LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 327

Search options

  1. Article ; Online: Translational medicine from observation to hypothesis to interpretation

    Wang Ena

    Journal of Translational Medicine, Vol 10, Iss Suppl 2, p A

    2012  Volume 44

    Keywords Medicine ; R
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article: The MAPK hypothesis: immune-regulatory effects of MAPK-pathway genetic dysregulations and implications for breast cancer immunotherapy.

    Bedognetti, Davide / Roelands, Jessica / Decock, Julie / Wang, Ena / Hendrickx, Wouter

    Emerging topics in life sciences

    2021  Volume 1, Issue 5, Page(s) 429–445

    Abstract: With the advent of checkpoint inhibition, immunotherapy has revolutionized the clinical management of several cancers, but has demonstrated limited efficacy in mammary carcinoma. Transcriptomic profiling of cancer samples defined distinct ... ...

    Abstract With the advent of checkpoint inhibition, immunotherapy has revolutionized the clinical management of several cancers, but has demonstrated limited efficacy in mammary carcinoma. Transcriptomic profiling of cancer samples defined distinct immunophenotypic categories characterized by different prognostic and predictive connotations. In breast cancer, genomic alterations leading to the dysregulation of mitogen-activated protein kinase (MAPK) pathways have been linked to an immune-silent phenotype associated with poor outcome and treatment resistance. These aberrations include mutations of MAP3K1 and MAP2K4, amplification of KRAS, BRAF, and RAF1, and truncations of NF1. Anticancer therapies targeting MAPK signaling by BRAF and MEK inhibitors have demonstrated clear immunologic effects. These off-target properties could be exploited to convert the immune-silent tumor phenotype into an immune-active one. Preclinical evidence supports that MAPK-pathway inhibition can dramatically increase the efficacy of immunotherapy. In this review, we provide a detailed overview of the immunomodulatory impact of MAPK-pathway blockade through BRAF and MEK inhibitions. While BRAF inhibition might be relevant in melanoma only, MEK inhibition is potentially applicable to a wide range of tumors. Context-dependent similarities and differences of MAPK modulation will be dissected, in light of the complexity of the MAPK pathways. Therapeutic strategies combining the favorable effects of MAPK-oriented interventions on the tumor microenvironment while maintaining T-cell function will be presented. Finally, we will discuss recent studies highlighting the rationale for the implementation of MAPK-interference approaches in combination with checkpoint inhibitors and immune agonists in breast cancer.
    Language English
    Publishing date 2021-02-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2882721-1
    ISSN 2397-8554 ; 2397-8554 ; 2397-8562
    ISSN (online) 2397-8554
    ISSN 2397-8554 ; 2397-8562
    DOI 10.1042/ETLS20170142
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Functional Genome Profiling to Understand Cancer Immune Responsiveness.

    Wang, Ena / Bedognetti, Davide / Marincola, Francesco M

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 2055, Page(s) 231–244

    Abstract: It has been almost two decades since we first proposed the use of minimally invasive serial biopsies to dissect the biology underlining cancer immune responsiveness (CIR) by looking for predictors of response, understanding mechanisms of action (MOA) of ... ...

    Abstract It has been almost two decades since we first proposed the use of minimally invasive serial biopsies to dissect the biology underlining cancer immune responsiveness (CIR) by looking for predictors of response, understanding mechanisms of action (MOA) of therapeutics and documenting strategies adopted by tumor cells to escape immune recognition. This approach led to the first description in 2002 of predictors of CIR, the characterization of the pharmacodynamics of several immune therapeutics, and the geneses of immune escape under immunological pressure prompted by successful treatment. The presumption was straightforward; study CIR where it occurs: the target organ. Since then, a large number of studies corroborated these early observations adding sophistication and accuracy to the investigations. Here, we summarize the history of functional genomic profiling as a discovery and validation tool for immune oncology (IO) and new insights that could be derived by single novel technologies.
    MeSH term(s) Biomarkers, Tumor/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genomics/methods ; Humans ; Immunotherapy/methods ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Treatment Outcome ; Tumor Escape
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2019-09-09
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9773-2_11
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Improving the therapeutic index in adoptive cell therapy: key factors that impact efficacy.

    Wang, Ena / Cesano, Alessandra / Butterfield, Lisa H / Marincola, Francesco

    Journal for immunotherapy of cancer

    2020  Volume 8, Issue 2

    Abstract: The therapeutic index (TI) is a quantitative assessment of a drug safety proportional to its effectiveness. The estimation is intuitive when the engagement of the product with its target is dependent on stable chemistry and predictable pharmacokinetics ... ...

    Abstract The therapeutic index (TI) is a quantitative assessment of a drug safety proportional to its effectiveness. The estimation is intuitive when the engagement of the product with its target is dependent on stable chemistry and predictable pharmacokinetics as is the case for small molecules or antibodies. But for therapeutics with complex biodistribution and context-dependent potency such as adoptive cell therapy (ACT) products, TI estimations need to consider a broader array of factors. These include product-dependent variability such as functional fitness, unpredictable pharmacokinetics due to non-specific trapping, sequestration and extravasation into normal tissues and variable rates of in vivo expansion. In the case of solid malignancies, additional modifiers dependent on individual tumor immune biology may affect pharmacodynamics, including differential trafficking to benign compared with cancer tissue, hampered engagement with target cells, immune suppression and cellular dysfunction due to unfavorable metabolic conditions. Here, we propose a patient-specific assessment of factors affecting on-tumor from off-tumor activity in disparate immunologic environments that impact ACT's clinical efficacy and may favorably balance the TI. for ACT products.
    MeSH term(s) Cell- and Tissue-Based Therapy/methods ; Humans ; Immunotherapy/methods ; Immunotherapy, Adoptive/methods ; Therapeutic Index ; Tumor Microenvironment
    Language English
    Publishing date 2020-10-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2020-001619
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: The Biology of Immune-Active Cancers and Their Regulatory Mechanisms.

    Bedognetti, Davide / Cesano, Alessandra / Marincola, Francesco M / Wang, Ena

    Cancer treatment and research

    2020  Volume 180, Page(s) 149–172

    Abstract: The development of cancer results from the evolutionary balance between the proliferating aptitude of cancer cells and the response of the host's tissues. Some cancers are characterized by genetic instability dependent upon impaired DNA repair mechanisms ...

    Abstract The development of cancer results from the evolutionary balance between the proliferating aptitude of cancer cells and the response of the host's tissues. Some cancers are characterized by genetic instability dependent upon impaired DNA repair mechanisms that lead to the chaotic disruption of multiple cellular functions often in excess of the cancer survival needs and may exert broad effects on surrounding tissues, some beneficial and some detrimental to cancer growth. Among them, inflammatory processes that accompany wound healing may initiate a reaction of the host against the neo-formation. This is possibly triggered by the release by dying cancer cells of molecules known as Damage-Associated Molecular Patterns (DAMPs) following a process termed Immunogenic Cell Death (ICD) that initiates an immune response through innate and adaptive mechanisms. Indeed, analysis of large cancer data sets has shown that ICD is strictly associated with the activation of other immune effector or immune-regulatory pathways. Here, we will describe how immune activation and compensatory immune-regulatory mechanisms balance anti-cancer immune surveillance and the roles that innate and adaptive immunity play including the weight that neo-epitopes may exert as initiators and sculptors of high-affinity memory and effector immune responses against cancer. We will discuss the evolutionary basis for the existence of immune checkpoints and how several theories raised to explain cancer resistance to immunotherapy represent a facet of a similar evolutionary phenomenon that we described in the Theory of Everything. We will show how the biology of immunogenicity and counterbalancing immune regulation is widespread across cancers independent of their ontogenesis while subtle idiosyncratic differences are discernible among them. Finally, we will suggest that overcoming immune resistance implies distinct approaches relevant to the immune context of individual cancers.
    MeSH term(s) Adaptive Immunity ; Alarmins/immunology ; Antigens, Neoplasm/immunology ; Epitopes ; Humans ; Immunity, Innate ; Immunogenic Cell Death ; Immunotherapy ; Neoplasms/immunology
    Chemical Substances Alarmins ; Antigens, Neoplasm ; Epitopes
    Language English
    Publishing date 2020-03-25
    Publishing country United States
    Document type Journal Article
    ISSN 0927-3042
    ISSN 0927-3042
    DOI 10.1007/978-3-030-38862-1_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article: MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells.

    Tomei, Sara / Volontè, Andrea / Ravindran, Shilpa / Mazzoleni, Stefania / Wang, Ena / Galli, Rossella / Maccalli, Cristina

    Journal of personalized medicine

    2021  Volume 11, Issue 4

    Abstract: Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM ...

    Abstract Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM displays poor prognosis and its resistance to common therapeutic approaches makes it a highly recurrent tumor. Several studies have identified a subpopulation of tumor cells, known as GBM cancer stem cells (CSCs) characterized by the ability of self-renewal, tumor initiation and propagation. GBM CSCs have been shown to survive GBM chemotherapy and radiotherapy. Thus, targeting CSCs represents a promising approach to treat GBM. Recent evidence has shown that GBM is characterized by a dysregulated expression of microRNA (miRNAs). In this study we have investigated the difference between human GBM CSCs and their paired autologous differentiated tumor cells. Array-based profiling and quantitative Real-Time PCR (qRT-PCR) were performed to identify miRNAs differentially expressed in CSCs. The Cancer Genome Atlas (TCGA) data were also interrogated, and functional interpretation analysis was performed. We have identified 14 miRNAs significantly differentially expressed in GBM CSCs (
    Language English
    Publishing date 2021-04-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm11040264
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: RNA amplification for successful gene profiling analysis

    Wang Ena

    Journal of Translational Medicine, Vol 3, Iss 1, p

    2005  Volume 28

    Abstract: Abstract The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. ... ...

    Abstract Abstract The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. Therefore, genetic studies offer the best opportunity to screen for novel insights of human pathology when little material is available. Precise estimates of DNA copy numbers in a given specimen are necessary. However, most studies investigate static variables such as the genetic background of patients or mutations within pathological specimens without a need to assess proportionality of expression among different genes throughout the genome. Comparative genomic hybridization of DNA samples represents a crude exception to this rule since genomic amplification or deletion is compared among different specimens directly. For gene expression analysis, however, it is critical to accurately estimate the proportional expression of distinct RNA transcripts since such proportions directly govern cell function by modulating protein expression. Furthermore, comparative estimates of relative RNA expression at different time points portray the response of cells to environmental stimuli, indirectly informing about broader biological events affecting a particular tissue in physiological or pathological conditions. This cognitive reaction of cells is similar to the detection of electroencephalographic patterns which inform about the status of the brain in response to external stimuli. As our need to understand human pathophysiology at the global level increases, the development and refinement of technologies for high fidelity messenger RNA amplification have become the focus of increasing interest during the past decade. The need to increase the abundance of RNA has been met not only for gene specific amplification, but, most importantly for global transcriptome wide, unbiased amplification. Now gene-specific, unbiased transcriptome wide amplification accurately maintains proportionality among all RNA species within a given specimen. This allows the utilization of clinical material obtained with minimally invasive methods such as fine needle aspirates (FNA) or cytological washings for high throughput functional genomics studies. This review provides a comprehensive and updated discussion of the literature in the subject and critically discusses the main approaches, the pitfalls and provides practical suggestions for successful unbiased amplification of the whole transcriptome in clinical samples.
    Keywords Gene profiling ; cDNA microarray ; RNA amplification ; polymerase ; high throughput analysis ; Medicine ; R
    Subject code 500 ; 612
    Language English
    Publishing date 2005-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: RNA amplification for successful gene profiling analysis.

    Wang, Ena

    Journal of translational medicine

    2005  Volume 3, Page(s) 28

    Abstract: The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. Therefore, ... ...

    Abstract The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. Therefore, genetic studies offer the best opportunity to screen for novel insights of human pathology when little material is available. Precise estimates of DNA copy numbers in a given specimen are necessary. However, most studies investigate static variables such as the genetic background of patients or mutations within pathological specimens without a need to assess proportionality of expression among different genes throughout the genome. Comparative genomic hybridization of DNA samples represents a crude exception to this rule since genomic amplification or deletion is compared among different specimens directly. For gene expression analysis, however, it is critical to accurately estimate the proportional expression of distinct RNA transcripts since such proportions directly govern cell function by modulating protein expression. Furthermore, comparative estimates of relative RNA expression at different time points portray the response of cells to environmental stimuli, indirectly informing about broader biological events affecting a particular tissue in physiological or pathological conditions. This cognitive reaction of cells is similar to the detection of electroencephalographic patterns which inform about the status of the brain in response to external stimuli. As our need to understand human pathophysiology at the global level increases, the development and refinement of technologies for high fidelity messenger RNA amplification have become the focus of increasing interest during the past decade. The need to increase the abundance of RNA has been met not only for gene specific amplification, but, most importantly for global transcriptome wide, unbiased amplification. Now gene-specific, unbiased transcriptome wide amplification accurately maintains proportionality among all RNA species within a given specimen. This allows the utilization of clinical material obtained with minimally invasive methods such as fine needle aspirates (FNA) or cytological washings for high throughput functional genomics studies. This review provides a comprehensive and updated discussion of the literature in the subject and critically discusses the main approaches, the pitfalls and provides practical suggestions for successful unbiased amplification of the whole transcriptome in clinical samples.
    Language English
    Publishing date 2005-07-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/1479-5876-3-28
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: The challenge of studying complex diseases undergoing complex treatments

    Wang Ena / Marincola Francesco M

    Journal of Translational Medicine, Vol 10, Iss Suppl 2, p A

    the metastatic cancer model

    2012  Volume 46

    Keywords Medicine ; R
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Book: Genomic and transcriptional evolution of metastatic melanoma

    Wang, Ena

    a case study

    (Clinical Center grand rounds)

    2009  

    Institution National Institutes of Health (U.S.)
    Author's details Ena Wang. Biomarkers of Parkinson Disease and related disorders / David S. Goldstein
    Series title Clinical Center grand rounds
    MeSH term(s) Melanoma/pathology ; Biomarkers ; Denervation ; Heart/innervation ; Neoplasm Metastasis/genetics ; Parkinson Disease ; Transcription, Genetic
    Language English
    Publisher National Institutes of Health
    Publishing place Bethesda, Md
    Document type Book
    Note Open-captioned. ; Title from screen banner (viewed Aug. 14, 2009). ; Streaming video (1 hr., 22 sec. : sd., col.).
    Database Catalogue of the US National Library of Medicine (NLM)

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top