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
Filter
  • American Association for Cancer Research (AACR)  (1.399)
Medientyp
Verlag/Herausgeber
  • American Association for Cancer Research (AACR)  (1.399)
Sprache
Erscheinungszeitraum
Fachgebiete(RVK)
  • 1
    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. B062-B062
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 6_Supplement_2 ( 2020-06-01), p. B062-B062
    Kurzfassung: Introduction: Exosomes are communication vesicles act as mediator of intracellular transfer of genetic information, act an important role in intercommunication between tumor cells and immune cells. However, the mechanism underlining this cell-cell communication is not well understanding, particularly in African American breast cancer patients. Recently, our lab has demonstrated that Kaiso, a novel bi-modal transcription factor is highly expressed in African American breast cancer and notably, high Kaiso expression correlates with breast cancer aggressiveness and the disparity in survival outcomes of breast cancer patients of African American compared to European American patients. However, the differential expression and biological consequences of Kaiso in immune signaling of breast cancer exosomes has not been studied yet. Herein we demonstrate the biological role of Kaiso in immune signaling in breast cancer exosomes. Methods: In this study we utilized Nanostring immune profiling technology along with multiple in vitro and in vivo assays were used to study the role of Kaiso in breast cancer immune escape. Results: Nanostring pan cancer immune profiling demonstrated that European American breast cancer exosomes exhibited higher expression of TILs markers, T cell activation markers and CD8+T Cells markers compared to African American, while we observed an increase in the expression of the anti-phagocytic molecule CD47 in breast cancer patient exosomes of African American compared to European American patients. In addition to that CD47 and SIRP-α (Signal Regulatory Protein) are highly expressed in Kaiso-scrambled MDA-MB-231 cells (sh-Scr) and exosomes, whereas THBS1, which is a regulator of CD47 expression and is regarded as angiogenesis inhibitor is significantly increased in sh-Kaiso MDA-231 cells and exosomes. Additionally, we observed that Kaiso directly binds methylated sequences in the promoter region of CD47 and THBS1 by ChIP assay. Furthermore, in vivo sh-Kaiso cells injected into athymic mice exhibited delayed tumor formation after four weeks with smaller tumor size as compared to sh-SCR cells, and we observed higher expression of THBS1 with lower expression of CD47 and SIRP-α molecules by IHC and exosomes isolated from invivo tumors, indicating that Kaiso is associated with macrophage mediated immune escape. Conclusion: These findings demonstrate the important role of kaiso in immune signaling through exosomes which may be related with more aggressive cancer phenotype in breast cancer specially in African Americans. Citation Format: Shakir U Ahmed, Brittany Davis, Benjamin Adu Addai, Balasubramanyanam Karanam, Melissa Davis, William Grizzle, Honghe Wang, Clayton C Yates. Kaiso influences immune signaling of breast cancer exosomes [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 B062.
    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 ...
  • 2
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 12_Supplement ( 2020-12-01), p. PO-085-PO-085
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 12_Supplement ( 2020-12-01), p. PO-085-PO-085
    Kurzfassung: Background: Breast cancer survivors constitute a significant percentage of cancer survivors in the United States, a population that is expected to grow with enhanced surgical procedures, improved cancer therapeutics and new radiation approaches. Although advances in diagnostics and treatment modalities have led to improved quality of life outcomes for breast cancer survivors, evidence suggest that this is not the case for all women. Black women are more likely to be diagnosed with luminal subtypes which are associated with higher mortality rates compared to other women. Additional evidence suggest that Black women experience a multitude of emotional challenges during their breast cancer trajectory which may be further compounded with the burden of chronic stressors coupled with their socioeconomic position (SEP). Given these inequities, the impact of cancer on the lives of black breast cancer survivors (BBCS) is underexplored and warrants further investigation so that we can have a better understanding of their health and well-being over time. To that end, the purpose of this study was to investigate the contribution of psychosocial predictors (SEP, chronic stress burden) on the quality of life in a sample of middle-income BBCS. We hypothesize that higher stress burden would negatively impact life course and higher SEP will positively enhance life course. Methods: A sample of 155 BBCS were recruited using a variety of recruitment strategies, including flyers, direct appeals to BBCS support groups and word-of-mouth across the state of California. Inclusion criteria were women who self-identified as African/Black American, age 25 year or older, diagnosis of breast cancer and at least 1-year post-active treatment. The women completed a demographic data questionnaire, including age, ethnicity, marital status, education, and income and the latter was used to establish SEP. In addition, level of chronic stress was measured with the chronic burden scale (CBS) (Gurung, Taylor, Kemeny, Myers, 2004) and the impact of cancer scale (IOCv2) (Crespi, Ganz, Peterson, Castillo, Caan, 2008) was used to assess quality of life for cancer survivors. Results: The sample of black women were relatively young when diagnosed (mean age at diagnosis 51.67 (SD=10.03). Most (38%) were married and were homeowners, approximately 48.4% reported having a college degree or higher. Results indicated that education was a significant predictor of quality of life for this cohort R2= .234 and Adjusted R Squared=.088. These survivors reported low to moderate levels of chronic stress (mean: 25.3), high positive impact of cancer ratings (mean: 4.10), and relatively low ratings of negative impact of breast cancer on their well-being (mean: 2.27). Conclusion: The study findings indicate a more positive quality of life trajectory in middle-class BBCS. Future studies are needed to confirm these results and to test whether there are differences in quality of life trajectory among black women who may differ on chronic stress and SEP. Citation Format: Claudia M. Davis, Hector F. Myers, Camille I. Davis, Amarachi C. Ihemedu, Nalo Hamilton. The impact of socioeconomic position and chronic stress burden on the quality of life among Black breast cancer survivors in California [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-085.
    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 ...
  • 3
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 10_Supplement ( 2010-10-01), p. A17-A17
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 10_Supplement ( 2010-10-01), p. A17-A17
    Kurzfassung: Background: Effective development and dissemination of cancer control messages to the public requires a firm understanding of individuals’ information-seeking practices and preferences, and cancer-relevant risk behaviors, attitudes, and knowledge. The Health Information National Trends Survey (HINTS) was developed by the U.S. National Cancer Institute (NCI) as a mechanism for collecting such data to inform effective health communication strategies across populations. It provides surveillance of the nation's investment in cancer communication tracking the effects of the changing communication environment on cancer-related knowledge, attitudes and behaviors. The University of Puerto Rico Comprehensive Cancer Center, the Puerto Rico Behavioral Risk Factors Surveillance System, and the NCI, implemented HINTS in Puerto Rico in 2009. HINTS Puerto Rico provides an opportunity to better understand the cancer information and education needs of the population and informed cancer control planning for Puerto Rico. In this study, we describe health and cancer information-seeking behaviors, sources of information and trust in information sources among the population in Puerto Rico. Methods: For HINTS-Puerto Rico, the Spanish version of HINTS 2007 telephone survey was carefully reviewed and edited for language appropriateness for the island population by the HINTS Puerto Rico team. Data was collected between April and June, 2009. Variables of interest for this analysis include: health and cancer information seeking and sources; trust in health information sources, use of the Internet for health, and sociodemographic characteristics (age, sex, education, and ethnic group, place of birth, annual household income, marital status, and employment status). We used multivariate logistic regression models for each of the outcomes of interest (health information seeking, cancer information seeking, and health-related use of the Internet) to estimate the odds ratios (ORs) and their 95% CIs for the association between sociodemographic characteristics and these behaviors. Results: A total of 639 (603 complete and 36 partially complete) interviews were conducted. Nearly one-third of respondents had ever looked for information about health (32.9%) or about cancer (28.1 %). The Internet was the most frequently reported source of information (56.4% of information seekers). The majority of respondents were generally positive in their characterization of their information-seeking experiences, and the most highly trusted sources of information were healthcare providers and government health agencies. College educated (OR=7.6,95% CI 3.0-19.3) and females (OR = 2.8,95% CI 1.6-5.0) were more likely to seek health information. Similarly, college educated (OR=5.4,95% CI 1.8-14.1) and females (OR=2.0,95% CI 1.2-3.3) were more likely to seek cancer information. Only 32.7% of respondents had ever accessed the Internet and college educated were more likely to use it (OR=12.2). Conclusion: Results provide insights into the health and cancer information-seeking behaviors and experiences of the population in Puerto Rico and contribute to the evidence base for cancer control planning on the island. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A17.
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2010
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 4
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 24, No. 10_Supplement ( 2015-10-01), p. A27-A27
    Kurzfassung: The Healthy Eating and Active Living in the Spirit (HEALS) educational and behavioral intervention (2009-2012) was designed to test the effect of a diet, physical activity, and stress reduction intervention on inflammation levels in African Americans at high risk of chronic inflammation and disease in a faith-based community. African-American churches, located in and around Columbia, South Carolina were randomized into a 12-month intervention arm or delayed-intervention arm that served as the study's control group. The 12-week intervention included weekly sessions on cooking, healthy recipes, physical activity, stress reduction, and tracking weight and blood pressure. After the 12-week intervention, participants were invited to attend monthly booster sessions for an additional 9 months to reinforce and expand on topics introduced in the initial 12-week phase. Control churches had to delay the intervention until after churches randomized to the intervention first completed the 12-month follow-up. Participants attended clinics at baseline, 12 weeks (immediately post-intervention for the intervention group), and at 1-year. Prior to each clinic visit participants completed a questionnaire packet to assess demographic characteristics, dietary intake, physical activity, depression/stress, health history, sleep habits, social support, and social desirability and approval. During clinic visits, participants had their blood pressure, height, weight, and percent body fat (via bioelectrical impedance assessment) measured. Physical activity levels were objectively measured using Bodymedia's SenseWear® physical activity armband monitors. Blood samples were collected to characterize inflammatory biomarkers (i.e., high-sensitivity c-reactive protein [CRP] and interleukin-6 [IL-6] ). Of the 627 potential participants from randomized churches, 434 attended clinic 1 (baseline, 233 intervention, 201 controls). Clinic 2 (12-weeks from baseline) was attended by 155 intervention and 155 control arm participants. A total of 113 intervention arm and 128 control arm participants attended Clinic 3 (12 months from baseline). The average age of the study population was 56.9±11.3 and the population was primarily female (80%) and obese (BMI=32.6±6.9kg/m2). Baseline lifestyle factors associated with inflammatory biomarkers included total active energy expenditure (quartile 4 compared to quartile 1: CRP = 2.0 vs. 3.6 mg/L, p=0.01) and minutes of moderate-to-vigorous physical activity minutes (quartile 4 compared to quartile 1: CRP=1.7 vs. 4.5 mg/L, p & lt;0.01; IL-6=1.5 vs. 2.1 pg/mL, p=0.01). Among male participants, the intervention group had significantly lower mean adjusted CRP values compared to controls (2.6 vs. 3.7mg/L, p=0.05) at the 12-week follow-up. However, this finding was not observed among female participants. At the 1-year follow-up no statistically significant differences for inflammatory markers between intervention and control arms were observed overall or separately in males and females. However, among male participants the difference in CRP between intervention and controls remained but was not statistically significant (2.6 vs. 3.9, p=0.17). A more beneficial effect from this diet, physical activity, and stress reduction behavioral and educational intervention was observed among African-American male participants than among African-American female participants. It is possible that a more intensive intervention is necessary to evince and sustain more noticeable changes in inflammation levels. Additionally, targeting those who are more motivated to make lifestyle changes may increase effectiveness of future lifestyle interventions. Citation Format: Michael D. Wirth, James R. Hebert, Heather M. Brandt, Lisa Davis, Briana Davis, Brook E. Harmon, Thomas G. Hurley, Ruby Drayton, Swann A. Adams, Steven N. Blair. Effects of the Healthy Eating and Active Living in the Spirit (HEALS) educational and behavioral intervention on inflammation among an African American faith community. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A27.
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2015
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 5
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 24 ( 2016-12-15), p. 6176-6191
    Kurzfassung: Purpose: Current prostate cancer management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TIC-tailored therapies appears to be a promising approach. Experimental Design: We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient-derived prostate cancer cells and xenograft models to characterize the effects of pharmacologic inhibitors of BMI-1. Results: We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell–like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacologic inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor–directed therapies, without toxic effects on normal tissues. Conclusions: Our data offer a paradigm for targeting TICs and support the development of BMI-1–targeting therapy for a more effective prostate cancer treatment. Clin Cancer Res; 22(24); 6176–91. ©2016 AACR.
    Materialart: Online-Ressource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2016
    ZDB Id: 1225457-5
    ZDB Id: 2036787-9
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 6
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3447-3447
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3447-3447
    Kurzfassung: In 2009 we showed that 2 µM tetrac given for 1 hour at 37oC prior to 250 kVP x-irradiation sensitized GL261 murine brain tumor cells. Radiosensitization was accomplished by increasing the alpha component in the linear-quadratic equation of cell survival (Cell Cycle, 8:2586-91). In 2011, we showed that tetrac also sensitized U87MG human brain tumor cells to 250 kVp x-rays (Cell Cycle, 10: 352-57). Again radiosensitization was accomplished by an increase in the αx-ray component. Tetrac also inhibited the repair of DNA double strand breaks in U87MG cells. However, tetrac which binds to the αvβ3 integrin receptor and inhibitssignaling from the αvβ3 receptor, penetrates the cell and has a thyromimetic effect which offsets radiosensitization. In this regard, we synthesized a nanoparticle tetrac formulation termed Nano-T. Nano-T also binds to the αvβ3 receptor but does notpenetrate the cell. Nano-T causes radiosensitization in vitro in H522 lung cancer cells, producing an added benefit compared to tetrac. We have also shown that daily treatment of in vivo human-MTC (h-MTC) solid tumors in mice with Nano-T for 20 days produced significant growth inhibition. It is our intent to combine Nano-T with ionizing radiation in vivo, and we have begun by studying the effects of tetrac on h-MTC cells in vitro. These h-MTC cells are show an in vitro cell culture doubling time of 96.2 hours and a clonogenicity of 3.16%. We irradiated cells in exponential growth with 250 kVp X-rays. Below we give the LQ survival parameters, and the surviving fraction at 2 Gy (SF2). Table 1. Initial Results of 250 kVp Single Dose X-irradiation on h-MTC CellsIn Vitro without and with Tetrac ≤ α SF2 Tetrac Oxygen (Gy-1 x 10-1) (Gy-2 x 10-2) Enhancment Enhancement Factor Factor Without Tetrac Oxic Cells - 0.033 0.0256 0.901 2.55 Hypoxic Cells 0.030 0.0023 0.922 With Tetrac Oxic Cells 0.472 0.0495 0.330 2.84 2.60 Hypoxic Cells 0.013 0.0256 0.803 2.84 First, h-MTC cells irradiated as oxic or hypoxic, exponentially growing cells are very radioresistant suggesting a large capacity to repair radiation damage. Second, tetrac sensitized both oxic and hypoxic h-MTC cells. These characteristics speak to our proposed Nano-T in treatment of h-MTC tumors in vivo. Nano-T should increase the radiosensitivity of both oxic and hypoxic cells and should also decrease the repair of radiation damage in conventional fractionated radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3447. doi:1538-7445.AM2012-3447
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2012
    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
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2673-2673
    Kurzfassung: INTRODUCTION. We measured the steady-state levels and post-x-irradiation repair of DNA DSBs by neutral comet assay in human U87MG glioblastoma cells in vitro in the absence and presence of tetrac. The results provide a mechanistic basis for our previous observations of radiosensitization and inhibition of cellular recovery after x-irradiation in murine GL261 cells by tetrac (A.H. Hercbergs et al., Cell Cycle 8:2586-2591, 2009). METHODS. U87MG cells on plastic slides were exposed to 2 nM tetrac for 1 h at 37°C. The slides were then placed on crushed ice and irradiated with doses from 0 to 75 Gy. Slides were then immersed in lysing solution at 50°C for 2 h. Slides were washed and placed in a gel electrophoresis unit. Electrophoresis was carried out at 0.66 V/cm for 25 min. Cells were stained with ethidium bromide and image analysis was carried out on an epifluorescence microscope at a total magnification of 400X, using an excitation filter of 515-535 nm and a barrier filter at 590 nm. We calculated the mean tail moment (TM) expressed in arbitrary units. TM was calculated with a CCD camera and software. Approximately 350 comets were analyzed per condition. RESULTS. We first demonstrated that human U87MG cells responded to tetrac exposure in a manner similar to that seen in murine GL261 cells. That is, we observed both radiosensitization and inhibition of radiation repair in cellular studies with both GL261 and U87MG cells. For radiosensitization. we observed a factor of approximately 2.2 in U87MG cells which is quite similar to that seen in GL261 cells. We demonstrated that DSB repair in U87 MG cells was inhibited by 2 nM tetrac by a factor of 72.5%, compared to repair observed in control U87MG cells. Again, this finding is similar to that obtained in murine glioma cells. We then demonstrated that exposure of non-irradiated U87MG cells (0 Gy) to tetrac increased the steady-state levels of DSBs, as indicated by a change in TM from 6.0 to 13.1, yielding a sensitization factor of 2.2. However, in graded single doses, tetrac did not affect the slope of the mean tail moment. Lastly, flow cytometric studies on control and tetrac-treated U87MG cells indicated these changes were not due to alteration in the cell cycle distribution of cells. CONCLUSIONS. These studies provide a linkage between cellular results, i.e., radiosensitization and inhibition of repair in fractionated repair studies, and biochemical endpoints that include increased numbers of DSBs in cells in the unirradiated state and decreased repair of DSBs in fractionated radiation experiments in tetrac-exposed cells. These studies suggest additional studies of possible inhibition of the activity of ATM kinase in tetrac-treated cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2011-2673
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2011
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 24 ( 2011-12-15), p. 7568-7575
    Kurzfassung: Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568–75. ©2011 AACR.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2011
    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: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 3, No. 11 ( 2004-11-01), p. 1355-1364
    Kurzfassung: Resveratrol, a naturally occurring stilbene with antitumor properties, caused mitogen-activated protein kinase [MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2)] activation, nuclear translocation of Ser15-phosphorylated p53, and p53-dependent apoptosis in hormone-insensitive DU145 prostate cancer cells. Exposure of these cells to epidermal growth factor (EGF) for up to 4 hours resulted in brief activation of MAPK followed by inhibition of resveratrol-induced signal transduction, p53 phosphorylation, and apoptosis. Resveratrol stimulated c-fos and c-jun expression in DU145 cells, an effect also suppressed by EGF. An inhibitor of protein kinase C (PKC)-α, -β, and -γ (CGP41251) enhanced Ser15 phosphorylation of p53 by resveratrol in the absence of EGF and blocked EGF inhibition of the resveratrol effect. EGF caused PKC-α/β phosphorylation in DU145 cells, an effect reversed by CGP41251. Activation of PKC by phorbol ester (phorbol 12-myristate 13-acetate) enhanced EGF action on ERK1/2 phosphorylation without significantly altering p53 phosphorylation by resveratrol. DU145 cells transfected with a dominant-negative PKC-α construct showed resveratrol-induced ERK1/2 phosphorylation and Ser15 phosphorylation of p53 but were unresponsive to EGF. Thus, resveratrol and EGF activate MAPK by discrete mechanisms in DU145 cells. The stilbene promoted p53-dependent apoptosis, whereas EGF opposed induction of apoptosis by resveratrol via a PKC-α-mediated mechanism. Resveratrol also induced p53 phosphorylation in LNCaP prostate cancer cells, an effect also inhibited by EGF. Inhibition of PKC activation in LNCaP cells, however, resulted in a reduction, rather than increase, in p53 activation and apoptosis, suggesting that resveratrol-induced apoptosis in these two cell lines occurs through different PKC-mediated and MAPK-dependent pathways.
    Materialart: Online-Ressource
    ISSN: 1535-7163 , 1538-8514
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2004
    ZDB Id: 2062135-8
    SSG: 12
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 10
    Online-Ressource
    Online-Ressource
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 14 ( 2006-07-15), p. 7270-7275
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 14 ( 2006-07-15), p. 7270-7275
    Kurzfassung: Recent evidence suggests that the thyroid hormone l-thyroxine (T4) stimulates growth of cancer cells via a plasma membrane receptor on integrin αVβ3. The contribution of this recently described receptor for thyroid hormone and receptor-based stimulation of cellular mitogen-activated protein kinase [MAPK; extracellular signal-regulated kinase 1/2 (ERK1/2)] activity, to enhancement of cell proliferation by thyroid hormone was quantitated functionally and by immunologic means in three glioma cell lines exposed to T4. At concentrations of 1 to 100 nmol/L, T4 caused proliferation of C6, F98, and GL261 cells, measured by accumulation of proliferating cell nuclear antigen (PCNA) and radiolabeled thymidine incorporation. This effect was inhibited by the T4 analogue, tetraiodothyroacetic acid, and by an αVβ3 RGD recognition site peptide, both of which block T4 binding to integrin αVβ3 but are not agonists. Activation of MAPK by T4 was similarly inhibited by tetraiodothyroacetic acid and the RGD peptide. The thyroid hormone 3,5,3′-triiodo-l-thyronine (T3) and T4 were equipotent stimulators of PCNA accumulation in C6, F98, and GL261 cells, but physiologic concentrations of T3 are 50-fold lower than those of T4. In conclusion, our studies suggest that glioblastoma cells are thyroid hormone dependent and provide a molecular basis for recent clinical observations that induction of mild hypothyroidism may improve duration of survival in glioblastoma patients. The present experiments infer a novel cell membrane receptor-mediated basis for the growth-promoting activity of thyroid hormone in such tumors and suggest new therapeutic approaches to the treatment of patients with glioblastoma. (Cancer Res 2006; 66(14): 7270-5)
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2006
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    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