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Evans, C, 5010
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/384134Surname: EVANS. Given Name(s) or Initials: C. Military Service Number or Last Known Location: 5010. Missing, Wounded and Prisoner of War Enquiry Card Index Number: 10055.228711
Item: [2016.0049.16427] "Evans, C, 5010
Santa Fe (ATSF) 5010
No full textA photograph print showing Santa Fe 5010, 2-10-4 (BLW), class 5001, Topeka, KS
Santa Fe (ATSF) 5010
No full textA photograph postcard showing the Santa Fe (ATSF) 5010, 2-10-4, westbound on horseshoe curves west of Blanchard, NM, 37 cars, 30 mph
Santa Fe (ATSF) 5010
No full textA photograph postcard showing the Santa Fe (ATSF) 5010, on mixed freight, no date or location
Santa Fe (ATSF) 5010
No full textA photograph print showing Santa Fe 5010, 2-10-4 (BLW), class 5001, taking on water, Topeka, KS
Abstract 5010: Activation of the notch signaling pathway confers a tumor-suppressive phenotype on melanoma-associated fibroblasts
No full textAbstract
Objectives. The tumor microenvironment (TME) is an emerging therapeutic target for cancer treatment. Cancer-associated fibroblasts (CAF) play a crucial role in cancer progression. We aim to target TME by altering intracellular signaling which determines the biological function of CAF. We have recently showed that the Notch signaling pathway likely functions as a molecular switch in controlling the tumor regulatory role of CAF in animal models and experimentally created “CAF”. Here, we investigated the status of Notch signaling in human melanoma-associated fibroblasts (MAF) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAF alter their tumor-regulating function.
Methods. We examined levels of Hes1, a canonical Notch target, in MAF of human malignant melanoma at different stages (I-IV) and fibroblasts in either adjacent or non-adjacent normal skin tissues using tissue microarray. MAF were isolated from human metastatic melanoma tissues. Notch pathway RT2-PCRArray and immunoblot were used to assess Notch pathway activity in MAF versus normal human dermal fibroblasts. Activation of Notch signaling pathway in MAF was achieved by lentiviral vector encoding active form of Notch1 (NIC). The effect of Notch1-engineered MAF on melanoma growth was tested by in vitro co-cultures and in a mouse co-xenograft model (n=6/group). Tumor angiogenesis was analyzed by immunochemistry.
Results. MAF expressed decreased levels of Hes1 compared with adjacent skin fibroblasts. Isolated MAF also exhibited lower Notch activity than normal human dermal fibroblasts. Notch1-engineered MAF significantly inhibited melanoma cell growth in vitro (p<0.01) and suppressed melanoma growth and tumor angiogenesis in mice (p<0.05).
Conclusions. Notch pathway activity is down-regulated in MAF. Increase of Notch pathway activity confers MAF with inhibition to melanoma growth and tumor angiogenesis. Our study demonstrates that Notch signaling is a critical molecular switch in determining the tumor regulatory role of MAF and provides potential targets for cancer therapeutic interventions on the TME.
Citation Format: Hongwei Shao, Mecker G. Moller, Long Cai, Leiming Zhang, Zhao-Jun Liu. Activation of the notch signaling pathway confers a tumor-suppressive phenotype on melanoma-associated fibroblasts [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 5010. doi:10.1158/1538-7445.AM2017-5010</jats:p
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Abstract 5010: Inhibition of discoidin domain receptor 1 (DDR1) as a new therapeutic strategy for osteosarcoma
No full textAbstract Osteosarcoma is the most common type of bone cancer. Current management for osteosarcoma includes neoadjuvant chemotherapy and surgery. Unfortunately, some patients eventually develop recurrent or metastatic diseases and treatment options are extremely limited. Discoidin domain receptor 1 (DDR1) is a unique collagen-activated tyrosine kinase that participates in various human diseases, including cancer. DDR1 promotes the adhesion, proliferation, differentiation, migration, and metastasis of cancer cells. However, the expression and function of DDR1 remain unknown in osteosarcoma. The purpose of this study is to assess the expression, clinical prognostic relationship, and functional roles of DDR1 in osteosarcoma. The correlation between DDR1 expression in tumor tissues and clinicopathological features and prognosis was assessed via immunohistochemical staining of a unique tissue microarray (TMA) constructed from osteosarcoma specimens. Furthermore, DDR1 expression in osteosarcoma cell lines was determined by Western blot. DDR1-specific siRNA and a highly selective DDR1 inhibitor, 7rh, were applied to determine the impact of DDR1 expression on osteosarcoma cell growth and proliferation. In addition, the effect of DDR1 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic DDR1 effects in an in vivo environment. The results demonstrate that higher DDR1 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. The expression of DDR1 is also inversely correlated to the response to neoadjuvant chemotherapy. Therapeutically, DDR1 knockdown with siRNA or selective inhibition with 7rh decreases the proliferation and growth of osteosarcoma cells. In conclusion, our study supports DDR1 expression as an independent predictor of poor prognosis and a promising therapeutic target for osteosarcoma. Citation Format: Jinglu Wang, Robert Walker, Francis Hornicek, Zhenfeng Duan. Inhibition of discoidin domain receptor 1 (DDR1) as a new therapeutic strategy for osteosarcoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5010
MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D
No full textIntroduction We previously reported the significant upregulation of eight circulating exosomal microRNAs (miRNAs) in patients with diabetic kidney disease (DKD). However, their specific roles and molecular mechanisms in the kidney remain unknown. Among the eight miRNAs, we evaluated the effects of miR-5010-5p on renal tubular epithelial cells under diabetic conditions in this study.Research design and methods We transfected the renal tubular epithelial cell line, HK-2, with an miR-5010-5p mimic using recombinant plasmids. The target gene of hsa-miR-5010-5p was identified using a dual-luciferase assay. Cell viability was assessed via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, mRNA and protein expression levels were determined via real-time PCR and western blotting, respectively.Results High glucose levels did not significantly affect the intracellular expression of miR-5010-5p in HK-2 cells. Transfection of the miR-5010-5p mimic caused no change in cell viability. However, miR-5010-5p-transfected HK-2 cells exhibited significantly decreased expression levels of inflammatory cytokines, such as the monocyte chemoattractant protein-1, interleukin-1β, and tumor necrosis factor-ɑ, under high-glucose conditions. These changes were accompanied by the restored expression of phosphorylated AMP-activated protein kinase (AMPK) and decreased phosphorylation of nuclear factor-kappa B. Dual-luciferase assay revealed that miR-5010-5p targeted the gene, protein phosphatase 2 regulatory subunit B delta (PPP2R2D), a subunit of protein phosphatase 2A, which modulates AMPK phosphorylation.Conclusions Our findings suggest that increased miR-5010-5p expression reduces high glucose-induced inflammatory responses in renal tubular epithelial cells via the regulation of the target gene, PPP2R2D, which modulates AMPK phosphorylation. Therefore, miR-5010-5p may be a promising therapeutic target for DKD
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