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  • 1
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    Abstract 4221: Association between SOX9 expression in Mexican patients with early colon cancer stage
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4221-4221
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4221-4221
    Abstract: Introduction. Colon cancer is the fourth leading cause of mortality worldwide. Between 30-40% of patients are diagnosed at early stage (I or II), sadly 20% will relapse. It is necessary to have a biomarker that identifies patients at high risk. SOX 9 is a transcription factor required for differentiation of different cells and is important for cell proliferation, senescence and lineage commitment. The exact role of SOX9 in carcinogenesis and cancer progression is controversial because could have oncogenic and tumor-suppressing functions. Reports show that strong levels of SOX 9 in colon cancer stage II are linked to low risk of relapse. Objective. The aim of this study was to investigate if the protein expression of SOX9 was associated with the stage, clinical characteristics and relapse of Mexican colon cancer patients. Methods. We obtained 97 samples embedded in paraffin. A pathologist blinded to the clinical information determined the immunoreactivity of SOX9 into 2 groups: low and high expression (by evaluating the percentage of positive nucleus and the tissue staining intensity). All statistical analyses were conducted with SPSS v.22 Statistics. Results. We include stage I (N= 34) and stage II (N=63) patients. The median follow-up period was 42 months. We found statistical difference between SOX9 expression and age (p=0.003), tumor localization (p=0.048) and stage (p & lt0.001) for whole patients group. Twelve patients (12.3%) relapsed, 7 (at locally level) and 5 with distant metastasis: liver (N=3) and retroperitoneal nodes (N=2), all had low SOX9 expression; one patient with local relapse had died (because of surgical complications). In the relapse group, we found a significant correlation between SOX9 expression and stage (p=0.038) but not with relapse free survival (RFS). Conclusion. We found interesting data even though this is a retrospective study with limitations. This study could not associated SOX9 and RFS, because there are few events. Nevertheless, we observe that 41% patients had a systemic relapse. In the other hand, the youngest patients ( & lt40 y) and the right colon had the highest SOX9 expression. With this result, we have decided to increase the sample size before any assumption, and perform NGS to the five systemic relapses. Citation Format: Erika Ruiz-Garcia, Tatiana Galicia, Edith Fernandez Figueroa, Saul Lino-Silva, Cesar Lopez-Camarillo, Laurence Marchat, German Calderillo, Juan Zinser, Abelardo Meneses-Garcia, Horacio Astudillo-de la Vega. Association between SOX9 expression in Mexican patients with early colon cancer stage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4221.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-4221
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 2
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    Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Global Oncology , No. 4 ( 2018-12), p. 1-5
    Details
    In: Journal of Global Oncology, American Society of Clinical Oncology (ASCO), , No. 4 ( 2018-12), p. 1-5
    Abstract: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. Methods Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. Results The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. Conclusion This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.
    Type of Medium: Online Resource
    ISSN: 2378-9506
    URL: Article
    DOI: 10.1200/JGO.2016.008912
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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    detail.hit.zdb_id: 2840981-4
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  • 3
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    Micro-RNAs as positive biomarkers of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 624-624
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 624-624
    Abstract: 624 Background: Neoadjuvant chemoradiotherapy (nCRT) follow by surgery, as treatment for locally advanced rectal carcinoma (LARC), has improve local disease control, increase of complete pathological response (cPR) and preserve anal sphincter. cPR is associated with better prognosis. CRT act mainly through induction of DNA damage. MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at post-transcriptional level. miRNAs are involved in the regulation of DNA damage/repair mechanism. Our goal was to measure expression of miRNAs involved in DNA damage/repair genes and correlated with cPR. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 20 Mexican patients with LARC treated with nCRT at National Cancer Institute of Mexico between 2010-2013. Treatment response was evaluated with Ryan Classification. Ten patients had cPR (Ryan Grade 0) meanwhile other 10 poor response (Ryan Grade 3). RNA extraction was done with RNeasy FFPE (Qiagen) Kit. RNA concentration and purity was assessed using NanoDrop 2000 Spectrophotometer. miRNAs expression were evaluated by real-time polymerase chain reaction (PCR) analysis with TaqMan Probes from Applied Biosystems. Statistical analysis was carried out with IBM SPSS Statistics 22.0. Differential expression between the two groups was performed with Chi square test. Results: There wasn’tsignificant difference betweenclinical/demographic features between the 2 groups. All patients received CRT at a total dose of 4500 cGy of pelvic irradiation, concomitantly with fluoropyrimidine. Surgical treatment was performed 14 weeks after completion of nCRT. The 2 miRNAs (188-5p and 590-5p) was overexpressed in the cPR group vs poor response group (p = 0.011 and p = 0.057, respectively). Conclusions: We evaluated the expression of miR590-5p and miR188-5p because they are related to DNA repair genes such as: MSH2, ERCC3, BRCC3 and XRCC5. We found overexpression in both miRNAs. Even though miR590 5p didn't reach statistical significance this maybe because of simple size.Our results now are been analyzed with a biological and functional genes network platform: Ingenuity Pathway Analysis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.624
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 4
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    Abstract 1786: Predictive value of LRP8, KPNA2 and GDF15 expression to anthracycline/taxane based chemotherapy response in patients with locally advanced breast cancer
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1786-1786
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1786-1786
    Abstract: Background: Chemotherapy plays a major role in its treatment, though overtreatment is frequent since its choice is based on clinicopathological prognostic data. The identification and validation of new predictive profiles or markers continues to be relevant. New findings may contribute to achieve better results in this area, as well as to provide new targets of the pathways involved in chemoresistance. Karyopherin α2 (KPNA2), low density lipoprotein receptor-related protein 8 (LRP8) and growth and differentiation factor 15 (GDF15), are three candidate predictive biomarkers in breast cancer, previously identified on DNA microarrays reports. Methods: Using tissue microarrays technology and immunohistochemistry, we compared the expression of these three markers between cases of breast cancer with response to chemotherapy (absence of recurrence), and those with failure (with recurrence). All patients received chemotherapy based on anthracyclines and taxanes. Potential confounding factors, as known recurrence and progression risk factors, were controlled for during the comparison. Results: 20 out of 63 patients had tumor recurrence. Potential confounding factors were similar among cases with response and failure to chemotherapy. For KPNA2 no differences were found between cases with response or failure. LRP8 showed higher expression in cases with failure to chemotherapy (mean 7.22 vs 14.01%, p =0.025). In Cox multivariable regression analysis, which included potential confounding factors as covariates, only LRP8 remained as a significant predictive factor (HR 1.28, p=0.016). GDF15 showed no expression in our cases, nor in an external set of cases. Conclusions: We demonstrated increased expression of LRP8 in breast cancer cases recurring after chemotherapy. KPNA2 and GDF 15 showed no predictive value for chemotherapy response in our study. LRP8 is a potential predictive marker worth of further investigation for its role in chemoresistance as well as for its potential validation. Note: This abstract was not presented at the meeting. Citation Format: Hector Maldonado-Mtz, Alonso-Luna Oscar, Ali Flores-Perez, Meneses-Garcia Abelardo, Erika B. Ruiz-Garcia, Cesar Lopez-Camarillo, Horacio Astudillo-de la Vega. Predictive value of LRP8, KPNA2 and GDF15 expression to anthracycline/taxane based chemotherapy response in patients with locally advanced breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2017-1786
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-1786
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
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    Clinical and functional analysis of SOX9 in colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 519-519
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 519-519
    Abstract: 519 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops within the intestinal epithelium, which is constantly self-renewing, developmental genes could promote the initiation and progression of cancer. SOX9 transcription factor is expressed especially in intestinal stem cells and in Paneth cells, thus alterations in expression could greatly promote neoplasia. However, the clinical significance and functional role of SOX9 in CRC remains unclear. The aim of this study is to investigate the association of SOX9 expression with relapse in CRC patients and initiate functional studies by evaluating the effects of silencing SOX9 in stem cells properties such as colonospheres formation in HCT116 CRC cells. Methods: 97 FFPE biopsies from CRC patients in stage I (N = 34) and stage II (N = 63) were analyzed. Immunoreactivity of SOX9 was classified as low and high expression groups based on the percentage of positive nucleus and tissue staining intensity. SOX9 silencing was achieved using a specific siRNA and Lipofectamine-RNAiMax and confirmed by qPCR 24 h postransfection. 40,000 HCT116 and HCT116-siSOX9 cells were seeded under adherent and ultra-low attachment conditions for tumorigenesis assays. After 72 h colonospheres were seeded and quantified. ROC analysis was used to assess the clinical correlation of SOX9 with relapse. Experimental data were expressed as means and differences tested by t-Student. Results: Data showed that 12.3% of patients relapsed. Interestingly, all of them showed lower SOX9 expression (p ≤ 0.05), regardless of their relapse free survival. In functional analysis, SOX9-deficient HCT116 cells formed smaller and less-compacted spheroid when compared to non-transfected HCT116 (p ≤ 0.05). Nonetheless, cell proliferation and migration under adherent condition were similar between the groups. Conclusions: This study did not find association between SOX9 expression and relapse. So far, in vitro assays results suggest that silencing of SOX9 inhibits colonospheres formation in HCT116 cells. Further investigation will be performed in order to evaluate the functional importance of SOX9 in chemotherapy response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.519
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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