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  1. Artikel ; Online: Natural Anti-Cancer Agents: Implications in Gemcitabine-Resistant Pancreatic Cancer Treatment.

    Marasini, Bishal / Sahu, Ravi P

    Mini reviews in medicinal chemistry

    2017  Band 17, Heft 11, Seite(n) 920–927

    Abstract: Background & objective: Pancreatic cancer is one of the most lethal malignancies accounting for the fourth leading cause of cancer-related deaths in the United States. Among several explored anticancer agents, Gemcitabine, a nucleoside analogue remained ...

    Abstract Background & objective: Pancreatic cancer is one of the most lethal malignancies accounting for the fourth leading cause of cancer-related deaths in the United States. Among several explored anticancer agents, Gemcitabine, a nucleoside analogue remained a front line chemotherapeutic agent for the treatment of pancreatic cancer. However, gemcitabine exerts a low response rate with limited progression free survival in patients due to cellular resistance of pancreatic tumors to this therapy. Several chemotherapeutic agents have been explored in combination with gemcitabine against pancreatic cancer with overall mixed responses and survival rates. Naturally occurring dietary agents possess promising anticancer properties and have been shown to target various oncogenic signaling pathways in in-vitro and in-vivo pancreatic cancer models.
    Results: Multiple studies using natural compounds have shown increased therapeutic efficacy of gemcitabine in pancreatic cancer models.
    Conclusion: This review is focused on recent updates on cellular, preclinical and clinical studies utilizing natural anticancer agents with gemcitabine against pancreatic cancer.
    Mesh-Begriff(e) Antineoplastic Agents/therapeutic use ; Biological Products/therapeutic use ; Combined Modality Therapy ; Curcumin/therapeutic use ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/drug therapy
    Chemische Substanzen Antineoplastic Agents ; Biological Products ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; Curcumin (IT942ZTH98)
    Sprache Englisch
    Erscheinungsdatum 2017
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2104081-3
    ISSN 1875-5607 ; 1389-5575
    ISSN (online) 1875-5607
    ISSN 1389-5575
    DOI 10.2174/1389557517666170315124438
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion.

    Ruprecht, Ruth M / Marasini, Bishal / Thippeshappa, Rajesh

    Vaccines

    2019  Band 7, Heft 4

    Abstract: The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant ... ...

    Abstract The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of different Ig classes in rhesus macaques (RMs) followed by mucosal simian-human immunodeficiency virus (SHIV) challenge. We gave anti-HIV-1 IgM, IgG, and dimeric IgA (dIgA) versions of the same human nmAb, HGN194 that targets the conserved V3 loop crown. Surprisingly, dIgA1 with its wide-open, flat hinge protected 83% of the RMs against intrarectal R5-tropic SHIV-1157ipEL-p challenge, whereas dIgA2, with its narrow hinge, only protected 17% of the animals-despite identical epitope specificities and in vitro neutralization curves of the two dIgA isotypes (Watkins et al.,
    Sprache Englisch
    Erscheinungsdatum 2019-11-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines7040194
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: A novel Ebola virus antibody-dependent cell-mediated cytotoxicity (Ebola ADCC) assay.

    Singh, Karnail / Marasini, Bishal / Chen, Xuemin / Spearman, Paul

    Journal of immunological methods

    2018  Band 460, Seite(n) 10–16

    Abstract: Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell- ... ...

    Abstract Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potential mechanism through which anti-Ebola antibodies may mediate protection. We developed a robust Ebola-specific ADCC assay for use in ongoing trials of Ebola vaccines. Stable cell lines for inducible Zaire ebolavirus glycoprotein (EBOV GP) expression were developed to provide a uniform source of target cells in the assay, and were combined with an existing human natural killer (NK) cell line as the effector cell. When applied to commercially available anti-EBOV GP monoclonal antibodies, the assay clearly differentiated antibody with high ADCC activity from those with low or no ADCC activity. Anti-EBOV ADCC activity was also detected in plasma samples from rhesus macaques immunized with a candidate Ebola vaccine. The Ebola ADCC assay reported here will be a useful tool in studying the functionality of anti-EBOV GP antibodies elicited by Ebola vaccines in ongoing and future clinical trials.
    Mesh-Begriff(e) Animals ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity ; Cell Line ; Cytotoxicity Tests, Immunologic/methods ; Ebola Vaccines/immunology ; Ebolavirus/immunology ; Female ; Hemorrhagic Fever, Ebola/immunology ; Humans ; Macaca mulatta ; Male ; Vaccination
    Chemische Substanzen Antibodies, Viral ; Ebola Vaccines
    Sprache Englisch
    Erscheinungsdatum 2018-06-15
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2018.06.002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 795: Hefte anzeigen Standort:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  4. Artikel ; Online: Mucosal AIDS virus transmission is enhanced by antiviral IgG isolated early in infection.

    Marasini, Bishal / Vyas, Hemant K / Lakhashe, Samir K / Hariraju, Dinesh / Akhtar, Akil / Ratcliffe, Sarah J / Ruprecht, Ruth M

    AIDS (London, England)

    2021  Band 35, Heft 15, Seite(n) 2423–2432

    Abstract: Objective: Antibody-dependent enhancement (ADE) affects host-virus dynamics in fundamentally different ways: i) enhancement of initial virus acquisition, and/or ii) increased disease progression/severity. Here we address the question whether anti-HIV-1 ... ...

    Abstract Objective: Antibody-dependent enhancement (ADE) affects host-virus dynamics in fundamentally different ways: i) enhancement of initial virus acquisition, and/or ii) increased disease progression/severity. Here we address the question whether anti-HIV-1 antibodies can enhance initial infection. While cell-culture experiments hinted at this possibility, in-vivo proof remained elusive.
    Design: We used passive immunization in nonhuman primates challenged with simian-human immunodeficiency virus (SHIV), a chimera expressing HIV-1 envelope. We purified IgG from rhesus monkeys with early-stage SHIV infection - before cross-neutralizing anti-HIV-1 antibodies had developed - and screened for maximal complement-mediated antibody-dependent enhancement (C'-ADE) of viral replication with a SHIV strain phylogenetically distinct from that harbored by IgG donor macaques. IgG fractions with maximal C'-ADE but lacking neutralization were combined to yield enhancing anti-SHIV IgG (enSHIVIG).
    Results: We serially enrolled naive macaques (Group 1) to determine the minimal and 50% animal infectious doses required to establish persistent infection after intrarectal SHIV challenge. The first animal was inoculated with a 1 : 10 virus-stock dilution; after this animal's viral RNA load was >104copies/ml, the next macaque was challenged with 10x less virus, a process repeated until viremia no longer ensued. Group 2 was pretreated intravenously with enSHIVIG 24 h before SHIV challenge. Overall, Group 2 macaques required 3.4-fold less virus compared to controls (P = 0.002). This finding is consistent with enhanced susceptibility of the passively immunized animals to mucosal SHIV challenge.
    Conclusion: These passive immunization data give proof of IgG-mediated enhanced virus acquisition after mucosal exposure - a potential concern for antibody-based AIDS vaccine development.
    Mesh-Begriff(e) AIDS Vaccines ; Animals ; Antiviral Agents ; HIV Antibodies ; HIV Infections ; HIV-1 ; Immunoglobulin G ; Simian Acquired Immunodeficiency Syndrome ; Simian Immunodeficiency Virus
    Chemische Substanzen AIDS Vaccines ; Antiviral Agents ; HIV Antibodies ; Immunoglobulin G
    Sprache Englisch
    Erscheinungsdatum 2021-08-16
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000003050
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2228: Hefte anzeigen Standort:
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  5. Artikel ; Online: A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses against Pathogenic Ebola Viruses in Rhesus Macaques.

    Singh, Karnail / Marasini, Bishal / Chen, Xuemin / Ding, Lingmei / Wang, Jaang-Jiun / Xiao, Peng / Villinger, Francois / Spearman, Paul

    Journal of virology

    2020  Band 94, Heft 9

    Abstract: The 2013-2016 Ebola outbreak in West Africa led to accelerated efforts to develop vaccines against these highly virulent viruses. A live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly ... ...

    Abstract The 2013-2016 Ebola outbreak in West Africa led to accelerated efforts to develop vaccines against these highly virulent viruses. A live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. Vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia Ankara (MVA) Ebola vaccine also appear promising and are progressing in clinical evaluation. However, the ability of current live vector-based approaches to protect against multiple pathogenic species of Ebola is not yet established, and eliciting durable responses may require additional booster vaccinations. Here, we report the development of a bivalent, spherical Ebola virus-like particle (VLP) vaccine that incorporates glycoproteins (GPs) from Zaire Ebola virus (EBOV) and Sudan Ebola virus (SUDV) and is designed to extend the breadth of immunity beyond EBOV. Immunization of rabbits with bivalent Ebola VLPs produced antibodies that neutralized all four pathogenic species of Ebola viruses and elicited antibody-dependent cell-mediated cytotoxicity (ADCC) responses against EBOV and SUDV. Vaccination of rhesus macaques with bivalent VLPs generated strong humoral immune responses, including high titers of binding, as well as neutralizing antibodies and ADCC responses. VLP vaccination led to a significant increase in the frequency of Ebola GP-specific CD4 and CD8 T cell responses. These results demonstrate that a novel bivalent Ebola VLP vaccine elicits strong humoral and cellular immune responses against pathogenic Ebola viruses and support further evaluation of this approach as a potential addition to Ebola vaccine development efforts.
    Mesh-Begriff(e) Africa, Western ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Disease Models, Animal ; Ebola Vaccines/immunology ; Ebolavirus/immunology ; Female ; Glycoproteins/immunology ; Hemorrhagic Fever, Ebola/immunology ; Immunization ; Macaca mulatta ; Male ; Vaccination ; Vaccines, Attenuated ; Vaccines, Virus-Like Particle/immunology ; Viral Envelope Proteins/immunology ; Viral Vaccines/immunology
    Chemische Substanzen Antibodies, Neutralizing ; Antibodies, Viral ; Ebola Vaccines ; Glycoproteins ; Vaccines, Attenuated ; Vaccines, Virus-Like Particle ; Viral Envelope Proteins ; Viral Vaccines
    Sprache Englisch
    Erscheinungsdatum 2020-04-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01884-19
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 609: Hefte anzeigen Standort:
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