Effect of S9788 on the efficiency of doxorubicin in vivo and in vitro in medullary thyroid carcinoma xenograft

1996 ◽  
Vol 7 (3) ◽  
pp. 321-330 ◽  
Author(s):  
C Massart ◽  
J Gibassier ◽  
M Raoul ◽  
A Denais ◽  
S Maugendre ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Medullary Thyroid ◽  
Carcinoma Xenograft

scholarly journals Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

2021 ◽  
Vol 22 (6) ◽  
pp. 3031
Author(s):  
Silvia Carra ◽  
Germano Gaudenzi ◽  
Alessandra Dicitore ◽  
Davide Saronni ◽  
Maria Celeste Cantone ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Propidium Iodide ◽  
Dna Flow Cytometry ◽  
Dependent Manner ◽  
Angiogenic Activity ◽  
Medullary Thyroid

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.

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.

Study on the degradation rule of calcitonin in vitro in patients with medullary thyroid carcinoma

2018 ◽  
Vol 507 (1-4) ◽  
pp. 106-109 ◽  
Author(s):  
Guoping Ou ◽  
Qiaolun Chen ◽  
Wanli Liu ◽  
Xiaohui Li ◽  
Shulin Chen ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Medullary Thyroid

scholarly journals Cytotoxic Activity of Camptothecin and Paclitaxel in Newly Established Continuous Human Medullary Thyroid Carcinoma Cell Lines

2004 ◽  
Vol 89 (5) ◽  
pp. 2397-2401 ◽  
Author(s):  
K. Kaczirek ◽  
M. Schindl ◽  
A. Weinhäusel ◽  
C. Scheuba ◽  
C. Passler ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cell Lines ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Medullary Thyroid ◽  
Cell Counts ◽  
In Vitro Investigation ◽  
Ic50 Values

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC50 values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC50 values were 3.5 ± 1.2 nmol/liter for CPT and 8.2 ± 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 ± 20 nmol/liter for CPT and 1 μmol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

scholarly journals Anti-tumor effects of shikonin derivatives on human medullary thyroid carcinoma cells

2017 ◽  
Vol 6 (2) ◽  
pp. 53-62 ◽  
Author(s):  
Carina Hasenoehrl ◽  
Gert Schwach ◽  
Nassim Ghaffari-Tabrizi-Wizsy ◽  
Robert Fuchs ◽  
Nadine Kretschmer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Carcinoma ◽  
Cell Viability ◽  
Medullary Thyroid Carcinoma ◽  
Petroleum Ether Extract ◽  
Migration And Invasion ◽  
Normal Human Skin ◽  
Medullary Thyroid ◽  
Shikonin Derivatives

New treatment options are needed for medullary thyroid carcinoma (MTC), a highly metastasizing neuroendocrine tumor that is resistant to standard radiotherapy and chemotherapy. We show that the following shikonin derivatives inhibit cell proliferation and cell viability of the MTC cell line TT: acetylshikonin, β,β-dimethylacrylshikonin, shikonin and a petroleum ether extract of the roots of Onosma paniculata containing several shikonin derivatives. The unsubstituted shikonin derivative was found to be the most effective compound with an IC50 of 1.1 µM. The cell viability of normal human skin fibroblasts, however, was not affected by the tested substances, indicating that shikonin derivatives might be selectively toxic for cancer cells. We further report that migration and invasion of TT cells were inhibited at non-toxic concentrations. Finally, shikonin was tested in vivo using the chick chorioallantoic membrane assay, where it significantly reduced tumor growth by inhibiting cell proliferation and inducing apoptosis. In summary, our results suggest that shikonin derivatives have the potential for the treatment of medullary thyroid carcinomas.

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