Journal: Cell Communication and Signaling : CCS

Article Title: Establishment of a mouse hepatocellular carcinoma tumoroid panel recapitulating inter- and intra- heterogeneity for disease modelling and combinatorial drug discovery

doi: 10.1186/s12964-025-02391-w

Figure Lengend Snippet: Alb-R26 Met primary HCC cells are characterised by heterogeneous expression and phosphorylation levels of signals and by resistance to RTKi. ( A ) Western blot of the indicated signalling proteins. Actin or Tubulin were used for normalization. HCC13 cells were used as a positive control (34). Quantifications are reported in Fig. S5B. Full western blot and ponceau staining are shown in Fig. S10-12. ( B ) Dot plot reporting the percentage of viable cells after treatment (1, 3, 10 µM) with the indicated RTKi (cabozantinib, lenvatinib, sorafenib, and regorafenib). Statistical analyses were performed using one-way ANOVA followed by Tukey’s multiple comparison. Levels of significance: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001

Article Snippet: The drugs used on cell cultures were: cabozantinib, lenvatinib, regorafenib, and sorafenib (1, 3, and 10μM; TargetMol: #T2586, #T0520, #T1792, #T0093L, respectively).

Techniques: Expressing, Phospho-proteomics, Western Blot, Positive Control, Staining, Comparison

Journal: Cell Communication and Signaling : CCS

Article Title: Establishment of a mouse hepatocellular carcinoma tumoroid panel recapitulating inter- and intra- heterogeneity for disease modelling and combinatorial drug discovery

doi: 10.1186/s12964-025-02391-w

Figure Lengend Snippet: Responsiveness of Alb-R26 Met tumoroids to romidepsin alone or in combination with cabozantinib. ( A ) Graph reporting the viability of tumoroids to 1.3 µM of cabozantinib, a dose chosen for its clinical relevance in relation to the average amount of drug found in patient serum, and allowing comparative analyses with outcomes using patient-derived tumoroids (49). Values are compared to non-treated control conditions. Statistical analyses were performed using one-way ANOVA, followed by Dunnett’s multiple comparison. Levels of significance: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001. ( B ) Graphs reporting the viability of tumoroids at 1.3 µM of cabozantinib plus increasing concentration of romidepsin (0.001, 0.003, 0.01, 0.03 µM). Values are compared to non-treated control conditions. The IC 50 values are indicated on each graph. Statistical analyses were performed using two-way ANOVA, followed by Sidak’s multiple comparison. Data were further analysed using Bonferroni correction, showing same significance outcomes. Levels of significance: *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001. ( C ) Brightfield pictures of tumoroids at the indicated conditions. Regarding tHCC18 morphology, we observed some cystic structures developing under cabozantinib (1.3 µM) without and with romidepsin (0.01 µM), possibly related to a dying process in relation to the thinner tumoroid borders, different from cystic tumoroid structures (see as example tHCC20 and tHCC21 in Fig. A and S7B). ( D ) Graph reporting the viability of all tumoroids treated with romidepsin plus cabozantinib to compare the treatment efficacy among them. The IC 50 values for each tumoroids are reported. Experiments were performed in ultra-low adherent plates

Article Snippet: The drugs used on cell cultures were: cabozantinib, lenvatinib, regorafenib, and sorafenib (1, 3, and 10μM; TargetMol: #T2586, #T0520, #T1792, #T0093L, respectively).

Techniques: Derivative Assay, Control, Comparison, Concentration Assay

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: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: Efficacy of TKIs on tumor growth, in vitro and in vivo . A, Dose–response curve of axitinib, cabozantinib, and lenvatinib treatment of UM-RC-3 and RENCA VHL − , mean + SD, n = 5/group; control, 0 mmol/L TKIs, 1% DMSO; IC 50 values of cell viability are reported. B, Experimental design and timeline of treatment schedule. C and D, Response to TKIs by UM-RC-3 ( C ) and RENCA VHL − ( D ) tumor cells in tibiae at day 11 of treatment; representative bioluminescence images and quantification are shown, mean ± SEM, n = 16 tibiae/group. E, Response of tumor cells in lungs to TKIs at day 11 of treatment; representative bioluminescence images and quantification are shown, mean ± SEM, n = 8/group. F, Stereomicroscope images of lungs (brightfield and GFP–green); Bar, 1 cm. P values by one-way ANOVA with Tukey honestly significant difference post hoc test; *, P < 0.05; **, P < 0.01; ***, P < 0.001. Axi, axitinib; Cabo, cabozantinib; Conc, concentration; Lenv, lenvatinib; Veh, vehicle.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques: In Vitro, In Vivo, Control, Concentration Assay

Journal: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: In vitro and in vivo effects of TKIs on blood vessels. A, Dose–response curve of axitinib, cabozantinib, and lenvatinib treatment of HUVECs, mean ± SD, n = 4. B, Schematic representation of the experimental approach. C and D, Impact of TKIs on vascularization of RENCA VHL − tumors in bone evaluated by IF analysis; representative images acquired by confocal microscopy (green, GFP; blue, DAPI; yellow, endomucin; red, laminin; C ) and quantification are shown ( D ); dotted line, tumor area; mean ± SEM, n = 4–10/group; bar, 100 μm. E and F, Impact of TKIs on vascularization of RENCA VHL − tumors in lungs; representative images acquired by confocal microscopy (green, GFP; blue, DAPI; red, CD31; E ) and quantifications are shown; dotted line, tumor area; mean ± SEM, n = 4–10/group; ar, 100 μm. P values by one-way ANOVA with Tukey honestly significant difference post hoc test; *, P < 0.05; **, P < 0.01; ***, P < 0.001. A, axitinib; BV, blood vessel; C, cabozantinib; Endo/Endom, endomucin; L, lenvatinib; Lam, laminin; RV − , RENCA VHL; V, vehicle.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques: In Vitro, In Vivo, Confocal Microscopy

Journal: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: TKIs’ effect on immune cell infiltration in bone tumors. A, Impact of TKIs on CD8 infiltration in RENCA VHL − tumors in bone evaluated by IF analysis; representative images acquired at the confocal microscope (green, GFP; blue, DAPI; yellow, CD8; red, laminin) are shown; dotted line, tumor area. Bar, 100 μm. B, Quantification of the number and distribution of CD8 + cells associated with tumor; mean ± SEM, n = 6–12/group. C, Representative images and quantification ( D and E ) of immune subsets infiltrating bone tumors by multiplex imaging (COMET, Lunaphore) post-TKI treatment, mean ± SEM, n = 3/group P values by one-way ANOVA with Tukey honestly significant difference post hoc test; *, P < 0.05; **, P < 0.01; ***, P < 0.0001. Inner tumor region >25 μm from the tumor edge. A, axitinib; C, cabozantinib; Inner reg, inner region; L, lenvatinib; Lam, laminin; lymph, lymphocytes; myel, myeloid; V, vehicle.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques: Microscopy, Multiplex Assay, Imaging

Journal: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: Ex vivo µCT analysis of TKIs’ effects on bone microarchitecture. A, Representative μCT micrographs of tibial metaphysis cross-sections extracted from mice treated with axitinib, cabozantinib, and lenvatinib or vehicle, Bar, 300 μm. B, Quantification of key bone histomorphometry parameters extrapolated from μCT analysis, mean ± SEM, n = 4/group. C, Impact of TKIs on TRAP + cells in RENCA VHL − tumors in bone evaluated by IF analysis; representative images acquired at the confocal microscope (green, GFP; white, DAPI; red, TRAP) are shown; arrow, TRAP + cells. Bar, 250 μm. P values by one-way ANOVA with Tukey honestly significant difference post hoc test; *, P < 0.05. A, axitinib; C, cabozantinib; L, lenvatinib; TRAP, tartrate-resistant acid phosphatase; V, vehicle.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques: Ex Vivo, Microscopy

Journal: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: Prolonged treatment with TKIs followed by withdrawal and survival analysis. A, Schematic representation of experimental design. B, Representative images of bioluminescence signal in tibiae and lungs. C, Bioluminescence signal of tumors in bone quantified over time; single tumors are shown. D, Analysis of survival over time after TKI treatment based on bone tumors (photon flux values of 3 × 10 6 were considered as the end point). Absolute numbers are reported in the table. P value (one-way ANOVA with Tukey honestly significant difference post hoc test) and median OS are shown. E, Bioluminescence signal of tumors in lungs quantified over time; F, Estimation of survival over time after TKI treatment based on lung tumors. Absolute numbers are reported in the table. P value (one-way ANOVA with Tukey honestly significant difference post hoc test), median OS and 95% CI of ratio after the log-rank (Mantel–Cox) test are shown. Axi, axitinib; Cabo, cabozantinib; ; Lenv, lenvatinib; MBP, median bone progression; WD, withdrawal; Veh, vehicle.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques:

Journal: Cancer Research Communications

Article Title: Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone

doi: 10.1158/2767-9764.CRC-24-0304

Figure Lengend Snippet: TKIs as a second-line treatment. A, Schematic representation of experimental design. B , D , and F, Representative images of bioluminescence signal in tibiae/lungs of mice and bioluminescence signal of tumors quantified over time; single tumors are shown. C , E , and G, Estimation of survival over time after TKI treatment based on bone and lung tumors. Absolute numbers are reported in the table. P value (one-way ANOVA with Tukey honestly significant difference post hoc test) with median OS and 95% CI of ratio after the log-rank (Mantel–Cox) test. Axi, axitinib; Cabo, cabozantinib; Lenv, lenvatinib; MBP, median bone progression; Rx, second-line treatment; WD, withdrawal.

Article Snippet: TKIs (axitinib, cabozantinib, and lenvatinib >99% purity) were purchased from TargetMol.

Techniques:

Journal: Cancers

Article Title: Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma

doi: 10.3390/cancers9070087

Figure Lengend Snippet: Overview of previous and current MET/HGF inhibitor clinical trials.

Article Snippet: Similar to crizotinib, cabozantinib/XL184 (Exelixis), is an oral type I inhibitor of MET, but its targets also include VEGF and AXL and has already been approved for the treatment of metastatic medullary thyroid cancer [ , ].

Techniques: Amplification