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  1. AU="J Joshua Smith"
  2. AU="Kotak, Dinesh"
  3. AU="Michael Holland"
  4. AU="Pauline, Staelen"
  5. AU="Mouna Esmaeilzadeh"
  6. AU=Congreve Miles
  7. AU="Li, Yunfeng" AU="Li, Yunfeng"
  8. AU="Shankar, Ganesh"
  9. AU="Ruginsk, Silvia G"
  10. AU="Aquilante, Francesco"
  11. AU="Dillon, Robert C"
  12. AU="Yuan Qu"
  13. AU="Dufour, A"
  14. AU="Hannus, Jill"
  15. AU="Rieber, Julia"
  16. AU="Gulmuradov, Tashpulat"
  17. AU="Romeu Fontanillas, Teresa"
  18. AU="Fleming, Renée"
  19. AU="Cao, Fang"
  20. AU="Sally J L Moore"
  21. AU="Moreno, Yolanda"
  22. AU="Vasiliy Ya. Kolyuchkin"

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  1. Artikel ; Online: A SMAD4‐modulated gene profile predicts disease‐free survival in stage II and III colorectal cancer

    Bryan C. Szeglin / Chao Wu / Michael R. Marco / Hyun Sung Park / Zeda Zhang / Bing Zhang / Julio Garcia‐Aguilar / R. Daniel Beauchamp / X. Steven Chen / J. Joshua Smith

    Cancer Reports, Vol 5, Iss 1, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Background Colorectal cancer is the second‐leading cause of cancer‐related mortality in the United States and a leading cause of cancer‐related mortality worldwide. Loss of SMAD4, a critical tumor suppressor and the central node of the ... ...

    Abstract Abstract Background Colorectal cancer is the second‐leading cause of cancer‐related mortality in the United States and a leading cause of cancer‐related mortality worldwide. Loss of SMAD4, a critical tumor suppressor and the central node of the transforming growth factor‐beta superfamily, is associated with worse outcomes for colorectal cancer patients; however, it is unknown whether an RNA‐based profile associated with SMAD4 expression could be used to better identify high‐risk colorectal cancer patients. Aim Identify a gene expression‐based SMAD4‐modulated profile and test its association with patient outcome. Methods and results Using a discovery dataset of 250 colorectal cancer patients, we analyzed expression of BMP/Wnt target genes for association with SMAD4 expression. Promoters of the BMP/Wnt genes were interrogated for SMAD‐binding elements. Fifteen genes were implicated and three tested for modulation by SMAD4 in patient‐derived colorectal cancer tumoroids. Expression of the 15 genes was used for unsupervised hierarchical clustering of a training dataset and two resulting clusters modeled in a centroid model. This model was applied to an independent validation dataset of stage II and III patients. Disease‐free survival was analyzed by the Kaplan‐Meier method. In vitro analysis of three genes identified in the SMAD4‐modulated profile (JAG1, TCF7, and MYC) revealed modulation by SMAD4 consistent with the trend observed in the profile. In the training dataset (n = 553), the profile was not associated with outcome. However, among stage II and III patients (n = 461), distinct clusters were identified by unsupervised hierarchical clustering that were associated with disease‐free survival (p = .02, log‐rank test). The main model was applied to a validation dataset of stage II/III CRC patients (n = 257) which confirmed the association of clustering with disease‐free survival (p = .013, log‐rank test). Conclusions A SMAD4‐modulated gene expression profile identified high‐risk stage II and III colorectal cancer ...
    Schlagwörter cancer biology ; colorectal cancer ; gene expression profile ; SMAD4 ; tumor suppressor genes ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Thema/Rubrik (Code) 610 ; 616
    Sprache Englisch
    Erscheinungsdatum 2022-01-01T00:00:00Z
    Verlag Wiley
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Feasibility and performance of the fecal immunochemical test (FIT) for average-risk colorectal cancer screening in Nigeria.

    Gregory C Knapp / Olusegun Alatise / Bolatito Olopade / Marguerite Samson / Olalekan Olasehinde / Funmilola Wuraola / Oluwole O Odujoko / Akinwunmi O Komolafe / Olujide O Arije / Philip E Castle / J Joshua Smith / Martin R Weiser / T Peter Kingham

    PLoS ONE, Vol 16, Iss 1, p e

    2021  Band 0243587

    Abstract: Introduction There is a paucity of prospective data on the performance of the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening in sub-Saharan Africa. The aim of this exploratory analysis was to evaluate the feasibility and ... ...

    Abstract Introduction There is a paucity of prospective data on the performance of the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening in sub-Saharan Africa. The aim of this exploratory analysis was to evaluate the feasibility and performance of FIT in Nigeria. Methods This was a prospective, single-arm study. A convenience sample of asymptomatic, average-risk individuals between 40-75 years of age were enrolled at Obafemi Awolowo University Teaching Hospital. Study participants returned in 48 hours with a specimen for ova and parasite (O&P) and qualitative FIT (50ug/g) testing. Participants with a positive FIT had follow-up colonoscopy and those with intestinal parasites were provided treatment. Results Between May-June 2019, 379 individuals enrolled with a median age of 51 years (IQR 46-58). In total, 87.6% (n = 332) returned for FIT testing. FIT positivity was 20.5% (95% CI = 16.3%-25.2%). Sixty-one (89.7%) of participants with a positive FIT had a follow-up colonoscopy (n = 61), of whom 9.8% (95%CI:3.7-20.2%) had an adenoma and 4.9% (95%CI:1.0-13.7%) had advanced adenomas. Presence of intestinal parasites was inversely related to FIT positivity (6.5% with vs. 21.1% without parasites, p = 0.05). Eighty-two percent of participants found the FIT easy to use and 100% would recommend the test to eligible family or friends if available. Conclusions Asymptomatic, FIT-based CRC screening was feasible and well tolerated in this exploratory analysis. However, the high FIT positivity and low positive predictive value for advanced neoplasia raises concerns about its practicality and cost effectiveness in a low-resource setting such as Nigeria.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 150
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors

    Cristina Valero / Mark Lee / Douglas Hoen / Kate Weiss / Daniel W. Kelly / Prasad S. Adusumilli / Paul K. Paik / George Plitas / Marc Ladanyi / Michael A. Postow / Charlotte E. Ariyan / Alexander N. Shoushtari / Vinod P. Balachandran / A. Ari Hakimi / Aimee M. Crago / Kara C. Long Roche / J. Joshua Smith / Ian Ganly / Richard J. Wong /
    Snehal G. Patel / Jatin P. Shah / Nancy Y. Lee / Nadeem Riaz / Jingming Wang / Ahmet Zehir / Michael F. Berger / Timothy A. Chan / Venkatraman E. Seshan / Luc G. T. Morris

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 9

    Abstract: There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and ... ...

    Abstract There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and progressive-free survival, as well as higher rate of response, in a multi-cancer cohort of patients treated with immune checkpoint inhibitors.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

    Olusegun Isaac Alatise / Gregory C. Knapp / Avinash Sharma / Walid K. Chatila / Olukayode A. Arowolo / Olalekan Olasehinde / Olusola C. Famurewa / Adeleye D. Omisore / Akinwumi O. Komolafe / Olaejinrinde O. Olaofe / Aba I. Katung / David E. Ibikunle / Adedeji A. Egberongbe / Samuel A. Olatoke / Sulaiman O. Agodirin / Olusola A. Adesiyun / Ademola Adeyeye / Oladapo A. Kolawole / Akinwumi O. Olakanmi /
    Kanika Arora / Jeremy Constable / Ronak Shah / Azfar Basunia / Brooke Sylvester / Chao Wu / Martin R. Weiser / Ken Seier / Mithat Gonen / Zsofia K. Stadler / Yelena Kemel / Efsevia Vakiani / Michael F. Berger / Timothy A. Chan / David B. Solit / Jinru Shia / Francisco Sanchez-Vega / Nikolaus Schultz / Murray Brennan / J. Joshua Smith / T. Peter Kingham

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 8

    Abstract: Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian ... ...

    Abstract Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Kaiso directs the transcriptional corepressor MTG16 to the Kaiso binding site in target promoters.

    Caitlyn W Barrett / J Joshua Smith / Lauren C Lu / Nicholas Markham / Kristy R Stengel / Sarah P Short / Baolin Zhang / Aubrey A Hunt / Barbara M Fingleton / Robert H Carnahan / Michael E Engel / Xi Chen / R Daniel Beauchamp / Keith T Wilson / Scott W Hiebert / Albert B Reynolds / Christopher S Williams

    PLoS ONE, Vol 7, Iss 12, p e

    2012  Band 51205

    Abstract: Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, ... ...

    Abstract Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the Apc(Min) mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (4×KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co-repressor functions for the MTG family, suggesting ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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