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  • American Association for Cancer Research (AACR)  (3)
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  • American Association for Cancer Research (AACR)  (3)
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  • 1
    Online Resource
    Online Resource
    Low Expression of Bax Predicts Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Treated with Definitive Chemoradiotherapy
    American Association for Cancer Research (AACR) ; 2007
    In:  Clinical Cancer Research Vol. 13, No. 14 ( 2007-07-15), p. 4146-4153
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 14 ( 2007-07-15), p. 4146-4153
    Abstract: Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-06-3063
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy
    American Association for Cancer Research (AACR) ; 2011
    In:  Molecular Cancer Therapeutics Vol. 10, No. 10 ( 2011-10-01), p. 1993-1999
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 10, No. 10 ( 2011-10-01), p. 1993-1999
    Abstract: Although erlotinib has become an important therapeutic option in addition to gemcitabine, the high frequency of KRAS mutations in pancreatic cancer probably limits the benefits. We retrospectively studied 136 pancreatic cancer patients with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to understand the clinical significance of KRAS mutations in pancreatic cancer patients treated with gemcitabine-based chemotherapy. KRAS mutations were analyzed by sequencing codons 12, 13, and 61. In this study, 71 (52.2%) of the 136 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 70) and 61 (n = 1) of KRAS. KRAS mutation was not associated with clinicopathologic parameters. Patients with KRAS mutations showed a worse response (11.3%) than those with wild-type KRAS (26.2%) and poor survival (mutant KRAS, 5.8 months vs. wild-type KRAS, 8.0 months; P = 0.001). Multivariate analysis revealed good prognostic factors for overall survival as well to moderately differentiated histology (P & lt; 0.001; HR = 0.437, 95% CI: 0.301–0.634), locally advanced disease (P & lt; 0.001; HR = 0.417, 95% CI: 0.255–0.681), response to first-line chemotherapy (P = 0.003; HR = 0.482, 95% CI: 0.297–0.780), and wild-type KRAS (P = 0.001; HR = 0.523, 95% CI: 0.355–0.770). However, the observed survival advantage is derived from the subgroup of patients treated with gemcitabine/erlotinib (9.7 vs. 5.2 months; P = 0.002), whereas no survival difference based on KRAS mutation status is obvious in the other subgroup of patients treated without erlotinib (7.0 vs. 7.0 months; P = 0.121). These results need to be further explored in upcoming prospective studies to provide a rationale for personalized medicine in pancreatic cancer. Mol Cancer Ther; 10(10); 1993–9. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.MCT-11-0269
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Abstract C122: Clinical implication of ERCC1 overexpression in advanced biliary tract adenocarcinoma patients treated with cisplatin-based palliative chemotherapy
    American Association for Cancer Research (AACR) ; 2009
    In:  Molecular Cancer Therapeutics Vol. 8, No. 12_Supplement ( 2009-12-10), p. C122-C122
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 8, No. 12_Supplement ( 2009-12-10), p. C122-C122
    Abstract: Several clinical studies have shown that excision repair cross-complementation group1 (ERCC1) overexpression is associated with resistance to platinum-based chemotherapy and poor prognoses in several tumors. However these studies have never been tried for biliary tract cancer.The aim of this study was to evaluate the significance of ERCC1 expression as a predictive marker, we analyzed the association between ERCC1 expression and treatment outcomes in advanced biliary adenocarcinoma patients treated with cisplatin-based palliative chemotherapy. 74 patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions between January 2002 and August 2008. Of 74 patients, 65 was assessed by immunohistochemistry from biopsy specimens. ERCC1 expression was positive in 33 out of 65 specimens (51%). 30 (46.2%) of 65 patients showed clinical benefits(including complete response, partial response and stable disease). Among 30 patients who obtained clinical benefits, eleven (37%) were positive for ERCC1 expression and nineteen (63%) were negative (p=0.048). With a median follow-up of 7.3 months (range, 0.8–47.5 months), median progression free survival (PFS) and overall survival (OS) were 3.0 months (95% CI, 1.3–4.7 months) and 7.8 months (95% CI, 5.9–9.7 months), for the total study population. Among patients treated with cisplatin, those who had ERCC1-negative tumors showed longer survival. On univariate analysis, PFS was 1.9 months for patients with ERCC1 positive tumor and 4.6 months for those with ERCC1 negative tumor (P = 0.014). OS was significantly longer in the ERCC1-negative group than in the ERCC1-positive group (9.1 vs 7.3 months, respectively; P = 0.017). A Cox proportional hazard model showed that negative ERCC1 expression (hazard ratio 0.401, 95% CI, 0.176–0.912; P = 0.029), clinical response (hazard ratio 0.290, 95% CI 0.120–0.705; P = 0.006), peritoneal metastasis (hazard ratio 0.260, 95% CI 0.082–0.828; P = 0.023) and primary cancer site (hazard ratio 0.228, 95% CI 0.064–0.814; P = 0.023) were significant independent prognostic factors for the prolongation of OS. These results suggest that advanced biliary tract adenocarcinoma patients with ERCC1-negative tumors show both clinical benefit and survial benefit from palliative chemotherapy with a cisplatin-containing regimen. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C122.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-09-C122
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2062135-8
    SSG: 12
    Location Call Number Limitation Availability
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