The development of novel diagnostic agents for the detection of breast cancer microcalcifications requires a reliable animal model. Based on previous work from our group, we hypothesized that a single systemic injection of recombinant bone morphogenetic protein-2 (rBMP-2) could be used to create such a model. The cDNA encoding mature human BMP-2 was expressed in BL21(DE3) bacteria, purified to homogeneity, and refolded as a dimer. Bioactivity was confirmed using a C2C12 alkaline phosphatase assay. rBMP-2 was radiolabeled with (99m)Tc, and its biodistribution and clearance were quantified after both intravenous (IV) and intraperitoneal (IP) injection. Fischer 344 rats bearing syngeneic R3230 breast tumors received a single intraperitoneal injection of rBMP-2 at a specified dose. Tumor microcalcification was quantified over time using micro-single photon emission computed tomography (SPECT) and microcomputed tomography (CT). rBMP-2 could be expressed in E. coli at high levels, isolated at >95% purity, and refolded to a bioactive dimer. Beta-phase half-life was 30.5 min after IV administration and 47.6 min after IP administration. Renal excretion was the primary mode of clearance. A single IP injection of >or=50 microg rBMP-2 when tumors were not yet palpable resulted in dose-dependent microcalcification in 8 of 8 R3230 tumors. No calcification was found in control tumors or in normal tissues and organs of animals injected with rBMP-2. Tumor calcification increased progressively between weeks 2 and 4 post-rBMP-2 injection. A single IP injection of rBMP-2 in rats bearing a syngeneic breast cancer will produce dose-dependent and time-dependent microcalcifications. This animal model lays the foundation for the development of novel diagnostic radiotracers for breast cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883641 | PMC |
| http://dx.doi.org/10.1007/s10549-009-0535-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into NEK2 inhibitors as antitumor agents: From mechanisms to potential therapeutics.
Eur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFAnalysis of circulating cell-free nuclear and mitochondrial DNA in plasma of Mexican patients with breast cancer.
Gac Med Mex
January 2025
División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara.
Background: The usefulness of circulating free DNA (cfDNA), nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) as potential biomarkers in cancer remains controversial.
Objective: To determine the concentration of cfDNA and plasma nDNA and mtDNA levels in breast cancer (BC) patients.
Material And Methods: This study included a total of 86 women (69 patients with BC and 17 women as a control group).
MTHFD2 promotes breast cancer cell proliferation through IFRD1 RNA m6A methylation-mediated HDAC3/p53/mTOR pathway.
Neoplasma
December 2024
Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis.
View Article and Find Full Text PDFIFIH1 promotes apoptosis through the TBK1/IRF3 pathway in triple-negative breast cancer.
Neoplasma
December 2024
Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast malignancy. Although some patients benefit from immune checkpoint therapy, current treatment methods rely mainly on chemotherapy. It is imperative to develop predictors of efficacy and identify individuals who will be sensitive to particular treatment regimens.
View Article and Find Full Text PDFUtility of systemic staging in breast cancer patients with a positive sentinel lymph node biopsy.
Ir J Med Sci
January 2025
Department of Breast Surgery, St. Vincent's University Hospital, Dublin 4, D04 T6F4, Ireland.
Background: CT thorax, abdomen and pelvis (CT-TAP) remains the standard in the identification of metastatic disease in patients with newly diagnosed breast cancer. In patients with proven micro and macro axillary nodal metastasis, the optimal radiological technique remains controversial. A consensus on which patients with axillary nodal disease should receive radiological staging for distant disease and how this should be performed is not currently available.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!