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  1. Article: Immune Checkpoint Inhibitors: Changing the Treatment Landscape in Esophagogastric Adenocarcinoma.

    Lynch, Emer / Duffy, Austin G / Kelly, Ronan J

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 1

    Abstract: In the West, recent decades have demonstrated an epidemiological trend towards esophago-gastric adenocarcinomas (EGAC), with considerable associated mortality. Historically, chemotherapy has represented the sole systemic treatment option in the advanced ... ...

    Abstract In the West, recent decades have demonstrated an epidemiological trend towards esophago-gastric adenocarcinomas (EGAC), with considerable associated mortality. Historically, chemotherapy has represented the sole systemic treatment option in the advanced EGAC setting, in addition to complementing the role of surgery and radiotherapy in the case of localized disease. Immune checkpoint inhibitors (ICIs) represent a novel systemic therapeutic choice and have revolutionized the management of other malignancies, including melanoma and renal cell carcinomas. This article considers the rationale for ICIs in EGAC, reviews the evidence supporting their role in the current standard of care in EGAC, and briefly considers ongoing trials and future directions for the ICI class in EGAC.
    Language English
    Publishing date 2023-01-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16010102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Role of Immunotherapy in Gastroesophageal Cancers-Advances, Challenges and Future Strategies.

    Lynch, Emer / Duffy, Austin G / Kelly, Ronan J

    Cancers

    2023  Volume 15, Issue 22

    Abstract: Background: Gastroesophageal cancers (GECs) carry considerable morbidity and mortality, and demonstrate geographical histological variances in addition to molecular heterogeneity. Consequently, the immunogenicity of the different subtypes, which can ... ...

    Abstract Background: Gastroesophageal cancers (GECs) carry considerable morbidity and mortality, and demonstrate geographical histological variances in addition to molecular heterogeneity. Consequently, the immunogenicity of the different subtypes, which can predict the likelihood of immunotherapy response, can vary. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of many cancer types over the past decade but has been slower to gain a foothold in the treatment paradigm of GECs.
    Methods: This article reviews the existing evidence and use approvals for immunotherapies and immune-based treatments in GECs, in the neoadjuvant, adjuvant and metastatic disease settings. The challenges of and limitations to ICI application in current clinical practice are examined. Ongoing clinical trials and future directions of research are also considered.
    Conclusion: ICI therapy has become an established treatment option within GECs, both perioperatively and in advanced disease. However, nuances in terms of its use are not yet fully understood. Ongoing research proposes to broaden the application of immunotherapies in GECs with the potential to continue to improve outcomes.
    Language English
    Publishing date 2023-11-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15225401
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Brave new world-new and emerging treatments for gastric cancer.

    Lynch, Emer / Duffy, Austin G / Kelly, Ronan J

    Chinese clinical oncology

    2023  Volume 12, Issue 5, Page(s) 54

    Abstract: Despite considerable international heterogeneity in the incidence and histological subtypes of gastric cancer (GC), in addition to more recent epidemiological trends, chemotherapy has long represented the main systemic therapeutic option in its treatment. ...

    Abstract Despite considerable international heterogeneity in the incidence and histological subtypes of gastric cancer (GC), in addition to more recent epidemiological trends, chemotherapy has long represented the main systemic therapeutic option in its treatment. For the roughly 20% of GC with human epidermal growth factor receptor 2 (HER2) overexpression, there is a more recently established role for the addition of HER2+ based therapy in the form of trastuzumab. However, while immune checkpoint inhibitors (ICIs) have revolutionised the treatment of other malignancies including melanoma and renal cell carcinoma over the past decade, they have only gained a foothold in GC in more recent years. This article reviews the existing evidence for ICIs in GC as a novel therapeutic option. It also looks to ongoing trials of immune checkpoint inhibition both in the perioperative and advanced setting, and in combination with other therapeutic targets including HER2+. Other investigational immune based therapies including chimeric antigen receptor T-cell (CAR-T) therapy and anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (anti-TIGIT) therapy are considered, in addition to reviewing the building evidence for alternative therapeutic targets currently under investigation in GC, including fibroblast growth factor receptor 2b (FGFR2b) and claudin 18.2 amongst others. These novel and evolving targets represent a brave new world in therapeutic intervention in GC, with the potential to transform outcomes for patients internationally.
    MeSH term(s) Humans ; Stomach Neoplasms/drug therapy ; Trastuzumab/therapeutic use ; Melanoma/drug therapy
    Chemical Substances Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2023-08-28
    Publishing country China
    Document type Review ; Journal Article
    ZDB-ID 2828547-5
    ISSN 2304-3873 ; 2304-3873
    ISSN (online) 2304-3873
    ISSN 2304-3873
    DOI 10.21037/cco-23-13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Altered quorum sensing and physiology of Staphylococcus aureus during spaceflight detected by multi-omics data analysis.

    Hauserman, Matthew R / Ferraro, Mariola J / Carroll, Ronan K / Rice, Kelly C

    NPJ microgravity

    2024  Volume 10, Issue 1, Page(s) 2

    Abstract: Staphylococcus aureus colonizes the nares of approximately 30% of humans, a risk factor for opportunistic infections. To gain insight into S. aureus virulence potential in the spaceflight environment, we analyzed RNA-Seq, cellular proteomics, and ... ...

    Abstract Staphylococcus aureus colonizes the nares of approximately 30% of humans, a risk factor for opportunistic infections. To gain insight into S. aureus virulence potential in the spaceflight environment, we analyzed RNA-Seq, cellular proteomics, and metabolomics data from the "Biological Research in Canisters-23" (BRIC-23) GeneLab spaceflight experiment, a mission designed to measure the response of S. aureus to growth in low earth orbit on the international space station. This experiment used Biological Research in Canisters-Petri Dish Fixation Units (BRIC-PDFUs) to grow asynchronous ground control and spaceflight cultures of S. aureus for 48 h. RNAIII, the effector of the Accessory Gene Regulator (Agr) quorum sensing system, was the most highly upregulated gene transcript in spaceflight relative to ground controls. The agr operon gene transcripts were also highly upregulated during spaceflight, followed by genes encoding phenol-soluble modulins and secreted proteases, which are positively regulated by Agr. Upregulated spaceflight genes/proteins also had functions related to urease activity, type VII-like Ess secretion, and copper transport. We also performed secretome analysis of BRIC-23 culture supernatants, which revealed that spaceflight samples had increased abundance of secreted virulence factors, including Agr-regulated proteases (SspA, SspB), staphylococcal nuclease (Nuc), and EsxA (secreted by the Ess system). These data also indicated that S. aureus metabolism is altered in spaceflight conditions relative to the ground controls. Collectively, these data suggest that S. aureus experiences increased quorum sensing and altered expression of virulence factors in response to the spaceflight environment that may impact its pathogenic potential.
    Language English
    Publishing date 2024-01-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2823626-9
    ISSN 2373-8065
    ISSN 2373-8065
    DOI 10.1038/s41526-023-00343-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Emerging Multimodality Approaches to Treat Localized Esophageal Cancer.

    Kelly, Ronan J

    Journal of the National Comprehensive Cancer Network : JNCCN

    2019  Volume 17, Issue 8, Page(s) 1009–1014

    Abstract: Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been ... ...

    Abstract Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been incremental at best. Esophageal cancer requires a concerted multidisciplinary approach, perhaps more so than any other tumor type given the integral role played by the esophagus in maintaining calorific intake and the propensity for early spread through the lymphatics. This review describes the latest in surgical techniques to minimize postoperative complications and examines previous and ongoing systemic therapy approaches. Strategies that harness a patient's own immune system hold great promise, and shifting checkpoint inhibitors from the metastatic setting to the neoadjuvant/adjuvant setting is currently being evaluated in phase II and III clinical trials. In addition, a much better understanding of the interplay between tumors and their immune microenvironment is clearly needed to better judge how best to engage each patient's immune system, and there will be likely demonstrable differences between early-stage tumors and metastatic disease. This review highlights emerging data, which demonstrate that, in addition to The Cancer Genome Atlas classification of esophageal squamous cell carcinoma having a distinct molecular makeup compared with esophageal adenocarcinoma, there are also differing responses to PD-1 inhibitors. Histology and the underlying immune milieu may have important ramifications for the management of localized disease in the future, above and beyond PD-L1 expression, microsatellite instability status, and tumor mutational burden.
    MeSH term(s) Combined Modality Therapy/adverse effects ; Combined Modality Therapy/methods ; Disease Management ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/etiology ; Esophageal Neoplasms/mortality ; Esophageal Neoplasms/therapy ; Humans ; Treatment Outcome
    Language English
    Publishing date 2019-08-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2250759-0
    ISSN 1540-1413 ; 1540-1405
    ISSN (online) 1540-1413
    ISSN 1540-1405
    DOI 10.6004/jnccn.2019.7337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6365: Show issues Location:
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  6. Article ; Online: The emerging role of immunotherapy for esophageal cancer.

    Kelly, Ronan J

    Current opinion in gastroenterology

    2019  Volume 35, Issue 4, Page(s) 337–343

    Abstract: Purpose of review: The management of esophageal cancer has not changed significantly over the last decade. Survival rates remain poor in locally advanced and metastatic disease. Newer treatment modalities are desperately needed if we are to improve 5- ... ...

    Abstract Purpose of review: The management of esophageal cancer has not changed significantly over the last decade. Survival rates remain poor in locally advanced and metastatic disease. Newer treatment modalities are desperately needed if we are to improve 5-year overall survival rates. Immunotherapeutic strategies hold great promise, but a much greater understanding of the immune microenvironment underlying squamous cell and esophageal adenocarcinoma is needed if we are to exploit the inherent cancer fighting capabilities of each patient's immune system.
    Recent findings: Here we describe current and future predictive biomarkers, provide a synopsis of the most significant trial results to date, and explain pivotal ongoing phase III trials.
    Summary: Recent findings suggest that esophageal squamous cell carcinoma may be more sensitive to single agent PD-1 inhibition than esophageal adenocarcinoma, and selecting patients according to PD-L1 combined positive score (CPS) of at least 10 or more may predict higher response rate. We await data indicating the optimal immuno-oncology (IO-IO) combinations that will allow more patients to respond, however it is likely that personalized immunotherapy may be required for the majority. At the present time, it is hoped that chemotherapy combined with PD-1 inhibition will be an optimal strategy, but we await confirmation from soon-to-be published phase III trials.
    MeSH term(s) Adenocarcinoma/therapy ; Esophageal Neoplasms/therapy ; Esophageal Squamous Cell Carcinoma/therapy ; Humans ; Immunologic Factors ; Immunotherapy ; Tumor Microenvironment
    Chemical Substances Immunologic Factors
    Language English
    Publishing date 2019-04-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632571-3
    ISSN 1531-7056 ; 0267-1379
    ISSN (online) 1531-7056
    ISSN 0267-1379
    DOI 10.1097/MOG.0000000000000542
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2072: 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)
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  7. Article ; Online: Dabrafenib and trametinib for the treatment of non-small cell lung cancer.

    Kelly, Ronan J

    Expert review of anticancer therapy

    2018  Volume 18, Issue 11, Page(s) 1063–1068

    Abstract: Introduction: ... ...

    Abstract Introduction: BRAF
    MeSH term(s) Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Humans ; Imidazoles/administration & dosage ; Imidazoles/adverse effects ; Imidazoles/pharmacology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mutation ; Oximes/administration & dosage ; Oximes/adverse effects ; Oximes/pharmacology ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Pyridones/administration & dosage ; Pyridones/adverse effects ; Pyridones/pharmacology ; Pyrimidinones/administration & dosage ; Pyrimidinones/adverse effects ; Pyrimidinones/pharmacology
    Chemical Substances Antineoplastic Agents ; Imidazoles ; Oximes ; Protein Kinase Inhibitors ; Pyridones ; Pyrimidinones ; trametinib (33E86K87QN) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; dabrafenib (QGP4HA4G1B)
    Language English
    Publishing date 2018-09-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2112544-2
    ISSN 1744-8328 ; 1473-7140
    ISSN (online) 1744-8328
    ISSN 1473-7140
    DOI 10.1080/14737140.2018.1521272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5907: 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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  8. Article ; Online: Immunotherapy for Esophageal and Gastric Cancer.

    Kelly, Ronan J

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2017  Volume 37, Page(s) 292–300

    Abstract: PD-L1 upregulation occurs in approximately 40% of gastroesophageal cancers. However, unlike other solid tumors, there is minimal PD-L1 expressed on the cancer cells; rather, expression occurs predominantly on infiltrating myeloid cells. Preliminary ... ...

    Abstract PD-L1 upregulation occurs in approximately 40% of gastroesophageal cancers. However, unlike other solid tumors, there is minimal PD-L1 expressed on the cancer cells; rather, expression occurs predominantly on infiltrating myeloid cells. Preliminary clinical data involving single-agent PD-1/PD-L1 inhibitors in metastatic gastroesophageal cancer have reported response rates of 22%-27% for patients with PD-L1
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; Cell Cycle Checkpoints/drug effects ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/immunology ; Esophageal Neoplasms/therapy ; Esophageal Neoplasms/virology ; Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human/pathogenicity ; Humans ; Immunotherapy ; Lymphocytes, Tumor-Infiltrating/immunology ; Nivolumab ; Programmed Cell Death 1 Ligand 2 Protein/antagonists & inhibitors ; Programmed Cell Death 1 Ligand 2 Protein/genetics ; Programmed Cell Death 1 Ligand 2 Protein/immunology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/immunology ; Stomach Neoplasms/therapy ; Stomach Neoplasms/virology
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents ; B7-H1 Antigen ; CD274 protein, human ; PDCD1LG2 protein, human ; Programmed Cell Death 1 Ligand 2 Protein ; Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2017-08-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.14694/EDBK_175231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Single agent anti PD-1 inhibitors in esophageal cancer-a first step in a new therapeutic direction.

    Walsh, Elaine M / Kelly, Ronan J

    Journal of thoracic disease

    2017  Volume 10, Issue 3, Page(s) 1308–1313

    Language English
    Publishing date 2017-04-30
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2573571-8
    ISSN 2077-6624 ; 2072-1439
    ISSN (online) 2077-6624
    ISSN 2072-1439
    DOI 10.21037/jtd.2018.03.43
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Checkpoint Inhibitors in Lung Cancer Are Not Immune from Cost-Effectiveness Analysis.

    Kelly, Ronan J / Smith, Thomas J

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2016  Volume 11, Issue 11, Page(s) 1814–1816

    Language English
    Publishing date 2016-11
    Publishing country United States
    Document type Editorial
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2016.07.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6664: Show issues Location:
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    Zs.MO 652: Show issues

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