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  1. Article: TERT expression increases with tumor grade in a cohort of

    Jalasutram, Anvesh / Caniglia, John L / Velpula, Kiran K / Guda, Maheedhara R / Bach, Sarah E / Tsung, Andrew J

    American journal of translational research

    2022  Volume 14, Issue 1, Page(s) 295–303

    Abstract: The molecular mechanisms underlying progression from astrocytoma to secondary glioblastoma are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in various cancers. ... ...

    Abstract The molecular mechanisms underlying progression from astrocytoma to secondary glioblastoma are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in various cancers. Upregulation of TERT is a likely mechanism by which malignant cells delay senescence and evade cell death. TERT activity is also the primary mechanism by which malignant cells replenish telomeres, with the other means of telomere replacement being the alternative lengthening of the telomeres (ALT) system. The ALT system is known to be upregulated in tumors harboring loss of function mutations in ATRX. This study analyzed aggregate data on TERT and ATRX expression in astrocytoma, anaplastic astrocytoma, and secondary glioblastoma and then supplemented the data with our findings. In data obtained from Oncomine, significantly higher TERT expression is seen in astrocytomas and secondary glioblastomas compared to normal brain tissue. Additionally, The Cancer Genome Atlas data shows that TERT expression is a significant predictor of overall survival in low-grade gliomas. However, studies comparing the expression of TERT across all grades of astrocytomas had not been performed to date. Using immunohistochemical staining, we showed that controlling for ATRX and IDH mutational status, TERT expression increased with tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that TERT expression increases as astrocytomas become more aggressive tumors, and probably plays a role in their progression.
    Language English
    Publishing date 2022-01-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2471058-1
    ISSN 1943-8141
    ISSN 1943-8141
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A potential role for Galectin-3 inhibitors in the treatment of COVID-19.

    Caniglia, John L / Guda, Maheedhara R / Asuthkar, Swapna / Tsung, Andrew J / Velpula, Kiran K

    PeerJ

    2020  Volume 8, Page(s) e9392

    Abstract: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of ... ...

    Abstract The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of COVID-19, there is an urgent need to identify therapies that may be effective in treatment. Recent evidence has implicated the development of cytokine release syndrome as the major cause of fatality in COVID-19 patients, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) observed in patients. Galectin-3 (Gal-3) is an animal lectin that has been implicated in the disease process of a variety of inflammatory conditions. Inhibitors of the small molecule Gal-3 have been shown to reduce the levels of both IL-6 and TNF-α in vitro and have shown anti-inflammatory effects in vivo. Additionally, a key domain in the spike protein of β-coronaviridae, a genus which includes SARS-CoV2, is nearly identical in morphology to human Gal-3. These spike proteins are critical for the virus' entry into host cells. Here we provide a systematic review of the available literature and an impetus for further research on the use of Gal-3 inhibitors in the treatment of COVID-19. Further, we propose a dual mechanism by which Gal-3 inhibition may be beneficial in the treatment of COVID-19, both suppressing the host inflammatory response and impeding viral attachment to host cells.
    Keywords covid19
    Language English
    Publishing date 2020-06-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.9392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immunopathology of galectin-3: an increasingly promising target in COVID-19.

    Caniglia, John L / Asuthkar, Swapna / Tsung, Andrew J / Guda, Maheedhara R / Velpula, Kiran K

    F1000Research

    2020  Volume 9, Page(s) 1078

    Abstract: The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported ... ...

    Abstract The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the "Cytokine Storm Syndrome" (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages
    MeSH term(s) Humans ; Betacoronavirus ; Coronavirus Infections/pathology ; COVID-19 ; Cytokine Release Syndrome/virology ; Galectin 3/immunology ; N-Acetylneuraminic Acid ; Pandemics ; Pneumonia, Viral/pathology ; SARS-CoV-2
    Chemical Substances Galectin 3 ; N-Acetylneuraminic Acid (GZP2782OP0)
    Keywords covid19
    Language English
    Publishing date 2020-09-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402 ; 2046-1402
    ISSN (online) 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.25979.2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Beyond glucose: alternative sources of energy in glioblastoma.

    Caniglia, John L / Jalasutram, Anvesh / Asuthkar, Swapna / Sahagun, Joseph / Park, Simon / Ravindra, Aditya / Tsung, Andrew J / Guda, Maheedhara R / Velpula, Kiran K

    Theranostics

    2021  Volume 11, Issue 5, Page(s) 2048–2057

    Abstract: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. With a designation of WHO Grade IV, it is also the most lethal primary brain tumor with a median survival of just 15 months. This is often despite aggressive treatment that ...

    Abstract Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. With a designation of WHO Grade IV, it is also the most lethal primary brain tumor with a median survival of just 15 months. This is often despite aggressive treatment that includes surgical resection, radiation therapy, and chemotherapy. Based on the poor outcomes and prevalence of the tumor, the demand for innovative therapies continues to represent a pressing issue for clinicians and researchers. In terms of therapies targeting metabolism, the prevalence of the Warburg effect has led to a focus on targeting glucose metabolism to halt tumor progression. While glucose is the dominant source of growth substrate in GBM, a number of unique metabolic pathways are exploited in GBM to meet the increased demand for replication and progression. In this review we aim to explore how metabolites from fatty acid oxidation, the urea cycle, the glutamate-glutamine cycle, and one-carbon metabolism are shunted toward energy producing pathways to meet the high energy demand in GBM. We will also explore how the process of autophagy provides a reservoir of nutrients to support viable tumor cells. By so doing, we aim to establish a foundation of implicated metabolic mechanisms supporting growth and tumorigenesis of GBM within the literature. With the sparse number of therapeutic interventions specifically targeting metabolic pathways in GBM, we hope that this review expands further insight into the development of novel treatment modalities.
    MeSH term(s) Animals ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Energy Metabolism ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Glucose/metabolism ; Humans
    Chemical Substances Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-01-01
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.53506
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A potential role for Galectin-3 inhibitors in the treatment of COVID-19

    Caniglia, John L. / Guda, Maheedhara R. / Asuthkar, Swapna / Tsung, Andrew J. / Velpula, Kiran K.

    PeerJ

    2020  Volume 8, Page(s) e9392

    Abstract: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of ... ...

    Abstract The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of COVID-19, there is an urgent need to identify therapies that may be effective in treatment. Recent evidence has implicated the development of cytokine release syndrome as the major cause of fatality in COVID-19 patients, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) observed in patients. Galectin-3 (Gal-3) is an animal lectin that has been implicated in the disease process of a variety of inflammatory conditions. Inhibitors of the small molecule Gal-3 have been shown to reduce the levels of both IL-6 and TNF-α in vitro and have shown anti-inflammatory effects in vivo. Additionally, a key domain in the spike protein of β-coronaviridae, a genus which includes SARS-CoV2, is nearly identical in morphology to human Gal-3. These spike proteins are critical for the virus’ entry into host cells. Here we provide a systematic review of the available literature and an impetus for further research on the use of Gal-3 inhibitors in the treatment of COVID-19. Further, we propose a dual mechanism by which Gal-3 inhibition may be beneficial in the treatment of COVID-19, both suppressing the host inflammatory response and impeding viral attachment to host cells.
    Keywords General Biochemistry, Genetics and Molecular Biology ; General Neuroscience ; General Agricultural and Biological Sciences ; General Medicine ; covid19
    Language English
    Publisher PeerJ
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.9392
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: A potential role for Galectin-3 inhibitors in the treatment of COVID-19

    Caniglia, John L. / Guda, Maheedhara R. / Asuthkar, Swapna / Tsung, Andrew J. / Velpula, Kiran K.

    PeerJ

    Abstract: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization With no standard of care for the treatment of ... ...

    Abstract The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization With no standard of care for the treatment of COVID-19, there is an urgent need to identify therapies that may be effective in treatment Recent evidence has implicated the development of cytokine release syndrome as the major cause of fatality in COVID-19 patients, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) observed in patients Galectin-3 (Gal-3) is an animal lectin that has been implicated in the disease process of a variety of inflammatory conditions Inhibitors of the small molecule Gal-3 have been shown to reduce the levels of both IL-6 and TNF-α in vitro and have shown anti-inflammatory effects in vivo Additionally, a key domain in the spike protein of β-coronaviridae, a genus which includes SARS-CoV2, is nearly identical in morphology to human Gal-3 These spike proteins are critical for the virus’ entry into host cells Here we provide a systematic review of the available literature and an impetus for further research on the use of Gal-3 inhibitors in the treatment of COVID-19 Further, we propose a dual mechanism by which Gal-3 inhibition may be beneficial in the treatment of COVID-19, both suppressing the host inflammatory response and impeding viral attachment to host cells
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #602799
    Database COVID19

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  7. Article: Pleiotropic role of macrophage migration inhibitory factor in cancer.

    Guda, Maheedhara R / Rashid, Matthew A / Asuthkar, Swapna / Jalasutram, Anvesh / Caniglia, John L / Tsung, Andrew J / Velpula, Kiran K

    American journal of cancer research

    2019  Volume 9, Issue 12, Page(s) 2760–2773

    Abstract: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that serves many roles in inflammation and immunity; however, it is also involved in carcinogenesis. This is a review of the clinical and experimental data published on MIF and its ... ...

    Abstract Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that serves many roles in inflammation and immunity; however, it is also involved in carcinogenesis. This is a review of the clinical and experimental data published on MIF and its role in various types of cancers such as glioblastomas, lung cancer, breast cancer, gastric cancer, melanoma, bladder cancer, and head and neck cancers. The goal of this review is to show MIFs role in various types of cancers. Data show that MIF is overexpressed in these malignancies in humans, and contributes to the deregulation of the cell cycle, angiogenesis, and metastasis. Clinical studies show that MIF overexpression in these types of tumors significantly decreases survival rate, and increases tumor aggression. There are multiple anti-MIF molecules that are currently being explored and investigations should be continued.
    Language English
    Publishing date 2019-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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