Journal: European Thyroid Journal

Article Title: Patient-derived medullary thyroid cancer organoids: a potential model for mechanistic studies on diagnostics and therapy

doi: 10.1530/ETJ-24-0405

Figure Lengend Snippet: Effect of TKIs on calcitonin and CEA concentrations in culture medium from MTOs. (A) Schematic of MTC tissue isolation, primary tissue culture, and the drug screening experiment. MTOs exposed to (B) vandetanib, (C) cabozantinib, (D) selpercatinib, and (E) pralsetinib. All; n = 4 patients; error bars represent SEM, normalized to DMSO controls; dotted lines * P < 0.05.

Article Snippet: Vandetanib (Selleck Chemicals, USA), cabozantinib (LKT Laboratories Inc., USA.), selpercatinib (Selleck Chemicals), and pralsetinib (Selleck Chemicals) were added to the medium of the MZ-CRC-1 MTC cell-line derived spheroids, cultured in an ultra-low attachment U-bottom plate, in a logarithmic dose de-escalation per TKI, 1 week after start of culture.

Techniques: Isolation, Drug discovery

Journal: Oncotarget

Article Title: Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts

doi: 10.18632/oncotarget.11826

Figure Lengend Snippet: Wild-type MCF7 cells were grown in complete medium (E2+) or in E2-deprived DCC medium (E2-) for 3 days, serum-starved for the last 24 hours and pre-treated with the indicated concentrations of A. sunitinib, B. cabozantinib, or C. NVP-BBT594 for 90 minutes before 30 minutes GDNF (20 ng/ml) stimulation. Total cell lysates were subjected to western blotting using the indicated antibodies. Tubulin was used as a loading control. Molecular size markers are in kDa.

Article Snippet: Cabozantinib and sunitinib were purchased from Tocris Bioscience.

Techniques: Western Blot, Control

Journal: Hepatology International

Article Title: Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma

doi: 10.1007/s12072-023-10603-z

Figure Lengend Snippet: The tumor immune microenvironment was altered by treatment with anti-VEGFR-2 antibody, regorafenib, or cabozantinib. Representative micrographs (left panel) and quantification (right panel) of CD3-positive, CD8-positive, Granzyme B-positive, and Foxp3-positive cells; F4/80-positive, Arginase-1-positive,and CD11c-positive areas; and NK1.1-positive cells in the VT, VEGFR2 antibody, regorafenib, and cabozantinib groups. Arrowheads represent positive cells. * p < 0.05, ** p < 0.01 vs. VT, one-way ANOVA. Data are presented as mean ± SEM. VT vehicle treatment, VEGFR2 vascular endothelial growth factor receptor 2, ns no significance

Article Snippet: The treatment groups were as follows: (I) Sorafenib; sorafenib tosylate (CAS No.: 475207-59-1; purchased from Santa Cruz Biotechnology, Inc., TX, USA), administered 30 mg/kg orally/once daily; (II) Lenvatinib; lenvatinib mesylate (CAS No.: 417716-92-8; kindly provided by Eisai co. ltd., Tokyo, Japan), administered 10 mg/kg/mouse orally/once daily; (III) VEGFR2 (VEGF receptor 2) antibody; DC101, an anti-VEGFR2 antibody, purchased from Bio X Cell (Lebanon, NH, USA), administered intraperitoneally thrice/week at a dose of 40 mg/kg; (IV) Regorafenib; regorafenib (CAS No.: 755037-03-7; purchased from Tokyo Chemical Industry, Tokyo, Japan), administered 3 mg/kg orally/once daily; (V) Cabozantinib; cabozantinib malate (CAS No.: 849217-68-1; purchased from ChemScene, Monmouth Junction, NJ, USA), administered 30 mg/kg orally/once daily; (VI) FGFR (FGF receptor) inhibitor; AZD4547, FGFR-1/2/3/4 inhibitor (CAS No.: 1035270-39-3; purchased from ChemScene), administered 12.5 mg/kg intraperitoneally/once daily; (VII) VT (vehicle treatment); PBS as vehicle was administered orally or intraperitoneally.

Techniques:

Journal: Hepatology International

Article Title: Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma

doi: 10.1007/s12072-023-10603-z

Figure Lengend Snippet: Immune checkpoint molecules altered by MTA treatment. Representative micrographs (upper panel) and quantification (lower panel) of PD-1- and PD-L1-positive cells in VT, sorafenib, lenvatinib, VEGFR2 antibody, and regorafenib cabozantinib groups. Arrowheads represent positive cells. * p < 0.05, ** p < 0.01 vs. VT, one-way ANOVA. Data are presented as mean ± SEM. VT vehicle treatment, VEGFR2 vascular endothelial growth factor receptor 2, ns not significant, PD-1 programmed cell death-1, PD-L1 programmed cell death ligand 1

Article Snippet: The treatment groups were as follows: (I) Sorafenib; sorafenib tosylate (CAS No.: 475207-59-1; purchased from Santa Cruz Biotechnology, Inc., TX, USA), administered 30 mg/kg orally/once daily; (II) Lenvatinib; lenvatinib mesylate (CAS No.: 417716-92-8; kindly provided by Eisai co. ltd., Tokyo, Japan), administered 10 mg/kg/mouse orally/once daily; (III) VEGFR2 (VEGF receptor 2) antibody; DC101, an anti-VEGFR2 antibody, purchased from Bio X Cell (Lebanon, NH, USA), administered intraperitoneally thrice/week at a dose of 40 mg/kg; (IV) Regorafenib; regorafenib (CAS No.: 755037-03-7; purchased from Tokyo Chemical Industry, Tokyo, Japan), administered 3 mg/kg orally/once daily; (V) Cabozantinib; cabozantinib malate (CAS No.: 849217-68-1; purchased from ChemScene, Monmouth Junction, NJ, USA), administered 30 mg/kg orally/once daily; (VI) FGFR (FGF receptor) inhibitor; AZD4547, FGFR-1/2/3/4 inhibitor (CAS No.: 1035270-39-3; purchased from ChemScene), administered 12.5 mg/kg intraperitoneally/once daily; (VII) VT (vehicle treatment); PBS as vehicle was administered orally or intraperitoneally.

Techniques:

Journal: Biomedical Chromatography

Article Title: Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS

doi: 10.1002/bmc.4758

Figure Lengend Snippet: Representative reconstructed ion chromatogram overlay of a mixture of the medium quality control samples. 1, niraparib; 2, olaparib; 3, cobimetinib; 4, cabozantinib; 5,dabrafenib; 6, regorafenib M2; 7, vemurafenib; 8, regorafenib

Article Snippet: The isotopes 13 C 2 H 3 ‐regorafenib, 2 H 8 ‐olaparib, 13 C 6 ‐vemurafenib, 13 C 6 ‐cobimetinib, 13 C 6 ‐niraparib, 2 H 4 ‐cabozantinib and 2 H 9 ‐dabarefenib used as internal standards, were acquired from Alsachim (Illkirch, France).

Techniques: Control

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Effects of vandetanib (VAN) (□) and cabozantinib (CAB) (■) on cell viability in TT ( a ) and MZ-CRC-1 ( b ) cell lines measured using an MTT assay. Cells were incubated for six days with vehicle (control), or with the drug at different concentrations, as described in the Material and Methods. Dose response curves were expressed as a nonlinear regression (curve fit) of log (concentration drug) versus the percentage of the control. Values represent the mean ± S.E.M. of at least three independent experiments in six replicates. Control (CTR) values have been set to 100%. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: MTT Assay, Incubation, Control, Concentration Assay

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Effects of vandetanib (VAN) and cabozantinib (CAB) on the cell cycle in medullary thyroid carcinoma (MTC) cell lines. Cell cycle analysis after six days of incubation with VAN and CAB in TT ( a – d ) and MZ-CRC-1 cell lines ( e – h ). Cells were detected using FACS analysis after staining with propidium iodide. Control (CTR) values have been set to 100%. Cell cycle distribution is expressed as the percentage of cells in the G 0 /G 1 , S, and G 2 /M phases compared to the untreated CTR. Values represent the mean ± S.E.M. of at least three independent experiments. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: Cell Cycle Assay, Incubation, Staining, Control

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Effects of vandetanib (VAN) and cabozantinib (CAB) on apoptosis in medullary thyroid carcinoma (MTC) cell lines. Cell death analysis after six days of incubation with VAN and CAB in TT ( a – c ) and MZ-CRC-1 cell lines ( d – f ) through flow cytometry with Annexin V and propidium iodine. The proportions of cells in early apoptosis ( a , d ), late apoptosis ( b , e ) and necrosis ( c , f ) were expressed as the percentage compared with the untreated control (CTR) and represent the mean ± S.E.M. of at least three independent experiments. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: Incubation, Flow Cytometry, Control

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Anti-angiogenic effect of vandetanib (VAN) and cabozantinib (CAB) on the physiological development of the zebrafish sub-intestinal vein (SIV) plexus. Representative fluorescence images of the SIV basket of 72 hpf Tg(fli1a:EGFP) y1 zebrafish embryos treated for 24 h with dimethyl sulfoxide (DMSO) ( a ), 5 × 10 −6 M VAN ( b ) and CAB ( c ). Following 24 h of VAN ( d ) and CAB ( e ) treatments at different concentrations, the number of vertical vessels comprising the SIV basket was counted and compared with that of the control (CTR) embryos. Graphed values represent the mean ± S.E.M. *** p < 0.001 versus the CTR. Embryos are shown anterior to the left.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: Fluorescence, Control

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Effect of vandetanib (VAN) and cabozantinib (CAB) treatments on tumor-induced angiogenesis after TT cell xenograft in zebrafish embryos. Representative fluorescence images of 72 hpf Tg(fli1a:EGFP) y1 zebrafish embryos implanted at 48 hpf with TT cells and subsequently treated for 24 h with dimethyl sulfoxide (DMSO) ( a , d ), VAN ( b , e ) and CAB ( c , f ). The red channel, corresponding to TT cells, was omitted in panels d, e, and f to highlight the tumor-induced microvascular network. Grafted larvae showed vessels in green that sprout from the sub-intestinal vein (SIV) toward the xenograft. Quantification of tumor-induced angiogenesis in TT-injected Tg(fli1a:EGFP) y1 embryos after 24 h of VAN ( g ) and CAB ( h ) treatments at different concentrations. Control (CTR) values have been set to 1.0. Graphed values represent the mean ± S.E.M. *** p < 0.001 versus CTR. Embryos are shown anterior to the left. Scale bar: 100 µm.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: Fluorescence, Injection, Control

Journal: International Journal of Molecular Sciences

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

doi: 10.3390/ijms22063031

Figure Lengend Snippet: Effect of vandetanib (VAN) and cabozantinib (CAB) treatments on tumor-induced angiogenesis after MZ-CRC-1 cell xenograft in zebrafish embryos. Representative fluorescence images of 72 hpf Tg(fli1a:EGFP) y1 zebrafish embryos implanted at 48 hpf with MZ-CRC-1 cells and subsequently treated for 24 h with dimethyl sulfoxide (DMSO) ( a , d ), VAN ( b , e ) and CAB ( c , f ). The red channel, corresponding to MZ-CRC-1 cells, was omitted in panels d, e, and f to highlight the tumor-induced microvascular network. Grafted larvae showed vessels in green that sprout from the sub-intestinal vein (SIV) toward the xenograft. Quantification of tumor-induced angiogenesis in MZ-CRC-1-injected Tg(fli1a:EGFP) y1 embryos after 24 h of VAN ( g ) and CAB ( h ) treatments at different concentrations. Control (CTR) values have been set to 1.0. Graphed values represent the mean ± S.E.M. * p < 0.05 versus the CTR; *** p < 0.001 versus the CTR. Embryos are shown anterior to the left. Scale bar: 100 µm.

Article Snippet: Vandetanib (VAN), and cabozantinib (CAB) were provided by Cayman Chemicals (Ann Arbor, MI, USA).

Techniques: Fluorescence, Injection, Control