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  • 1
    Online Resource
    Online Resource
    Clinicopathological and Prognostic Value of Survivin Expression in Surgically Resected Pancreatic Ductal Adenocarcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 14 ( 2022-07-18), p. 3494-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 14 ( 2022-07-18), p. 3494-
    Abstract: Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p 〈 0.001) and high cytoplasmic (p 〈 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4–129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04–3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14143494
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Magnetic-Based Enrichment of Rare Cells from High Concentrated Blood Samples
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 4 ( 2020-04-10), p. 933-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-04-10), p. 933-
    Abstract: Here, we tested two magnetic-bead based systems for the enrichment and detection of rare tumor cells in concentrated blood products. For that, the defined numbers of cells from three pancreatic cancer cell lines were spiked in 108 peripheral blood mononuclear cells (PBMNCs) concentrated in 1 mL, mimicking diagnostic leukapheresis (DLA) samples, and samples were processed for circulating tumor cells (CTC) enrichment with the IsoFlux or the KingFisher systems, using different types of magnetic beads from the respective technology providers. Beads were conjugated with different anti-EpCAM and MUC-1 antibodies. Recovered cells were enumerated and documented by fluorescent microscopy. For the IsoFlux system, best performance was obtained with IsoFlux CTC enrichment kit, but these beads compromised the subsequent immunofluorescence staining. For the KingFisher system, best recoveries were obtained using Dynabeads Biotin Binder beads. These beads also allowed one to capture CTCs with different antibodies and the subsequent immunofluorescence staining. KingFisher instrument allowed a single and streamlined protocol for the enrichment and staining of CTCs that further prevented cell loss at the enrichment/staining interface. Both IsoFlux and KingFisher systems allowed the enrichment of cell line cells from the mimicked-DLA samples. However, in this particular experimental setting, the recovery rates obtained with the KingFisher system were globally higher, the system was more cost-effective, and it allowed higher throughput.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12040933
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
    Online Resource
    Sarcopenia and Myosteatosis as Prognostic Markers in Patients with Advanced Cholangiocarcinoma Undergoing Palliative Treatment
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 19 ( 2021-09-23), p. 4340-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 19 ( 2021-09-23), p. 4340-
    Abstract: Background: Cholangiocarcinoma (CCA) represents the second most common primary liver cancer and is characterized by a very poor outcome, but reliable prognostic markers are largely missing. Sarcopenia, the progressive loss of muscle mass and strength, as well as myosteatosis have been associated with an unfavorable outcome in several clinical conditions, including cancer. Here, we evaluated the prognostic relevance of sarcopenia and myosteatosis using routine abdominal CT (computed tomography) scans in advanced stage CCA patients undergoing palliative treatment. Methods: Routine abdominal CT scans were used to assess the skeletal muscle and the psoas muscle index (L3SMI/L3PMI) at the level of the third lumbar vertebra as radiological indices for sarcopenia as well as the mean skeletal muscle attenuation (MMA) as a surrogate for myosteatosis. Results were correlated with clinical data and outcomes. Results: Using a calculated optimal cut-off value of 71.95 mm2/cm, CCA patients with an L3SMI value below this cut-off showed a significantly reduced median overall survival (OS) of only 250 days compared to 450 days in patients with a higher L3SMI. Moreover, the median OS of CCA patients with an L3PMI above 6345 mm2/cm was 552 days compared to 252 days in patients with a lower L3PMI. Finally, CCA patients with an MMA above 30.51 Hounsfield Units survived significantly longer (median OS: 430 days) compared to patients with an MMA value below this ideal cut-off (median OS: 215 days). The prognostic relevance of L3SMI, L3PMI, and MMA was confirmed in uni- and multivariate Cox regression analyses. Conclusion: Routine abdominal CT scans represent a unique opportunity to evaluate sarcopenia as well as myosteatosis in advanced CCA patients. We identified the L3SMI/L3PMI as well as the MMA as negative prognostic factors in CCA patients undergoing palliative therapy, arguing that the “opportunistic” evaluation of these parameters might yield important clinical information in daily routine.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10194340
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 4
    Online Resource
    Online Resource
    Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver—The Role of P-Selectin/PSGL-1 Interactions
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 17 ( 2020-09-03), p. 6431-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 17 ( 2020-09-03), p. 6431-
    Abstract: We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21176431
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 7 ( 2022-07-11), p. 1660-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 7 ( 2022-07-11), p. 1660-
    Abstract: Background: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. Patients and Methods: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). Results: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170–4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197–14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. Conclusions: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10071660
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 6
    Online Resource
    Online Resource
    Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 18 ( 2022-09-12), p. 4428-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 18 ( 2022-09-12), p. 4428-
    Abstract: Background: Tumor resection represents the only potentially curative therapy for patients with biliary tract cancer. Nevertheless, disease recurrence is observed in about 50% of patients, leading to a 5-years survival rate of less than 50%. The Golgi protein 73 (GP73), a type II Golgi transmembrane protein, exerts important functions of intracellular protein processing and transportation. Circulating GP73 has recently been suggested as a prognostic marker following resection of hepatocellular carcinoma (HCC) but its role in the context of BTC has remained unknown. In this study, we evaluate a potential role of circulating GP73 as a novel biomarker in patients with resectable BTC. Methods: GP73 serum levels were measured by immunoassay in n = 97 BTC and n = 40 HCC patients as well as n = 31 healthy controls. Results were correlated with clinical data. Results: Serum GP73 levels were significantly elevated in BTC patients compared to healthy controls but lower compared to HCC patients. The combination of GP73/CA19-9 showed a sensitivity and specificity of 83.5% and 90.3% regarding the differentiation of BTC patients and healthy controls. BTC patients with baseline GP73 levels above the ideal cut-off value (42.47 ng/mL) showed a significantly reduced median overall survival (193 days) compared to patients with preoperative GP73 levels below this cut-off (882 days). These results were confirmed in uni- and multivariate Cox-regression analysis including several clinicopathological parameters such as age, ECOG performance status, tumor stage as well as established tumor markers and parameters of liver and kidney function. Conclusions: GP73 represents a previously unrecognized biomarker in the patients with resectable BTC that identifies patients with an impaired postoperative outcome. If larger clinical trials confirmed these findings, measurement of GP73 serum levels might become a novel tool in the challenging preoperative stratification process of patients with resectable BTC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14184428
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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