scholarly journals Thyroid Cancer Detection by Ultrasound Molecular Imaging with SHP2-Targeted Perfluorocarbon Nanoparticles

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
ZhongQian Hu ◽  
Bin Yang ◽  
Tiankuan Li ◽  
Jia Li
Keyword(s):  
Thyroid Cancer ◽  
Molecular Imaging ◽  
Diagnostic Accuracy ◽  
Protein Tyrosine Phosphatases ◽  
Ultrasound Contrast Agents ◽  
Human Thyroid ◽  
Thyroid Tumour ◽  
Ultrasound Molecular Imaging

Background. Contrast-enhanced ultrasound imaging has been widely used in the ultrasound diagnosis of a variety of tumours with high diagnostic accuracy, especially in patients with hepatic carcinoma, while its application is rarely reported in thyroid cancer. The currently used ultrasound contrast agents, microbubbles, cannot be targeted to molecular markers expressed in tumour cells due to their big size, leading to a big challenge for ultrasound molecular imaging. Phase-changeable perfluorocarbon nanoparticles may resolve the penetrability limitation of microbubbles and serve as a promising probe for ultrasound molecular imaging. Methods. 65 thyroid tumour samples and 40 normal samples adjacent to thyroid cancers were determined for SHP2 expression by IHC. SHP2-targeted PLGA nanoparticles (NPs-SHP2) encapsulating perfluoropentane (PFP) were prepared with PLGA-PEG as a shell material, and their specific target-binding ability was assessed in vitro and in vivo, and the effect on the enhancement of ultrasonic imaging induced by LIFU was studied in vivo. Results. In the present study, we verified that tumour overexpression of SHP2 and other protein tyrosine phosphatases regulated several cellular processes and contributed to tumorigenesis, which could be introduced to ultrasound molecular imaging for differentiating normal from malignant thyroid diagnostic nodes. The IHC test showed remarkably high expression of SHP2 in human thyroid carcinoma specimens. In thyroid tumour xenografts in mice, the imaging signal was significantly enhanced by SHP2-targeted nanoparticles after LIFU induction. Conclusion. This study provides a basis for preclinical exploration of ultrasound molecular imaging with NPs-SHP2 for clinical thyroid nodule detection to enhance diagnostic accuracy.

scholarly journals BRAF activates and physically interacts with PAK to regulate cell motility

2014 ◽  
Vol 21 (6) ◽  
pp. 865-877 ◽  
Author(s):  
Samantha K McCarty ◽  
Motoyasu Saji ◽  
Xiaoli Zhang ◽  
Christina M Knippler ◽  
Lawrence S Kirschner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Motility ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Thyroid ◽  
Thyroid Cancer Cell ◽  
Cancer Cell Motility ◽  
Thyroid Cancer Cell Lines

Increased p21-activated kinase (PAK) signaling and expression have been identified in the invasive fronts of aggressive papillary thyroid cancers (PTCs), including those withRET/PTC, BRAFV600E, and mutantRASexpression. Functionally, thyroid cancer cell motilityin vitrois dependent on group 1 PAKs, particularly PAK1. In this study, we hypothesize that BRAF, a central kinase in PTC tumorigenesis and invasion, regulates thyroid cancer cell motility in part through PAK activation. Using three well-characterized human thyroid cancer cell lines, we demonstrated in all cell lines thatBRAFknockdown reduced PAK phosphorylation of direct downstream targets. In contrast, inhibition of MEK activity either pharmacologically or with siRNA did not reduce PAK activity, indicating MEK is dispensable for PAK activity. Inhibition of cell migration through BRAF loss is rescued by overexpression of either constitutive active MEK1 or PAK1, demonstrating that both signaling pathways are involved in BRAF-regulated cell motility. To further characterize BRAF–PAK signaling, immunofluorescence and immunoprecipitation demonstrated that both exogenously overexpressed and endogenous PAK1 and BRAF co-localize and physically interact, and that this interaction was enhanced in mitosis. Finally, we demonstrated that acute induction of BRAFV600E expressionin vivoin murine thyroid glands results in increased PAK expression and activity confirming a positive signaling relationshipin vivo. In conclusion, we have identified a signaling pathway in thyroid cancer cells which BRAF activates and physically interacts with PAK and regulates cell motility.

Ultrasound molecular imaging of arterial thrombi with novel microbubbles modified by cyclic RGD in vitro and in vivo

2012 ◽  
Vol 107 (01) ◽  
pp. 172-183 ◽  
Author(s):  
Yulin Liao ◽  
Li Yang ◽  
Ruizhu Huang ◽  
Juefei Wu ◽  
Jiajia Xie ◽  
...  
Keyword(s):  
Shear Stress ◽  
Molecular Imaging ◽  
Molecular Probe ◽  
Great Promise ◽  
Rgd Peptides ◽  
Abdominal Aortic ◽  
Aortic Thrombus ◽  
Ultrasound Molecular Imaging

SummaryDespite immense potential, ultrasound molecular imaging (UMI) of arterial thrombi remains very challenging because the high-shear arterial flow limits binding of site-targeted microbubbles to the thrombi. The linear Arg-Gly-Asp (RGD) peptides have been successfully applied to evaluate venous, atrial, and arteriolar thrombi, but have thus far failed in the detection of arterial thrombi. Cyclic RGD (Arg-Gly-Asp-D-Phe-Cys) is a cyclic conformation of linear RGD peptides, which has much higher binding-affinity and selectivity for binding to the glycoprotein (GP) IIb/IIIa receptor than its linear counterpart and thus is likely to be an optimal targeted molecular probe for ultrasound molecular imaging of arterial thrombi. In this study, we sought to assess the feasibility of a novel microbubble conjugated with cyclic RGD (Mb-cyclic RGD) in UMI of arterial thrombi in vitro and in vivo. As expected, Mb-cyclic RGD had greater GP IIb/IIIa-targeted binding capability in all shear stress conditions. In addition, the shear stress at half-maximal detachment of Mb-cyclic RGD was 5.7-fold higher than that of microbubbles with nonspecific peptide (Mb-CON) (p<0.05). Mb-cyclic RGD enhanced the echogenicity of the platelet-rich thrombus in vitro whereas Mb-CON did not produce enhancement. In the in vivo setting, optimal signal enhancement of the abdominal aortic thrombus was displayed with Mb-cyclic RGD in all cases. Mean video intensity of the abdominal aortic thrombi with Mb-cyclic RGD was 3.2-fold higher than that with Mb-CON (p<0.05). The novel Mb-cyclic RGD facilitated excellent visualisation of arterial thrombi using UMI and showed great promise for clinical applications.

scholarly journals In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

Biomaterials ◽  
2017 ◽  
Vol 118 ◽  
pp. 63-73 ◽  
Author(s):  
Hua Zhang ◽  
Elizabeth S. Ingham ◽  
M. Karen J. Gagnon ◽  
Lisa M. Mahakian ◽  
Jingfei Liu ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
In Vitro Characterization ◽  
Targeted Microbubbles ◽  
Ultrasound Molecular Imaging

scholarly journals Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies

2019 ◽  
Vol 39 (12) ◽  
pp. 2520-2530 ◽  
Author(s):  
Mukesh Punjabi ◽  
Lifen Xu ◽  
Amanda Ochoa-Espinosa ◽  
Alexandra Kosareva ◽  
Thomas Wolff ◽  
...  
Keyword(s):  
Shear Stress ◽  
Molecular Imaging ◽  
Pulsatile Flow ◽  
Ex Vivo ◽  
Circulation Model ◽  
Wild Type ◽  
Double Knockout ◽  
Ultrasound Molecular Imaging

Objective: Contrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MB cAbVcam1-5 ) and microbubble with a control nanobody (MB VHH2E7 ) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MB cAbVcam1-5 and MB VHH2E7 . Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×10 5 per microbubble. Compared with MB VHH2E7 , MB cAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm 2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MB cAbVcam1-5 in early ( P =0.0003 versus MB VHH2E7 ) and late atherosclerosis ( P =0.007 versus MB VHH2E7 ); in wild-type mice, there were no differences between MB cAbVcam1-5 and MB VHH2E7 . CEUMI in human endarterectomy specimens showed a 100% increase in signal for MB cAbVcam1-5 versus MB VHH2E7 (20.6±27.7 versus 9.6±14.7, P =0.0156). Conclusions: CEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.

Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells

2017 ◽  
Vol 115 ◽  
pp. 288-298 ◽  
Author(s):  
Chieh-Hsiang Lu ◽  
Shu-Hsin Chen ◽  
Yi-Sheng Chang ◽  
Yi-Wen Liu ◽  
Jin-Yi Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Thyroid Cancer ◽  
Therapeutic Agent ◽  
Human Thyroid ◽  
Cycle Arrest ◽  
Thyroid Cancer Cells ◽  
Program Cell Death

scholarly journals Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4266
Author(s):  
Fang-Ping Kung ◽  
Yun-Ping Lim ◽  
Wen-Ying Chao ◽  
Yi-Sheng Zhang ◽  
Hui-I Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Thyroid ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Apoptosis Pathway

Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL.

scholarly journals Bubble Trouble: Conquering Microbubble Limitations in Contrast Enhanced Ultrasound Imaging by Nature-Inspired Ultrastable Echogenic Nanobubbles

2019 ◽  
Author(s):  
Al de Leon ◽  
Reshani Perera ◽  
Christopher Hernandez ◽  
Michaela Cooley ◽  
Olive Jung ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Sulfur Hexafluoride ◽  
Tumor Development ◽  
Ultrasound Contrast Agents ◽  
The Body ◽  
Signal Decay ◽  
Mechanical Deformations ◽  
Cell Envelopes

AbstractAdvancement of ultrasound molecular imaging applications requires not only a reduction in size of the ultrasound contrast agents (UCAs) but also a significant improvement in the in vivo stability of the shell-stabilized gas bubble. The transition from first generation to second generation UCAs was marked by an advancement in stability as air was replaced by a hydrophobic gas, such as perfluoropropane and sulfur hexafluoride. Further improvement can be realized by focusing on how well the UCAs shell can retain the encapsulated gas under extreme mechanical deformations. Here we report the next generation of UCAs for which we engineered the shell structure to impart much better stability under repeated prolonged oscillation due to ultrasound, and large changes in shear and turbulence as it circulates within the body. By adapting an architecture with two layers of contrasting elastic properties similar to bacterial cell envelopes, our ultrastable nanobubbles (NBs) withstand continuous in vitro exposure to ultrasound with minimal signal decay and have a significant delay on the onset of in vivo signal decay in kidney, liver, and tumor. Development of ultrastable NBs can potentially expand the role of ultrasound in molecular imaging, theranostics, and drug delivery.

scholarly journals Evodiamine inhibits human thyroid cancer cells in vitro and in vivo

2015 ◽  
Author(s):  
Ying-Ray Lee ◽  
Chieh-Hsiang Lu ◽  
Yi-Sheng Chang ◽  
Shu-Hsin Chen ◽  
Yi-Wen Liu
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Thyroid Cancer Cells

scholarly journals Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer

2017 ◽  
Vol 38 (11) ◽  
pp. 1533-1542 ◽  
Author(s):  
Qin Xie ◽  
Hui Chen ◽  
Jing Ai ◽  
Ying-lei Gao ◽  
Mei-yu Geng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Human Thyroid

scholarly journals Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer

2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Hyo Jeong Lee ◽  
Pyeonghwa Jeong ◽  
Yeongyu Moon ◽  
Jungil Choi ◽  
Jeong Doo Heo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitor ◽  
Point Mutations ◽  
Carcinoma Cells ◽  
Medullary Thyroid ◽  
Potent Inhibition ◽  
Kinase Inhibitory Activity

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.

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