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Bhadra, Sanchita, Mary M. Lozano, and Jaquelin P. Dudley. "BALB/Mtv-Null Mice Responding to Strong Mouse Mammary Tumor Virus Superantigens Restrict Mammary Tumorigenesis." Journal of Virology 83, no. 1 (October 15, 2008): 484–88. http://dx.doi.org/10.1128/jvi.01374-08.
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ABSTRACT The absence of endogenous mouse mammary tumor viruses (MMTVs) in the congenic mouse strain, BALB/Mtv-null, restricts the early steps of exogenous C3H MMTV infection, preventing the superantigen (Sag) response and mammary tumorigenesis. Here we demonstrate that BALB/Mtv-null mice also resist tumor induction by FM MMTV, which encodes a stronger Sag compared to C3H MMTV. In contrast to infections with C3H MMTV, Mtv-null mice show FM-MMTV Sag-specific responses comparable to those observed in susceptible BALB/c mice. Neither virus shows significant replication in the spleen or mammary gland. Thus, Mtv-null mice restrict MMTV replication and mammary tumorigenesis even after a robust Sag response.
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Matsuzawa, A., H. Nakano, S. Sakamoto, T. Yoshimoto, and H. Nariuchi. "Dramatic hyperplasia of mtv-2+ lymph node grafts in mtv-2- recipients and selective stimulation of V beta 14+ T cells in recipients' lymph nodes in the DDD mouse." Journal of Immunology 154, no. 4 (February 15, 1995): 1644–52. http://dx.doi.org/10.4049/jimmunol.154.4.1644.
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Abstract DDD/1 (DDD) mice contrast strikingly with DDD-mtv-2/mtv-2 (DDD-mtv-2) congenics in their marked lymph node (LN) T cell paucity. To clarify the possible difference in LN function between them, reciprocal LN grafting experiments were conducted. DDD-mtv-2 LN grafts in DDD recipients underwent hyperplasia as dramatic as 10-to 20-fold increase in weight between 3 and 4 wk after implantation. Lymphoid cells in hyperplastic LN grafts were of recipient origin. Similar hyperplasia of mtv-2-heterozygous LN grafts also occurred on various hybrid backgrounds involving DDD mice. Moreover, LN grafts from BALB/c mice infected with mtv-2-derived exogenous mouse mammary tumor virus (MMTV) swelled in MMTV-free BALB/c recipients. Genetic analysis of DDD x (DDD x DDD-mtv-2)F1 backcross progeny demonstrated that LN hyperplasia was closely linked to mtv-2. The frequencies of V beta 5+ and V beta 8+ T cells unresponsive to mtv-2-encoded superantigen (SAg) changed with practically the same kinetics in both LN grafts and recipients' LN. Thus, the cells responsible for LN hyperplasia were polyclonal. V beta 14+ CD4+ cells responsive to mtv-2 SAg were specifically stimulated in recipients' LN but selectively deleted in hyperplastic LN grafts. DDD mice carrying hyperplastic mtv-2+ LN grafts or pretreated with mtv-2+ spleen cells developed an unresponsive state in terms of influx of mtv-2- lymphoid cells into mtv-2+ LN grafts. These results indicate that mtv-2 gene products including SAg may stimulate mtv-2- lymphoid cells of recipients and cause them to migrate into mtv-2+ LN grafts in a nonspecific manner with resulting LN hyperplasia.
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Rudy, C. K., E. Kraus, E. Palmer, and B. T. Huber. "Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7." Journal of Experimental Medicine 175, no. 6 (June 1, 1992): 1613–21. http://dx.doi.org/10.1084/jem.175.6.1613.
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Mls-1 is an endogenous superantigen that leads to in vivo deletion and in vitro stimulation of T cell receptor (TCR) V beta 6-, 7-, 8.1-, and 9-expressing cells. The MA/MyJ mouse deletes the identical set of TCR from its mature T cell repertoire; however, it does not contain Mtv-7, the murine mammary tumor provirus (MMTV), whose sag gene encodes Mls-1. Interestingly, the superantigen activity of this mouse strain segregates with a new mammary tumor provirus, Mtv-43, not seen in other inbred strains. The predicted amino acid sequence of the sag gene of Mtv-43 was compared with that of Mtv-7. Strikingly, the COOH terminus of the two molecules is very similar, while all other MMTV-encoded superantigens differ 100% in this segment.
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Waanders, G. A., A. N. Shakhov, W. Held, O. Karapetian, H. Acha-Orbea, and H. R. MacDonald. "Peripheral T cell activation and deletion induced by transfer of lymphocyte subsets expressing endogenous or exogenous mouse mammary tumor virus." Journal of Experimental Medicine 177, no. 5 (May 1, 1993): 1359–66. http://dx.doi.org/10.1084/jem.177.5.1359.
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Murine T cell reactivity with products of the minor lymphocyte stimulatory (Mls) locus correlates with the expression of particular variable (V) domains of the T cell receptor (TCR) beta chain. It was recently demonstrated that Mls antigens are encoded by an open reading frame (ORF) in the 3' long terminal repeat of either endogenous or exogenous mouse mammary tumor virus (MMTV). Immature thymocytes expressing reactive TCR-V beta domains are clonally deleted upon exposure to endogenous Mtv's. Mature T cells proliferate vigorously in response to Mls-1a (Mtv-7) in vivo, but induction of specific anergy and deletion after exposure to Mtv-7-expressing cells in the periphery has also been described. We show here that B cells and CD8+ (but not CD4+) T cells from Mtv-7+ mice efficiently induce peripheral deletion of reactive T cells upon transfer to Mtv-7- recipients, whereas only B cells stimulate specific T cell proliferation in vivo. In contrast to endogenous Mtv-7, transfer of B, CD4+, or CD8+ lymphocyte subsets from mice maternally infected with MMTV(SW), an infectious homologue of Mtv-7, results in specific T cell deletion in the absence of a detectable proliferative response. Finally, we show by secondary transfers of infected cells that exogenous MMTV(SW) is transmitted multidirectionally between lymphocyte subsets and ultimately to the mammary gland. Collectively our data demonstrate heterogeneity in the expression and/or presentation of endogenous and exogenous MMTV ORF by lymphocyte subsets and emphasize the low threshold required for induction of peripheral T cell deletion by these gene products.
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Baribaud, Frédéric, Susanne Wirth, Ivan Maillard, Sandrine Valsesia, Hans Acha-Orbea, and Heidi Diggelmann. "Identification of Key Amino Acids of the Mouse Mammary Tumor Virus Superantigen Involved in the Specific Interaction with T-Cell Receptor Vβ Domains." Journal of Virology 75, no. 16 (August 15, 2001): 7453–61. http://dx.doi.org/10.1128/jvi.75.16.7453-7461.2001.
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ABSTRACT Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class II by the variable region of the beta chain (Vβ) of the T-cell receptor. The C-terminal 30 to 40 amino acids of the superantigen of different MMTVs display high sequence variability that correlates with the recognition of particular T-cell receptor Vβ chains. Interestingly, MMTV(SIM) andmtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor Vβ specificities. To determine the importance of these few differences for specific Vβ interaction, we studied superantigen responses in mice to chimeric and mutant MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We show that only a few changes (two to six residues) within the C terminus are necessary to modify superantigen recognition by specific Vβs. Thus, the introduction of the MMTV(SIM) residues 314-315 into themtv-8 superantigen greatly decreased its Vβ12 reactivity without gain of MMTV(SIM)-specific function. The introduction of MMTV(SIM)-specific residues 289 to 295, however, induced a recognition pattern that was a mixture of MMTV(SIM)- and mtv-8-specific Vβ reactivities: both weak MMTV(SIM)-specific Vβ4 and fullmtv-8-specific Vβ11 recognition were observed while Vβ12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8superantigen established normal MMTV(SIM)-specific Vβ4 reactivity and completely abolished mtv-8-specific Vβ5, -11, and -12 interactions. These new functional superantigens with mixed Vβ recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor Vβ domain within the 30 C-terminal residues of the viral superantigen.
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Foo-Phillips, M., C. A. Kozak, M. A. Principato, and R. Abe. "Characterization of the Mlsf system. II. Identification of mouse mammary tumor virus proviruses involved in the clonal deletion of self-Mlsf-reactive T cells." Journal of Immunology 149, no. 11 (December 1, 1992): 3440–47. http://dx.doi.org/10.4049/jimmunol.149.11.3440.
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Abstract The genetic linkage of loci encoding stimulatory Mlsa and Mlsc determinants with proviruses of mouse mammary tumour viruses (MMTV) has been shown. We previously have reported that the ligand(s) for V beta 5, V beta 11, and V beta 12 behaves as a novel minor lymphocyte-stimulating (Mls) determinant(s), Mlsf, to induce the strong proliferation of unprimed T cells, and that this ligand(s) also functions as a self-Ag for the clonal deletion of self-reactive T cells. In the accompanying paper (Part I), a unique polymorphism characteristic of the Mlsf gene product is presented. In order to determine the genetic basis for this novel Mls system, we examined the progeny of multiple genetic crosses to identify the MMTV proviral loci involved in the clonal deletion of self-Mlsf-reactive T cells. Results from these investigations indicated that at least three known MMTV proviruses, Mtv-8, Mtv-9, and Mtv-11 are involved in the expression of Mlsf gene products. Presence of Mtv-9 results in the complete deletion of V beta 5, V beta 11, and V beta 12; Mtv-8 is associated with the complete deletion of V beta 12, but only a partial deletion of V beta 11 (primarily CD4-positive T cell subset) with little or no deletion of V beta 5; and Mtv-11 induces the complete deletion of V beta 11 and V beta 12, but no deletion of V beta 5. Given the significant sequence homology in the C-terminal portion of the open reading frame (ORF) region among these three MMTV and the almost equivalent effect of these three MMTV provirus upon the V beta 12 repertoire, their apparent hierarchic effect upon the V beta 5 and V beta 11 repertoires suggests that affinity differences in recognition of the same determinant by different TCR V beta may play a significant role in the clonal deletion of self-reactive T cells.
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Kang, J., E. Ido, J. Pawling, U. Beutner, B. T. Huber, and N. Hozumi. "Expression of Mtv-7 sag gene in vivo using a retroviral vector results in selective inactivation of superantigen reactive T cells." Journal of Immunology 152, no. 3 (February 1, 1994): 1039–46. http://dx.doi.org/10.4049/jimmunol.152.3.1039.
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Abstract T cells expressing specific TCR V beta chains are intrathymically eliminated in mice expressing the murine Mls (minor lymphocyte stimulating) superantigens. Recently, in vitro studies have shown that the endogenous mouse mammary tumor virus (MMTV)-7 sag gene encodes Mls-1 Ag. The demonstrated ability of MMTV superantigen proteins to react with TCRs has led to the postulate that other infectious retroviruses may use superantigen-like molecules to modify the host's immune system. In this report, successful retrovirus-mediated Mtv-7 sag gene transfer into pluripotent hematopoietic stem cells is described. In two different strains of Mls-1- host mice (CBA/Ca and BALB/c) reconstituted with Mtv-7 sag gene expressing bone marrow cells, low levels of ectopic Mtv-7 sag gene expression on syngeneic donor hematopoietic stem cell-derived population alone can induce partial clonal deletion of Mls-1 reactive V beta 6+ and V beta 8.1+ T cells, and complete clonal inactivation of V beta 8.1+ T cells.
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Whitney, J. "TV needs MTV like MTV needs computers." ACM SIGGRAPH Computer Graphics 21, no. 1 (January 1987): 9–11. http://dx.doi.org/10.1145/24548.24550.
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Viatra, Aji Windu. "ANALISIS TANDA VISUAL CHANNEL IDENTITY MTV (MUSIC TELEVISION) INDONESIA." Jurnal Dimensi DKV Seni Rupa dan Desain 5, no. 1 (April 1, 2020): 33. http://dx.doi.org/10.25105/jdd.v5i1.6861.
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<p><strong> Abstract</strong></p><p>The Analysis of MTV (Music Television) Indonesia Channel Identity Visual Symbol. Channel identity can create picture, image, character and identity of a television station. MTV has made the best use of this form of corporate promotion program. Through their channel identity, MTV created images and pictures in accordance with their basic concepts. This research analyzed the MTV (Music Television) channel identity and logo. The analysis procedure carried on the MTV logos including MTV Indonesia, MTV China, MTV Russia, MTV United Kingdom, MTV Japan, and MTV India. This study used a multidisciplinary approach namely the historical, aesthetics, and semiotics approach. The method used in this research was qualitative method, with analytic descriptive analysis. The data was collected through literature study and observation. The data then grouped according to the basic concepts of MTV local culture exploration, and studied by looking at the process of visual idiom design concepts, shapes, characters, colors, and work techniques. The result of this research is interpretation of the visual sign and meaning of the MTV logo as a visual communication media and mass communication which contained certain value and meaning to persuate their audiens.</p><p> </p><p><br /><strong>Abstrak</strong></p><p>Analisis Tanda Visual Channel Identity MTV (Music Television) Indonesia. Channel identity stasiun televisi dapat membentuk citra, image, karakter dan menjadi identitas sebuah stasiun televisi. MTV telah memanfaatkan sebaik mungkin bentuk program promosi korporat ini. Melalui channel identity, MTV membentuk image dan citra sesuai dengan konsep dasar yang dimiliki. Penelitian ini menganalisis channel identity dan logo stasiun televisi MTV (Music Television). Analisis makna dilakukan pada logo MTV beberapa negara yaitu MTV Indonesia, MTV China, MTV Rusia, MTV United Kingdom, MTV Jepang, dan MTV India. Kajian ini menggunakan pendekatan multidisplin, yakni pendekatan historis, estetika, dan semiotika. Metode penelitian yang digunakan adalah metode kualitatif, dengan analisis deskriptif analitik. Data dikumpulkan melalui studi pustaka dan observasi. Data dikelompokkan sesuai dengan konsep dasar eksplorasi budaya lokal MTV, yang akan dikaji dengan melihat pada proses konsep perancangan idiom visual, bentuk, karakter, warna, dan teknik pengerjaan. Hasil dari penelitian ini adalah interpretasi makna tanda-tanda visual yang digunakan pada logo MTV sebagai media komunikasi visual dan komunikasi massa yang mengandung nilai dan makna tertentu sebagai langkah persuasi kepada pemirsanya. Kata kunci: channel identity, logo, MTV (music television), MTV Indonesia<br />*) J</p>
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Mohan, N., D. Mottershead, M. Subramanyam, U. Beutner, and B. T. Huber. "Production and characterization of an Mls-1-specific monoclonal antibody." Journal of Experimental Medicine 177, no. 2 (February 1, 1993): 351–58. http://dx.doi.org/10.1084/jem.177.2.351.
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Superantigens (SAGs) represent a new class of antigens, characterized as T cell receptor (TCR) V beta-reactive elements. Bacterial toxins constitute the major group of exogenous SAGs, while the mouse mammary tumor virus (MMTV)-encoded Mls molecules represent the endogenous SAGs. Mls-1 is the prototype of the latter SAGs, because it elicits a very potent T cell stimulatory response in vitro in unprimed T cells expressing the TCR V beta 6 or 8.1 chains. In vivo, Mls-1 causes deletion of immature T cells bearing the V beta 6, 7, 8.1, or 9 chains. Although Mls-1 was functionally discovered > 20 yr ago, it has not been possible to raise antibodies against this molecule. We have previously cloned and sequenced the Mtv-7 sag gene, which encodes Mls-1. Sequence comparisons with other MMTV sag genes suggested that the polymorphic 3' end encodes the TCR V beta specificity of these SAGs. We have, therefore, immunized hamsters with a 14-amino acid peptide from the deduced COOH-terminal sequence of the Mtv-7 sag gene. We describe here the production of a monoclonal antibody (mAb), 3B12, which is peptide specific and reacts with a recombinant baculovirus product of Mtv-7 sag. This mAb blocks Mls-1-specific T cell recognition and detects the Mls-1 protein on the surface of the B cell hybridoma LBB.A, but not on LBB.11, which is an Mtv-7 loss variant of LBB.A. Transfection of the Mtv-7 sag gene into LBB.11 renders this cell functionally Mls-1+ as well as positive for 3B12 binding, confirming the specificity of this mAb. It is well documented that B cells and CD8+ T cells express T cell stimulatory Mls-1 determinants, and we show here that this functional profile correlates with the expression of MMTV-specific mRNA. However, primary lymphocytes derived from Mls-1+ mice do not stain with 3B12, even after in vitro activation with mitogens or phorbol ester.
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Weinstein, Deena, R. Serge Denisoff, and E. Ann Kaplan. "Inside MTV." Contemporary Sociology 18, no. 3 (May 1989): 415. http://dx.doi.org/10.2307/2073875.
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Polan, Dana. "Sz/Mtv." Journal of Communication Inquiry 10, no. 1 (January 1986): 48–54. http://dx.doi.org/10.1177/019685998601000105.
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Berg, Bryan, and Dianne Turner. "MTV unleashed." TechTrends 38, no. 3 (April 1993): 28–31. http://dx.doi.org/10.1007/bf02763795.
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Eicher, E. M., and B. K. Lee. "The NXSM recombinant inbred strains of mice: genetic profile for 58 loci including the Mtv proviral loci." Genetics 125, no. 2 (June 1, 1990): 431–46. http://dx.doi.org/10.1093/genetics/125.2.431.
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Abstract We report the construction of 17 recombinant inbred (RI) strains of mice derived from the progenitor strains NZB/BINRe and SM/J and the typing of this RI strain set, designated NXSM, for 58 loci distributed on 16 autosomes and the X chromosome. Two backcrosses involving NZB/BINJ and SM/J were constructed to confirm chromosomal assignments and determine gene orders suggested from NXSM RI strain data. From these results we recommend that chromosomal assignments and gene orders suggested from analyses of RI strain sets be confirmed using data obtained by other means. We also typed NZB/BINJ and SM/J for mammary tumor proviral (Mtv) loci. Both strains share three previously described Mtv loci: Mtv-7, Mtv-14 and Mtv-17. In addition, NZB/BINJ contains the previously described Mtv-3 and Mtv-9 loci and two new Mtv proviral loci: Mtv-27 located on chromosome (Chr) 1 and Mtv-28 located on the X chromosome. SM/J contains the previously described loci Mtv-6 and Mtv-8. Four LTR, mink cell focus-forming murine leukemia viral loci were identified and mapped: Ltrm-1 on Chr 12, Ltrm-2 on Chr 16, Ltrm-3 on Chr 5, and Ltrm-4 on Chr 13. The Tgn locus was positioned proximal to the Ly-6 locus on Chr 15.
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Barnett, Anna, Farah Mustafa, Thomas J. Wrona, Mary Lozano, and Jaquelin P. Dudley. "Expression of Mouse Mammary Tumor Virus Superantigen mRNA in the Thymus Correlates with Kinetics of Self-Reactive T-Cell Loss." Journal of Virology 73, no. 8 (August 1, 1999): 6634–45. http://dx.doi.org/10.1128/jvi.73.8.6634-6645.1999.
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ABSTRACT Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is expressed at the surface of antigen-presenting cells in conjunction with major histocompatibility complex (MHC) type II molecules. The Sag-MHC complex is recognized by entire subsets of T cells, leading to cytokine release and amplification of infected B and T cells that carry milk-borne MMTV to the mammary gland. Expression of Sag proteins from endogenous MMTV proviruses carried in the mouse germ line usually results in the deletion of self-reactive T cells during negative selection in the thymus and the elimination of T cells required for infection by specific milk-borne MMTVs. However, other endogenous MMTVs are unable to eliminate Sag-reactive T cells in newborn mice and cause partial loss of reactive T cells in adults. To investigate the kinetics of Sag-reactive T-cell deletion, backcross mice that contain single or multiple MMTVs were screened by a novel PCR assay designed to distinguish among highly related MMTV strains. Mice that containedMtv-17 alone showed slow kinetics of reactive T-cell loss that involved the CD4+, but not the CD8+, subset. Deletion of CD4+ or CD8+ T cells reactive with Mtv-17 Sag was not detected in thymocytes. Slow kinetics of peripheral T-cell deletion by Mtv-17 Sag also was accompanied by failure to detect Mtv-17 sag-specific mRNA in the thymus, despite detectable expression in other tissues, such as spleen. Together, these data suggest thatMtv-17 Sag causes peripheral, rather than intrathymic, deletion of T cells. Interestingly, the Mtv-8 provirus caused partial deletion of CD4+Vβ12+ cells in the thymus, but other T-cell subsets appeared to be deleted only in the periphery. Our data have important implications for the level of antigen expression required for elimination of self-reactive T cells. Moreover, these experiments suggest that mice expressing endogenous MMTVs that lead to slow kinetics of T-cell deletion will be susceptible to infection by milk-borne MMTVs with the same Sag specificity.
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Sayama, Kazutoshi, Tetsuya Kaneko, and Akio Matsuzawa. "Pregnancy dependence of mammary tumours in DDD mice congenic for Mtv-2, DDD/1-Mtv-2/Mtv-2." Laboratory Animals 28, no. 1 (January 1, 1994): 44–49. http://dx.doi.org/10.1258/002367794781065889.
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Mammary tumours developed in 110 (95.7%) of 115 DDD/1- Mtv-2/Mtv-2 (DDD/1- Mtv-2) and 24 (47·1%) of 51 DDD/1fDDD/1- Mtv-2 (DDD/1f Mtv-2) force-bred female mice during a one-year period. The mean tumour age±SE was 220±7 and 269±7 days, respectively. These tumours were examined for responsiveness to pregnancies by comparing their growth after transplantation between virgin and breeding recipients. Of 73 tumours from DDD/1- Mtv-2 mice, 9 (12%) were completely pregnancy-dependent (CPD), 3 (4%) pregnancy-dependent (PD), 9 (12%) pregnancy-responsive (PR), and 52 (71%) pregnancy-independent (PD), and of 25 tumours from DDD/1f Mtv-2 mice, one (4%) was CPD, one (4%) PR, and 23 (92%) PI. Although most tumours were heterogeneous in morphology and there was no clear relation between morphology and PO properties, most CPD tumours were type P and considered to be connected with mammary plaques. When 9 CPD tumours from DDD/1- Mtv-2 mice were serially transplanted in breeders, 6, 2 and one progressed to lose pregnancy dependence within 3, 8 and 18 generations, respectively. DDD/1- Mtv-2 mice will provide a model for studies on progression of mammary tumours from hormone-dependent to autonomous states.
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Ardavín, C., G. Waanders, I. Ferrero, F. Anjuère, H. Acha-Orbea, and H. R. MacDonald. "Expression and presentation of endogenous mouse mammary tumor virus superantigens by thymic and splenic dendritic cells and B cells." Journal of Immunology 157, no. 7 (October 1, 1996): 2789–94. http://dx.doi.org/10.4049/jimmunol.157.7.2789.
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Abstract Tolerance against superantigens (SAgs) encoded by endogenous mouse mammary tumor virus (Mtv) loci involves the intrathymic deletion of SAg-reactive T cells expressing a particular TCR V beta-chain, presumably upon presentation of the SAg by specialized APC. However, although the role of dendritic cells (DC) in the induction of tolerance against conventional Ags has been demonstrated, little is known about the role played by DC in tolerance induction against Mtv SAgs. Moreover, there is conflicting evidence concerning the capacity of DC to express and present Mtv SAgs. In this report we have analyzed the expression of Mtv SAgs in highly purified thymic and splenic DC and B cells by reverse transcriptase-PCR, using primers amplifying Mtv SAg-specific spliced mRNAs. DC express Mtv SAgs at levels comparable to B cells, but display a differential expression pattern of the various Mtv loci compared with B cells. Furthermore, our results show that DC are able to induce the deletion of SAg-reactive thymocytes in an in vitro assay, indicating that Mtv SAgs are functionally expressed on the DC surface. Collectively, our data are consistent with the hypothesis that DC play a role in the induction of intrathymic tolerance to Mtv SAgs.
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Roengvoraphoj, Olarn, Arteda Gjika, Erik Mille, Julian Taugner, Lukas Käsmann, Chukwuka Eze, Claus Belka, and Farkhad Manapov. "The impact of residual metabolic primary tumor volume after completion of thoracic irradiation in patients with inoperable stage III NSCLC." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 9049. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.9049.
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9049 Background: The metabolic tumor volume (MTV) is a functional and volumetric PET/CT parameter that has been investigated in recent years with respect to its predictive and prognostic value in different tumor entities. In this study, we investigated the role of residual MTV after completion of thoracic irradiation in inoperable stage III non-small cell lung cancer (NSCLC). Methods: We analyzed retrospective and prospective data of 56 patients with inoperable stage III NSCLC treated with chemoradiotherapy (CRT) and chemoradioimmunotherapy (CRT-IO). All patients received an 18F-FDG-PET/CT 3 to max. 6 months after completion of thoracic irradiation. The measurement of the residual MTV of the primary tumor was performed by calculating the SUVmean of the liver + 2SD as threshold. The patients were divided into the following groups: residual-MTV < 1ml; residual-MTV 1-25ml and residual-MTV > 26ml. Survival, local recurrence, and distant metastasis rates were calculated using the Kaplan-Meier method from the last day of thoracic irradiation. Results: The median follow-up was 45 months (range 16-74) in the CRT group and 16 months in the CRT-IO group (range13-19). Twenty-two (39%) patients had a residual MTV < 1ml (1st group), 19 (34%) a residual MTV between 1-25ml (2nd group) and 15 (27%) a residual MTV > 25ml (3rd group) after completion of thoracic irradiation. Median overall survival was 61, 20 and 12 months (p = 0.006) in the 1st, 2nd and 3rd groups, respectively. 12-month survival was 86%, 50% and 33% after CRT vs. 88%, 71% and 50% after CRT-IO in the 1st, 2nd and 3rd groups, respectively. The median time to in-field recurrence in the 1st, 2nd and 3rd groups was 51, 20 and 15 months (p = 0.011). The prognostic value of the residual MTV on OS was confirmed exclusively in the CRT patient cohort (p = 0.04), but not in the CRT-IO patient cohort (p = 0.174). Residual MTV demonstrated no influence on the local recurrence rate in the CRT-IO patient cohort, but only in patients treated with CRT (p = 0.007). Conclusions: Patients with inoperable stage III NSCLC in whom the residual MTV was < 1ml after completion of thoracic irradiation showed significantly better survival than patients with a residual MTV of 1-25ml and MTV > 25ml. The subgroup analysis confirmed the prognostic value of residual MTV only in patients who received chemoradiotherapy without consolidation immunotherapy.
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Morishima, C., C. Norby-Slycord, K. R. McConnell, R. J. Finch, A. J. Nelson, A. G. Farr, and A. M. Pullen. "Expression of two structurally identical viral superantigens results in thymic elimination at distinct developmental stages." Journal of Immunology 153, no. 11 (December 1, 1994): 5091–103. http://dx.doi.org/10.4049/jimmunol.153.11.5091.
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Abstract Mouse mammary tumor virus proviral integrants encode superantigens. Developing thymocytes bearing TCRs with particular V beta elements encounter these endogenous viral superantigens as self molecules in the thymus and are consequently clonally eliminated. To study this mechanism of tolerance induction, we have bred B10.BR-Mtv-1 and B10.BR-Mtv-6 mice, which carry either Mtv-1 or Mtv-6 proviruses but are otherwise genetically identical. The protein products of these mouse mammary tumor virus integrants, vSAG1 and vSAG6, both interact with V beta 3+ T cells and have identical amino acid sequences. Interestingly, vSAG6 expression results in the complete deletion of V beta 3+ peripheral T cells, whereas vSAG1 expression results in only partial deletion. Flow cytometric analyses indicate that B10.BR-Mtv-6 mice delete V beta 3+ thymocytes at the immature CD4+8+ stage, whereas B10.BR-Mtv-1 mice delete only mature CD4+ or CD8+ cells. In addition, the two strains exhibit different time courses of thymic deletion: neonatal B10.BR-Mtv-6 mice eliminate V beta 3+ T cells by day 2, in contrast to B10.BR-Mtv-1 mice in which deletion does not occur until day 15. RNase protection assays demonstrate that B10.BR-Mtv-6 mice have significantly greater thymic vSAG6 mRNA expression levels than vSAG1 levels in B10.BR-Mtv-1 animals, correlating with a more complete deletion of reactive thymocytes at an earlier point in the maturational sequence.
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Moore, N. C., G. Anderson, D. E. McLoughlin, J. J. Owen, and E. J. Jenkinson. "Differential expression of Mtv loci in MHC class II-positive thymic stromal cells." Journal of Immunology 152, no. 10 (May 15, 1994): 4826–31. http://dx.doi.org/10.4049/jimmunol.152.10.4826.
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Abstract Despite the important role played by endogenous superantigen in shaping the T cell repertoire, little is known concerning the expression of the different Mtv loci in cells of the thymic microenvironment involved in repertoire selection. Here we have examined the expression of a panel of Mtv Ags by different MHC class II+ stromal cel types using reverse transcriptase-PCR and monitored the effects of these stromal cells on the development of cells expressing Mtv-reactive TCR V beta elements in closed thymic organ culture systems. Although Mtv-6 and Mtv-8/9 mRNAs are expressed in normal thymus lobe organ cultures, no Mtv expression was detected in MHC class II+ thymic epithelial cells. In contrast a striking pattern of differential expression was observed in dendritic cells of thymic origin that were devoid of Mtv-8/9 but expressed readily detectable levels of Mtv-6. This pattern of Mtv gene expression correlated well with TCR V beta repertoire development. TCRV beta 3+ T cells, normally deleted in response to Mtv-6, were virtually absent from the single positive thymocyte compartment in thymic organ cultures where dendritic cells are present but were present in reaggregate cultures where the only MHC class II-positive cells were thymic epithelial cells. On the other hand, V beta 11+ T-cells were not deleted in organ cultures, possibly reflecting the absence of Mtv-8/9 expression in dendritic cells. Our studies suggest that the influence Mtvs have on shaping the T cell repertoire not only depends on their expression within a particular strain but also on their tissue specific expression in relation to MHC class II, which is necessary for their presentation.
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Voltin, Conrad-Amadeus, Jasmin Mettler, Horst Mueller, Michael Fuchs, Christian Baues, Markus Dietlein, Andreas Engert, Peter Borchmann, Carsten Kobe, and Paul J. Bröckelmann. "Metabolic Tumor Volume for Early Response Assessment in Early-Stage Unfavorable Hodgkin Lymphoma Treated with Nivolumab in the GHSG Nivahl Phase II Trial." Blood 134, Supplement_1 (November 13, 2019): 4020. http://dx.doi.org/10.1182/blood-2019-123641.
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Background: Metabolic tumor volume (MTV) measured by FDG-PET/CT is becoming established as an independent risk factor for treatment failure in Hodgkin lymphoma (HL). Moreover, response to treatment with novel agents including checkpoint inhibitors may be better reflected by a decrease in MTV than by currently used response criteria. Our aim was to evaluate the early response to first-line HL treatment with the PD-1 inhibitor nivolumab using MTV. Methods: The analysis set included 59 patients with newly diagnosed, early-stage unfavorable HL treated within the prospective, multicenter, open label, randomized, phase II NIVAHL trial of the German Hodgkin Study Group (GHSG). Patients in NIVAHL were randomized to receive either four double cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine (4x Nivo-AVD, group A, n=31) or a sequential therapy starting with 4x nivolumab monotherapy followed by 2xNivo-AVD and 2x AVD (group B, n=28). Early response to treatment was assessed at a 1st interim restaging after either 2x Nivo-AVD or 4x nivolumab. All NIVAHL patients who underwent PET at both initial staging and early response assessment, with images available to the central review panel for quantitative analysis before April 30th 2019, were included. MTV was calculated using a fixed SUV threshold of 4 for both staging and restaging. Results: Patient characteristics of the MTV analysis subset presented here did not differ in any relevant way from the overall NIVAHL trial population. Median age of the 59 patients was 27 years (range 18-57) with a female predominance (61%). All patients presented with stage II disease (IIB 27%) and ≥3 involved areas was the most common risk factor (75%) followed by elevated erythrocyte sedimentation rate (51%), extranodal disease (17%) and large mediastinal mass (14%). Mean MTV at initial staging was 124 ml (range 4 - 578 ml) and 177 ml (11 - 581 ml) in groups A and B, respectively. In both groups a marked decrease in MTV was observed at the 1st interim restaging (Figure 1): After 2x Nivo-AVD all patients in group A showed a reduction of MTV >80% (mean percentage change in MTV -99.8%). In group B a reduction of MTV >80% was observed in 26/28 patients (93%), while in 2/28 patients an increase <10% was observed (mean percentage change in MTV -91%; Figure 1). The mean residual MTV at interim restaging after 2x Nivo-AVD was 0.4 ml (range 0 - 8) in group A and 11 ml after 4x nivolumab in group B (range 0 - 176). The reduction of MTV was observed irrespective of initial MTV with a similar mean percentage change in patients above and below the median MTV in both groups. When applying the Deauville score, however, the number of patients presenting with a Deauville score ≥4 was higher in the group with an initial MTV above the median MTV than in the group where initial MTV lay below the median value. Using the Lugano criteria and a Deauville score of 4 or higher as cut-off for PET-positivity, early interim complete remission was observed in 81% of patients after 2xNivo-AVD, as compared to 51% after 4x nivolumab monotherapy. Further analyses regarding MTV and response at the 2nd and end-of-treatment restaging as well as survival data are not yet available due to limited follow-up. These data will be available at the time of presentation and shown at the meeting. Conclusions: Marked reductions of MTV demonstrate an excellent early efficacy for both 2x Nivo-AVD and 4x nivolumab as 1st-line therapy for early-stage unfavorable HL. The unexpectedly and previously unreported high MTV reduction with nivolumab monotherapy indicates a relevant potential of anti-PD1 mono- or debulking-therapy in the 1st-line treatment of early-stage unfavorable HL. Early interim response assessment based on MTV may help to identify HL patients treated with anti-PD1 antibodies in whom a significant reduction or even omission of chemotherapy could be considered. MTV appears to have the potential to accurately measure response to immune checkpoint inhibition. However, correlation of early MTV reduction with response at the end of treatment or with survival data is pending. Disclosures Borchmann: Novartis: Honoraria, Research Funding. Bröckelmann:Bristol-Myers Squibb: Honoraria, Other: Travel Support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD Sharpe & Dohme: Research Funding.
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Naseh, Maryam, Amirreza Dehghanian, Sara Keshtgar, and Farzaneh Ketabchi. "Lung injury in brain ischemia/reperfusion is exacerbated by mechanical ventilation with moderate tidal volume in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 319, no. 2 (August 1, 2020): R133—R141. http://dx.doi.org/10.1152/ajpregu.00367.2019.
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Ischemic stroke is one of the most frequent causes of injury in the central nervous system which may lead to multiorgan dysfunction, including in the lung. The aim of this study was to investigate whether brain ischemia/reperfusion with or without mechanical ventilation leads to lung injury. Male Sprague-Dawley rats were assigned to four groups: Sham, 1-h brain ischemia (MCAO)/24-h reperfusion (I/R), mechanical ventilation with moderate tidal volume (MTV), and I/R+MTV. The pulmonary capillary permeability ( Kfc) was measured in the isolated perfused lung. Mean arterial blood pressure (MAP), heart rate (HR), blood-gas variables, histopathological parameters, lung glutathione peroxidase, and TNF-α were measured. Kfc in the I/R, MTV, and I/R+MTV groups were higher than that in the Sham group. In the I/R, MTV, and I/R+MTV groups, arterial partial pressures of oxygen and the arterial partial pressure of oxygen/fraction of inspired oxygen ratios were lower, whereas arterial partial pressures of carbon dioxide were higher than those in the Sham group. The histopathological score in the I/R group was more than that in the Sham group, and in the MTV and I/R+MTV groups were higher than those in the Sham and I/R groups. Furthermore, there were stepwise rises in TNF-α in the I/R, MTV, and I/R+MTV groups, respectively. There was no significant difference in MAP between groups. However, HR in the MTV group was higher than that in the Sham group. Brain ischemia/reperfusion leads to pulmonary capillary endothelial damage and the impairment of gas exchange in the alveolar-capillary barrier, which is exacerbated by mechanical ventilation with moderate tidal volume partially linked to inflammatory reactions.
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Song, Moo-Kon, Joo-seop Chung, Ho-Jin Shin, Joon Ho Moon, Jeong Ok Lee, Ho Sup Lee, Sang-Min Lee, Gyeong Won Lee, and Suee Lee. "Metabolic Tumor Volume Has Potential Clinical Impact Compared with SUVmax in Primary Gastrointestinal Diffuse Large B Cell lymphoma." Blood 118, no. 21 (November 18, 2011): 4983. http://dx.doi.org/10.1182/blood.v118.21.4983.4983.
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Abstract Abstract 4983 Background: Primary gastrointestinal (GI) lymphoma is the most commonly involved extranodal site and represents 10–15% of all Non-Hodgkin's Lymphoma cases. Recent studies showed that the prognostic value of early 18F-FDG PET using maximum standardized uptake volume (SUVmax) on pretreatment was important prognostic factor in primary GI diffuse large B cell lymphoma (DLBCL). However, initial tumor burden is still an important subject associated with prognosis even extranodal DLBCL. The purpose of this study was to assess the prognostic impact of metabolic tumor volume (MTV) as tumor burden using by PET scan technique compared with initial SUVmax in primary GI DLBCL. Patients and methods: From April, 2006 to July, 2009, 125 stage IE (58 patients) or IIE (67 patients) primary GI DLBCL patients with localized lymph node involvement were enrolled and assigned to 6 or 8 cycles of R-CHOP therapy. Median follow-up was 36 months. Median age was 62 years (range, 20–79 years). Seventy-four patients were male and remainders were female. Numbers of patients above 60 years were 71. Twenty-five patients had an Eastern Cooperative Oncology Group performance status of more than two. Calculatory system by computer automatically delineated a extranodal target lesions above SUV, 2.5 and MTV of GI lesion was 3-dimensional reconstructed by fusion software. The SUVmax was collected from predominant GI lesion and calculated based on the attenuation-corrected images, the amount of injected 18F-FDG and body weight. Results: The extranodal sites of GI tract were included stomach and duodenum (64 patients, 51.2%), jejunum (10 patients, 8%), terminal ileum (30 patients, 24%), cecum (7 patients, 5.6%), ascending colon (8 patients, 6.4%), transverse colon (3 patients, 2.4%) and decending colon (3 patients, 2.4%). We used ROC curve analysis. 158.3cm3 was decided as best ideal cut-off value of MTV and 15.5 was decided as the cut-off value of SUVmax. Several factors (age, sex, disease status and IPI score) between high MTV (≥158.3cm3) and low MTV group (<158.3cm3) were not significantly different. However, SUVmax higher in high MTV group than low MTV group (p<0.001). In response by revised International Workshop Criteria, low MTV group had excellent response rates than high MTV group (CR, p<0.001; PR, p=0.014; SD & PD, p<0.001). Moreover, 3-year PFS was higher in low MTV group than high MTV group (low MTV group, 96.7%; high MTV group, 37.1%; p<0.001) and 3-year OS was also higher in low MTV group than high MTV group (low MTV group, 97.8%; high MTV group, 42.9%; p<0.001). The PFS and OS were higher in low SUVmax group (<15.5) than high SUVmax group (≥15.5) (p<0.001, p<0.001, respectively). In univariate analysis, high IPI score is still important prognostic factor for PFS and OS (PFS: HR, 4.181 [1.844-9.478] p=0.001 & OS: HR, 4.300 [1.801-10.263] p=0.001). High MTV and high SUVmax were also poor prognostic factors for PFS and OS (high MTV; PFS: HR, 26.543 [7.923-88.231] p<0.001 & OS: HR, 32.458 [7.579-139.018] p<0.001) (high SUVmax; PFS: HR, 6.998 [2.399-20.418] p<0.001 & OS: HR, 13.976 [3.257-59.979] p<0.001). In multivariate analysis, high MTV group (PFS: HR, 19.850 [5.193-75.870] p<0.001 & OS: HR, 17.918 [3.694-86.904] p<0.001) and high IPI score (PFS: HR, 2.659 [1.136-6.223] p=0.024 & OS: HR, 2.866 [1.175-6.989] p=0.021) were independent prognostic factors for PFS and OS. However, SUVmax had not significant value for survival. Conclusion: In primary GI DLBCL, high MTV is very important and potential prognostic factor compared with SUVmax for predicting the survival. Therefore, more aggressive treatment strategy would be performed in primary GI DLBCL patients having initial high tumor burden. Disclosures: No relevant conflicts of interest to declare.
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Dean, Erin A., Rahul S. Mhaskar, Hong Lu, Mina S. Mousa, Gabriel S. Krivenko, Aleksandr Lazaryan, Christina A. Bachmeier, et al. "High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma." Blood Advances 4, no. 14 (July 23, 2020): 3268–76. http://dx.doi.org/10.1182/bloodadvances.2020001900.
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Abstract High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.
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Yang, J. N., and J. Dudley. "Endogenous Mtv-8 or a closely linked sequence stimulates rearrangement of the downstream V kappa 9 gene." Journal of Immunology 149, no. 4 (August 15, 1992): 1242–51. http://dx.doi.org/10.4049/jimmunol.149.4.1242.
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Abstract Mtv-8 is an endogenous retrovirus located 4.6 kb upstream of a V kappa region gene (called V kappa 9M) within the kappa-Ig locus. The proximity of these two genes resulted in several effects. Using a newly developed RNase protection assay for measuring transcription from a single endogenous provirus, we found that Mtv-8 transcription could be detected after juxtaposition of the kappa-enhancers to the normally silent provirus. Reciprocally, using the polymerase chain reaction we observed that the frequency of V kappa 9M rearrangement was 5- to 10-fold higher in spleens from Mtv-8-positive mice (BALB/c, C58.C, A/J, and B6) compared to spleens from mice that lacked the Mtv-8 provirus (C58, C.C58, NZB, and PERA/Ei). Molecular cloning and sequencing of the V kappa 9M gene from C.C58 mice (containing the kappa-locus from C58 mice on a BALB/c background) indicated that at least some Mtv-8-negative strains have a functional V kappa 9M gene. Together these data suggest that Mtv-8 or a closely linked gene enhances V kappa 9M rearrangement. Since Mtv-8 also reportedly produces a superantigen, it appears that Mtv-8 may influence both the T cell and B cell repertoires.
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Unterrainer, Marcus, Julian Taugner, Lukas Käsmann, Chukwuka Eze, Wolfgang G. Kunz, Amanda Tufman, Niels Reinmuth, Claus Belka, and Farkhad Manapov. "Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e20558-e20558. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e20558.
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e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18F-FDG PET/CT using a standard threshold (hepatic SUVmean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml & > 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.
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Li, Jiancheng, and Weijie Sun. "PS02.067: PREDICTIVE VALUE OF 18F-FDG PET-CT METABOLIC PARAMETERS PRIOR TO TREATMENT ON SHORT-TERM CURATIVE EFFECTS OF ESOPHAGEAL CANCER." Diseases of the Esophagus 31, Supplement_1 (September 1, 2018): 139. http://dx.doi.org/10.1093/dote/doy089.ps02.067.
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Abstract Background To investigate predictive value of pre-treatment maximal standardized uptake value (SUVmax) and metabolic tumor volume (MTV) on short-term curative effects in esophageal cancer patients. Methods Retrospective analysis was made for 98 cases of patients with esophageal cancer treated by radiotherapy or radiotherapy combined with chemotherapy in Fujian Cancer Hospital. Before treatment, 18F-FDG PET-CT scan was performed. PET/CT images prior to treatment were read by two doctors with a high-level professional title using double-blind method. SUVmax and MTV were determined and averaged. 1–3 months after treatment, an experienced deputy director of PET/CT center and a radiotherapist evaluated the curative effect of all patients according to the Response Evaluation Criteria in Solid Tumor (RECIST). Results There were no significant differences of SUVmax and MTV between two groups in age, gender, cancer site, and differential extent (P > 0.05). Factors related to SUVmax were lesion length, depth of invasion, lymph node metastasis and clinical stage, while differences were statistically significant (P < 0.05). SUVmax & MTV were positively correlated with lesion length, depth of invasion, lymph node metastasis and clinical stage. The effective rate was 67.3% (66/98). SUVmax (r = -0.283, P = 0.049) and MTV(r = -0.379, P = 0.007) were negatively correlated with short-term curative effects, but the curative effect of MTV was higher than that of SUVmax. Conclusion There were no significant effects of clinical factors e.g. age, gender, esophageal cancer site, and differential extent on SUVmax and MTV, but length of lesion, depth of invasion, lymph node metastasis and clinical stage had significant effect on SUVmax and MTV. SUVmax and MTV prior to treatment can predict short-term curative effects of radiotherapy or radiotherapy combined with chemotherapy for esophageal cancer patients, but MTV is more predictive than SUVmax. Disclosure All authors have declared no conflicts of interest.
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Lee, Jeong Won, Chang Moo Kang, Sang Mi Lee, Jae-Hoon Lee, and Jong Doo Lee. "Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with pancreatic cancer." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 190. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.190.
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190 Background: In this study, we aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose (18F-FDG) PET/CT in pancreatic cancer patients who underwent resection with curative intent. Methods: Eighty-seven patients with pancreatic ductal adenocarcinoma who underwent 18F-FDG PET/CT and subsequent surgical resection with curative intent with (30 patients) or without (57 patients) neoadjuvant therapy were retrospectively enrolled in this study. The maximum standardized uptake value (SUVmax), MTV, and TLG were measured on 18F-FDG PET/CT in all patients. The prognostic significance of SUVmax, MTV, TLG, and tumor factors for predicting recurrence-free survival was evaluated by univariate and multivariate analyses. Results: Of the 87 patients enrolled, 57 (64%) experienced recurrence during the follow-up period, and the 1-year recurrence-free survival rate was 52%. Among the variables determined to be significant on univariate analysis including tumor size, pT stage, the presence of lymph node metastasis, SUVmax, MTV, and TLG, only tumor size, MTV, and TLG were significant prognostic factors on multivariate analysis (p < 0.05). Patients with low MTV (71%) or TLG (74%) had significantly higher 1-year recurrence-free survival rates than those with high MTV (42%) or TLG (38%; p < 0.05). In the 57 patients who did not undergo neoadjuvant treatment, MTV and TLG remained significant predictive factors for tumor recurrence, along with tumor size and SUVmax. Conclusions: MTV and TLG are independent prognostic factors for predicting recurrence in patients with pancreatic cancer. Thus, 18F-FDG PET/CT can provide useful prognostic information for patients undergoing resection of pancreatic cancer with curative intent irrespective of neoadjuvant treatment.
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Woodland, D. L., F. E. Lund, M. P. Happ, M. A. Blackman, E. Palmer, and R. B. Corley. "Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci." Journal of Experimental Medicine 174, no. 5 (November 1, 1991): 1255–58. http://dx.doi.org/10.1084/jem.174.5.1255.
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Superantigens are defined by their ability to stimulate T cells based predominantly on their V beta expression and ability to delete T cells in the thymus when expressed endogenously. We show here that the expression of one endogenous superantigen, Etc-1, is controlled by the expression of the open reading frame region of the 3' long terminal repeat of the mouse mammary tumor proviral gene, Mtv-9. We show that Mtv-8 controls a superantigen with similar specificity, and that both Mtv-8 and Mtv-9 stimulate some V beta 17+ T cells. A third provirus, Mtv-6, controls a superantigen with specificity for V beta 3. Data presented raise the possibility that endogenous superantigens may compete for class II molecules in a single B cell.
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Woff, Erwin, Pashalina Kehagias, Caroline Vandeputte, Tarek Kamoun, Thomas Guiot, Lieveke Ameye, Karen Paula Geboes, et al. "Baseline cell-free DNA (cfDNA) and metabolic tumor volume (MTV) independently predict outcome in metastatic chemorefractory colorectal cancer (mCRC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 11569. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11569.
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11569 Background: No validated prognostic biomarker is currently available for mCRC. This trial assessed cfDNA and MTV before treatment with regorafenib as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS) in mCRC. Methods: After signed informed consent, mCRC patients were enrolled in a prospective non-randomized trial aiming to define unlikelihood to benefit from regorafenib (EudraCT number: 2012-005655-16) and assessed for cfDNA and FDG PET/CT MTV at baseline. cfDNA was extracted from 3mL of plasma and quantified using the Qubit 2.0 fluorometer. All target lesions were delineated on FDG PET/CT using a PERCIST-based threshold and their volumes were summed to obtain total MTV. MTV and cfDNA optimal cutoffs for OS and PFS prediction were determined by the Contal and O’Quigley’s method. MTV, cfDNA, age, gender, Body Mass Index (low, normal, high, obese), ECOG PS, number of chemotherapy lines (NCL), previous use of bevacizumab and presence of a KRAS mutation were included in a multivariate analysis. Results: MTV and cfDNA of 132 evaluable/141 eligible patients were well correlated (Spearman’s correlation coefficient = 0.70; p < 0.001) and risk groups for both PFS and OS were identified on the basis of cfDNA (cfDNA < 1 µg/mL; cfDNA≥1 µg/mL) and MTV (MTV < 100 cm³; 100-300 cm³; > 300 cm³). The multivariate analysis retained cfDNA, MTV, NCL, and obesity as independent parameters for PFS prediction, and cfDNA, MTV, NCL, BMI, and previous use of bevacizumab as independent parameters for OS prediction. Prognostic scores for PFS and OS were developed based on regression coefficients from the final Cox proportional hazards models. Prognostic scores for PFS (1.8 vs 5.3 months, HR: 3.15 for score ≥-3 vs < -3, (95% CI, 2.08-4.76); p < 0.001) and for OS (4.2 vs 13.9 months, HR: 4.59 for score ≥-6 vs < -6: (95% CI, 2.92-7.21); p < 0.001) both identified patients with much contrasted outcomes. Conclusions: Baseline cfDNA and MTV along with BMI parameters predict outcome in patients with mCRC before regorafenib onset. These parameters not related to treatment should be considered, if validated in further studies, as stratification factors in future clinical trials. Clinical trial information: 2012-005655-16.
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Matsumoto, Yoshihiro, Shingo Baba, Makoto Endo, Nokitaka Setsu, Keiichiro Iida, Jun-Ichi Fukushi, Kenichi Kawaguchi, et al. "Metabolic Tumor Volume by 18F-FDG PET/CT Can Predict the Clinical Outcome of Primary Malignant Spine/Spinal Tumors." BioMed Research International 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/8132676.
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Background and Purpose. Primary malignant spine/spinal tumors (PMSTs) are rare and life-threatening diseases. In this study, we demonstrated the advantage of volume-based 18F-FDG PET/CT metabolic parameter, metabolic tumor volume (MTV), for assessing the aggressiveness of PMSTs. Materials and Methods. We retrospectively reviewed 27 patients with PMSTs and calculated SUVmax, MTV, and total lesion glycolysis (TLG) to compare their accuracy in predicting progression-free survival (PFS) and overall survival (OS) by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to compare the reliability of the metabolic parameters and various clinical factors. Results. MTV exhibited greater accuracy than SUVmax or TLG. The cut-off values for PFS and OS derived from the AUC data were MTV 45 ml and 83 ml and TLG 250 SUV⁎ml and 257 SUV⁎ml, respectively. MTV above cut-off value, but not TLG, was identified as significant prognostic factor for PFS by log-lank test (p=0.04). In addition, MTV was the only significant predictive factors for PFS and OS in the multivariate analysis. Conclusions. MTV was a more accurate predictor of PFS and OS in PMSTs compared to TLG or SUVmax and helped decision-making for guiding rational treatment options.
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King, L. B., F. E. Lund, D. A. White, S. Sharma, and R. B. Corley. "Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9." Journal of Immunology 144, no. 8 (April 15, 1990): 3218–27. http://dx.doi.org/10.4049/jimmunol.144.8.3218.
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Abstract We have previously shown that the steady state levels of transcripts encoded by an endogenous mouse mammary tumor virus (MMTV) increase during LPS-induced differentiation of both normal B lymphocytes and an inducible B cell lymphoma, CH12. A large body of evidence suggests that MMTV expression is primarily limited to mammary tissues and that expression in cell lines from nonmammary tissues is accompanied by viral amplification and alterations in the transcriptional control regions of the viral long terminal repeat. We have, therefore, carefully characterized MMTV expression in CH12 cells and in other cells of the B lineage in order to determine if the expression of MMTV transcripts in differentiating B cells results from the "abnormal" transcriptional regulation seen in other nonmammary tissue. In this manuscript, we present evidence that MMTV transcripts are expressed in a variety of cells of the B lineage and that the levels of constitutive expression vary among the different cells. On the other hand, T cell lymphomas lacking amplified MMTV do not contain proviral transcripts, suggesting that MMTV transcription may be preferentially expressed in B lymphocytes. We demonstrate that MMTV transcripts are up-regulated during cytokine-mediated as well as LPS-mediated differentiation, and that most, if not all, expression is due to the activity of a single proviral gene, Mtv-9, in CH12 cells. Furthermore, the expression of MMTV transcripts in CH12 cells neither requires nor is accompanied by amplification of the provirus. Sequence analysis demonstrates that the U3 region of the expressed Mtv-9 long terminal repeat contains neither deletions nor insertions, and the well-characterized enhancer and promoter sites in the glucocorticoid response element which are known to be involved in transcriptional regulation of MMTV in mammary tissues have not been disrupted. These data suggest that the Mtv-9 locus behaves as a normal somatic gene which is differentially regulated during B cell development and differentiation. Unlike the events which lead to MMTV expression in other nonmammary tissues, B cells may express transcription factor(s) which are capable of inducing expression of endogenous MMTV proviral genes during the natural course of differentiation. Analysis of the mechanisms which control the expression of this gene should be useful in characterizing the molecular events which govern B cell differentiation.
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Surh, C. D., D. P. Gold, S. Wiley, D. B. Wilson, and J. Sprent. "Rat T cell response to superantigens. I. V beta-restricted clonal deletion of rat T cells differentiating in rat-->mouse chimeras." Journal of Experimental Medicine 179, no. 1 (January 1, 1994): 57–62. http://dx.doi.org/10.1084/jem.179.1.57.
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T cells of mice display V beta-specific reactivity for a spectrum of mouse mammary tumor virus (Mtv) antigens; confrontation with these antigens during ontogeny causes substantial "holes" in the T cell repertoire. Since endogenous Mtv antigens are rare in other species, the question arises whether V beta-specific recognition of Mtv antigens is unique to mice. To examine this question, rat T cells were allowed to differentiate from stem cells in severe combined immunodeficiency (SCID) mice. These rat-->mouse xenochimeras were prepared under a variety of conditions. The results show that rat T cells are strongly reactive to mouse Mtv antigens, both in terms of tolerogenicity and immunogenicity. In fact, the V beta specificity of rat and mouse T cells for Mtv antigens is almost indistinguishable.
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Lee, J. Y., J. H. Heo, J. Han, S. J. Jang, K. Kim, J. Kim, Y. M. Shim, B. T. Kim, and J. Y. Choi. "Prognostic significance of volume-based 18F-FDG PET/CT parameter in patients with surgically resected non-small cell lung cancer." Nuklearmedizin 55, no. 01 (2016): 7–14. http://dx.doi.org/10.3413/nukmed-0754-15-07.
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SummaryAim: We investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) parameters compared with other factors including several immunohistochemical biomarkers in patients with surgically resected non-small cell lung cancer (NSCLC). Patients, methods: Study participants: 290 patients with surgically resected and histopathologically confirmed NSCLC. The maxmum standardized uptake value (SUVmax) and metabolic tumour volume (MTV) of the primary tumour were obtained on 18F-FDG PET/ computed tomography (CT) for initial staging and Ki-67 labeling index (LI), p16, CD31 and cyclin E were evaluated in the primary tumours by immunohistochemical staining. Survival analyses for variables including PET parameters, immunohistochemical biomarker and other clinical factors were performed using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: In univariate analyses, tumour stage, tumour size, and MTV were significant prognostic factors for decreased overall survival (OS) and disease-free survival (DFS). Multivariate analyses showed MTV and tumour stage were significant predictors of poor OS (MTV, hazard ratio (HR) = 1.135, p = 0.015; stage, HR = 0.644, p = 0.025) and DFS (MTV, HR = 1.128, p = 0.043; stage, HR = 0.541, p = 0.009). Conclusion: The MTV of primary tumours is a significant prognostic factor for survival along with tumour stage in patients with surgically resected NSCLC. The MTV can predict OS and DFS better than immuno histochemical biomarkers.
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Hossain, Muhammad Muazzem. "Adoption of More-than-voice Technology: The Role of Country Affiliation." International Journal of Emerging Technology and Advanced Engineering 13, no. 2 (February 4, 2023): 16–25. http://dx.doi.org/10.46338/ijetae0223_03.
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—Plethora of uses of mobile phones exist across the globe. The use of mobile phones beyond voice calls is known as the more-than-voice (MTV) technology. The widespread use of MTV technology is evident among the bottom of pyramid (BoP) around the world. The BoP represents a significant portion of the world population that not only can afford MTV technology but also can serve as a huge consumer base for services based on this technology. This study examines the factors affecting the acceptance of MTV technology by the BoP users and investigates whether their country affiliation plays a differing role in the adoption of the technology in the Indian subcontinent. Data were obtained from the Teleuse@BOP4 study. Partial least square (PLS) was performed to test the research model. The findings suggest that the perceived usefulness, ease of use, facilitating conditions, acumen to use, and propensity to use are the significant predictors of the adoption of the MTV technology. The findings also suggest that country affiliation plays a significant moderating role in the relationships between facilitating conditions and intention, and propensity to use and intention. This study then provides the practical and academic implications of both significant and insignificant findings. Keywords—More-than-voice technology, MTV technology, MTV services, consumer acceptance, technology adoption, country affiliation.
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Vinogradova, Yu N., M. S. Tlostanova, A. A. Ivanova, A. Yu Pakhomov, and N. V. Ilyin. "Methodological Aspects of Measuring Metabolic Tumor Volume in Patients with Diffuse B-Cell Large Cell Lymphoma by PET/CT with 18F-FDG." Journal of oncology: diagnostic radiology and radiotherapy 4, no. 4 (November 26, 2021): 28–39. http://dx.doi.org/10.37174/2587-7593-2021-4-4-28-39.
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Introduction: Metabolic Tumor Volume (MTV) and Total Tumor Lesion Glycolysis (TLG) are used in 18F-fluorodeoxyglucose Positron-Emission Tomography combined with Computed Tomography (18F-FDG PET/CT) as functional markers, indicating tracer uptake in whole tumor. MTV and TLG are not yet engaged in clinical practice, because volume measurement accuracy depends on the selected measurement method, and optimal MTV and TLG segmentation is not established.Purpose: Assessment of accuracy of metabolic tumor volume measurement ways, using 18F-FDG PET/CT in patients with Diffuse Large B-Cell Lymphoma (DLBCL).Material and methods: Baseline 18F-FDG PET/CT performed in 21 patients with DLBCL. Tumor Volume (TV), measured on contrast enhanced CT (CTTV), considered as reference. While measuring MTV, we aimed to achieve a 1:1 ratio between CTTV and MTV. If anatomical and metabolic tumor contours matched, MTV was considered true (MTVtrue). Overall MTV and TLG measurements are 254. Tumor contouring, using relative thresholds, was made around Standardized Uptake Value (SUVmax) of tracer in tumor and intact liver.Results: On CT, the size of the lesions varied from 24 to 241 mm, M = 103.4±62.3, Me = 93 (48.5–155.5). In 15 (71.4 %) foci, hypodense areas of necrosis were determined. PET imaging revealed high tracer uptake in all foci of varying degrees of intensity. SUVmax values in tumors ranged from 5.8 to 30.5, Me = 20.4 (17.3–23.2). No significant correlation was found between the size of the foci and SUVmax (ρ = 0.17, p = 0.4744). The best accuracy in measuring MTV was observed when several thresholds were applied: VOIPERCIST, VOI2.5, VOIauto-contour, as well as VOI10 %, VOI15 % and VOI20 %. The optimal absolute threshold values were SUV values in the range from 2 to 3, and relative values in the range from 10 % to 20 % of the SUVmax in the tumor. MTV underestimation was more often determined using relative cut-off indices in the range of25–50 % and SUV thresholds ≥ 5.3.Conclusion: The results obtained showed that the use of a single threshold value for MTV segmentation in patients with DLBCL is not advisable. The choice of the MTV measurement method should be carried out individually for each lesion, taking into account its shape, size and structure, as well as the intensity and uniformity of tracer uptake in the tumor and adjacent anatomical structures.
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Dean, Erin, Hong Lu, Aleksandr Lazaryan, Gabriel S. Krivenko, Christina A. Bachmeier, Julio C. Chavez, Marco L. Davila, et al. "Association of high baseline metabolic tumor volume with response following axicabtagene ciloleucel in refractory large B-cell lymphoma." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 7562. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.7562.
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7562 Background: Axicabtagene ciloleucel (axi-cel) is an anti-CD19 targeted Chimeric Antigen Receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). High tumor burden, by sum of the product of diameters (SPD) in ≥ 6 reference lesions, was associated with lower durable responses rates in the ZUMA-1 trial (Locke F.L. ASCO. 2018). Although metabolic tumor volume (MTV) predicts worse outcomes with chemotherapy in lymphoma (Guo B. PLoSOne. 2019), its prognostic significance remains unclear with axi-cel therapy. Methods: MTV was measured by MIM Software using a 41% SUVmax threshold with manual lesion contour adjustment and radiologist review. Low and high MTV groups were defined based on median cutoff value. Cytokine release syndrome (CRS) was graded by Lee et al. ( Blood. 2014). Neurotoxicity (NT) was graded by CTCAEv4. Toxicities, overall response rate (ORR), and complete response rate (CR) were evaluated via Fisher’s test; PFS and OS via Kaplan-Meier and log-rank test. Results: 48 patients with LBCL, or its variants, that received axi-cel at Moffitt from June 2015 to October 2018 were included. 31 were male, and median age was 63 years (range, 28-76). CRS occurred in 43/47 (91.5%) and NT in 32/47 (68.1%) patients. Grade 3-4 CRS in 2/47 (4.3%) and NT in 12/47 (25.5%). Median follow up for survivors was 8.9 months (range, 1.4- 36.8 months). CR was achieved in 31/48 (64.6 %) and ORR in 39/48 (81.3%). Median for the low MTV group was 35.1 mL (range, 4.24-132.8 mL), and for the high MTV group 455.5 mL (range, 162.2-1221.4 mL). High MTV was not predictive of G1-4 NT or G3-4 NT (OR = 1.14, P = 0.99; OR = 1.66, P = 0.52). Similarly, high MTV was not predictive of G1-4 CRS or G3-4 CRS (OR = 0.29, P = 0.348; OR = 1.05, P = 0.99). Low MTV was predictive of ORR (OR = 11.50, P = 0.026) and CR (OR = 9.8, P = 0.002). Patients with high MTV had inferior PFS (HR = 3.296, 95% CI 1.42-7.64, P = 0.008) and OS (HR = 6.68, 95% CI 2.56-17.32, P = 0.003). Conclusions: High baseline MTV is associated with decreased and less durable response following axi-cel. As survival data mature, future analyses will aim to assess the role of MTV as an independent prognostic tool in axi-cel recipients with LBCL.
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Wirth, Susanne, Annelyse Vessaz, Claude Krummenacher, Frédéric Baribaud, Hans Acha-Orbea, and Heidi Diggelmann. "Regions of Mouse Mammary Tumor Virus Superantigen Involved in Interaction with the Major Histocompatibility Complex Class II I-A Molecule." Journal of Virology 76, no. 21 (November 1, 2002): 11172–75. http://dx.doi.org/10.1128/jvi.76.21.11172-11175.2002.
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ABSTRACT To study the major histocompatibility complex class II I-E dependence of mouse mammary tumor virus (MMTV) superantigens, we constructed hybrids between the I-E-dependent MMTV(GR) and the I-E-independent mtv-7 superantigens and tested them in vivo. Our results suggest that, although the C-terminal third mediates I-A interaction, additional binding sites are located elsewhere in the superantigen.
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Ellis, Paul. "MTV vs. Channel V." Asian Case Research Journal 05, no. 02 (December 2001): 167–201. http://dx.doi.org/10.1142/s0218927501000147.
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The American music channel MTV was the first to broadcast music television in Asia when it entered the market via Star TV's satellite feed in 1991. However, when Rupert Murdoch's News Corporation acquired Star TV two years later, MTV left the scene over a disagreement regarding the amount of local programming and a new player emerged in the form of Star TV's own Channel V. In contrast to the global approach of MTV, Channel V placed more emphasis on local artists and VJs and for a while enjoyed a monopoly position in the market. Later, in 1995, MTV returned to Asia with a new strategy of adapting the content while projecting a common brand image. MTV has since enjoyed rapid growth in the region resulting in fierce competition between the two channels. In 1999 the rivalry manifested itself in an escalating war of words between Steve Smith of Channel V and Frank Brown of MTV with each alleging that the other was misrepresenting distribution figures. The case documents this feud and its effect on advertisers in the context of the emerging Asian market for televised music.
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Le Thiec, Maelle, Aude Testard, Ludovic Ferrer, Camille Guillerminet, Olivier Morel, Bruno Maucherat, Daniela Rusu, et al. "Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer." Cancers 12, no. 6 (June 9, 2020): 1512. http://dx.doi.org/10.3390/cancers12061512.
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Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient’s sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cut-off for discrimination between a low and high risk of event occurrence was 40 cm3. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.
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Chan, Derwin King-Chung, and Martin S. Hagger. "Transcontextual Development of Motivation in Sport Injury Prevention Among Elite Athletes." Journal of Sport and Exercise Psychology 34, no. 5 (October 2012): 661–82. http://dx.doi.org/10.1123/jsep.34.5.661.
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The present study investigated the transcontextual process of motivation in sport injury prevention. We examined whether general causality orientation, perceived autonomy support from coaches (PAS), self-determined motivation (SD-Mtv), and basic need satisfaction in a sport context predicted SD-Mtv, beliefs, and adherence with respect to sport injury prevention. Elite athletes (N = 533) completed self-report measures of the predictors (Week 1) and the dependent variables (Week 2). Variance-based structural equation modeling supported hypotheses: SD-Mtv in a sport context was significantly predicted by PAS and basic need satisfaction and was positively associated with SD-Mtv for sport injury prevention when controlling for general causality orientation. SD-Mtv for sport injury prevention was a significant predictor of adherence to injury-preventive behaviors and beliefs regarding safety in sport. In conclusion, the transcontextual mechanism of motivation may explain the process by which distal motivational factors in sport direct the formation of proximal motivation, beliefs, and behaviors of sport injury prevention.
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Ignatowicz, L., J. W. Kappler, P. Marrack, and M. T. Scherer. "Identification of two V beta 7-specific viral superantigens." Journal of Immunology 152, no. 1 (January 1, 1994): 65–71. http://dx.doi.org/10.4049/jimmunol.152.1.65.
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Abstract The commonly used strains of laboratory mice have mouse mammary tumor viruses (MTV) integrated at various locations in their DNA. The number and position of these integrants varies from one strain of mouse to another. It has recently been shown that the genomes of many of the MTV code for superantigens. The predicted amino acid sequences of these superantigens and their specificity for TCR V beta differs for each MTV integrant. This study contains the predicted amino acid sequence and V beta specificity of two MTV superantigens that had not previously been analyzed. The results show that both of these MTV superantigens are specific for TCR that bear V beta 7, but unlike the MTV7 superantigen not for receptors bearing V beta 6 or V beta 8.1. The data also support the conclusion of previous studies that the COOH-terminal sequence of these proteins is a major factor in controlling their V beta reactivity.
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Fernandes, Annemarie Therese, Jonathan Taylor Whaley, Kevin Teo, John Peter Plastaras, James M. Metz, Rodolfo F. Perini, Daniel A. Pryma, and Smith Apisarnthanarax. "Predicting outcomes in locally advanced rectal cancer using pretreatment FDG-PET imaging." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 495. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.495.
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495 Background: FDG-PET/CT imaging has been shown to have clinical utility in the management of rectal cancers. The purpose of this study was to investigate multiple FDG-PET/CT parameters to predict for outcome after neoadjuvant chemoradiation (CRT) in patients (pts) with locally advanced rectal adenocarcinoma. Methods: We retrospectively evaluated pts with locally-advanced (T2-4, N0-2, M0) rectal adenocarcinoma treated with neoadjuvant CRT who received FDG-PET/CT scans for radiation therapy planning. We evaluated the impact of SUVmax and metabolic tumor volume (MTV, determined by using PET Edge MimVista), as well as dual-time point PET parameters of retention index (RI, difference in SUVmax between the two PET scans) and RI/time. Endpoints of pathologic complete response (pCR), tumor grade, margin status and pathologic downstaging were assessed using t-test, ANOVA or non-parametric analysis when appropriate. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan Meier estimates. Results: Of the 28 consecutive pts with FDG-PET/CT planning scans identified, 25 pts underwent surgical resection. All patients received a 5-FU based concurrent chemotherapy regimen with RT (median RT dose: 50.4 Gy). Median follow-up was 21 months. The median MTV was 45 cc. Compared to pts with a MTV>45 cc, pts with a MTV <45 cc had improved PFS (2-yr PFS: 86% vs. 60%, p=0.04) and improved OS (2-yr OS: 100% vs. 51%, p=0.01). The correlation between MTV and T-stage was not statistically significant (23% of pts with MTV>45 had T4 tumors vs. 0% of pts with MTV<45, p=0.17). MTV did not correlate with the other endpoints (pCR, tumor grade, margin status, pathologic downstaging). SUVmax did not correlate with any of the identified endpoints. Of the patients with dual-time point PET/CT scans (N=19), RI and RI/time did not correlate with any of the identified endpoints. Conclusions: Pretreatment MTV correlates with PFS and OS in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. For pts with large MTVs, more aggressive treatment approaches should be considered. Dual-time point FDG-PET imaging does not appear to add clinical value in this patient population.
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Islam, Prioty, Jordan Goldstein, Ila Sethi, Daniel Lee, and Christopher Flowers. "Interim metabolic tumor volume to predict response in diffuse large B-cell lymphoma." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 7557. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.7557.
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7557 Background: DLBCL is a heterogeneous disease with varied clinical outcomes following treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). [18F] fluorodeoxyglucose (FDG) – positron emission tomography (PET)/computed tomography (CT) imaging is ubiquitously used in monitoring of DLBCL. PET-derived metrics for analysis of tumor FDG uptake include: tumor maximum standardized uptake value (SUV); metabolically active tumor volume (MTV); and total lesion glycolysis (TLG), calculated from the intensity of FDG uptake in tumor volume. We evaluated the predictive value of interim SUV, MTV and TLG for patients (pts) with DLBCL treated with R-CHOP. Methods: Pts with DLBCL treated at Emory University 2005-2016 were eligible. Cases were included if there was a diagnosis of DLBCL confirmed by record review, available information on date of diagnosis, date of last contact or date of death. Analyses were restricted to patients who received R-CHOP and had PET/CT scans available at baseline, Cycle 2 or 4 and end of treatment. Maximum SUV, MTV, and TLG were calculated using MIM software for tumor with an SUV threshold of > 4. Logistic regression analysis was used to calculate the predictive value of interim PET/CT metrics on end of treatment response. Results: Pre-treatment PET/CT scans for 42 patients were identified, along with 28 interim and 31 post-treatment scans. The mean pre-treatment MTV was 303ml (range 4 – 1,327) and mean TLG was 3188 (range 28 – 16,176). MTV and TLG were undetectable in 79% of interim scans and 74% of the post-treatment scans. A Deauville score of 3 or less was observed in 71% of the interim PET/CT scans and 56% of the post-treatment scans. A positive interim MTV was correlated with a positive post-treatment MTV and post-treatment Deauville score at 0.58 and 0.66, respectively, and a positive interim MTV result was a significant predictor of a positive post-treatment MTV result (p = 0.02). Conclusions: PET-derived metrics of assessing interim tumor response to therapy offer significant predictive value for end of treatment response, and can guide a response-adapted treatment approach for DLBCL pts that builds on the R-CHOP backbone.
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Firestone, G. L., N. J. John, and K. R. Yamamoto. "Glucocorticoid-regulated glycoprotein maturation in wild-type and mutant rat cell lines." Journal of Cell Biology 103, no. 6 (December 1, 1986): 2323–31. http://dx.doi.org/10.1083/jcb.103.6.2323.
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Glucocorticoid hormones can regulate the posttranslational maturation of mouse mammary tumor virus (MTV) precursor polyproteins in M1.54, a stably infected rat hepatoma cell line. We have used complement-mediated cytolysis to recover variants of M1.54 that fail to express MTV cell surface glycoproteins in a hormone-regulated manner (Firestone, G.L., and K.R. Yamamoto, 1983, Mol. Cell. Biol., 3:149-160). One such clonal isolate, CR4, is similar to wild-type with respect to synthesis of MTV mRNAs, production of the MTV glycoprotein precursor (gPr74env) and a glycosylated maturation product (gp51), and hormone-induced processing of two MTV phosphoproteins. In contrast, three viral cell surface glycoproteins (gp78, gp70, and gp32) and one extracellular species (gp70s), which derive from gPr74env in glucocorticoid-treated wild-type cells, fail to appear in CR4. CR4 showed no apparent alterations in proliferation rate, cell shape, or expression of total functional mRNA and bulk glycoproteins. We conclude that the genetic lesion in CR4 defines a highly selective hormone-regulated glycoprotein maturation pathway that alters the fate of a restricted subset of precursor species.
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Ellsworth, Elizabeth, Margot Kennard Larson, and Albert Selvin. "MTV Presents: Problematic Pleasures." Journal of Communication Inquiry 10, no. 1 (January 1986): 55–63. http://dx.doi.org/10.1177/019685998601000106.
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MacFarlane, John. "MTV honors AIDS campaigners." Nature Medicine 7, no. 12 (December 2001): 1264. http://dx.doi.org/10.1038/nm1201-1264b.
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Hanna, Robert C. "The Mtv of Motivation." Kappa Delta Pi Record 33, no. 4 (July 1997): 129–31. http://dx.doi.org/10.1080/00228958.1997.10532004.
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Lorch, Sue. "Metaphor, Metaphysics, and MTV." Journal of Popular Culture 22, no. 3 (December 1988): 143–55. http://dx.doi.org/10.1111/j.0022-3840.1988.2203_143.x.
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Gold, D. P., C. D. Surh, K. S. Sellins, K. Schroder, J. Sprent, and D. B. Wilson. "Rat T cell responses to superantigens. II. Allelic differences in V beta 8.2 and V beta 8.5 beta chains determine responsiveness to staphylococcal enterotoxin B and mouse mammary tumor virus-encoded products." Journal of Experimental Medicine 179, no. 1 (January 1, 1994): 63–69. http://dx.doi.org/10.1084/jem.179.1.63.
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The previous paper in this series demonstrates that rat T cells developing de novo in the presence of mouse mammary tumor virus (Mtv) antigens in rat-->severe combined immunodeficiency (SCID) mouse xenochimeras display a distinct pattern of V beta-restricted deletion; this deletion pattern is remarkably similar to that occurring during thymic development of mouse T cells in Mtv+ strains. In addition, T cells developing in the absence of Mtv antigens in these rat-->mouse xenochimeras are tolerant of host antigens, but show strong primary proliferative responses in cultures stimulated with Mtv-7+ (Mlsa) mouse cells; like the mouse, these rat T cell responses are dominated by V beta 6 and V beta 8 T cells. Here, we continue analysis of rat T cell responses to superantigens; we show that T cells from Lewis and Fischer 344 rats expressing V beta 8.2 display an important all-or-nothing difference in their responses to Mtv-7 superantigens. This all-or-none strain difference in the response to Mtv-7 applies also to the response by V beta 8.2 and V beta 8.5 T cells to the soluble superantigen staphylococcal enterotoxin B. Because these two rat strains express different alleles of these two V beta 8 family members, this finding identifies additional, hitherto unreported residues of the T cell receptor beta chain important in T cell responses to superantigens.