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  1. Article: 5-Azacytidine-Mediated Modulation of the Immune Microenvironment in Murine Acute Myeloid Leukemia.

    Ebelt, Nancy D / Manuel, Edwin R

    Cancers

    2022  Volume 15, Issue 1

    Abstract: Cancer cells accumulate epigenetic modifications that allow escape from intrinsic and extrinsic surveillance mechanisms. In the case of acute myeloid leukemias (AML) and myelodysplastic syndromes, agents that disrupt chromatin structure, namely ... ...

    Abstract Cancer cells accumulate epigenetic modifications that allow escape from intrinsic and extrinsic surveillance mechanisms. In the case of acute myeloid leukemias (AML) and myelodysplastic syndromes, agents that disrupt chromatin structure, namely hypomethylating agents (HMAs), have shown tremendous promise as an alternate, milder treatment option for older, clinically non-fit patients. HMAs reprogram the epigenetic landscape in tumor cells through the reversal of DNA hypermethylation. Therapeutic effects resulting from these epigenetic changes are incredibly effective, sometimes resulting in complete remissions, but are frequently lost due to primary or acquired resistance. In this study, we describe syngeneic murine leukemias that are responsive to the HMA 5-azacytidine (5-Aza), as determined by augmented expression of a transduced luciferase reporter. We also found that 5-Aza treatment re-established immune-related transcript expression, suppressed leukemic burden and extended survival in leukemia-challenged mice. The effects of 5-Aza treatment were short-lived, and analysis of the immune microenvironment reveals possible mechanisms of resistance, such as simultaneous increase in immune checkpoint protein expression. This represents a model system that is highly responsive to HMAs and recapitulates major therapeutic outcomes observed in human leukemia (relapse) and may serve as a pre-clinical tool for studying acquired resistance and novel treatment combinations.
    Language English
    Publishing date 2022-12-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15010118
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  2. Article: Targeted Depletion of Hyaluronic Acid Mitigates Murine Breast Cancer Growth.

    Zamloot, Vic / Ebelt, Nancy Danielle / Soo, Catherine / Jinka, Shweta / Manuel, Edwin R

    Cancers

    2022  Volume 14, Issue 19

    Abstract: Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and ... ...

    Abstract Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and proliferation and regulates both pro- and anti-inflammatory cytokine production through tumor-associated macrophages. The highly negative charge of HA enables its uptake of vast amounts of water that greatly increases the tumor interstitial fluidic pressure, which, combined with the presence of other extracellular matrix components such as collagen, results in tumor stroma with abnormal vasculature, hypoxia, and increased drug resistance. Thus, the degradation of HA in breast cancer may attenuate growth and improve permeability to anticancer agents. Previous methods to deplete tumor HA have resulted in significant off-tumor effects due to the systemic use of mammalian hyaluronidases. To overcome this, we developed a hyaluronidase-secreting
    Language English
    Publishing date 2022-09-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14194614
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  3. Article ; Online: Targeting desmoplasia in pancreatic cancer as an essential first step to effective therapy.

    Ebelt, Nancy D / Zamloot, Vic / Manuel, Edwin R

    Oncotarget

    2020  Volume 11, Issue 38, Page(s) 3486–3488

    Abstract: Pancreatic cancer is considered one of the most lethal cancers in the US. It contributes to an estimated 47,000 deaths annually and is predicted to surpass prostate, breast and colorectal cancers as the leading cause of cancer-related death. Although ... ...

    Abstract Pancreatic cancer is considered one of the most lethal cancers in the US. It contributes to an estimated 47,000 deaths annually and is predicted to surpass prostate, breast and colorectal cancers as the leading cause of cancer-related death. Although major advancements in cancer treatment have improved outcomes for many cancer types, survival rate for pancreatic cancer has not improved in nearly four decades despite tremendous effort. One attribute of pancreatic cancer that is considered a major barrier to effective treatment is the formation of fibrotic tissue around tumor cells known as desmoplasia. A number of promising approaches have been developed to deplete fibrotic components in pancreatic tumors to enhance drug delivery, some of which have been tested in clinical trials of advanced, unresectable pancreatic cancer. Here, we discuss previous efforts, shortcomings and new considerations for developing more effective agents to eliminate desmoplasia.
    Language English
    Publishing date 2020-09-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.27745
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  4. Article ; Online: Resistance phenotype and virulence potential of

    Yescas-Zazueta, Viviana / Rocha-Gracia, Rosa Del Carmen / González-Bonilla, Cesar R / Ayala-Zavala, J Fernando / Enciso-Martínez, Yessica / Carreón-León, Eder A / González Corona, Brigitte A / Valencia, Dora / Ballesteros-Monrreal, Manuel G / Barrios-Villa, Edwin

    Microbiology (Reading, England)

    2024  Volume 170, Issue 4

    Abstract: Introduction. ...

    Abstract Introduction.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Plasmids/genetics ; Virulence/genetics ; Microbial Sensitivity Tests ; Enterobacteriaceae/genetics ; Enterobacteriaceae/drug effects ; Enterobacteriaceae/pathogenicity ; Enterobacteriaceae/isolation & purification ; Enterobacteriaceae/classification ; Phylogeny ; Virulence Factors/genetics ; Humans ; Enterobacteriaceae Infections/microbiology ; Phenotype ; Drug Resistance, Bacterial/genetics ; Quinolones/pharmacology ; beta-Lactams/pharmacology ; Drug Resistance, Multiple, Bacterial/genetics ; Food Microbiology
    Chemical Substances Anti-Bacterial Agents ; Virulence Factors ; Quinolones ; beta-Lactams
    Language English
    Publishing date 2024-04-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.001457
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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Utilizing Salmonella to treat solid malignancies.

    Ebelt, Nancy D / Manuel, Edwin R

    Journal of surgical oncology

    2017  Volume 116, Issue 1, Page(s) 75–82

    Abstract: Despite intensive research into novel treatment strategies for cancer, it remains the second most common cause of death in industrialized populations. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with dismal prognosis. Currently, ...

    Abstract Despite intensive research into novel treatment strategies for cancer, it remains the second most common cause of death in industrialized populations. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with dismal prognosis. Currently, surgical resection offers the best chance for extended survival, yet recurrence remains high and is associated with poor outcome. Systemic treatment has evolved from non-specific, cytotoxic chemotherapy to the use of cancer-targeting agents, profoundly changing treatment approaches in the metastatic and adjuvant settings. One promising approach, highlighted in this review, uses the inherent capacity of Salmonella to colonize and eliminate solid tumors.
    MeSH term(s) Animals ; Biological Therapy/methods ; Carcinoma, Pancreatic Ductal/immunology ; Carcinoma, Pancreatic Ductal/therapy ; Disease Models, Animal ; Gene Transfer Techniques ; Humans ; Immunotherapy/methods ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/therapy ; Salmonella typhimurium/genetics ; Transformation, Bacterial
    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 82063-5
    ISSN 1096-9098 ; 0022-4790
    ISSN (online) 1096-9098
    ISSN 0022-4790
    DOI 10.1002/jso.24644
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 706: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Collagenase-Expressing

    Ebelt, Nancy D / Zamloot, Vic / Zuniga, Edith / Passi, Kevin B / Sobocinski, Lukas J / Young, Cari A / Blazar, Bruce R / Manuel, Edwin R

    Cancers

    2021  Volume 13, Issue 14

    Abstract: Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a ... ...

    Abstract Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel
    Language English
    Publishing date 2021-07-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13143565
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  7. Article ; Online: Early Detection of Alzheimer’s Disease

    Manuel Curado / Francisco Escolano / Miguel A. Lozano / Edwin R. Hancock

    Entropy, Vol 22, Iss 465, p

    Detecting Asymmetries with a Return Random Walk Link Predictor

    2020  Volume 465

    Abstract: Alzheimer’s disease has been extensively studied using undirected graphs to represent the correlations of BOLD signals in different anatomical regions through functional magnetic resonance imaging (fMRI). However, there has been relatively little ... ...

    Abstract Alzheimer’s disease has been extensively studied using undirected graphs to represent the correlations of BOLD signals in different anatomical regions through functional magnetic resonance imaging (fMRI). However, there has been relatively little analysis of this kind of data using directed graphs, which potentially offer the potential to capture asymmetries in the interactions between different anatomical brain regions. The detection of these asymmetries is relevant to detect the disease in an early stage. For this reason, in this paper, we analyze data extracted from fMRI images using the net4Lap algorithm to infer a directed graph from the available BOLD signals, and then seek to determine asymmetries between the left and right hemispheres of the brain using a directed version of the Return Random Walk (RRW). Experimental evaluation of this method reveals that it leads to the identification of anatomical brain regions known to be implicated in the early development of Alzheimer’s disease in clinical studies.
    Keywords Alzheimer’s disease ; neural embedding ; random walk ; link prediction ; brain asymmetries ; fMRI networks ; Science ; Q ; Astrophysics ; QB460-466 ; Physics ; QC1-999
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment.

    Marzagalli, Monica / Ebelt, Nancy D / Manuel, Edwin R

    Seminars in cancer biology

    2019  Volume 59, Page(s) 236–250

    Abstract: Cutaneous melanoma is the most common skin cancer with an incidence that has been rapidly increasing in the past decades. Melanomas are among the most immunogenic tumors and, as such, have the greatest potential to respond favorably to immunotherapy. ... ...

    Abstract Cutaneous melanoma is the most common skin cancer with an incidence that has been rapidly increasing in the past decades. Melanomas are among the most immunogenic tumors and, as such, have the greatest potential to respond favorably to immunotherapy. However, like many cancers, melanomas acquire various suppressive mechanisms, which generally act in concert, to escape innate and adaptive immune detection and destruction. Intense research into the cellular and molecular events associated with melanomagenesis, which ultimately lead to immune suppression, has resulted in the discovery of new therapeutic targets and synergistic combinations of immunotherapy, targeted therapy and chemotherapy. Tremendous effort to determine efficacy of single and combination therapies in pre-clinical and clinical phase I-III trials has led to FDA-approval of several immunotherapeutic agents that could potentially be beneficial for aggressive, highly refractory, advanced and metastatic melanomas. The increasing availability of approved combination therapies for melanoma and more rapid assessment of patient tumors has increased the feasibility of personalized treatment to overcome patient and tumor heterogeneity and to achieve greater clinical benefit. Here, we review the evolution of the immune system during melanomagenesis, mechanisms exploited by melanoma to suppress anti-tumor immunity and methods that have been developed to restore immunity. We emphasize that an effective therapeutic strategy will require coordinate activation of tumor-specific immunity as well as increased recognition and accessibility of melanoma cells in primary tumors and distal metastases. This review integrates available knowledge on melanoma-specific immunity, molecular signaling pathways and molecular targeting strategies that could be utilized to envision therapeutics with broader application and greater efficacy for early stage and advanced metastatic melanoma.
    MeSH term(s) Animals ; Biomarkers ; Cell Communication ; Cytokines/metabolism ; Energy Metabolism ; Humans ; Immune System/immunology ; Immune System/metabolism ; Immunity ; Melanoma/etiology ; Melanoma/metabolism ; Melanoma/pathology ; Signal Transduction ; Tumor Escape/genetics ; Tumor Escape/immunology ; Tumor Microenvironment/immunology
    Chemical Substances Biomarkers ; Cytokines
    Language English
    Publishing date 2019-08-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1016/j.semcancer.2019.08.002
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2922: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Early Detection of Alzheimer's Disease: Detecting Asymmetries with a Return Random Walk Link Predictor.

    Curado, Manuel / Escolano, Francisco / Lozano, Miguel A / Hancock, Edwin R

    Entropy (Basel, Switzerland)

    2020  Volume 22, Issue 4

    Abstract: Alzheimer's disease has been extensively studied using undirected graphs to represent the correlations of BOLD signals in different anatomical regions through functional magnetic resonance imaging (fMRI). However, there has been relatively little ... ...

    Abstract Alzheimer's disease has been extensively studied using undirected graphs to represent the correlations of BOLD signals in different anatomical regions through functional magnetic resonance imaging (fMRI). However, there has been relatively little analysis of this kind of data using directed graphs, which potentially offer the potential to capture asymmetries in the interactions between different anatomical brain regions. The detection of these asymmetries is relevant to detect the disease in an early stage. For this reason, in this paper, we analyze data extracted from fMRI images using the
    Language English
    Publishing date 2020-04-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2014734-X
    ISSN 1099-4300 ; 1099-4300
    ISSN (online) 1099-4300
    ISSN 1099-4300
    DOI 10.3390/e22040465
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  10. Article: Developing Effective Salmonella-based Approaches to Treat Pancreatic Cancer.

    Chen, Jeremy / Diamond, Don J / Manuel, Edwin R

    Pancreatic disorders & therapy

    2016  Volume 6, Issue 1, Page(s) 1–2

    Language English
    Publishing date 2016-02-18
    Publishing country United States
    Document type Journal Article
    ISSN 2165-7092
    ISSN 2165-7092
    DOI 10.4172/2165-7092.1000167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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