scholarly journals Development of Tyrosine-Based RadiotracerTc99m-N4-Tyrosine for Breast Cancer Imaging

2012 ◽  
Vol 2012 ◽  
pp. 1-9
Author(s):  
Fan-Lin Kong ◽  
Mohammad S. Ali ◽  
Alex Rollo ◽  
Daniel L. Smith ◽  
Yinhan Zhang ◽  
...  

The purpose of this study was to develop an efficient way to synthesizeTc99m-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (Tc99m-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled withTc99mwith high radiochemical purity (>95%). Cellular uptake ofTc99m-N4-Tyrosine was much higher than that ofTc99m-N4 and the clinical gold standard18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cellsin vitro. Tissue uptake and dosimetry estimation in normal rats revealed thatTc99m-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that althoughTc99m-N4-Tyrosine appeared to be inferior to18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging.Tc99m-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging.

2017 ◽  
Vol 11 (1) ◽  
pp. 15-27 ◽  
Author(s):  
S. Pasquereau ◽  
F. Al Moussawi ◽  
W. Karam ◽  
M. Diab Assaf ◽  
A. Kumar ◽  
...  

The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis. In this review, we will discuss the potential implication of HCMV in breast cancer with emphasis on the role played by macrophages.


Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 292 ◽  
Author(s):  
Laura Bray ◽  
Constanze Secker ◽  
Berline Murekatete ◽  
Jana Sievers ◽  
Marcus Binner ◽  
...  

Bone is the most common site for breast-cancer invasion and metastasis, and it causes severe morbidity and mortality. A greater understanding of the mechanisms leading to bone-specific metastasis could improve therapeutic strategies and thus improve patient survival. While three-dimensional in vitro culture models provide valuable tools to investigate distinct heterocellular and environmental interactions, sophisticated organ-specific metastasis models are lacking. Previous models used to investigate breast-to-bone metastasis have relied on 2.5D or singular-scaffold methods, constraining the in situ mimicry of in vitro models. Glycosaminoglycan-based gels have demonstrated outstanding potential for tumor-engineering applications. Here, we developed advanced biphasic in vitro microenvironments that mimic breast-tumor tissue (MCF-7 and MDA-MB-231 in a hydrogel) spatially separated with a mineralized bone construct (human primary osteoblasts in a cryogel). These models allow distinct advantages over former models due to the ability to observe and manipulate cellular migration towards a bone construct. The gels allow for the binding of adhesion-mediating peptides and controlled release of signaling molecules. Moreover, mechanical and architectural properties can be tuned to manipulate cell function. These results demonstrate the utility of these biomimetic microenvironment models to investigate heterotypic cell–cell and cell–matrix communications in cancer migration to bone.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10101-10101
Author(s):  
J. Hartman ◽  
K. Lindberg ◽  
J. Inzunza ◽  
J. Wan ◽  
A. Ström ◽  
...  

10101 Background: Estrogens are well known stimulators of breast cancer cell growth in vitro as well as in vivo. Two different estrogen receptors exist, namely estrogen receptor (ER) α and β. ERα mediates the proliferative effect of estrogen in breast cancer cells and we have earlier shown that ERβ inhibits cell-cycle progression in vitro. Estrogens are well known stimulators of in vivo breast cancer cell growth as well as angiogenesis, and the effect is mediated through ERα. The function of ERβ in this context is not well understood. Methods: We have used ERα-positive T47D breast cancer cells stably transfected with a Tet/Off regulated ERβ expression vector system. The ERβ-inducible tumor cells are studied in vitro as well as in vivo. Results: By transplanting ERβ-inducible breast cancer cells into SCID-mice, we show that ERβ inhibits tumor growth and reduces the volume of established tumors. Furthermore, we show by immunohistochemistry, that the number of blood microvessels in the tumor periphery is decreased by ERβ expression, counteracting the well-known pro-angiogenic effect of ERα. By Western blot analysis on tumor extracts, we show that the concentration of the important pro-angiogenic growth factors VEGF and bFGF, normally expressed by breast tumor cells, is decreased in the ERβ-expressing tumors compared to the normal tumors. To exclude that the observed anti-angiogenic effect is just a result of reduced tumor growth, we incubated Tet/Off regulated ERβ expressing cells in vitro, during non-hypoxic conditions. We found that the expression of ERβ leads to decreased expression of VEGF and PDGFβ at the mRNA and protein-levels. In transient transfection assays, we found estrogen-ERα mediated up regulation of VEGF, PDGFβ and bFGF-promoter activities in T47D cells, and these activities were all suppressed following co-transfection with an ERβ-expression vector. Conclusions: We conclude that ERβ inhibits growth factor expression at transcriptional level in breast cancer cells; taken together, our data indicates that ERβ inhibits growth and angiogenesis of tumors formed by T47D breast cancer cells. This makes ERβ an interesting therapeutic target in breast cancer and perhaps treatment with the newly designed ERβ-selective ligands might work as a new anti-proliferative and anti-angiogenic therapy. No significant financial relationships to disclose.


2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Tayyab Imtiaz ◽  
Fareeha Anwar ◽  
Uzma Saleem ◽  
Bashir Ahmad ◽  
Sundas Hira ◽  
...  

Background and objectives: Breast cancer is a heterogeneous disease that poses the highest incidence of morbidity among women and presents many treatment challenges. In search of novel breast cancer therapies, several triazine derivatives have been developed for their potential chemotherapeutic activity. This study aims to evaluate the N-nitroso-N-methyl urea (NMU)–induced anti–mammary gland tumor activity of 2,4,6 (O-nitrophenyl amino) 1,3,5-triazine (O-NPAT).Methods: The in silico modeling and in vitro cytotoxicity assay were performed to strengthen the research hypothesis. For in vivo experimentation, 30 female rats were divided into five groups. Group I (normal control) received normal saline. Group II (disease control) received NMU (50 mg/kg). Group III (standard control) was treated with tamoxifen (5 mg/kg). Groups IV and V received O-NPAT at a dose level of 30 and 60 mg/kg, respectively. For tumor induction, 3 intraperitoneal doses of NMU were given at a 3-week interval, whereas all treatment compounds were administered orally for 14 consecutive days. Biochemical and oxidative stress markers were estimated for all experimental animals. DNA strand breakage alongside inflammatory markers was also measured for the analysis of inflammation. The hormonal profile of progesterone and estrogen was also estimated.Results: The test compound presented a significant reduction in organ weight and restored the hepatic and renal enzymes. O-NPAT treatments enhanced the antioxidant enzyme level of catalase (CAT), superoxide dismutase (SOD), and total sulfhydryl (TSH), with a highly significant reduction in lactate dehydrogenase (LDH) and lipid peroxidation. Also, the decrease in fragmented DNA, hormonal levels (estradiol and progesterone), and inflammatory cytokines (IL-6 and TNF-α) justified the dosage efficacy further supported by histopathological findings.Conclusion: All results indicated the anti–breast tumor activity of O-NPAT and presented its possibility of exploitation for beneficial effects in breast cancer treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiafeng Gao ◽  
Yi-Nan Zhang ◽  
Jingwen Cui ◽  
Jiatong Zhang ◽  
Yuexiang Ming ◽  
...  

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) that mediate T-cell immune responses. Breast cancer is one of the most commonly diagnosed diseases and its mortality rate is higher than any other cancer in both humans and canines. Plantain polysaccharide (PLP), extracted from the whole plant of Plantago asiatica L., could promote the maturation of DCs. In this research, we found that PLP could upregulate the maturation of DCs both in vitro and in vivo. PLP-activated DCs could stimulate lymphocytes’ proliferation and differentiate naive T cells into cytotoxic T cells. Tumor antigen-specific lymphocyte responses were enhanced by PLP and CIPp canine breast tumor cells lysate-pulsed DCs, and PLP and CIPp-cell-lysate jointly stimulated DCs cocultured with lymphocytes having the great cytotoxicity on CIPp cells. In the 4T1 murine breast tumor model, PLP could control the size of breast tumors and improve immunity by recruiting DCs, macrophages, and CD4+ and CD8+ T cells in the tumor microenvironment. These results indicated that PLP could achieve immunotherapeutic effects and improve immunity in the breast tumor model.


2020 ◽  
Vol 10 (22) ◽  
pp. 8298
Author(s):  
Yuliana Jiménez-Gaona ◽  
María José Rodríguez-Álvarez ◽  
Vasudevan Lakshminarayanan

This paper provides a critical review of the literature on deep learning applications in breast tumor diagnosis using ultrasound and mammography images. It also summarizes recent advances in computer-aided diagnosis/detection (CAD) systems, which make use of new deep learning methods to automatically recognize breast images and improve the accuracy of diagnoses made by radiologists. This review is based upon published literature in the past decade (January 2010–January 2020), where we obtained around 250 research articles, and after an eligibility process, 59 articles were presented in more detail. The main findings in the classification process revealed that new DL-CAD methods are useful and effective screening tools for breast cancer, thus reducing the need for manual feature extraction. The breast tumor research community can utilize this survey as a basis for their current and future studies.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Heng-Huan Lee ◽  
Ying-Nai Wang ◽  
Wen-Hao Yang ◽  
Weiya Xia ◽  
Yongkun Wei ◽  
...  

AbstractHuman ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.


2018 ◽  
Vol 11 (3) ◽  
pp. 65
Author(s):  
Alicia Vall-Sagarra ◽  
Shanna Litau ◽  
Clemens Decristoforo ◽  
Björn Wängler ◽  
Ralf Schirrmacher ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180372 ◽  
Author(s):  
Brittany N. Balhouse ◽  
Logan Patterson ◽  
Eva M. Schmelz ◽  
Daniel J. Slade ◽  
Scott S. Verbridge

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