Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was approximately 2 x 10(-5) at early passages and increased up to approximately 7 x l0(-3) at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of C3H 10T(1/2) mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T(1/2) cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G(1)-phase arrest (one set of data on G(1)-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells.
Download full-text PDF |
Source |
---|
Biochem Pharmacol
January 2025
Colorectal cancer (CRC), one of the diseases posing a threat to global health, according to the latest data, is the third most common cancer globally and the second leading cause of cancer-related deaths. The development and refinement of novel structures of small molecular compounds play a crucial role in tumor treatment and overcoming drug resistance. In this study, our objective was to screen and characterize novel compounds for overcoming drug resistance via the B Lymphoma Mo-MLV insertion region 1 (Bmi-1) reporter screen assay.
View Article and Find Full Text PDFBiofabrication
January 2025
Biomedical Engineering Department, Technion Israel Institute of Technology, Technion City, Haifa 32000, Haifa, Haifa, 3200003, ISRAEL.
Best cosmetic outcomes of breast reconstruction using tissue engineering techniques rely on the scaffold architecture and material, which are currently both to be determined. This study suggests an approach for a rational design of breast-shaped scaffold architecture, in which structural analysis is implemented to predict its stiffness and adjust it to that of the native tissue. This approach can help achieve the goal of optimal scaffold architecture for breast tissue engineering.
View Article and Find Full Text PDFArthritis Res Ther
January 2025
Xin'an Medicine Research Center, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), No 2, West Zheshan Road, Wuhu, Anhui, 241000, China.
Background: Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes.
Methods: Fresh RA patients' whole blood was transfused into NOD-SCID mice.
PLoS One
January 2025
Department of Pathology, Yale School of Medicine, Yale University, New Haven, Connecticut, United States of America.
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!