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  1. Article: Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT).

    Emmett, Louise / John, Nikeith / Pathmanandavel, Sarennya / Counter, William / Ayers, Maria / Sharma, Shikha / Agrawal, Shikha / Poole, Aron / Hovey, Elizabeth / Pranavan, Ganes / Gedye, Craig / Mallesara, Girish / Guminski, Alex / Lee, Adrian / Stockler, Martin R / Hickey, Adam / Eu, Peter / Joshua, Anthony M / Crumbaker, Megan /
    Nguyen, Andrew

    Therapeutic advances in medical oncology

    2023  Volume 15, Page(s) 17588359231156392

    Abstract: Background: 177: Objective: This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising : Design: Retrospective analysis of a clinical : Methods: In all, 125 men were treated ... ...

    Abstract Background: 177
    Objective: This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising
    Design: Retrospective analysis of a clinical
    Methods: In all, 125 men were treated with 6-weekly
    Results: Overall PSA50% response rate (PSARR) was 60% (75/125), median PSA-PFS 6.1 months (95%CI: 5.5-6.7), and median OS 16.8 months (95%CI: 13.5-20.1). 35% (41/116) were classified as RG 1, 34% (39/116) RG 2, and 31% (36/116) RG 3. PSARRs by RG were 95% (38/41), 74% (29/39), and 8% (3/36); median PSA-PFS rates were 12.1 months (95%CI: 9.3-17.4), 6.1 months (95%CI: 5.8-9.0), and 2.6 months (95%CI: 1.6-3.1); and OS rates were 19.2 months (95%CI: 16.8-20.7), 13.2 months (95%CI: 12.0-18.8), and 11.2 months (95%CI: 8.7-15.6) for RG 1, 2, and 3, respectively. The median months of 'treatment holiday' for RG 1 was 6.1 months (IQR: 3.4-8.7). Nine men had received prior
    Conclusion: Personalising dosing regimens using early response biomarkers with
    Plain language summary: Lutetium-PSMA therapy is a new therapy for metastatic prostate cancer that is well tolerated and effective. However, not all men respond equally, with some responding very well and others progressing early. Personalising treatments require tools that can accurately measure treatment responses, preferably early in the treatment course, so adjustments to treatment can be made. Lutetium-PSMA can measure tumour sites after each therapy by taking whole body 3D images at 24 h using a small radiation wave from the treatment itself. This is called a SPECT scan. Previous work has shown that both prostate-specific antigen (PSA) response and changes in tumour volume on a SPECT scan can predict how patients will respond to treatment as early as dose 2. This study demonstrates that stratifying how men are treated based on the results of the 6-week SPECT scan and PSA response potentially allows a third of men to have break in treatment and that these men have both longer time to disease progression and OS. Men with an increase in tumour volume and increase in PSA early in treatment (6 weeks) had shorter time to disease progression and OS. Men with early biomarker disease progression were offered alternative treatments early in an attempt to allow the opportunity to allow a more effective potential therapy, if one was available. The study is an analysis of a clinical programme, and was not a prospective trial. As such, there are potential biases that could influence results. Hence, while the study is encouraging for the use of early response biomarkers to guide better treatment decisions, this must be validated in a well-designed clinical trial.
    Language English
    Publishing date 2023-03-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2503443-1
    ISSN 1758-8359 ; 1758-8340
    ISSN (online) 1758-8359
    ISSN 1758-8340
    DOI 10.1177/17588359231156392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Biphasic and cardiomyocyte-specific IFIT activity protects cardiomyocytes from enteroviral infection.

    Taishi Kimura / Claudia T Flynn / Mehrdad Alirezaei / Ganes C Sen / J Lindsay Whitton

    PLoS Pathogens, Vol 15, Iss 4, p e

    2019  Volume 1007674

    Abstract: Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. ... ...

    Abstract Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. Using IFIT locus knockout (IFITKO) cardiomyocytes we show that, in the absence of the IFIT locus, viral replication is dramatically increased, indicating that constitutive IFIT expression suppresses CVB replication in this cell type. IFNβ pre-treatment strongly suppresses CVB3 replication in wild type (wt) cardiomyocytes, but not in IFITKO cardiomyocytes, indicating that other interferon-stimulated genes (ISGs) cannot compensate for the loss of IFITs in this cell type. Thus, in isolated wt cardiomyocytes, the anti-CVB3 activity of IFITs is biphasic, being required for protection both before and after T1IFN signaling. These in vitro findings are replicated in vivo. Using novel IFITKO mice we demonstrate accelerated CVB3 replication in pancreas, liver and heart in the hours following infection. This early increase in virus load in IFITKO animals accelerates the induction of other ISGs in several tissues, enhancing virus clearance from some tissues, indicating that-in contrast to cardiomyocytes-other ISGs can offset the loss of IFITs from those cell types. In contrast, CVB3 persists in IFITKO hearts, and myocarditis occurs. Thus, cardiomyocytes have a specific, biphasic, and near-absolute requirement for IFITs to control CVB infection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Biphasic and cardiomyocyte-specific IFIT activity protects cardiomyocytes from enteroviral infection.

    Kimura, Taishi / Flynn, Claudia T / Alirezaei, Mehrdad / Sen, Ganes C / Whitton, J Lindsay

    PLoS pathogens

    2019  Volume 15, Issue 4, Page(s) e1007674

    Abstract: Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. ... ...

    Abstract Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. Using IFIT locus knockout (IFITKO) cardiomyocytes we show that, in the absence of the IFIT locus, viral replication is dramatically increased, indicating that constitutive IFIT expression suppresses CVB replication in this cell type. IFNβ pre-treatment strongly suppresses CVB3 replication in wild type (wt) cardiomyocytes, but not in IFITKO cardiomyocytes, indicating that other interferon-stimulated genes (ISGs) cannot compensate for the loss of IFITs in this cell type. Thus, in isolated wt cardiomyocytes, the anti-CVB3 activity of IFITs is biphasic, being required for protection both before and after T1IFN signaling. These in vitro findings are replicated in vivo. Using novel IFITKO mice we demonstrate accelerated CVB3 replication in pancreas, liver and heart in the hours following infection. This early increase in virus load in IFITKO animals accelerates the induction of other ISGs in several tissues, enhancing virus clearance from some tissues, indicating that-in contrast to cardiomyocytes-other ISGs can offset the loss of IFITs from those cell types. In contrast, CVB3 persists in IFITKO hearts, and myocarditis occurs. Thus, cardiomyocytes have a specific, biphasic, and near-absolute requirement for IFITs to control CVB infection.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/physiology ; Cells, Cultured ; Coxsackievirus Infections/metabolism ; Coxsackievirus Infections/prevention & control ; Coxsackievirus Infections/virology ; Enterovirus B, Human/pathogenicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocarditis/metabolism ; Myocarditis/prevention & control ; Myocarditis/virology ; Myocytes, Cardiac/enzymology ; RNA-Binding Proteins ; Virus Replication
    Chemical Substances Adaptor Proteins, Signal Transducing ; Carrier Proteins ; Ifit1 protein, mouse ; RNA-Binding Proteins
    Language English
    Publishing date 2019-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1007674
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Complete ulnar innervation of the thenar muscles combined with normal sensory fibres in a subject with no peripheral nerve lesion.

    Ganes, T

    Electromyography and clinical neurophysiology

    1992  Volume 32, Issue 10-11, Page(s) 559–563

    Abstract: A complete ulnar innervation of all thenar muscles, including the opponens, have to our knowledge been described only in patients with severe traumatic lesions of the median nerve. The present study reports a subject with exclusive ulnar innervation of ... ...

    Abstract A complete ulnar innervation of all thenar muscles, including the opponens, have to our knowledge been described only in patients with severe traumatic lesions of the median nerve. The present study reports a subject with exclusive ulnar innervation of the thenar muscles in the right hand. The patient had no anamnestic or objective signs of peripheral nerve lesions. While his sensory and motor ulnar nerve fibres were normal, electrophysiological examination of the right median nerve showed normal course of the sensory fibres but apparently no motor fibres to the thenar muscles.
    MeSH term(s) Adult ; Electromyography ; Humans ; Male ; Median Nerve/anatomy & histology ; Median Nerve/physiology ; Muscles/innervation ; Muscles/physiology ; Neural Conduction/physiology ; Thumb/innervation ; Ulnar Nerve/anatomy & histology ; Ulnar Nerve/physiology
    Language English
    Publishing date 1992-10
    Publishing country Belgium
    Document type Case Reports ; Journal Article
    ZDB-ID 80224-4
    ISSN 0301-150X
    ISSN 0301-150X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Ifit2 deficiency restricts microglial activation and leukocyte migration following murine coronavirus (m-CoV) CNS infection.

    Jayasri Das Sarma / Amy Burrows / Patricia Rayman / Mi-Hyun Hwang / Soumya Kundu / Nikhil Sharma / Cornelia Bergmann / Ganes C Sen

    PLoS Pathogens, Vol 16, Iss 11, p e

    2020  Volume 1009034

    Abstract: ... impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain ...

    Abstract The interferon-induced tetratricopeptide repeat protein (Ifit2) protects mice from lethal neurotropic viruses. Neurotropic coronavirus MHV-RSA59 infection of Ifit2-/- mice caused pronounced morbidity and mortality accompanied by rampant virus replication and spread throughout the brain. In spite of the higher virus load, induction of many cytokines and chemokines in the brains of infected Ifit2-/- mice were similar to that in wild-type mice. In contrast, infected Ifit2-/- mice revealed significantly impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain, possibly contributing to the lack of viral clearance. These two deficiencies were associated with a lower level of microglial expression of CX3CR1, the receptor of the CX3CL1 (Fractalkine) chemokine, which plays a critical role in both microglial activation and leukocyte recruitment. The above results uncovered a new potential role of an interferon-induced protein in immune protection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Intravesical Gemcitabine versus Intravesical Bacillus Calmette-Guérin for the Treatment of Non-Muscle Invasive Bladder Cancer: An Evaluation of Efficacy and Toxicity.

    Prasanna, Thiru / Craft, Paul / Balasingam, Gayathri / Haxhimolla, Hodo / Pranavan, Ganes

    Frontiers in oncology

    2017  Volume 7, Page(s) 260

    Abstract: Background: Intravesical Bacillus Calmette-Guérin (BCG) remains the standard adjuvant treatment for non-muscle invasive bladder cancer (NMIBC) following transurethral resection; however, BCG failure and related toxicities are common.: Objectives: To ... ...

    Abstract Background: Intravesical Bacillus Calmette-Guérin (BCG) remains the standard adjuvant treatment for non-muscle invasive bladder cancer (NMIBC) following transurethral resection; however, BCG failure and related toxicities are common.
    Objectives: To compare the efficacy and toxicity of intravesical BCG and gemcitabine in the treatment of NMIBC.
    Methods: Retrospective data were collected in the region of Canberra, Australia from January 2010 to December 2015. The survival cutoff was December 2016. Primary end point was disease-free survival (DFS) and secondary end point was toxicity. After optimal transurethral resection all patients received weekly intravesical BCG or gemcitabine for 6 weeks and maintenance treatment according to their risk. The recurrence was defined as histology proven tumor recurrence (any grade), or appearance of carcinoma
    Results: One hundred and three patients were evaluable, 52 treated with BCG and 51 with gemcitabine with a median age of 77 and 78, and were mostly male. Approximately half of each received maintenance therapy. The groups were well balanced, apart from some difference in cancer risk groups. Twenty-one percent in the BCG group and 29% in the gemcitabine group had received prior BCG. Median follow up was 15.0 months. Median DFS was 19.6 months for BCG, whereas median DFS was not reached with gemcitabine. There was a trend toward improved DFS with gemcitabine in multivariate analysis, HR: 0.49 (95% CI: 0.22-1.06,
    Conclusion: Intravesical gemcitabine was associated with a trend toward better DFS with significantly lower toxicity when compared with BCG. Intravesical BCG remains the standard first-line adjuvant therapy; however, intravesical gemcitabine could be a reasonable alternative in cases where BCG is contraindicated and for patients who are intolerant or refractory to BCG. A prospective phase 3 trial is needed to confirm the benefits of gemcitabine over BCG.
    Language English
    Publishing date 2017-11-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2017.00260
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Retina, synsbaner og synscortex. Neurofysiologiske undersøkelser.

    Ganes, T

    Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke

    1987  Volume 107, Issue 22, Page(s) 1774–1776

    Title translation The retina, visual pathways and visual cortex. Neurophysiological studies.
    MeSH term(s) Electrooculography ; Electroretinography ; Evoked Potentials, Visual ; Humans ; Retina/physiology ; Visual Cortex/physiology ; Visual Pathways/physiology
    Language Norwegian
    Publishing date 1987-08-10
    Publishing country Norway
    Document type English Abstract ; Journal Article
    ZDB-ID 603504-8
    ISSN 0807-7096 ; 0029-2001
    ISSN (online) 0807-7096
    ISSN 0029-2001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Ifit2 deficiency restricts microglial activation and leukocyte migration following murine coronavirus (m-CoV) CNS infection.

    Das Sarma, Jayasri / Burrows, Amy / Rayman, Patricia / Hwang, Mi-Hyun / Kundu, Soumya / Sharma, Nikhil / Bergmann, Cornelia / Sen, Ganes C

    PLoS pathogens

    2020  Volume 16, Issue 11, Page(s) e1009034

    Abstract: ... impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain ...

    Abstract The interferon-induced tetratricopeptide repeat protein (Ifit2) protects mice from lethal neurotropic viruses. Neurotropic coronavirus MHV-RSA59 infection of Ifit2-/- mice caused pronounced morbidity and mortality accompanied by rampant virus replication and spread throughout the brain. In spite of the higher virus load, induction of many cytokines and chemokines in the brains of infected Ifit2-/- mice were similar to that in wild-type mice. In contrast, infected Ifit2-/- mice revealed significantly impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain, possibly contributing to the lack of viral clearance. These two deficiencies were associated with a lower level of microglial expression of CX3CR1, the receptor of the CX3CL1 (Fractalkine) chemokine, which plays a critical role in both microglial activation and leukocyte recruitment. The above results uncovered a new potential role of an interferon-induced protein in immune protection.
    MeSH term(s) Animals ; Apoptosis Regulatory Proteins/deficiency ; Apoptosis Regulatory Proteins/metabolism ; Cell Movement/immunology ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Cytokines/metabolism ; Interferons/metabolism ; Leukocytes/cytology ; Leukocytes/metabolism ; Leukocytes/virology ; Mice, Inbred C57BL ; Microglia/metabolism ; Murine hepatitis virus/metabolism ; Murine hepatitis virus/pathogenicity ; RNA-Binding Proteins/metabolism ; Virus Replication/immunology
    Chemical Substances Apoptosis Regulatory Proteins ; Cytokines ; Ifit2 protein, mouse ; RNA-Binding Proteins ; Interferons (9008-11-1)
    Language English
    Publishing date 2020-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1009034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Synaptic and non-synaptic components of the human cervical evoked response.

    Ganes, T

    Journal of the neurological sciences

    1982  Volume 55, Issue 3, Page(s) 313–326

    Abstract: The human cervical evoked response comprises a main negative wave and a following positivity. The peak of the negative wave, N13, is preceded by a small notch, N11, on the ascending negativity and is followed by another notch, N14, on the descending ... ...

    Abstract The human cervical evoked response comprises a main negative wave and a following positivity. The peak of the negative wave, N13, is preceded by a small notch, N11, on the ascending negativity and is followed by another notch, N14, on the descending negative slope. The mechanisms of the components in the human cervical evoked response are still subject to discussion. In the present study conventional neurophysiological techniques were applied to see whether the components were of synaptic or non-synaptic origin. Resistance to high-frequency stimulation, refractoriness as tested by train or double shock conditioning stimuli and the effect of graded stimulation revealed that N11 and N14 fulfilled the criteria of a non-synaptic origin. N13 and the positive wave had properties pointing to a synaptic origin, the latter evidently reflecting an inhibitory mechanism. Each component in the human cervical evoked response both morphologically and functionally resembled the well known subcomponents in the spinal cord dorsum potential in experimental animals.
    MeSH term(s) Brachial Plexus/physiology ; Evoked Potentials ; Humans ; Median Nerve/physiology ; Radial Nerve/physiology ; Spinal Cord/physiology ; Spinal Nerve Roots/physiology ; Spinal Nerves/physiology ; Synapses/physiology ; Ulnar Nerve/physiology
    Language English
    Publishing date 1982-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80160-4
    ISSN 1878-5883 ; 0022-510X ; 0374-8642
    ISSN (online) 1878-5883
    ISSN 0022-510X ; 0374-8642
    DOI 10.1016/0022-510x(82)90129-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization.

    Song, Qiaoling / Datta, Shyamasree / Liang, Xue / Xu, Xiaohan / Pavicic, Paul / Zhang, Xiaonan / Zhao, Yuanyuan / Liu, Shan / Zhao, Jun / Xu, Yuting / Xu, Jing / Wu, Lihong / Wu, Zhihua / Zhang, Minghui / Zhao, Zhan / Lin, Chunhua / Wang, Yuxin / Han, Peng / Jiang, Peng /
    Qin, Yating / Li, Wei / Zhang, Yingying / Luo, Yonglun / Sen, Ganes / Stark, George R / Zhao, Chenyang / Hamilton, Thomas / Yang, Jinbo

    Cellular & molecular immunology

    2023  Volume 20, Issue 2, Page(s) 143–157

    Abstract: Due to their broad functional plasticity, myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury (APAP-ALI). A comprehensive understanding of cellular diversity and intercellular crosstalk is ... ...

    Abstract Due to their broad functional plasticity, myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury (APAP-ALI). A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment. Here, we identified the function of IFN-I in the myeloid compartment during APAP-ALI. Utilizing single-cell RNA sequencing, we characterized the cellular atlas and dynamic progression of liver CD11b+ cells post APAP-ALI in WT and STAT2 T403A mice, which was further validated by immunofluorescence staining, bulk RNA-seq, and functional experiments in vitro and in vivo. We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages, leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+ restorative macrophage maturation, contributing to efficient liver repair. Overall, we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.
    MeSH term(s) Animals ; Mice ; Acetaminophen ; Chemical and Drug Induced Liver Injury/metabolism ; Liver/metabolism ; Neutrophils/metabolism ; Macrophages ; Mice, Inbred C57BL ; Membrane Glycoproteins/metabolism ; Receptors, Immunologic/metabolism
    Chemical Substances Acetaminophen (362O9ITL9D) ; Trem2 protein, mouse ; Membrane Glycoproteins ; Receptors, Immunologic
    Language English
    Publishing date 2023-01-04
    Publishing country China
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2435097-7
    ISSN 2042-0226 ; 1672-7681
    ISSN (online) 2042-0226
    ISSN 1672-7681
    DOI 10.1038/s41423-022-00966-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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