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  • American Association for Cancer Research (AACR)  (5)
  • 2005-2009  (5)
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  • American Association for Cancer Research (AACR)  (5)
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  • 2005-2009  (5)
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  • 1
    Online Resource
    Online Resource
    Impact of E2F-1 Expression on Clinical Outcome of Gastric Adenocarcinoma Patients with Adjuvant Chemoradiation Therapy
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 1 ( 2008-01-01), p. 82-88
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 1 ( 2008-01-01), p. 82-88
    Abstract: Purpose: There are no reliable prognostic markers that identify gastric cancer patients who may benefit from adjuvant chemoradiation therapy. E2F-1 was shown to be associated with radiosensitivity and chemosensitivity in certain tumor types. Therefore, we analyzed expression and prognostic significance of E2F-1 along with thymidylate synthase (TS) in R0-resected gastric adenocarcinoma patients, who underwent adjuvant chemoradiation therapy with 5-fluorouracil (5-FU) and leucovorin. Experimental Design: The chemosensitivity to 5-FU and radiosensitivity were tested in three E2F-1–overexpressed gastric cancer cell lines in vitro. The expressions of TS and E2F-1 were analyzed in 467 R0-resected primary gastric cancer patients, who received adjuvant chemoradiation therapy with 5-FU and leucovorin using tissue microarray. Results: The E2F-1 immunopositivity rate was 22.2% (103 of 465 samples) with a cutoff value of 5% immunoreactivity, whereas the TS-positive expression occurred in 19.0% of the 463 tumors tested. Using stepwise Cox proportional hazards regression modeling, multivariate analyses showed that the E2F-1 immunopositivity predicted more favorable survival as compared with the E2F-1 immunonegativity with borderline statistical significance [P = 0.050, hazard ratio (HR) = 0.702, 95% confidence interval, 0.487, 1.013]. However, the E2F-1 immunopositivity did not retain its statistical significance at multivariate analys is for predicting disease-free survival (data not shown, P = 0.270), but stage was the only influential factor for disease-free survival in stages IB to IV (M0) patients (P & lt; 0.001). TS immunopositivity did not influence survival (P = 0.459) or disease-free survival (P = 0.447). Conclusion: E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-0612
    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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    Online Resource
  • 2
    Online Resource
    Online Resource
    Expression of DBC1 and SIRT1 Is Associated with Poor Prognosis of Gastric Carcinoma
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 13 ( 2009-07-01), p. 4453-4459
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 13 ( 2009-07-01), p. 4453-4459
    Abstract: Purpose: SIRT1 (silent mating-type information regulation 2 homologue 1) expression has been reported to predict poor survival in some cancers. We therefore investigated the expression levels of SIRT1 and its negative regulator, DBC1 (deleted in breast cancer 1), in gastric cancer patients. Experimental Design: We evaluated immunohistochemical expression of DBC1, SIRT1, and p53 using 3-mm tumor cores from 177 gastric cancer patients for tissue microarray. Results: Positive expressions of DBC1 and SIRT1 were seen in 62% (109 of 177) and in 73% (130 of 177) of patients, respectively. Expression of DBC1 was significantly correlated with tumor stage (P = 0.007), lymph node metastasis (P & lt; 0.001), tumor invasion (P = 0.001), venous invasion (P = 0.001), histologic types (P & lt; 0.001), p53 expression (P & lt; 0.001), and SIRT1 expression (P & lt; 0.001). SIRT1 expression was also significantly correlated with tumor stage (P & lt; 0.001), lymph node metastasis (P & lt; 0.001), tumor invasion (P & lt; 0.001), histologic types (P & lt; 0.001), and p53 expression (P = 0.001). In addition, expression of DBC1 was significantly associated with shorter overall survival and relapse-free survival by univariate analysis (P & lt; 0.001 and P & lt; 0.001, respectively). SIRT1 expression was also significantly associated with shorter overall survival and relapse-free survival by univariate analysis (P = 0.001 and P = 0.001, respectively). Multivariate analysis showed that tumor stage and expression of DBC1 were independent prognostic factors significantly associated with overall survival and relapse-free survival. Conclusion: This study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for gastric carcinoma patients.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-3329
    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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    Online Resource
  • 3
    Online Resource
    Online Resource
    Cyclooxygenase-2 Is an Independent Prognostic Factor in Gastric Carcinoma Patients Receiving Adjuvant Chemotherapy and Is Not Associated with EBV Infection
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 1 ( 2009-01-01), p. 291-298
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 1 ( 2009-01-01), p. 291-298
    Abstract: Purpose: Cyclooxygenase-2 (COX-2) is believed to be involved in carcinogenesis in patients with chronic gastritis with Helicobacter pylori infection. EBV is detected in ∼10% of gastric carcinomas and H. pylori induces EBV reactivation in the gastric epithelium. We aimed to evaluate significance of COX-2 in gastric carcinoma occurred in EBV and H. pylori prevalent area. Experimental Design: Tissue microarray samples from 457 gastric carcinoma patients who underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ hybridization for EBV and immunohistochemistry for COX-2 and other gastric carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1). Results: EBV infection was observed in 10.9% of gastric carcinomas and was associated with proximal tumor location, increased numbers of lymph node, and E-cadherin expression (P & lt; 0.01). COX-2 overexpression was closely associated with intestinal histologic type and lower tumor stage (P = 0.01). Univariate analysis showed that pT, pN, lymph node ratio, American Joint Committee on Cancer stage, numbers of negative lymph nodes, and resection margin & lt;1 cm were significant prognostic factors. The Cox proportional hazards regression analysis indicated that lack of COX-2 expression and resection margin & lt;1 cm were independent prognostic factors for disease-free survival (P = 0.008 and 0.03, respectively) and overall survival (P = 0.01 and 0.007, respectively). Conclusions: EBV infection is not associated with COX-2 expression or survival in gastric carcinoma. Lack of COX-2 expression is an independent prognostic factor in both overall and disease-free survival in gastric carcinoma. Our results indicate that COX-2 may play a role in the progression of gastric carcinoma regardless of EBV infection and is closely associated with histologic differentiation and prognosis.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-0848
    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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    Online Resource
  • 4
    Online Resource
    Online Resource
    Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 17, No. 9 ( 2008-09-01), p. 2260-2267
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 17, No. 9 ( 2008-09-01), p. 2260-2267
    Abstract: Despite significant advances in the detection and treatment of hepatocellular carcinoma, the prognosis of patients with hepatocellular carcinoma remains very poor, in part due to the high incidence of recurrence. This study was aimed at identifying a prognostic indicator of recurrence in patients with hepatocellular carcinoma. We retrospectively analyzed CpG island hypermethylation of the p14, p15, p16, GSTP1, integrin α4, SYK, and CDH1 genes in fresh-frozen tissues from 265 patients with hepatocellular carcinoma using the methylation-specific PCR. The expression levels of p16 and p53 were evaluated by immunohistochemistry. CpG island hypermethylation was detected in 6% for p14, 21% for p15, 67% for p16, 75% for GSTP1, 23% for integrin α4, 12% for SYK, and 57% for CDH1. Recurrence was observed in 102 (38%) of the 265 patients. There was no association between the risk for recurrence and hypermethylation of any gene studied. However, p16 methylation was associated with a poor survival after surgery for recurrent stage I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval, 1.15-14.20; P = 0.03). In addition, the hazard of failure after recurrence was about 3.80 (95% confidence interval, 1.03-14.20; P = 0.04) times higher in patients with p16 methylation than in those without. Negative expression of p16 at a protein level was also associated with poor survival in recurrent stage I to II hepatocellular carcinomas, but p53 expression did not have a synergistic effect on the poor prognosis. In conclusion, the present study suggests that p16 methylation may be associated with a poor prognosis in recurrent early-stage hepatocellular carcinomas. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2260–7)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-08-0236
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 5
    Online Resource
    Online Resource
    p34SEI-1 Inhibits Apoptosis through the Stabilization of the X-Linked Inhibitor of Apoptosis Protein: p34SEI-1 as a Novel Target for Anti–Breast Cancer Strategies
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 3 ( 2009-02-01), p. 741-746
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 3 ( 2009-02-01), p. 741-746
    Abstract: The p34SEI-1 protein exerts oncogenic effects via regulation of the cell cycle, which occurs through a direct interaction with cyclin-dependent kinase 4. Such regulation can increase the survival of various types of tumor cells. Here, we show that the antiapoptotic function of p34SEI-1 increases tumor cell survival by protecting the X-linked inhibitor of apoptosis protein (XIAP) from degradation. Our findings show that p34SEI-1 inhibits apoptosis. This antiapoptotic effect was eliminated by the suppression of p34SEI-1 expression. We also determined that direct binding of p34SEI-1 to the BIR2 domain prevents ubiquitination of XIAP. Interestingly, p34SEI-1 expression is absent or weak in normal tissues but is strongly expressed in tissues obtained from patients with breast cancer. Furthermore, the expression levels of p34SEI-1 and XIAP seem to be coordinated in human breast cancer cell lines and tumor tissues. Thus, our findings reveal that p34SEI-1 uses a novel apoptosis-inhibiting mechanism to stabilize XIAP. [Cancer Res 2009;69(3):741–6]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-08-1189
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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