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Abstract 4559: SMAD3 mediates oxaliplatin resistance in esophageal adenocarcinoma
No full textAbstract Background: Resistance to conventional treatments is a significant barrier to esophageal adenocarcinoma (EAC) therapy. TGF-β signaling appears to be important for EAC tumorigenesis; however, its role in EAC chemoresistance remains understudied. This study investigates the role of SMAD3 in EAC resistance to the frontline chemotherapeutic drug oxaliplatin. Methods: Publicly available datasets were analyzed to determine SMAD3 expression in EAC versus normal samples. Western blot, quantitative real-time polymerase chain reaction, immunofluorescence staining, and flow cytometric analyses were utilized to validate bioinformatic results. Human EAC cell lines (OE33 and OE19) were treated with pharmacologic inhibitors or transfected with small interfering RNA and assessed for DNA damage and apoptotic cell death. Patient-derived organoids and patient-derived xenograft models of EAC were used to confirm our findings in vivo. Results: SMAD3 was significantly upregulated in EAC versus normal tissue samples. Total and phosphorylated SMAD3 protein levels were upregulated in EAC tissues accompanied by increased expression of several genes regulated by SMAD3. Notably, oxaliplatin-resistant EAC cells exhibited overexpression of SMAD3. Chemotherapy non-responding patients showed enrichment of SMAD3 gene expression when compared to responders in the clinical dataset GSE165252. Knockdown or inhibition of SMAD3 hindered DNA repair and sensitized EAC cells to oxaliplatin treatment in vitro and in vivo. Mechanistically, SMAD3 promoted ATM phosphorylation by interacting with protein phosphatase 2A (PP2A) and sequentially inhibiting the binding of PP2A to ATM. Conclusion: Our results reveal a pivotal role for SMAD3 in mediating oxaliplatin resistance in EAC and thus hold a significant potential in guiding future drug development and combination strategies. Citation Format: Farah Ballout, Heng Lu, Nadeem Bhat, Lei Chen, Dunfa Peng, Zheng Chen, Alexander Zaika, Oliver McDonald, Wael El-Rifai. SMAD3 mediates oxaliplatin resistance in esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4559
Brief characteristics of the respondents (N = 4559), Harar, Ethiopia.
No full textBrief characteristics of the respondents (N = 4559), Harar, Ethiopia.</p
Block Card 4559 Overland Parkway
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling (Toledo, Ohio) | Cape Cod style | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4559 Overland Parkway (Toledo, Ohio
Block Card 4559 Vermaas Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: dwelling | 4559 Vermaas Avenue (Toledo, Ohio) | Bungalow Style | North Toledo (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | Alfred Bailey Addition (Toledo, Ohio
Block Card 4559 Copland Boulevard
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 4559 Copland Boulevard (Toledo, Ohio) | dwelling | Miami Heights Addition (Toledo, Ohio) | South Toledo (Toledo, Ohio
Konstantinos Laskaris, der Matrit. 4559 und das Etymologicum Genuinum
No full textIn the MS. Madrid, BN, 4559 mainly transmitting a lexicon being a mixture of Etymologicum Gudianum and Etymologicum Magnum plus supplements from the Suda, Constantine Laskaris supplemented a bifolium (ff. 324r-326v) for integrating the alphabetic section tau, almost completely missing in the core text. In doing this, he excerpted the MS. Vat. gr. 1818, the cod. A of the Etymologicum Genuinum. Since a folium in the latter manuscript is now damaged, the Matrit. 4559 will be useful for reconstructiong the text of the Etymologicum Genuinum for this part of the text
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Linked collectors and determiners for: The Trichoptera of Panama X. The Quebrada Rambala drainage, with description of 19 new species of microcaddisflies (Trichoptera: Hydroptilidae).
No full textNatural history specimen data linked to collectors and determiners held within, "The Trichoptera of Panama X. The Quebrada Rambala drainage, with description of 19 new species of microcaddisflies (Trichoptera: Hydroptilidae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/d8f38b1a-d989-4559-8f58-95878de25602">https://bionomia.net/dataset/d8f38b1a-d989-4559-8f58-95878de25602</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/d8f38b1a-d989-4559-8f58-95878de25602">https://gbif.org/dataset/d8f38b1a-d989-4559-8f58-95878de25602</a>. Formatted as a Frictionless Data package
Biodistribution and kinetics of radiolabeled proteins in rats with focal infection
No full textContains fulltext :
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