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  • American Society of Clinical Oncology (ASCO)  (3)
  • 1
    Online Resource
    Online Resource
    Frequency of Hsa-miR9 aberrant methylation in metastatic breast cancers.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e21092-e21092
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21092-e21092
    Abstract: e21092 Background: MicroRNAs (miRNAs) are a recently discovered class of very small non-coding RNAs involved in the regulation of gene expression by interfereing with mRNA translation. It has been shown that human miR-9 expression levels are reduced in breast cancer samples due to the aberrant methylation of its promoter region . Methods: We analyzed74breast cancer cases treated by surgery at the IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. Pathological assessment included evaluation of histological type, grade and stage. Estrogen receptor (ER), progesterone receptor (PgR), Ki-67 labeling index and Her2 amplification were also evaluated. Six of the 74 patients showed metastases at the diagnosis, and 8 patients developed metastases during the follow up. The median follow up time for the patients cohort was 44 months (range 28-57+). All metastatic patients (n=14) died from the disease. Genomic DNA extracted from 6 normal breast tissues obtained by reductive mammoplasty, and tumour samples was subjected to bisulphite treatment and the converted DNA was used as a template for MSP using primers specific for the methylated hsa-miR9 sequence. Results: Methylation at the hsa-miR9 promoter region was detected in 33 of 74 (44%) breast tumours and none of the 6 normal breast tissues (p=0.02). Interestingly, hsa-miR9 methylation was significantly more frequent in patients with syncronous or metachronous distant metastases (8 of 14, 57%) as compared with patients free from metastases (11 of 33, 32%) (p=0.02 χ 2 Test). In particular, methylation was detected in all 5 tumours showing only bone metastases (100%), whereas methylation was less frequent (33%) in the group characterized by the the presence of visceral metastases (P=0.03 χ 2 Test). Conclusions: Our results suggest that hsa-miR9 methylation in breast cancer is associated with tumour metastatic behaviour and might represent a novel biomarker for monitoring breast cancer patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e21092
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Hypermethylation of the KEAP1 gene in colorectal cancer and association with disease progression.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e14655-e14655
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e14655-e14655
    Abstract: e14655 Background: Aberrant methylation of the KEAP1 (Kelch-like ECH-associated protein 1) gene promoter is emerging as a main mechanism of dysregulation of the NrF2 (nuclear factor-erythroid 2-related factor 2 ) which plays a pivotal role in the cellular response to oxidative stress. Under basal conditions, Nrf2 is retained in the cytoplasm by the binding with Keap1 and it is maintained at a reduced level by the Keap1-dependent ubiquitination and proteasomal degradation systems. Reduced Keap1 expression by promoter aberrant methylation allows Nrf2 to translocate in the nucleus and to activate the detoxification pathway leading ultimately to drug resistance. Methods: We determined KEAP1 promoter methylation status in 50 metastatic colorectal cancer (CRC) and 9 normal colonic mucosa samples by using quantitative methylation specific PCR in real time (QMSP). The median age of the patients cohort was 65 (IQR 57-74) years. At diagnosis 12 patients were staged Duke D and 38 were staged as Duke C. As first line treatment the FOLFOX or FOLFIRI therapeutical schemes were used. Results: Methylation was detected in 20 out of 50 CRC (40%) and methylation levels were significantly higher in tumour samples (Median 0.65, IQR 0-8.28) as compared with normal colonic mucosa (Median 0, IQR 0-0.08) (P=0.03). Tumours from patients who experieced disease progression had significantly higher methylation levels (Median 0.53; IQR 0-7.61) as compared with patients showing partial response (Median 0, IQR 0-2.21) or disease stability (Median 0, IQR 0-0) (P=0.03 Kruskall Wallis Test). Conclusions: Our results suggest that Keap1 aberrant methylation is a frequent event in colorectal cancer and is associated with response to chemotherapeutical treatments.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e14655
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Evaluation of microRNA-10b expression as a novel predictive marker of metastases development and patients’ survival in breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 576-576
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 576-576
    Abstract: 576 Background: MicroRNA-10b was found highly expressed in metastatic breast cancer cell lines and able to generate metastases in mice models. The aim of this study is to evaluate the putative association between miR10b expression and disease progression. Methods: We selectedfrom our tumor bank 150 consecutive breast cancers with at least three years follow up. For each case frozen paired tumor and normal tissue and complete clinical data were available. Pathological examination was performed to ensure that each tumour sample contained more than 70% of cancer cells resulting in 114 samples suitable for RNA extraction. RNA quality was measured and only samples with RIN≥7.0 were analyzed (n=101) by a relative quantification method. Results: miR10b relative expression in tumor to normal samples (RERs) was significantly higher in the subgroup of patients with metastases (median 0.25 IQR 0.11-1.02) as compared with patients without metastases (median 0.09 IQR 0.04-0.29) (P=0.023 Mann Whitney Test). The association between miR-10b RERs and survival was evaluated in the group of patients without metastases at diagnosis (n=90). In univariate Cox regression model, patients with high miR-10b RERs had a higher risk of distant metastases development (HR 4.91, P=0.02) and disease related death (HR 6.02; P=0.01). In a multivariate Cox regression model adjusted for tumor size, lymph node metastases, grade, ER, PgR status, and Ki67 labeling index (n=79), higher miR-10b RERs were still associated with increased risk of distant metastases development (HR18.84; P 〈 0.001) and disease related death (HR 13.39; P=0.003) (Table). Conclusions: We show that in breast cancer patients miR-10b expression is associated with worse prognosis on a short term follow up. These results suggest that miR-10b expression could be used for individual patient’s risk assessment and perhaps as potential therapeutical target. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.576
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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