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  • 1
    Online Resource
    Online Resource
    Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resection
    Springer Science and Business Media LLC ; 2009
    In:  Journal of Cancer Research and Clinical Oncology Vol. 135, No. 3 ( 2009-3), p. 439-449
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 135, No. 3 ( 2009-3), p. 439-449
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-008-0469-0
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 1459285-X
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  • 2
    Online Resource
    Online Resource
    Selection of reference genes for real-time PCR in human hepatocellular carcinoma tissues
    Springer Science and Business Media LLC ; 2008
    In:  Journal of Cancer Research and Clinical Oncology Vol. 134, No. 9 ( 2008-9), p. 979-986
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 134, No. 9 ( 2008-9), p. 979-986
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-008-0369-3
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 1459285-X
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  • 3
    Online Resource
    Online Resource
    Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 18 ( 2007-06-20), p. 2586-2593
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18 ( 2007-06-20), p. 2586-2593
    Abstract: To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3 + , CD4 + , CD8 + , Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3 + , CD4 + , CD8 + TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8 + cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P 〈 .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). Conclusion Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2006.09.4565
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 3 ( 2009-02-01), p. 971-979
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 3 ( 2009-02-01), p. 971-979
    Abstract: Purpose: The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery. Experimental Design: Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3+ regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay. Results: Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3+ lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set. Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-1608
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 5
    Online Resource
    Online Resource
    Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization
    Springer Science and Business Media LLC ; 2005
    In:  Journal of Cancer Research and Clinical Oncology Vol. 131, No. 7 ( 2005-7), p. 429-438
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 131, No. 7 ( 2005-7), p. 429-438
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-004-0616-1
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
    detail.hit.zdb_id: 1459285-X
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  • 6
    Online Resource
    Online Resource
    Peritumoral Activated Hepatic Stellate Cells Predict Poor Clinical Outcome in Hepatocellular Carcinoma After Curative Resection
    Oxford University Press (OUP) ; 2009
    In:  American Journal of Clinical Pathology Vol. 131, No. 4 ( 2009-04-01), p. 498-510
    Details
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 131, No. 4 ( 2009-04-01), p. 498-510
    Abstract: The inflammatory components of the liver remnant after hepatocellular carcinoma (HCC) resection are of prognostic importance. We evaluated prognostic potential of peritumoral activated hepatic stellate cells (HSCs) in 130 HCC cases. The messenger RNA (mRNA) levels of the functional genes in HSCs (ie, seprase, osteonectin, and tenascin-C), quantitated by real-time quantitative polymerase chain reaction, and the density of peritumoral Foxp3+ T-regulatory cells (Tregs) and CD68+ macrophages (MΦ), assessed immunohistochemically in tissue microarray sections, were positively correlated with the density of peritumoral activated HSCs. The density (P = .007 for recurrence-free survival [RFS] and P =.021 for overall survival [OS] ) and functional genes (seprase, P = .001 for RFS; osteonectin, P = .007 for RFS and P =.021 for OS) of peritumoral activated HSCs independently contributed to high recurrence or death rates, as did peritumoral Tregs or MΦ. Moreover, peritumoral HSCs were related to more early recurrences. It is important to note that the density of peritumoral activated HSCs, in combination with seprase and osteonectin mRNA or density of Tregs and MΦ, might predict prognoses more effectively.
    Type of Medium: Online Resource
    ISSN: 1943-7722 , 0002-9173
    URL: Article
    DOI: 10.1309/AJCP86PPBNGOHNNL
    RVK:
    YV 2000
    RVK:
    XA 18700
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 2039921-2
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  • 7
    Online Resource
    Online Resource
    Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma
    Springer Science and Business Media LLC ; 2009
    In:  Journal of Cancer Research and Clinical Oncology Vol. 135, No. 5 ( 2009-5), p. 715-722
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 135, No. 5 ( 2009-5), p. 715-722
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-008-0506-z
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 1459285-X
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  • 8
    Online Resource
    Online Resource
    Effect of Rapamycin Alone and in Combination with Sorafenib in an Orthotopic Model of Human Hepatocellular Carcinoma
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 16 ( 2008-08-15), p. 5124-5130
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 16 ( 2008-08-15), p. 5124-5130
    Abstract: Purpose: Novel therapeutic strategies are needed to prevent the tumor recurrence or metastasis after liver transplantation for hepatocellular carcinoma (HCC). This study was to investigate the effect of rapamycin, alone and in combination with sorafenib, on HCC in vivo. Experimental Design: Xenograft of a highly metastatic human HCC tumor (LCI-D20) was used to evaluate primary tumor growth and lung metastasis after treatment with rapamycin alone or in combination with sorafenib. Tumor cell proliferation was determined by Ki-67 immunostaining. To detect tumor cell apoptosis, the terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling assay was used. Tumor angiogenesis was investigated by using a monoclonal anti-CD31 antibody. A vascular endothelial growth factor ELISA kit was used to measure vascular endothelial growth factor protein levels in the mice serum. Results: Rapamycin, alone and in combination with sorafenib, strongly inhibited primary tumor growth and lung metastases in LCI-D20 model. Furthermore, the combination therapy significantly enhanced the effect of antitumor on primary tumor growth compared with single treatment with either rapamycin (P & lt; 0.001) or sorafenib (P & lt; 0.001). Rapamycin alone inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Nevertheless, the combination therapy showed a significant inhibition of tumor cell proliferation (P & lt; 0.05). Additionally, the combination therapy also further enhanced suppression of tumor cell angiogenesis compared with rapamycin treatment (P & lt; 0.01). However, the induction of apoptosis in combination therapy group was not significantly higher than in the rapamycin-treated group (P & gt; 0.05). Conclusions: The combination therapy of rapamycin and sorafenib could be a new and promising therapeutic approach to the treatment of HCC and prevention of HCC recurrence after liver transplantation.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-4774
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 9
    Online Resource
    Online Resource
    CD24 Is a Novel Predictor for Poor Prognosis of Hepatocellular Carcinoma after Surgery
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 17 ( 2009-09-01), p. 5518-5527
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 17 ( 2009-09-01), p. 5518-5527
    Abstract: Purpose: To investigate the role of CD24 in tumor invasion and prognostic significance in hepatocellular carcinoma (HCC). Experimental Design: CD24 expression was measured in stepwise metastatic HCC cell lines, tumor, peritumoral tissues, and normal liver tissues by quantitative real-time PCR and Western blot. The role of CD24 in HCC was investigated by CD24 depletion using small interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect expression of CD24, β-catenin, and proliferating cell nuclear antigen. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CD24 was overexpressed in the highly metastatic HCC cell line and in tumor tissues of patients with recurrent HCC. Depletion of CD24 caused a notable decrease in cell proliferation, migration, and invasiveness in vitro. Univariate and multivariate analyses revealed that CD24 was a significant predictor for overall survival and relapse-free survival. CD24 expression was correlated with poor prognosis independent of α-fetoprotein, tumor-node-metastasis stage, and Edmondson stage. High CD24 expression was significantly associated with cytoplasmic and nuclear accumulation of β-catenin (P = 0.023), high tumor proliferative status (P = 0.018), and diffused intrahepatic recurrence and distant metastasis (P = 0.026). Adjuvant transcatheter arterial chemoembolization after surgery reduced the rate of early recurrence (≤1 year) in CD24+ HCC patients (P = 0.024) but had no significant effect in CD24− patients (P = 0.284). Conclusions: Overexpression of CD24 in HCC was associated with high invasiveness and metastatic potential, high tumor proliferation status, and activation of the Wnt/β-catenin pathway. CD24 may be a novel predictor for poor prognosis of HCC patients after surgery. (Clin Cancer Res 2009;15(17):5518–27)
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-09-0151
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 10
    Online Resource
    Online Resource
    Association of Autophagy Defect with a Malignant Phenotype and Poor Prognosis of Hepatocellular Carcinoma
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Research Vol. 68, No. 22 ( 2008-11-15), p. 9167-9175
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 22 ( 2008-11-15), p. 9167-9175
    Abstract: Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The role of autophagy and the prognostic value of autophagic genes are largely unknown in HCC. Here, we showed decreased expression of autophagic genes and their corresponding autophagic activity and increased expression of the antiapoptotic gene Bcl-xL in HCC cell lines compared with a normal hepatic cell line. We also found decreased expression of the autophagic gene Beclin 1 in 44 HCC tissue samples compared with adjacent nontumor tissues. In addition, we found that the most aggressive malignant HCC cell lines and HCC tissues with recurrent disease displayed much lower autophagic levels, especially when Bcl-xL was overexpressed. Interestingly, in a tissue microarray study consisting of 300 HCC patients who underwent curative resection, the expression of Beclin 1 was only significantly correlated with disease-free survival (DFS; P & lt; 0.0001) and overall survival (OS; P & lt; 0.0001) in the Bcl-xL+ group. Multivariate and univariate analyses also revealed that Beclin 1 expression was an independent predictor for DFS and OS in Bcl-xL+ patients. In addition, we found a significant correlation between Beclin 1 expression and tumor differentiation in Bcl-xL+ but not in Bcl-xL− HCC patients. In conclusion, our data showed expression of autophagic genes and their corresponding autophagic activities were suppressed in HCC. The autophagy defects synergized with altered apoptotic activity might facilitate tumor malignant differentiation, which results in a more aggressive cancer cell phenotype and poor prognosis of HCC. [Cancer Res 2008;68(22):9167–75]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-08-1573
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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