tumor (GCT) of the mobile spine treated surgically. Our goal was to determine which factors influenced local recurrence. GCT is a benign, locally aggressive tumor that rarely occurs in the spine. The management of local recurrence can be challenging. We performed a retrospective analysis of GCTs of the mobile spine managed between 1970 and 2005. Median follow-up was 145 months with a minimum of 2 years or until death. We used the Kaplan-Meier method to test whether Enneking stage, surgery type, and surgical margin had statistically significant impact on local recurrence. The log rank test was used for comparison, and a P value of less than 0.05 was deemed significant. Of the 49 patients, 11 (22%) local recurrences occurred. The latest recurrence occurred at 60 months. Age less than 25 years was associated with a worse relapse-free survival (P = 0.03). En bloc resection was associated with better local control with Enneking stage III tumors (P = 0.01); however, intralesional resection provided adequate control of Enneking stage II tumors. There were 6 (12%) cases of metastasis, and 2 patients died from the progression of their disease. One patient died from the complications of the surgery. En bloc resection should be considered for Enneking stage III GCTs of the mobile spine. The choice of en bloc resection must be balanced with the inherent risks of the procedure. Intralesional resection of Enneking stage II tumors provides adequate local control. Patients should be followed for at least 5 years because local relapse can occur late.

  10. Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

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    Sigmund Brabrand

    2015-02-01

    Full Text Available Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs, is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors, of these three patients in whom both tumors were available (six tumors and two patients each with only one available tumor (two tumors. Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21, some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA, and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.

  11. Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors.

    Science.gov (United States)

    Huang, Xiang; Zhang, Rong; Mao, Ying; Zhou, Liang-Fu; Zhang, Chao

    2016-08-01

    Intracranial germ cell tumors (IGCTs) are a group of rare pediatric brain tumors which include various subtypes. The current understanding of the etiology of the tumors and their optimal management strategies remain controversial. The data on IGCTs were collected from articles published in the past 20 years, and the origin and etiology of IGCTs at molecular level as well as the relative roles of varied treatment strategies in different prognosis groups according to Matsutani's classification were reviewed. Recent cellular and molecular evidence suggests that IGCTs may arise from the transformation of endogenous brain cells; and findings in the molecular characterization of IGCTs suggest roles of CCND2, RB1, and PRDM14 in the pathogenesis of IGCTs and identify the KIT/RAS and AKT1/mTOR pathways as potential therapeutic targets in future. According to Matsutani's classification of IGCTs, the good prognosis group includes both germinomas and mature teratomas. For germinomas, both radiation alone and reduced-dose radiotherapy in combination with adjuvant chemotherapy are effective, while complete surgical excision is recommended for mature teratomas. In the intermediate prognosis group, immature teratoma has been successfully treated with gamma knife surgery. However, for intermediate prognosis IGCTs other than immature teratomas, gross total resection with adjuvant chemotherapy and radiotherapy or gamma knife surgery may be necessary to achieve cure. In the poor prognosis group, survival outcomes are unsatisfactory, and complete surgical resection combined with more intensive chemotherapy and radiotherapy remains the best available treatment option at this time. IGCTs should be strictly classified according to their pathological categories before administering pathology-specific treatments. Although open microsurgical excision is the traditional surgical strategy for IGCTs, recent publications also support the role of endoscopic surgical options for pineal region

  12. Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery

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    Von Borstel, Donald; Strle, Nicholas A. [Oklahoma State University Medical Center, Department of Radiology, Tulsa, OK (United States); Taguibao, Roberto A. [University of California, Irvine, UCI Medical Center, Department of Pathology, Orange, CA (United States); Burns, Joseph E. [University of California, Irvine, UCI Medical Center, Department of Radiological Sciences, Orange, CA (United States)

    2017-04-15

    Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis. (orig.)

  13. Consumption of alcoholic beverages in adolescence and adulthood and risk of testicular germ cell tumor.

    Science.gov (United States)

    Biggs, Mary L; Doody, David R; Trabert, Britton; Starr, Jacqueline R; Chen, Chu; Schwartz, Stephen M

    2016-12-01

    The etiology of testicular germ cell tumor (TGCT) remains obscure and accumulating evidence suggests that postnatal environmental or lifestyle factors may play a role. To investigate whether consumption of alcoholic beverages during adolescence or adulthood is associated with TGCT risk, we analyzed data from a USA population-based case-control study of 540 18-44 year-old TGCT cases and 1,280 age-matched controls. Participants were queried separately about consumption of beer, wine and liquor during grades 7-8, grades 9-12 and the 5 years before reference date (date of diagnosis for cases and corresponding date for controls). We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of TGCT risk with alcoholic beverage consumption during the different periods, both total and by specific beverage types and separately for seminomas and nonseminomas. Compared with nondrinkers in the 5 years before reference date, the OR (95% CI) for 1-6, 7-13 and ≥14 drinks per week were 1.20 (0.85, 1.69), 1.23 (0.81, 1.85) and 1.56 (1.03, 2.37), respectively (p-trend = 0.04). The corresponding results for alcohol consumption in grades 9-12 were 1.39 (1.06, 1.82), 1.07 (0.72, 1.60), 1.53 (1.01, 2.31) (p-trend = 0.05). Alcohol consumption in grades 7-8 was uncommon and no statistically significant associations with TGCT were observed. Associations with alcohol consumption in the 5 years before reference date appeared stronger for nonseminomas than for seminomas, but the differences were not statistically significant (p≥0.10). Associations were similar across different alcoholic beverage types. Consumption of alcoholic beverages may be associated with an increased TGCT risk. © 2016 UICC.

  14. Long-Term Outcomes of Sacrococcygeal Germ Cell Tumors in Infancy and Childhood

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    Rangsan Niramis

    2015-01-01

    Full Text Available Purpose. The aim of this study was to evaluate long-term outcomes of sacrococcygeal germ cell tumors (SC-GCTs over a 15-year period. Materials and Methods. A retrospective review was conducted of all pediatric patients treated for SC-GCTs at our hospital from 1998 to 2012. Results. Fifty-seven patients were treated for SC-GCTs with the most common in Altman’s classification type I. Age at surgery ranged from one day to 5.6 years. Tumor resection and coccygectomy were primarily performed in about 84% of the cases. Pathology revealed mature, immature, malignant sacrococcygeal teratomas (SCTs, and endodermal sinus tumors (ESTs in 41 (72%, 4 (77%, 6 (10.5%, and 6 (10.5%, respectively. Recurrence of discase occurred in 3 of 41 patients with mature teratomas (7.3%; 2 recurrences with mature teratomas and one recurrence with EST. Five of 6 malignant SCTs and 3 of 6 ESTs responded well to the treatment. Alpha-fetoprotein (AFP level was elevated in both malignant teratomas and ESTs. No immediate patient death was noted in any of the 57 cases, but 4 patients with malignant tumors and distant metastasis succumbed at home within 2 years of the initial treatment. Conclusion. Benign SCTs have a significant recurrence rate of approximately 7%. Close follow-up with serial AFP level monitoring should be done for 5 years after initial tumor resection and coccygectomy. The survival rate for malignant SC-GCTs with distant metastasis was unfavorable in the present study.

  15. Pediatric germ cell tumors and parental infertility and infertility treatment: a Children's Oncology Group report.

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    Puumala, Susan E; Ross, Julie A; Wall, Melanie M; Spector, Logan G

    2011-10-01

    Few risk factors have been established for childhood germ cell tumors (GCT). Parental infertility and infertility treatment may be associated with GCT development but these risk factors have not been fully investigated. A case-control study of childhood GCT was conducted through the Children's Oncology Group (COG). Cases, under the age of 15 years at diagnosis, were recruited through COG institutions from January 1993 to December 2002. Controls were obtained through random digit dialing. Information about infertility and infertility treatment along with demographic factors was collection through maternal interviews. Subgroups created by gender, age at diagnosis, and tumor location were examined separately. Statistical analysis was performed using multivariate logistic regression models. Overall, no association between GCT and infertility or its treatment was found. In subgroup analysis, females whose mothers had two or more fetal losses were found to be at increased risk for non-gonadal tumors (Odds ratio (OR)=3.32, 95% Confidence interval (CI)=1.12-9.88). Younger maternal age was associated with a lower risk of gonadal GCT in females (OR=0.52, 95% CI=0.28-0.96). There was an increased risk of all GCT and gonadal GCT in males born to older mothers (OR=2.88, 95% CI=1.13-7.37 and OR=3.70, 95% CI=1.12-12.24). While no association between parental infertility or its treatment and childhood GCT was found overall, possible associations with maternal age and history of recurrent fetal loss were found in subgroups defined by gender. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Responses and adverse effects of carboplatin-based chemotherapy for pediatric intracranial germ cell tumors

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    Suntae Ji

    2011-03-01

    Full Text Available Purpose : Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs. However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy. Methods : We examined 35 patients (27 men and 8 women diagnosed with IC-GCTs between August 2004 and April 2008 and received riskadapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR or high-risk (HR groups and a retrospective analysis was performed using information from the medical records. Results : Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS was 95.7 %. The EFS rate was 100% in the LR group and 90% in the HR group, respectively. Conclusion : Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatinbased treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.

  17. Giant cell tumors of the tendon sheath may present radiologically as intrinsic osseous lesions

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    Schepper, A.M. de; Bloem, J.L. [Leiden University Medical Center, Department of Radiology, Albinusdreef 2, P.O. Box 9600, RC Leiden (Netherlands); Hogendoorn, P.C.W. [Leiden University Medical Center, Department of Pathology, Albinusdreef 2, P.O. Box 9600, RC Leiden (Netherlands)

    2007-02-15

    The purpose of this study was to explain radiographic features of giant cell tumors of the tendon sheath (GCTTS), in particular, osseous extension, by correlating imaging findings with histology in order to increase the accuracy of radiological diagnosis. In a series of 200 consecutive osseous (pseudo) tumors of the hand, on radiography, six patients presented with an intrinsic osseous lesion caused by a histologically confirmed neighboring GCTTS. Available radiographs, computed tomography (CT), and contrast-enhanced magnetic resonance (MR) images were correlated with histology. Radiography showed osseous lesions consisting of well-defined cortical defects in four (one of whom also demonstrated cortical scalloping) and a slightly expansile, well-defined osteolytic lesion in two patients. MR obtained in four patients showed the extraosseous tumor invading/eroding bone and causing cortical scalloping (three and one patients, respectively). Extension depicted on MR was confirmed on the two available resection specimens. All lesions were polylobular (cauliflower or mushroom like) and neighbored tendon sheaths. Dense collagen and hemosiderin-loaded macrophages explained the high CT attenuation and the low MR signal intensity on T2-weighted images that was observed in all four MR and in all two CT scans. The high density of proliferative capillaries explained the marked enhancement observed in all four patients with gadolinium (Gd)-chelate-enhanced MR imaging. GCTTS is a soft tissue (pseudo) tumor that may invade bone and as a consequence mimick an intrinsic osseous lesion on radiographs. In such cases, specific MR and CT features that can be explained by histological findings can be used to suggest the correct diagnosis. (orig.)

  18. Differentiation of primary chordoma, giant cell tumor and schwannoma of the sacrum by CT and MRI

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    Si, Ming-Jue, E-mail: smjsh@hotmail.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Wang, Cheng-Sheng [Department of Radiology, Union Hospital, Fujian Medical University, Fuzhou 350001 (China); Ding, Xiao-Yi, E-mail: dingxiaoyi1965@hotmail.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yuan, Fei, E-mail: yuanfeirj@hotmail.com [Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Du, Lian-Jun; Lu, Yong [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Zhang, Wei-Bin [Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China)

    2013-12-01

    Objective: To evaluate criteria to differentiate sacral chordoma (SC), sacral giant cell tumor (SGCT) and giant sacral schwannoma (GSS) with CT and MRI. Materials and methods: CT and MR images of 22 SCs, 19 SGCTs and 8 GSSs were reviewed. The clinical and imaging features of each tumor were analyzed. Results: The mean ages of SC, SGCT and GSS were 55.1 ± 10.7, 34.3 ± 10.7 and 42.4 ± 15.7 years old. SCs (77.3%) were predominantly located in the midline of lower sacrum, while most SGCTs (73.7%) and GSSs (87.5%) were eccentrically located in upper sacrum. There were significant differences in age, location, eccentricity, morphology of bone residues, intratumoral bleeding and septations. Multiple small cysts were mainly observed in SGCTs (73.7%) with large central cysts in GSSs (87.5%). SGCTs expanded mainly inside sacrum while SCs and GSSs often extended into pelvic cavity (P = 0.0022). Involvement of sacroiliac joints and muscles were also different. Ascending extension within sacral canal was only displayed in SCs. The preservation of intervertebral discs showed difference between large and small tumors (P = 0.0002), regardless of tumor type (P = 0.095). No significant difference was displayed in gender (P = 0.234) or tumor size (P = 0.0832) among three groups. Conclusion: Age, epicenter of the lesion (midline vs. eccentric and upper vs. lower sacral vertebra), bone residues, cysts, bleeding, septation, expanding pattern, muscles and sacroiliac joint involvement can be criteria for diagnosis. Fluid–fluid level is specific for SGCTs and ascending extension within the sacral canal for SCs. The preservation of intervertebral discs is related to tumor size rather than tumor type.

  19. K-RAS and N-RAS mutations in testicular germ cell tumors

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    Bekir Muhammet Hacioglu

    2017-05-01

    Full Text Available Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55% pure seminoma cases and 19 (45% non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen. In total, a RAS mutation was present in 12 patients (27%: 7 seminoma (29% and 5 non-seminoma cases (26% [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

  20. Antihistaminic and cardiorespiratory effects of diphenhydramine hydrochloride in anesthetized dogs undergoing excision of mast cell tumors.

    Science.gov (United States)

    Sanchez, Andrea; Valverde, Alexander; Sinclair, Melissa; Mosley, Cornelia; Singh, Ameet; Mutsaers, Anthony J; Hanna, Brad; Johnson, Ron; Gu, Yu; Beaudoin-Kimble, Michelle

    2017-10-01

    OBJECTIVE To evaluate the effects of IV diphenhydramine hydrochloride administration on cardiorespiratory variables in anesthetized dogs undergoing mast cell tumor (MCT) excision. DESIGN Randomized, blinded clinical trial. ANIMALS 16 client-owned dogs with MCTs. PROCEDURES In a standardized isoflurane anesthesia session that included mechanical ventilation, dogs received diphenhydramine hydrochloride (1 mg/kg [0.45 mg/lb], IV; n = 8) or an equivalent volume of saline (0.9% NaCl) solution (IV; control treatment; 8) 10 minutes after induction. Cardiorespiratory variables were recorded throughout anesthesia and MCT excision, and blood samples for determination of plasma diphenhydramine and histamine concentrations were collected prior to premedication (baseline), throughout anesthesia, and 2 hours after extubation. RESULTS Cardiorespiratory values in both treatment groups were acceptable for anesthetized dogs. Mean ± SD diastolic arterial blood pressure was significantly lower in the diphenhydramine versus control group during tumor dissection (52 ± 10 mm Hg vs 62 ± 9 mm Hg) and surgical closure (51 ± 10 mm Hg vs 65 ± 9 mm Hg). Mean arterial blood pressure was significantly lower in the diphenhydramine versus control group during surgical closure (65 ± 12 mm Hg vs 78 ± 11 mm Hg), despite a higher cardiac index value. Plasma histamine concentrations were nonsignificantly higher than baseline during maximal manipulation of the tumor and surgical preparation in the diphenhydramine group and during surgical dissection in the control group. CONCLUSIONS AND CLINICAL RELEVANCE IV administration of diphenhydramine prior to MCT excision had no clear clinical cardiorespiratory benefits over placebo in isoflurane-anesthetized dogs.

  1. Fine needle aspiration cytology of an ovarian luteinized follicular cyst mimicking a granulosa cell tumor. A case report.

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    Dejmek, Annika

    2003-01-01

    Fine needle aspiration is a valuable tool in the diagnosis of ovarian cysts, especially in the young and when a nonneoplastic cyst is suspected. High cellularity, epitheliallike clusters and cellular atypia in aspirates from functional cysts are known features that may lead to an erroneous diagnosis of malignancy. Granulosa cells in ovarian cystic fluids may originate in follicular cysts or cystic granulosa cell tumors. In luteinized follicular cysts the cells usually have ample cytoplasm and tend to form clusters. This report draws attention to a case where abundant, dispersed cells lacking cytoplasm led to the incorrect diagnosis of a granulosa cell tumor. In an ovarian cystic aspirate from a 34-year-old woman, the fluid was highly cellular, with a striking predominance of cells interpreted as granulosa cells. Granulosa cells are often found in aspirates from functional cysts, but striking cellularity, prominent nuclear grooves and lack of luteinization made us consider a granulosa cell tumor rather than a follicle-derived cyst. Surgery was performed, and histology revealed a benign serous cystadenoma but also numerous maturing follicles and follicular cysts with thick layers of granulosa cells. The aspirate obviously did not represent the cystadenoma but one of the prominent follicular cysts. An understanding of the cytologic features of functional ovarian cysts, including the pitfalls, is necessary to avoid a false diagnoses of a neoplastic lesion. For a correct interpretation of the cytologic findings, close communication with the clinician and with the radiologist performing the aspiration is of vital importance.

  2. Weight reduction and pioglitazone ameliorate polycystic ovary syndrome after removal of a Sertoli-stromal cell tumor

    Directory of Open Access Journals (Sweden)

    Saito T

    2012-11-01

    Full Text Available Tsuyoshi Baba,1 Toshiaki Endo,1 Keiko Ikeda,1 Ayumi Shimizu,1 Miyuki Morishita,1 Yoshika Kuno,1 Hiroyuki Honnma,2 Tamotsu Kiya,3 Shin-ichi Ishioka,1 Tsuyoshi Saito11Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, 2Asada Ladies Clinic, Kasugai, Aichi, 3Ena Ladies Clinic, Ishikari, Hokkaido, JapanAbstract: This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient's serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient's serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism.Keywords: etiology, hyperandrogenism, pioglitazone, polycystic ovary syndrome, Sertoli-stromal cell tumor, weight reduction

  3. MRI and CT findings of the giant cell tumors of the skull; five cases and a review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwagi, Nobuo [Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-Chome, Higashinari, Osaka 537-0025 (Japan)]. E-mail: kasiwagi-no@mc.pref.osaka.jp; Hirabuki, Norio [Department of Radiology, Yao Municipal Hospital (Japan); Andou, Kumiko [Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawachou, Nishinomiya-city, Hyogo 663-8851 (Japan); Yoshifumi, Narumi [Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-Chome, Higashinari, Osaka 537-0025 (Japan); Tanaka, Hisashi [Department of Radiology, Osaka University Medical School, 2-2 Yamadaoka, 565-0871 Suita-city, Osaka (Japan); Morino, Hideo [Department of Pathology, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki-city, Hyogo (Japan); Taki, Takuyu [Department of Neurosurgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki-city, Hyogo (Japan); Ishikura, Reiichi [Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawachou, Nishinomiya-city, Hyogo 663-8851 (Japan); Hirota, Seiichi [Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawachou, Nishinomiya-city, Hyogo 663-8851 (Japan); Onishi, Hiromitu [Department of Radiology, Osaka University Medical School, 2-2 Yamadaoka, 565-0871 Suita-city, Osaka (Japan); Nakamura, Hironobu [Department of Radiology, Osaka University Medical School, 2-2 Yamadaoka, 565-0871 Suita-city, Osaka (Japan)

    2006-06-15

    Purpose: To investigate CT and MR findings of giant cell tumors (GCTs) of the skull, an unusual site for such tumors. Materials and methods: CT and MR features of five histologically proven giant cell tumors of the skull were retrospectively reviewed. We also reviewed 22 cases in the literature that included MR or CT findings. Results: Three of the tumors originated from the temporal bone with predominantly medial extension, and the other two were centered in the body of the sphenoid bone and featured symmetrical soft tissue extension. CT images with bone window settings showed reactive bone changes for all three tumors of the temporal bone, suggesting slow growth for example, an expanded intradiploic space, expansive remodelling and development of foci of pressure erosion. GCTs of the sphenoid bone showed purely osteolytic changes without remodelling. Although the MR signals and enhancement patterns varied, all the tumors of the temporal bone had a markedly low intensity area on T2-weighted images, which was not seen in the tumors of the sphenoid bone. The findings for our cases generally corresponded to those reported in the literature. Conclusion: Giant cell tumors of the skull have two preferential sites and may have characteristic tendencies as to their extent. Bone changes and MR signals appear to show differences between the two sites.

  4. FLU VACCINATION

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  5. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  6. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  7. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  8. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT be ... What is live, attenuated influenza vaccine-LAIV (nasal spray)?A dose of flu vaccine is recommended every flu season. Children younger ...

  9. The clinical impact of {sup 18}F-FDG PET/CT in extracranial pediatric germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Adam; Vali, Reza; Marie, Eman; Shammas, Amer [The Hospital for Sick Children and University of Toronto, Department of Medical Imaging, Nuclear Medicine, Toronto, ON (Canada); Shaikh, Furqan [The Hospital for Sick Children and University of Toronto, Division of Haematology and oncology, Toronto, ON (Canada)

    2017-10-15

    Extracranial germ cell tumors are an uncommon pediatric malignancy with limited information on the clinical impact of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the literature. The purpose of this study was to evaluate and compare the clinical impact on management of {sup 18}F-FDG PET/CT with diagnostic computed tomography (CT) in pediatric extracranial germ cell tumor. The list of {sup 18}F-FDG PET/CT performed for extracranial germ cell tumor between May 2007 and November 2015 was obtained from the nuclear medicine database. {sup 18}F-FDG PET/CT and concurrent diagnostic CT were obtained and independently reviewed. Additionally, the patients' charts were reviewed for duration of follow-up and biopsy when available. The impact of {sup 18}F-FDG PET/CT compared with diagnostic CT on staging and patient management was demonstrated by chart review, imaging findings and follow-up studies. During the study period, 9 children (5 males and 4 females; age range: 1.6-17 years, mode age: 14 years) had 11 {sup 18}F-FDG PET/CT studies for the evaluation of germ cell tumor. Diagnostic CTs were available for comparison in 8 patients (10 {sup 18}F-FDG PET/CT studies). The average interval between diagnostic CT and PET/CT was 7.2 days (range: 0-37 days). In total, five lesions concerning for active malignancy were identified on diagnostic CT while seven were identified on PET/CT. Overall, {sup 18}F-FDG PET/CT resulted in a change in management in 3 of the 9 patients (33%). {sup 18}F-FDG PET/CT had a significant impact on the management of pediatric germ cell tumors in this retrospective study. Continued multicenter studies are required secondary to the rarity of this tumor to demonstrate the benefit of {sup 18}F-FDG PET/CT in particular clinical scenarios. (orig.)

  10. Continuous Intraoperative Intraperitoneal Hyperthermic Chemoperfusion (CIIPHCP) in the treatment of advanced stage and recurrent granulosa cell tumors. Report of two cases.

    Science.gov (United States)

    Chatzigeorgiou, K; Economou, S; Zafiriou, G; Minopoulos, G; Manolas, K; Chatzigeorgiou, N

    2002-07-01

    Treatment of advanced stages and recurrent ovarian granulosa cell tumors, has not been established yet. The effectiveness of radiation therapy could not be proven. Systemic chemotherapy has shown promising results, but with severe side effects and high incidence of relapse. We report of one patient with advanced stage III C, and one patient with bulky recurrent ovarian granulosa cell tumors. Both patients were treated with a combination of surgical debulking, Continuous Intraoperative Intraperitoneal Hyperthermic Chemoperfusion (CIIPHCP) with Cisplatin and one of them with adjuvant systemic chemotherapy. CIIPHCP appears to offer a promising procedure in addition to surgical debulking and systemic chemotherapy for treatment of advanced or recurrent ovarian granulosa cell tumors. The present report is the first concerning the question of adding Intraoperative Hyperthermic Chemoperfusion in the treatment of advanced or recurrent ovarian granulosa cell tumors.

  11. Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model.

    Science.gov (United States)

    Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David

    2014-08-01

    Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  12. Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors

    OpenAIRE

    Middlebrook, Brooke S.; Eldin, Karen; Li, Xiaohui; Shivasankaran, Sujatha; Pangas, Stephanie A.

    2009-01-01

    Granulosa cell tumors (GCTs) of the ovary are rare sex cord stromal tumors. Although generally indolent, GCTs recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. Very little is known regarding GCT etiology. Because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying GCTs and provide models for developing diagnostic and treatment strategies. We recently developed...

  13. Economics of fusion research

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    1977-10-15

    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics.

  14. Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors

    Science.gov (United States)

    Skotheim, Rolf I.; Schjølberg, Aasa R.; Røislien, Jo; Lothe, Ragnhild A.; Clausen, Ole Petter F.

    2010-01-01

    Background: Testicular germ cell tumors (TGCTs) are characterized by an aneuploid DNA content. Aberrant expression of spindle proteins such as the Aurora kinases and the spindle checkpoint proteins MAD2 and BUB1B, are thought to contribute to the development of chromosomal instability and DNA aneuploidy in cancer. The importance of these spindle proteins remains unknown in the development of TGCTs, thus we have explored the expression levels of these proteins in normal and malignant testicular tissues. Materials and Methods: Using tissue microarrays the expression levels of Aurora kinase A (AURKA), Aurora kinase B (AURKB), BUB1B and MAD2 were measured in normal, preneoplastic and malignant testicular tissues of different histological subtypes from 279 orchidectomy specimens by means of immunohistochemistry. Results: All the spindle proteins except for AURKB were expressed in normal testis. Sixty-eight and 36%, respectively, of the primary spermatocytes in the normal testis were positive for BUB1B and MAD2, while only 5% of the cells were positive for AURKA. There was a significantly lower expression of the spindle checkpoint proteins in carcinoma in situ compared to normal testis (P=0.008 and P=0.043 for BUB1B and MAD2, respectively), while the level of AURKA was increased, however, not significantly (P=0.18). The extent of spindle protein expression varied significantly within the different histological subtypes of TGCTs (P<0.001 for AURKB, BUB1B and MAD2, P=0.003 for AURKA). The expression of AURKA was significantly elevated in both non-seminomas (P=0.003) and seminomas (P=0.015). The level of BUB1B was significantly decreased in non-seminomas (P<0.001). A similar tendency was observed for MAD2 (P=0.11). Conclusions: In carcinoma in situ of TGCTs the spindle checkpoint proteins MAD2 and BUB1B are significantly less expressed compared to normal testis, while the expression of AURKA is increased. We suggest that these changes may be of importance in the transition

  15. Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Burum-Auensen Espen

    2010-01-01

    Full Text Available Background: Testicular germ cell tumors (TGCTs are characterized by an aneuploid DNA content. Aberrant expression of spindle proteins such as the Aurora kinases and the spindle checkpoint proteins MAD2 and BUB1B, are thought to contribute to the development of chromosomal instability and DNA aneuploidy in cancer. The importance of these spindle proteins remains unknown in the development of TGCTs, thus we have explored the expression levels of these proteins in normal and malignant testicular tissues. Materials and Methods: Using tissue microarrays the expression levels of Aurora kinase A (AURKA, Aurora kinase B (AURKB, BUB1B and MAD2 were measured in normal, preneoplastic and malignant testicular tissues of different histological subtypes from 279 orchidectomy specimens by means of immunohistochemistry. Results: All the spindle proteins except for AURKB were expressed in normal testis. Sixty-eight and 36%, respectively, of the primary spermatocytes in the normal testis were positive for BUB1B and MAD2, while only 5% of the cells were positive for AURKA. There was a significantly lower expression of the spindle checkpoint proteins in carcinoma in situ compared to normal testis (P=0.008 and P=0.043 for BUB1B and MAD2, respectively, while the level of AURKA was increased, however, not significantly (P=0.18. The extent of spindle protein expression varied significantly within the different histological subtypes of TGCTs (P< 0.001 for AURKB, BUB1B and MAD2, P=0.003 for AURKA. The expression of AURKA was significantly elevated in both non-seminomas (P=0.003 and seminomas (P=0.015. The level of BUB1B was significantly decreased in non-seminomas (P< 0.001. A similar tendency was observed for MAD2 (P=0.11. Conclusions: In carcinoma in situ of TGCTs the spindle checkpoint proteins MAD2 and BUB1B are significantly less expressed compared to normal testis, while the expression of AURKA is increased. We suggest that these changes may be of importance in the

  16. [Diagnosis and treatment of diffuse tenosynovial giant cell tumor arising from temporomandibular joints].

    Science.gov (United States)

    Meng, J H; Guo, Y X; Luo, H Y; Guo, C B; Ma, X C

    2016-12-18

    To retrospectively analyze the clinical features, treatment and prognosis to the diffuse tenosynovial giant cell tumor (D-TSGCT) arising from the temporomandibular joint (TMJ), and to give a reference for the early diagnosis and treatment of this disease. In this study, 15 patients finally diagnosed as D-TSGCT of TMJ histopathologically at the Peking University Hospital of Stomatology from October 2003 to August 2015 were selected and reviewed. Their clinical manifestations, imaging and histological features, diagnoses and differential diagnoses, treatments and follow-ups were summarized and discussed. D-TSGCT of TMJ showed obvious female predominance (12/15), the main symptoms included painful preauricular swelling or mass, limited mouth-opening and mandibular deviation with movement. D-TSGCT on computed tomography (CT) scan often showed ill-defined soft tissue masses around TMJ, enhancement after contrast administration, usually with widening of the joint spaces and with bone destruction of the condyle, the fossa and even the skull base. On magnetic resonance images (MRI), the majority of lesions on T1 weighted images and T2 weighted images both showed the characteristics of low signals (6/11). The lesions could extend beyond the joints (9/11) and into the infratemporal fossa (4/11) and the middle cranial fossa (4/11). Surgical resection was performed in 14 cases and biopsy in 1 case. Postoperative radiotherapy was performed in 3 cases. In follow-ups, 3 cases showed recurrence postoperatively. D-TSGCT arising from TMJ should be differentiated with TMJ disorders, other tumors and tumor-like lesions of TMJ and parotid neoplasms, etc. CT and MRI examinations have important values in the diagnosis and treatment design of D-TSGCT. Because of the local aggressive and extensive behavior, complete resection should be performed as soon as possible. Postoperative radiotherapy was helpful for the extensive lesions including destruction of skull base and may be a good

  17. Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Atallah, Vincent [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Honore, Charles [Department of Digestive Surgery, Gustave-Roussy Institute, Paris (France); Orbach, Daniel; Helfre, Sylvie [Department of Pediatric Oncology, Curie Institute, Paris (France); Ducassou, Anne [Department of Radiation Oncology, Universitary Cancer Institute, Toulouse (France); Thomas, Laurence [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Levitchi, Mihai-Barbu [Department of Radiation Oncology, Alexis-Vautrin Center, Nancy (France); Mervoyer, Augustin [Department of Radiation Oncology, Cancerologie de l' ouest Institute, Nantes (France); Naji, Salem [Department of Radiation Oncology, Paoli-Calmette Institute, Marseille (France); Dupin, Charles [Department of Radiation Oncology, Universitary Hospital, Bordeaux (France); Bosco-Levy, Pauline J. [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Philippe-Chomette, Pascale [Department of Pediatric Surgery, University Paris 7 Denis Diderot, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris (France); Kantor, Guy; Henriques de Figueiredo, Benedicte [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Sunyach, Marie-Pierre [Department of Radiation Oncology, Leon-Berard Center, Lyon (France); Sargos, Paul, E-mail: p.sargos@bordeaux.unicancer.fr [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France)

    2016-07-15

    Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

  18. Risk stratification for venous thromboembolism in patients with testicular germ cell tumors.

    Directory of Open Access Journals (Sweden)

    Angelika Bezan

    Full Text Available Patients with testicular germ cell tumors (TGCT have an increased risk for venous thromboembolism (VTE. We identified risk factors for VTE in this patient cohort and developed a clinical risk model.In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich.Venous thromboembolic events occurred in 34 (5.2% patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS and a retroperitoneal lymphadenopathy (RPLN were the strongest predictors of VTE (p<0.0001. As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence: cS IA-B 8/463 patients (1.7%, cS IS-IIB 5/86 patients (5.9%, cS IIC 3/21 patients (14.3% and cS IIIA-C 15/70 patients (21.4%. This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence: cS IA-B (0.5%, cS IS-IIB (6.0%, cS IIC (11.1% and cS IIIA-C (19.1%. Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007.According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy.

  19. The histogenic origin of melanoma arising in respiratory epithelium of a teratomatous germ cell tumor of the mediastinum: an enigma unraveled from an unlikely source.

    Science.gov (United States)

    McNab, Patricia; Quigley, Brian; Mendoza, Tania; Hakam, Ardeshir; Khalil, Farah; Fishman, Mayer; Altiok, Soner

    2012-01-01

    Mixed germ cell tumors are rare neoplasms that are known to occur in the anterior mediastinum. Characterized by two or more types of germ cell components, these tumors comprise upwards of 25% of mediastinal germ cell tumors. Even rarer are those harboring somatic-type malignancies such as carcinoma, sarcoma, and hematopoietic malignancies. To date, however, there are no known cases of melanoma arising in a malignant mixed germ cell tumor of the anterior mediastinum. We describe the first case of malignant melanoma with spindle and epithelioid components arising from respiratory epithelium in a mediastinal malignant mixed germ cell tumor of a 32-year-old male. In addition, we also provide evidence supporting the theory of neuroendocrine cells as the origin of melanoma arising in the respiratory epithelium. This case emphasizes the need to carefully evaluate all germ cell tumors, not only for a myriad of benign embryological components, but also for malignancies arising in these components, as they might change the prognosis and patient's course of treatment. This microscopic approach should bring to light the diversity of mixed germ cell tumors in addition to somatic malignancies with corresponding biologic potentials.

  20. Cancer Vaccines

    Science.gov (United States)

    ... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...