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Berlin Brandenburg

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  • 1
    Language: English
    In: International Journal of Oncology, August 2011, Vol.39(2), pp.515-520
    Description: We performed this study in order to evaluate the impact of the chemokine CXCL12 and its single-nucleotide polymorphism (SNP) rs1801157 on clinicopathological parameters and survival in patients undergoing surgery for esophagogastric cancer. The expression pattern of CXCL12 and its polymorphisms were analyzed by RT-PCR and PCR-RFLP in 69 consecutive fresh-frozen samples of human esophagogastric junction and gastric adenocarcinomas and statistically analyzed. Expression of the CXCL12 (SNP rs1801157) polymorphisms GA/AA significantly correlated with distant metastasis (P=0.026), but not with prognosis. However, CXCL12 expression was not significantly associated with the tumor infiltration depth, lymphatic metastasis and grading. As CXCL12 polymorphisms mediate tumor cell dissemination in esophagogastric cancer, they could represent a marker indicating advanced disease. Antagonists targeting the CXCL12/ CXCR4 axis may be a novel therapeutic option in this entity.
    Keywords: Medicine;
    ISSN: 1019-6439
    E-ISSN: 17912423
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  • 2
    Language: English
    In: Oncology Reports, March 2008, Vol.19(3), pp.697-704
    Description: As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors α and β (PDGFRα/β) in human colorectal cancer. The co-expression pattern of PDGFRα/β was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRα and PDGFRβ. The majority of human colorectal cancer specimens revealed a PDGFRα (83%) or PDGFRβ (60%) expression. While PDGFRα showed a predominantly cytoplasmic staining in tumor cells as well as in stromal pericytes, PDGFRβ was restricted to stromal pericytes only. Furthermore, PDGFRα expression significantly correlated with lymph node metastasis (P=0.0082) and advanced UICC stages III/IV (P=0.018) in older patients (P=0.043). PDGFRβ expression only revealed a trend towards lymphatic dissemination (P=0.099). Co-expression of PDGFRα/β occurred in 57% of the colorectal cancer samples, whereas another 29% of the samples depicted mono-expression of PDGFRα or PDGFRβ. Notably, PDGFRα/β expression significantly correlated with lymphatic metastasis (P=0.007) and advanced UICC stages III/IV (P=0.017) in older patients (P=0.03). In summary, our results revealed that PDGFRα/β expression significantly correlates with lymphatic dissemination and therefore encourages application of PDGFRα/β RTK-inhibitors within a combination therapy.
    ISSN: 1021-335X
    Source: Spandidios Publications (Spandidos Publications Ltd.)
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  • 3
    Language: English
    In: Oncology Reports, December 2006, Vol.16(6), pp.1159-1164
    Description: Certain chemokines have been proposed to distinctly contribute to tumor growth, dissemination and local immune escape. Expression of the chemokine receptor CXCR4 has been linked to tumor progression in diverse tumor entities. The aim of this study was to evaluate if the expression of CXCR4 influences progression of human pancreatic cancer. CXCR4 expression of pancreatic cancer was retrospectively assessed by immunohistochemistry in 103 patients with pancreatic cancer. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human pancreatic cancer revealed variable intensities of CXCR4 expression. Strong CXCR4 expression was significantly associated with advanced UICC stages (P=0.03) and revealed a trend for hematogenous metastasis (P=0.09) and progressed local tumor stages (P=0.15). In summary, strong expression of CXCR4 was significantly associated with advanced pancreatic cancer.
    Keywords: Adenocarcinoma -- Metabolism ; Pancreatic Neoplasms -- Metabolism ; Receptors, Cxcr4 -- Biosynthesis;
    ISSN: 1021-335X
    E-ISSN: 17912431
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  • 4
    Language: English
    In: Oncology Reports, July 2006, Vol.16(1), pp.109-113
    Description: Despite many pathophysiological analyses, the process of tumor dissemination of hepatocellular carcinoma (HCC) remains vague. In diverse tumor entities, expression of the chemokine receptor, CCR7, has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, whether CCR7 exerts similar effects in human HCC. CCR7 expression analysis was performed in vitro on human hepatoma cell lines (Huh7, Hep3B, wt HepG2, p53 dominant negative transfected HepG2). In addition, CCR7 expression was evaluated in 39 patients with hepatocellular cancer and correlated with both, tumor and patients characteristics. Human hepatocellular carcinoma samples and hepatoma cell lines displayed variable intensities of CCR7 expression. In patients, CCR7 expression was significantly associated with progressed local tumors (P=0.02) and lymphatic metastasis (P=0.02). Strong expression of CCR7 promotes intrahepatic and lymphatic HCC dissemination.
    Keywords: Medicine;
    ISSN: 1021-335X
    E-ISSN: 17912431
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  • 5
    Language: English
    In: Oncology Reports, October 2008, Vol.20(4), pp.845-850
    Description: This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)α/β and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRα (91%), PDGFRβ (85%) and EGFR1 (97%) expression at different intensities. Ninety-four percent of the esophageal adenocarcinomas expressed at least four out of six RTKs. Similarly, squamous cell cancers revealed VEGFR1 (100%), VEGFR2 (100%), VEGFR3 (53%), PDGFRα (100%), PDGFRβ (87%) and EGFR1 (100%) expression at different intensities. All esophageal squamous cell carcinomas expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα and EGFR1 was expressed by tumor cells, PDGFRβ was restricted to stromal cells, which also depicted a PDGFRα expression. Our results revealed a high rate of RTK co-expression in esophageal adenocarcinoma and squamous cell cancer and may encourage application of multi-target RTK inhibitors within a multimodal concept as a promising novel approach for innovative treatment strategies.
    Keywords: Adenocarcinoma -- Enzymology ; Carcinoma, Squamous Cell -- Enzymology ; Esophageal Neoplasms -- Enzymology ; Receptor Protein-Tyrosine Kinases -- Analysis;
    ISSN: 1021-335X
    E-ISSN: 17912431
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