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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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59 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Organotypic platform for studying cancer cell metastasis

Highlights: • Liver and brain slices can be stable, realistic in vitro 3D models. • Cell stiffness and adhesion to the tissue play determinant roles in cellular invasion in 3D. • MEK inhibitors can lead to increased cell stiffness and adhesion forces, and consequently reduced cancer cell invasion. • MDA-MB-231 breast cancer cells migrate faster and deeper into brain tissue compared to liver tissue. Metastasis is the leading cause of mortality in cancer patients. To migrate to distant sites, cancer cells would need to adapt their behaviour in response to different tissue environments. Thus, it is essential to study this process in models that can closely replicate the tumour microenvironment. Here, we evaluate the use of organotypic liver and brain slices to study cancer metastasis. Morphological and viability parameters of the slices were monitored daily over 3 days in culture to assess their stability as a realistic 3D tissue platform for in vitro metastatic assays. Using these slices, we evaluated the invasion of MDA-MB-231 breast cancer cells and of a subpopulation that was selected for increased motility. We show that the more aggressive invasion of the selected cells likely resulted not only from their lower stiffness, but also from their lower adhesion to the surrounding tissue. Different invasion patterns in the brain and liver slices were observed for both subpopulations. Cells migrated faster in the brain slices (with an amoeboid-like mode) compared to in the liver slices (where they migrated with mesenchymal or collective migration-like modes). Inhibition of the Ras/MAPK/ERK pathway increased cell stiffness and adhesion forces, which resulted in reduced invasiveness. These results illustrate the potential for organotypic tissue slices to more closely mimic in vivo conditions during cancer cell metastasis than most in vitro models.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Serum amyloid A1: Innocent bystander or active participant in cell migration in triple-negative breast cancer?

Highlights: • SAA1 knockdown reduced cell viability in triple-negative breast cancer cells. • SAA1 knockdown induced a S to G{sub 2}/M cell cycle shift in MDA-MB-231 cells. • SAA1 silencing inhibited cell migration in MDA-MB-231 and HCC70 cells. • SAA1 silencing altered epithelial-to-mesenchymal transition markers in MDA-MB-231 cells. The Serum Amyloid A (SAA) family of proteins is associated with various pathological conditions, including cancer. However, their role in cancer is incompletely understood. Here, we investigated the role of SAA1 in cell cycle regulation, apoptosis, survival signaling, metabolism, and metastasis in models of triple-negative breast cancer (TNBC), using RNAi. Our data show that in untransformed epithelial cells (MCF12A), the knockdown of SAA1 induces the expression of cell cycle regulators (MCM2, p53), the activation of DNA repair (PARP synthesis), and survival signaling (NFκB). In contrast, knockdown of SAA1 in the TNBC cell line (MDA-MB-231) induced the expression p16 and shifted cells in the cell cycle from the S to G{sub 2}/M phase, without the activation of DNA repair. Moreover, in SAA1-deficient MDA-MB-231 and HCC70 cells, metabolism (NADH oxidation) continually increased while cell migration (% wound closure and the rate of wound closure) decreased. However, silencing of SAA1 altered epithelial and mesenchymal markers in MCF12A (E-cadherin, Laminin 1β, Vimentin) and MDA-MB-231 (α-Smooth muscle actin) cells, associated with the metastatic program of epithelial-mesenchymal transition. Nonetheless, our data provide evidence that SAA1 could potentially serve as a therapeutic target in TNBC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

sMicroRNA-28-5p acts as a metastasis suppressor in gastric cancer by targeting Nrf2

The transcription factor nuclear factor (erythroid-2)-related factor 2 (Nrf2) can principally serve a mode of protection for both the normal cells and cancer cells from cellular stress, and elevates cancer cell survival. microRNA-28 (miR-28) has been involved in the regulation of Nrf2 expression in breast epithelial cells. However, no comprehensive analysis has been conducted regarding the function of miR-28-5p regulating Nrf2 in gastric cancer (GC). In this study, we aimed to evaluate their interaction and biological roles in the migration and invasion of GC cells. The expression of Nrf2 in the cancer tissues harvested from 42 patients with GC was examined by an array of molecular techniques comprising of Immunohistochemical staining, RT-qPCR and Western blot analysis. Kaplan-Meier method was adopted for analysis of the correlation of Nrf2 with the prognosis of GC patients. Interaction between miR-28-5p and Nrf2 was determined using the bioinformatics analysis and dual luciferase reporter gene assay. Gain- and loss-of-function studies of miR-28-5p and Nrf2 were conducted to elucidate their effects on GC cell migration, invasion and metastasis, as well as expression pattern of several epithelial-mesenchymal transition (EMT)-related proteins. Results indicated that the expression pattern of Nrf2 was significantly upregulated in GC tissues and indicative of poor prognosis of GC patients. miR-28-5p was verified to target Nrf2 and downregulate its expression. GC cells with overexpression of miR-28-5p or Nrf2 knockdown exhibited a marked reduction in the migrated and invasive abilities, along with the N-cadherin expression yet an increase of E-cadherin expression. Furthermore, miR-28-5p exerted an inhibitory function on the metastatic and tumorigenicity of GC cells. In conclusion, miR-28-5p is a comprehensive tumor suppressor that inhibits GC cell migration and invasion through repressing the Nrf2 expression. Therefore, miR-28-5p may serve as a potential biomarker for the prognosis of GC and a novel therapeutic target in advanced GC.

60 APPLIED LIFE SCIENCES↗