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  1. Article ; Online: Checkpoint inhibitor responses can be regulated by the gut microbiota - A systematic review.

    Zeriouh, Mariam / Raskov, Hans / Kvich, Lasse / Gögenur, Ismail / Bennedsen, Astrid Louise Bjørn

    Neoplasia (New York, N.Y.)

    2023  Volume 43, Page(s) 100923

    Abstract: Background: Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ... ...

    Abstract Background: Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ICI would be valuable. This systematic review aimed to investigate the association between fecal gut microbiota composition and ICI-treatment response in patients with cancer.
    Methods: EMBASE, Medline, and Cochrane Library databases were searched using the "Participants, Interventions, Comparisons, and Outcomes" (PICO) process to locate studies including participants with solid cancers treated with ICI intervention. The comparator was the gut microbiota, and the outcomes were oncological outcomes such as response rates and progression-free survival. Study data were synthesized qualitatively in a systematic narrative synthesis, and the risk of bias in the studies was assessed.
    Results: Two reviewers screened 2092 abstracts independently, and 140 studies were read as full-text reports and assessed for eligibility. Eighteen studies were included with 775 patients with different types of solid cancers who received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Distinct patterns were observed in the patients' fecal samples. Some bacterial species were reported to be present in responders and non-responders, while others were present only in one group. The most reported species associated with better prognosis were Faecalibacterium prausnitzii, Streptococcus parasanguinis, Bacteroides caccae, and Prevotella copri. In contrast, the most reported species associated with poor prognosis were Blautia obeum and Bacteroides ovatus.
    Conclusion: Distinct microbiota features were associated with good and poor prognoses in ICI-treated patients with cancer.
    MeSH term(s) Humans ; Gastrointestinal Microbiome ; Microbiota ; Databases, Factual
    Language English
    Publishing date 2023-08-19
    Publishing country United States
    Document type Systematic Review ; Journal Article ; Review
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2023.100923
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: [Increasing incidence of colorectal cancer in young patients].

    Cai, Luyi / Bennedsen, Astrid Louise Bjørn / Qvortrup, Camilla / Gögenur, Ismail

    Ugeskrift for laeger

    2020  Volume 182, Issue 1

    Abstract: For the past decades, an increase in the incidence of colorectal cancer in young patients has been reported in several countries, including Denmark, and efforts need to be taken in order to halt this tendency. This review characterises the clinical and ... ...

    Abstract For the past decades, an increase in the incidence of colorectal cancer in young patients has been reported in several countries, including Denmark, and efforts need to be taken in order to halt this tendency. This review characterises the clinical and pathological attributes of young patients with early-onset colorectal cancer (EOCRC). Risk factors such as smoking and sedentary lifestyle have been found to be associated with EOCRC. Further studies are needed to evaluate, if the age of patients entering the Danish screening programme for bowel cancer should be lowered.
    MeSH term(s) Adult ; Colorectal Neoplasms/epidemiology ; Denmark/epidemiology ; Humans ; Incidence ; Mass Screening ; Risk Factors
    Language Danish
    Publishing date 2020-01-13
    Publishing country Denmark
    Document type Journal Article ; Review
    ZDB-ID 124102-3
    ISSN 1603-6824 ; 0041-5782
    ISSN (online) 1603-6824
    ISSN 0041-5782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Deeper sections reveal residual tumor cells in rectal cancer specimens diagnosed with pathological complete response following neoadjuvant treatment.

    Slumstrup, Lasse / Eiholm, Susanne / Bennedsen, Astrid Louise Bjørn / Jepsen, Dea Natalie Munch / Gögenur, Ismail / Fiehn, Anne-Marie Kanstrup

    Virchows Archiv : an international journal of pathology

    2022  Volume 480, Issue 5, Page(s) 1041–1049

    Abstract: Guidelines and requirements for diagnosing pathological complete response (pCR) in rectal adenocarcinoma following neoadjuvant treatment vary, and there is currently no consensus on the appropriate number of sections to examine per formalin-fixed, ... ...

    Abstract Guidelines and requirements for diagnosing pathological complete response (pCR) in rectal adenocarcinoma following neoadjuvant treatment vary, and there is currently no consensus on the appropriate number of sections to examine per formalin-fixed, paraffin-embedded (FFPE) tissue block. The consequences of systematic use of deeper sections on the diagnostic accuracy and prognosis for patients classified as ypT0 rectal cancer were investigated. In this retrospective study, 23 out of 155 patients who underwent neoadjuvant therapy and surgical resection between 2015 and 2020 were diagnosed with ypT0 rectal cancer. Three additional deeper sections were cut from each FFPE block from the primary tumor site and reviewed for presence of residual tumor cells. Additional sections revealed residual viable tumor cells in seven patients (30.4%), reducing the rate of pCR in the cohort from 14.8 to 10.3%. Of the seven patients, three patients later had local recurrence or distant metastasis during the follow-up period, compared with one patient with no residual tumor cells in deeper sections (p = 0.07). A nonsignificant reduction in disease-free survival (p = 0.08) was observed in the patients with residual tumor. Systematic use of deeper sections in evaluation of tumor regression in rectal cancer reveals the presence of residual tumor cells in a subset of patients originally diagnosed with pCR based on a single section per FFPE block. Although the results are not statistically significant, it cannot be excluded that accurately distinguishing complete from near-complete response may be clinically relevant for prognostic prediction.
    MeSH term(s) Chemoradiotherapy ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Neoplasm, Residual/pathology ; Neoplasm, Residual/therapy ; Rectal Neoplasms/pathology ; Rectal Neoplasms/therapy ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2022-01-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-022-03287-7
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  4. Article ; Online: An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer.

    Bennedsen, Astrid Louise Bjørn / Cai, Luyi / Hasselager, Rune Petring / Özcan, Aysun Avci / Mohamed, Khadra Bashir / Eriksen, Jens Ole / Eiholm, Susanne / Bzorek, Michael / Fiehn, Anne-Marie Kanstrup / Hviid, Thomas Vauvert F / Gögenur, Ismail

    BMC cancer

    2022  Volume 22, Issue 1, Page(s) 62

    Abstract: Background: The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in ... ...

    Abstract Background: The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells' ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer.
    Methods: We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated.
    Results: We included 188 patients undergoing colon cancer resections in 2011-2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64-6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06-0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68-157.32] and HR = 7.56, 95%CI [1.06-54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS.
    Conclusions: In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.
    MeSH term(s) Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/mortality ; Colonic Neoplasms/pathology ; Colonic Neoplasms/surgery ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Retrospective Studies
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-01-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-022-09169-0
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  5. Article ; Online: Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial.

    Gögenur, Mikail / Balsevicius, Lukas / Bulut, Mustafa / Colak, Nesibe / Justesen, Tobias Freyberg / Fiehn, Anne-Marie Kanstrup / Jensen, Marianne Bøgevang / Høst-Rasmussen, Kathrine / Cappelen, Britt / Gaggar, Shruti / Tajik, Asma / Zahid, Jawad Ahmad / Bennedsen, Astrid Louise Bjørn / D'Ondes, Tommaso Del Buono / Raskov, Hans / Sækmose, Susanne Gjørup / Hansen, Lasse Bremholm / Salanti, Ali / Brix, Susanne /
    Gögenur, Ismail

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 5

    Abstract: Background: In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral ...

    Abstract Background: In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.
    Methods: We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.
    Results: A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm
    Conclusions: Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts.
    Trial registration number: NCT04591379.
    MeSH term(s) Humans ; Female ; Middle Aged ; Aged ; Male ; B7-H1 Antigen/metabolism ; Colorectal Neoplasms/pathology ; Influenza Vaccines ; Up-Regulation ; DNA Mismatch Repair ; Neoadjuvant Therapy ; Rectal Neoplasms ; CD8-Positive T-Lymphocytes
    Chemical Substances CD274 protein, human ; B7-H1 Antigen ; Influenza Vaccines
    Language English
    Publishing date 2023-05-10
    Publishing country England
    Document type Clinical Trial, Phase II ; Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-006774
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

    Andersen, Helene Schou / Bennedsen, Astrid Louise Bjørn / Burgdorf, Stefan Kobbelgaard / Eriksen, Jens Ravn / Eiholm, Susanne / Toxværd, Anders / Riis, Lene Buhl / Rosenberg, Jacob / Gögenur, Ismail

    International journal of colorectal disease

    2017  Volume 32, Issue 7, Page(s) 983–990

    Abstract: Introduction: Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for ... ...

    Abstract Introduction: Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques.
    Methods: Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients.
    Results: Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node.
    Conclusion: Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.
    Language English
    Publishing date 2017-07
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 84975-3
    ISSN 1432-1262 ; 0179-1958
    ISSN (online) 1432-1262
    ISSN 0179-1958
    DOI 10.1007/s00384-017-2777-9
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