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  1. Article ; Online: EpCAM-positive circulating tumor cells and serum AFP levels predict outcome after curative resection of hepatocellular carcinoma

    Lorenz Kocheise / Martin Schoenlein / Berit Behrends / Vincent Joerg / Christian Casar / Thorben W. Fruendt / Thomas Renné / Asmus Heumann / Jun Li / Samuel Huber / Ansgar W. Lohse / Klaus Pantel / Sabine Riethdorf / Henning Wege / Kornelius Schulze / Johann von Felden

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 10

    Abstract: Abstract Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high ... ...

    Abstract Abstract Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high predictive value for early HCC recurrence after curatively intended resection, most likely indicating micro-metastases at the time of resection. However, sensitivity remains low. The objective of this study was to evaluate a composite test comprising both CTC and AFP to identify patients at high risk for early HCC recurrence. We prospectively enrolled 58 patients undergoing curative intended resection for HCC at a tertiary referral center. Blood specimens were obtained prior to resection and analyzed for EpCAM-positive CTC and serum AFP levels. A positive result was defined as either detection of CTC or AFP levels ≥ 400 ng/ml. Eight patients tested positive for CTC, seven for AFP, and two for both markers. A positive composite test was significantly associated with shorter early recurrence-free survival (5 vs. 16 months, p = 0.005), time to recurrence (5 vs. 16 months, p = 0.011), and overall survival (37 vs. not reached, p = 0.034). Combining CTC and AFP identified patients with poor outcome after surgical resection, for whom adjuvant or neoadjuvant therapies may be particularly desirable.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH

    Anna Woestemeier / Pasquale Scognamiglio / Yu Zhao / Jonas Wagner / Franziska Muscate / Christian Casar / Francesco Siracusa / Filippo Cortesi / Theodora Agalioti / Simone Müller / Adrian Sagebiel / Leonie Konczalla / Ramez Wahib / Karl-Frederick Karstens / Anastasios D. Giannou / Anna Duprée / Stefan Wolter / Milagros N. Wong / Anne K. Mühlig /
    Agata A. Bielecka / Vikas Bansal / Tianran Zhang / Oliver Mann / Victor G. Puelles / Tobias B. Huber / Ansgar W. Lohse / Jakob R. Izbicki / Noah W. Palm / Stefan Bonn / Samuel Huber / Nicola Gagliani

    JCI Insight, Vol 8, Iss

    2023  Volume 1

    Abstract: A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of ... ...

    Abstract A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.
    Keywords Hepatology ; Immunology ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Author Correction

    Annemieke Abel / Christiane Steeg / Francis Aminkiah / Otchere Addai-Mensah / Marylyn Addo / Nicola Gagliani / Christian Casar / Denis Dekugmen Yar / Ellis Owusu-Dabo / Thomas Jacobs / Maria Sophia Mackroth

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    Differential expression pattern of co-inhibitory molecules on CD4+ T cells in uncomplicated versus complicated malaria

    2018  Volume 1

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2 −/− mice

    Roja Barikbin / Laura Berkhout / Julia Bolik / Dirk Schmidt-Arras / Thomas Ernst / Harald Ittrich / Gerhard Adam / Ann Parplys / Christian Casar / Till Krech / Khalil Karimi / Gabriele Sass / Gisa Tiegs

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 11

    Abstract: Abstract Multi drug resistance protein 2 knockout mice (Mdr2 −/−) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, ... ...

    Abstract Abstract Multi drug resistance protein 2 knockout mice (Mdr2 −/−) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2 −/− mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4+ and CD8+ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2 −/− mice. Long-term effects of HO-1 induction included increased CD8+ T cell infiltration as well as delayed and reduced tumour growth in one-year-old animals. Unexpectedly, DNA double-strand breaks were detected predominantly in macrophages of 65-week-old Mdr2 −/− mice, while DNA damage was reduced in response to early HO-1 induction in vivo and in vitro. Overall, early induction of HO-1 in Mdr2 −/− mice had a beneficial short-term effect on liver function and reduced hepatic T cell accumulation. Long-term effects of early HO-1 induction were increased CD8+ T cell numbers, decreased proliferation as wells as reduced DNA damage in liver macrophages of aged animals, accompanied by delayed and reduced tumour growth.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Differential expression pattern of co-inhibitory molecules on CD4+ T cells in uncomplicated versus complicated malaria

    Annemieke Abel / Christiane Steeg / Francis Aminkiah / Otchere Addai-Mensah / Marylyn Addo / Nicola Gagliani / Christian Casar / Denis Dekugmen Yar / Ellis Owusu-Dabo / Thomas Jacobs / Maria Sophia Mackroth

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 9

    Abstract: Abstract The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or ... ...

    Abstract Abstract The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells. Children with complicated malaria had higher frequencies of CTLA-4+ or PD-1+ CD4+ T cells than children with uncomplicated malaria. Conversely, children with uncomplicated malaria showed a higher proportion of CD4+ T cells expressing CD39 and Granzyme B, compared to children with complicated malaria. In contrast, asymptomatically infected children expressed only low levels of co-inhibitory molecules. Thus, different CD4+ T cell phenotypes are associated with complicated versus uncomplicated malaria, suggesting a two-sided role of CD4+ T cells in malaria pathogenesis and protection. Deciphering the signals that shape the CD4+ T cell phenotype in malaria will be important for new treatment and immunization strategies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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