Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
  • 1
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 2008
    In:  Biochemical and Biophysical Research Communications Vol. 371, No. 3 ( 2008-07), p. 521-524
    In: Biochemical and Biophysical Research Communications, Elsevier BV, Vol. 371, No. 3 ( 2008-07), p. 521-524
    Materialart: Online-Ressource
    ISSN: 0006-291X
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2008
    ZDB Id: 1461396-7
    SSG: 12
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 3_suppl ( 2015-01-20), p. 613-613
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 613-613
    Kurzfassung: 613 Background: The 12-gene colon cancer assay (Oncotype DX) can identify groups of stage II colon cancer patients with lower or higher recurrence risk, but distribution of scores based on race/ethnicity has not been assessed. This study compared the distribution of Recurrence Score results and gene expression profiles between African American (AA) and Caucasian (CA) stage II colon cancer patients. Methods: Stage II colon cancer patients were identified from tumor registry data from four institutions: University of Arkansas for Medical Sciences, Little Rock; Veterans Administration Medical Center, Little Rock; Baptist Medical Center, Memphis, and University of Alabama at Birmingham. The 12-gene assay and mismatch repair (MMR) status were performed on formalin-fixed paraffin-embedded tissues by Genomic Health (Redwood City, CA). T-test and Wilcoxon test were used to compare data from the two groups (SAS Enterprise Guide 5.1). Results: Of the 244 subjects, there were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median ages (years) were 66 for AAs and 68 for CAs. Age, gender, surgery year, pathologic T-Stage, tumor location, number of nodes examined, lympho-vascular invasion, and MMR status were not significantly different between groups (p 〉 0.05). Recurrence Score results between AAs (mean 27.9; SD 12.8) and CAs (mean 28.1; SD 11.8) were not statistically different (p 〉 0.05). The proportion of patients with high Recurrence Score values (≥41) was similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups, (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC3 and GADD45B) was significantly different between the racial groups (p 〉 0.05). After controlling for clinical and pathologic covariates, means and distributions of Recurrence Score and gene expression profiles still showed no statistical significance between racial groups (p 〉 0.05). Conclusions: In a cohort of AA and CA stage II colon cancer patients with similar clinical characteristics, the distribution of Recurrence Score results and gene expression data were similar between AA and CA patients.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2015
    ZDB Id: 2005181-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4031-4031
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4031-4031
    Kurzfassung: Objective: To determine gene expression profile of Stage II colorectal cancers (CRCs) based on disease recurrence and patient race/ethnicity. Background: About 25-35% of Stage II CRCs recur after potentially curative surgery. Furthermore, the incidence, recurrence, and mortality rates for CRC are higher in African Americans (AAs) relative to Caucasian Americans (CAs), even when they are diagnosed with early stage disease. Differences in tumor biology may contribute to this race-based disparity. Thus, identification of these ‘high-risk’ patients is an unmet medical need. Methods: Using GeneChip microarray technology, we obtained gene expression profiles for Stage II CRCs from 16 AA and 30 CA patients. Samples from recurrent disease, within 5 years post-surgery (n=5 in AA, n= 9 in CA) were compared against non-recurrent, within 10 years post-surgery, (n=11 in AA, and n=21 in CA) samples. The data were analyzed for expression differences at the gene level comparing AA with CA patients and further analyzed for functions and pathways. Results: In the samples of recurrent CRCs, a significant number of genes (n=561) were differentially expressed, with a false-discovery rate of ≤5%. Further analyses showed 253 genes differentially expressed within the AA recurrent subgroup and 317 genes in CA recurrent subgroup. In recurrent CRCs, there were 9 genes common to AA and CA patients, suggesting a common gene signature specific for Stage II disease. Canonical pathway analyses and interaction network analyses for these differentially expressed genes revealed that ERK/MAPK, protein kinase A, and CDK5 signaling were the top three affected signaling pathways in recurrent samples from AAs. In contrast, RhoA, integrin, and cell cycle control signaling were the top three affected pathways in Stage II CRCs of CAs. This suggests, for samples from CAs and AAs, a distinct race-based gene expression and downstream effects on pathways. Conclusion: A common gene expression signature, specific for stage II, together with a race-specific expression profile may have therapeutic implications for AA and CA patients. Citation Format: Trafina Jadhav, Dongquan Chen, Balananda-Dhurjati Kumar Putcha, Temesgen Samuel, James Posey, Martin Heslin, Upender Manne. Distinct gene expression profile of recurrent stage II colorectal cancers in African American and Caucasian American patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4031. doi:10.1158/1538-7445.AM2013-4031
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2013
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 4
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. LB-287-LB-287
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. LB-287-LB-287
    Kurzfassung: Background: Triple-negative (negative for estrogen receptor, progesterone receptor, and HER-2 receptor) breast cancers (TNBCs) are aggressive, difficult to treat, and more likely to recur compared to other subtypes. TNBCs are more commonly found in African American (AA) than Caucasian (CA) patients. Since The Cancer Genome Atlas (TCGA) and other studies have reported a higher incidence of mutations in the TP53 gene in TNBCs, we sequenced p53 in TNBCs collected from AAs and CAs by use of a NextGen sequencing platform (Personal Genome Machine, PGM of Ion Torrent) to assess whether genetic variants in TP53 vary based on patient race. Methods: Genomic DNA was extracted from 18 (10 AAs and 8 CAs) macro-dissected TNBC tumors and their matching normal tissues. Primers were designed using the Ion AmpliseqTM designer (Life Technologies) for a panel of non-silent somatic mutations (PIK3CA, TP53, MAP3K1, MAP2k4, GATA3, MLL3, CDH1, PTEN, PIK3R1, and AKT1) as well as missense point mutations (SF3B1, CDKN1B, RB1, AFF2, NF1, PTPN22, and PTPRD) reported in the TCGA breast cohort study. Using 10 ng of DNA from each sample, 1,541 target sequences were obtained from this panel of genes. Each target sequence was ∼100 bp. These sequences were amplified, and DNA libraries were generated using a protocol recommended by the manufacturer (Ion Torrent, Life Technologies). Samples were barcoded with the Ion Xpress Barcode Adapters, multiplexed for emulsion PCR on Ion OneTouch-2, and sequenced on a PGM sequencer (Life Technologies). Sequencing was performed on 318 chips, and the data were processed using the Ion reporter 4.0 (Life Technologies). Tumor-normal pairs were compared, and the variants were called and further filtered by the Ingenuity variant analysis plug-in. Cancer-driver variants, as identified by Ingenuity, were analyzed according to patient race and molecular subtype. Statistical analyses were performed using the Mann-Whitney or Fisher Exact probability test. Furthermore, we validated our findings with the TCGA data (NIH) using the cBio portal. The TNBC status of TCGA cases was determined based on the clinical data available on the TCGA data portal. Results: In the panel of genes, cumulative mutations and mutation frequencies of individual genes were not significantly different between AAs and CAs. However, the number of cases with TP53 mutations was higher in CAs (7 of 8, 88%) as compared to AAs (3 of 10, 33%) (p=0.027). Of note, 6 of 7 TNBCs of CAs had mutations in the DNA-binding domain (DBD) of TP53. In contrast, all three TNBCs of AAs had mutations both within and outside the DBD of TP53. Analyses of TCGA data on TNBCs suggested that the frequency of TP53 mutations between CAs (28 of 40, 70%) and AAs (3 of 9, 33%) (p=0.058) was similar to the mutation frequency observed in our analyses. Conclusion: In TNBCs, the TP53 mutation frequency, especially in the DBD, is higher in CA patients relative to AA patients. These studies were supported by the Charles Barkley Foundation and by NIH 2U54-CA118948. Citation Format: Balananda-Dhurjati Kumar Putcha*, Shantel Hebert-Magee*, Trafina Jadhav, Andra R. Frost, Isam-Eldin Eltoum, Upender Manne. Racial disparity in the TP53 mutation spectra in triple-negative breast cancers: Validation with TCGA data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-287. doi:10.1158/1538-7445.AM2014-LB-287
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2014
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 5
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 2776-2776
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 2776-2776
    Kurzfassung: Purpose: A single nucleotide polymorphism (SNP) in exon-4 of the TP53 gene (Arg72Pro) has been associated with an increased risk of developing various human malignancies. Since a 16-base pair polymorphism (insertion/duplication) intron-3 (PIN3) is in linkage disequilibrium with Arg72Pro of TP53, we assessed whether these two polymorphisms serve as breast cancer risk alleles for African Americans (AAs) and non-Hispanic Caucasians (CAs). Methods: Genomic DNA was extracted from formalin-fixed, paraffin-embedded invasive ductal carcinoma tissues [cases, n = 120 (AAs = 55 and CAs = 65)] and from blood of healthy women [controls, n = 152 (AA = 74 and CAs = 78)] . Exon-4 of TP53 was amplified by PCR using exon-specific primers, followed by Sanger sequencing. Identification of SNP was done by using DNASTAR software. TP53 PIN3 polymorphism was detected by amplifying genomic DNA using specific primers followed by gel electrophoresis. The A1 allele (no duplication) resulted in 162 bp fragment and the A2 allele (with 16 bp duplication) resulted in 178 bp fragment. The phenotypes of Arg72Pro (Arg/Arg, Arg/Pro, and Pro/Pro) were correlated with PIN3 status, clinicopathologic features, race/ethnicity, and patient survival using the χ2 test and Kaplan-Meier analyses. A p value of & lt;0.05 was considered statistically significant. Results: In cases, the Arg/Arg/, Pro/Arg, and Pro/Pro phenotypes were 15%, 31%, and 55% in AAs and 57%, 29%, and 14% in CAs (p & lt;0.001), respectively. A similar distribution was observed in controls (16%, 42%, and 42% in AAs and 56%, 37%, and 6% in CAs) (p & lt;0.001). When compared to ER positive, a higher frequency of Arg/Pro or Pro/Pro was noted in estrogen-negative breast cancers (p = 0.03) in both racial groups. However, no significant survival difference in these racial groups was observed when Pro carriers were compared with Arg/Arg cases (log rank, p = 0.565). Frequencies of PIN3 polymorphisms (A1A1, A1A2, and A2A2) were similar in both cases and controls; however, overall A1A1 frequency was higher than the other two genotypes of PIN3. The phenotype Pro/Pro, was strongly associated with A1A1 polymorphism in both racial groups of breast cancer patients (p & lt;0.000078). Conclusion: These preliminary findings suggest that Arg72Pro polymorphism and PIN3 in TP53 are related with higher breast cancer susceptibility for both African American and non-Hispanic Caucasian patients. This work was supported by a pilot grant from UAB Breast SPORE grant of the National Institutes of Health/National Cancer Institute (5P50CA089019). Citation Format: Trafina Jadhav, Jesus Salazar-Gonzalez, Shantel Hebert-Magee, Michael Behring, Balananda-Dhurjati Putcha, Jeehyun Helen Bae, Andra Frost, Isam-Eldin Eltoum, Sejong Bae, Upender Manne. Codon 72 and Intron-3 polymorphisms in TP53 are risk factors for breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2776. doi:10.1158/1538-7445.AM2015-2776
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2015
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 6
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4004-4004
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4004-4004
    Kurzfassung: Background: MicroRNAs (miRNAs) may serve as biomarkers for breast cancer (BC) diagnosis and prognosis. Since their clinical value based on race/ethnicity and molecular subtypes has not been studied, we evaluated the prognostic significance of a panel of miRNAs in luminal and triple-negative BCs (TNBCs) of African Americans (AAs) and non-Hispanic Caucasians (CAs). Methods: TaqMan® assays were used to quantify levels of miR-21, miR-106a, miR-206, miR-155, miR-210, and miR-335 in 151 BCs and corresponding normal tissues of 80 AAs (luminal = 24 and TNBCs = 56) and 71 CAs (luminal = 27 and TNBC = 44). Fold changes in levels between tumor-normal pairs were used to categorize the tumors into high- and low-expression groups. The levels of miRNAs were correlated with molecular subtype, patient race/ethnicity, and overall survival by Kaplan-Meier univariate and Cox regression multivariate analyses. Further, the added predictive value of these miRNAs to a baseline prediction model consisting of standard clinical risk factors was evaluated at 2-, 5-, and 8-years post-surgery based on positive predictive curves. Results: In BC tissues, miR-21, miR-106a, miR-155, miR-206, and miR-210 were up-regulated, and miR-335 was down-regulated. For the combined population, univariate and multivariate analyses showed that high levels of miR-21 (adjusted HR = 2.91, 95% CI: 1.27-6.62) and miR-106a (adjusted HR = 2.49, 95% CI: 1.04-5.97) and down-regulation of miR-335 (adjusted HR = 2.97, 95% CI: 1.35-5.54) were associated with poor survival. In multivariate analyses by race, high miR-21 (HR = 7.35, 95% CI: 2.46-21.98) and low miR-335 (HR = 14.13, 95% CI: 2.93-68.13) were indicators of poor survival in only CA patients. Additionally, expression levels of miR-21 aided in identifying risk of death in CA patients with either molecular subtype. In CAs, differences in the area under the positive predictive curve (ΔAUC) between the models with and without miR-21 were 0.077 (95% CI = 0.007-0.154) and 0.053 (95% CI = 0.002-0.128) at 5 and 8 years after surgery, respectively. In TNBCs of both racial groups, addition of miR-106a increased predictive accuracy at 5 (ΔAUC = 0.026, 95% CI = 0.001-0.068) and 8 years (ΔAUC = 0.022, 95% CI = 0-0.061) post-surgery. No miRNA was helpful in identifying patients at high risk of death due to luminal BCs or to AA ethnicity. Conclusions: High levels of miR-106a and miR-21 and low levels of miR-335 are independent prognostic markers of BCs. Furthermore, miR-21 has added predictive value above the standard clinical risk factors for CAs and miR-106a has added predictive value for TNBCs. In evaluation of the clinical utility of miRNAs, patient race and molecular types of BCs should be considered. This work was supported by a pilot grant from UAB Breast SPORE grant of the National Institutes of Health/National Cancer Institute (5P50CA089019). Citation Format: Balananda-Dhurjati Kumar Putcha, Trafina Jadhav, Michael P. Behring, Sejong Bae, Andra R. Frost, Isam-Eldin Eltoum, Li Chen, Heidi L. Weiss, William E. Grizzle, Upender Manne. Prognostic value of miRNAs in breast cancer varies with patient race and molecular subtype. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4004. doi:10.1158/1538-7445.AM2015-4004
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2015
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 7
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 23, No. 11_Supplement ( 2014-11-01), p. PR5-PR5
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11_Supplement ( 2014-11-01), p. PR5-PR5
    Kurzfassung: Background: MicroRNAs (miRNAs) are a class of conserved, non-coding RNAs that are dysregulated in various cancers, including breast cancers. The potential of miRNAs to serve as biomarkers for breast cancer diagnosis and prognosis is being explored, but their clinical value based on race/ethnicity and molecular subtypes (luminal and triple negative breast cancers, TNBCs) has not been examined. Thus, we evaluated expression levels of a panel of miRNAs in luminal (A and B) breast cancers and TNBCs of African Americans (Blacks) and non-Hispanic Caucasians (Whites). We further evaluated the prognostic value of miRNAs based on molecular type of breast cancer and patient race. Methods: TaqMan® miRNA assays were used to quantify expression of miR-181a, miR181b, miR-21, miR-106a, miR-155, miR-210, miR-335, miR-206, and miR-126 in 105 breast cancers (luminal=51 and TNBCs=54) and their corresponding benign/normal tissues. Cancer tissuefrom 48 Blacks (luminal=23 and TNBCs=25) and 57 Whites (luminal=28 and TNBC=29) were analyzed. Fold change in the expression levels between tumor-normal pairs were determined using the 2-∆∆Ct method. A cutoff value for each miRNA was determined by utilizing the Cutoff Finder software application [PLoS ONE 7(12):e51862, 2012]. The cutoff values were used to categorize the tumors into two groups (High expression or positive and low expression or negative). The expression status of tumors was correlated with patient overall survival by univariate Kaplan-Meier analysis. Results: Since the survival probabilities of Blacks and Whites with TNBCs (log rank, p=0.899) were similar, TNBCs from both racial groups were pooled. Similarly, no survival differences were noted in patients of both racial groups with luminal breast cancers (log rank, p=0.178). Therefore, luminal cancers of Blacks and Whites were also pooled together to perform survival analyses based on miRNA expression levels. MiRNA expression profiling studies indicated that, in both the racial groups, miR-181a, miR-181b, miR-21, miR-106a, miR-155, and miR-210 were up-regulated in luminal cancers and TNBCs. In contrast, miR-335, miR-206, and miR-126 were down-regulated in both molecular types. When the prognostic value of miRNAs was evaluated in each molecular type separately, it was found that over-expression of miR-106a (p=0.037) and miR-210 (p=0.039) were associated with poor prognosis of TNBCs. However, none of the evaluated miRNAs were useful in assessing the prognosis of patients with luminal cancers. Conclusions: These findings suggest that increased expression of miR-106a and miR-210 were poor prognostic indicators of TNBCs collected from both Black and White patients. Additionally, our results suggest that in the evaluation of clinical utility of miRNAs molecular types of breast cancer should be considered. This study was funded in part by the National Cancer Institute of the National Institute of Health UAB/TU/MSM Partnership grant (U54 CA118948). This abstract is also presented as Poster C21. Citation Format: Balananda-Dhurjati Kumar Putcha, Trafina Jadhav, Shantel Hebert-Magee, Jeehyun Helen Bae, Andra R. Frost, Isam-Eldin Eltoum, Sejong Bae, Upender Manne. Prognostic value of miRNAs in breast cancer: Molecular type and patient race. [abstract] . In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR5. doi:10.1158/1538-7755.DISP13-PR5
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2014
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 8
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3820-3820
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3820-3820
    Kurzfassung: Background: ST6Gal-1 sialyltransferase, a type II membrane protein that catalyzes the transfer of sialic acid to the N-glycans of certain receptors, is upregulated in several cancers, including colorectal cancers (CRCs), and its levels correlate with metastatic potential. Therefore, we investigated its prognostic value in CRCs. Methodology: Formalin-fixed, paraffin-embedded CRC tissues from African Americans (Blacks) (n=50) and non-Hispanic Caucasians (Whites) (n=51) patients were evaluated for immunohistochemical (IHC) expression of ST6Gal-1. IHC expression was assessed using an anti-human ST6Gal-1 polyclonal antibody (R & D Systems) with antigen retrieval. The antibody-antigen complex was detected by the Immpact NovaRed system (Vector Labs). A semiquantitative immunostaining scoring system (ISS) on a scale of 0-4 was developed to assess the ST6Gal-1 expression, and a cutoff value (1.2 ISS) was determined by the bootstrap method. This value was used to classify tumors as low- or high-ST6Gal-I expressors. Previously, these tissues were evaluated for p53 nuclear accumulation (p53nac), an indicator of abnormal p53, by IHC. ST6Gal-1 expression levels were correlated with demographic and clinicopathologic features and with patient survival. Results: Increased ST6Gal-1 expression was observed in all CRCs as compared to their corresponding normal tissues. The overall frequency of CRCs with increased ST6Gal-1 expression was 80%; it was more commonly found in Blacks (88%, 44 of 50) than in Whites (70%, 36 of 51) (X2 p=0.031). Also, increased expression was associated with p53nac, and ST6Gal-1 expression was higher in CRCs that exhibited p53nac (87%, 42 of 48) relative to CRCs without p53nac (70%, 35 of 50) (X2 p = 0.034). Moreover, patients with CRCs with high ST6Gal-1 had lower median survival (29.3 months) relative to those with low ST6Gal-1 expression (58.5 months). Conclusions: These preliminary findings suggest that increased expression of ST6Gal-1 expression, found predominantly in Blacks patients and in CRCs with abnormal p53, is associated with poor patient survival. Citation Format: Trafina Jadhav, Saksham Narang, Jeehyun Bae, Matthew Schultz, Isam-Eldin Eltoum, Susan Bellis, Sejong Bae, Upender Manne. Expression of ST6Gal-1 in colorectal cancer and patient prognosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3820. doi:10.1158/1538-7445.AM2014-3820
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2014
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4953-4953
    Kurzfassung: Introduction: Colorectal cancer (CRC) and other solid tumors rely on production of pro-inflammatory cytokines and growth factors to support their rapid growth. Posttranscriptional control of these factors involves interplay between RNA stabilizing and destabilizing factors. We have observed that the protein tristetraprolin (TTP), a RNA destabilizer, is down-regulated in CRCs and that interleukin (IL)-8, a proinflammatory cytokine, is up-regulated. We hypothesized that loss of negative regulation by TTP selectively favors expression of growth factors and protooncogenes that promote tumor progression. Furthermore, new evidence suggests that TTP is associated estrogen receptor-α (ERα) and functions as a co-repressor of ERα activation interaction with histone deacetylases on the gene promoter; nuclear TTP is linked to this tumor suppressor function. Since CRCs of African Americans (AAs) often present worse outcomes relative to those of Caucasian Americans (CAs), we analyzed the expression of TTP and its targets and assessed its subcellular localization in primary CRCs of AA and CA patients and in cultured colon cancer cells. Its effects on disease progression were also determined. Methods: Paired normal and CRC tissues from 45 patients (AA = 26 and CA = 19), were evaluated by qPCR for mRNA expression levels of TTP, IL-8, and VEGF. Tissue sections were also assayed for immunophenotypic expression by immunohistochemistry, and the staining patterns (nuclear and cytoplasmic) were assessed. To determine TTP effects on the NF-kB pathway, colon cancer cells (CCL235, HCT116 and LoVo) were stimulated with TNF-α, and total RNA was analyzed for TTP, IL-8, VEGF, and cIAP2 expression; interaction of TTP and ERα was also assessed. Results: In 31 of 45 CRCs, there was down-regulated expression of TTP mRNA, and low TTP levels correlated with advanced tumor stage. Low levels of TTP were present in 21 of 26 AAs and in 12 of 19 CAs. There was an inverse correlation between TTP and IL-8 expression in relation to tumor stage. There was an agreement between mRNA expression and immunophenotypic profiles for TTP and IL-8. Furthermore, there was reduced or a lack of nuclear staining of TTP in malignant cells relative to normal/benign epithelial cells. In cultured colon cancer cells, TTP mRNA levels inversely correlated with levels of IL-8, VEGF, and cIAP2 mRNAs, suggesting interactions of TTP with these cell survival factors. Conclusions: Reduced expression of TTP was noted in tumors, especially in CRCs of AAs, and a loss or decreased nuclear expression of TTP was observed in malignant cells. Lower TTP levels correlated with advanced tumor stage. These preliminary findings suggest that TTP negatively regulates the expression of cell survival factors in the NF-kB pathway. This work was supported by funds from the NIH/NCI (a career development supplement to grant U54-CA118948). Citation Format: Esther A. Suswam, Balananda-Dhurjati K. Putcha, Amit K. Tiwari, Trafina Jadhav, Kiera D. Walker, Lualhati Harkins, Samir Amer, Isam-Eldin Eltoum, Sejong Bae, Upender Manne. Molecular and cellular localization profiles of tristetraprolin in colorectal cancer: Implications for tumor progression in diverse patient populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4953. doi:10.1158/1538-7445.AM2015-4953
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2015
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 10
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 6_Supplement_2 ( 2020-06-01), p. C044-C044
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 6_Supplement_2 ( 2020-06-01), p. C044-C044
    Kurzfassung: Inter-ethnic differential gene expression in stage II recurrent colorectal cancers Prachi Bajpai1, Amr Elholy1, Michael Behring1, Dongquan Chen2, 3, Kevin Hale1, Sumit Agrawal1, Hyung-Gyoon Kim1, Trafina Jadhav1, Temegsen Samuel4, Upender Manne1, 3 1Department of Pathology, 2Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA, 3O’Neal Comprehensive Cancer Center of UAB, Birmingham; 4Department of Pathobiology, College of Veterinary Medicine, Tuskegee University, Tuskegee, Alabama, USA Background and Objective: For colorectal cancer (CRC), the second most common cause of cancer-related death in the US, there are racial/ethnic disparities in incidence and mortality. Of these patients, 25-35% with pathologic Stage II CRCs exhibit recurrence after surgery with curative intent. Relative to Caucasian (CA) patients, African American (AA) patients with CRC have a 20% higher stage-specific mortality. The present study delineates a distinct gene expression profile, specific for Stage II CRCs, based on disease recurrence and patient race/ethnicity. Methods: We obtained gene expression profiles for Stage II CRCs from 16 AA and 30 CA patients by the use of Affymetrix GeneChip microarrays. Samples from patients with recurrent disease, within 5 years post-surgery, were compared to those with non-recurrent CRCs within 5 years post-surgery. For comparison between AA with CA patients, gene expression was assessed. Results: For recurrent CRCs, there were nine genes common to AA and CA patients, suggesting a common gene signature specific for Stage II disease. For tumors, relative to their corresponding normal tissues, there was higher expression of five of these genes; the direction of association with disease recurrence was distinct with race/ethnicity. GFM2, DCAF17, and GEN1 had a positive association with recurrence in CAs and a negative association with recurrence in AAs. Additionally, for recurrent patients, TAPBP and FEZ were upregulated in AAs and downregulated in CAs (False Discovery Rate & lt;0.05 for all genes). BCL2L2, OXA1L, AHNAK2, and MEGF6 were consistently overexpressed in CRCs of both race/ethnicity groups. Currently, we are validating these findings in a prospective Stage II CRC cohort to correlate observations with time to recurrence. Conclusion: The present study identifies molecular signatures, specific for Stage II CRCs, for patients of two ethnic backgrounds, and contribute to a better understanding of the CRC health disparities for AAs and CA. This work was supported by a NIH/NCI grant (U54CA118948). Citation Format: Prachi Bajpai, Amr Elholy, Michael Behring, Dongquan Chen, Kevin Hale, Sumit Agrawal, Hyung-Gyoon Kim, Trafina Jadhav, Temegsen Samuel, Upender Manne. Inter-ethnic differential gene expression in stage II recurrent colorectal cancers [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C044.
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2020
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie auf den KOBV Seiten zum Datenschutz