Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Ribociclib, a selective cyclin D kinase 4/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo.

doi: 10.1016/j.biopha.2019.108602

Figure Lengend Snippet: Fig. 2. LEE011 inhibits cell proliferation and promotes apoptosis by targeting the Rb-E2F1 pathway in C33A but not HeLa. A. C33A and HeLa cells were treated with increasing concentrations of LEE011, and the morphologic changes of cells were observed by microscopy after 48 h of LEE011 treatment (the magnification is 200X, scale bar, 100 μm). B. The expression of proteins in Rb-E2F1 pathway and apoptosis in C33A cells were detected by western blotting after 2 days of LEE011 treatment. C. The expression of proteins in Rb-E2F1 pathway and apoptosis in HeLa cells were detected by western blotting after 2 days of LEE011 treatment.

Article Snippet: :434.54 g/mol, HY-15777,MCE) was solubilized in 2.3013 ml of DMSO and 10 mM stock solution was made,2 mg of LEE011 powder was solubilized into 20 mM stock solution.

Techniques: Microscopy, Expressing, Western Blot

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Ribociclib, a selective cyclin D kinase 4/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo.

doi: 10.1016/j.biopha.2019.108602

Figure Lengend Snippet: Fig. 3. LEE011 induces cell cycle G1 arrest in C33 A but not HeLa. A.B. After treatment of C33A cell lines with LEE011 (10 μM) during 48 h, G0/G1 portion increased with 19.23% (P < 0.05), S portion decreased with 9.68% (P < 0.05), and G2/M portion decreased with10.18% (P < 0.05). C.D. After treatment of HeLa cell lines with LEE011 (10 μM) during 48 h, there are no significant changes in the cell cycle process.

Article Snippet: :434.54 g/mol, HY-15777,MCE) was solubilized in 2.3013 ml of DMSO and 10 mM stock solution was made,2 mg of LEE011 powder was solubilized into 20 mM stock solution.

Techniques:

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Ribociclib, a selective cyclin D kinase 4/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo.

doi: 10.1016/j.biopha.2019.108602

Figure Lengend Snippet: Fig. 4. LEE011 induces cell apoptosis in C33A but not HeLa. A.B. After treatment of C33A cell lines with LEE011 (10 μM) during 48 h, the apoptotic index increased 2.24 times more (31.7%) than control (14.13%) in C33A (P < 0.05). Alive cells are shown in the lower left part of the panel (Q3); Early apoptotic cells are shown in the lower right part of the panel (Q4); Late apoptotic cells are shown in the higher right part of the panel (Q2); Necrotic cells are shown in Q1. Apoptotic cells were exhibited as annexin V + cells. C.D. In HeLa cells, treatment with 10 μM of LEE011 resulted in apoptosis augmentation with no significant changes compared with control. Alive cells are shown in the lower left part of the panel (Q8); Early apoptotic cells are shown in the lower right part of the panel (Q7); Late apoptotic cells are shown in the higher right part of the panel (Q6); Necrotic cells are shown in Q5. Apoptotic cells were exhibited as annexin V + cells.

Article Snippet: :434.54 g/mol, HY-15777,MCE) was solubilized in 2.3013 ml of DMSO and 10 mM stock solution was made,2 mg of LEE011 powder was solubilized into 20 mM stock solution.

Techniques: Control

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Ribociclib, a selective cyclin D kinase 4/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo.

doi: 10.1016/j.biopha.2019.108602

Figure Lengend Snippet: Fig. 5. The effects of LEE011 treatment on tumor growth in vivo. A. After euthanasia, tumors were extracted from both of control group and LEE011 treated group. The sizes of tumors extracted from LEE011 group were smaller than the control group in C33A xenograft models. However, the sizes of tumors in the control group and LEE011 treated group had no difference in HeLa Xenografts. B–C. Treated with 200 mg/kg, LEE011 significantly inhibited tumor growth in C33A xenograft models (P < 0.05). Tumor growth had no change in HeLa xenograft models.D.LEE011 had no effect on body weight in C33A xenografts, but caused the HeLa models lost weight. E. The antiproliferative effect of LEE011 was confirmed by Ki- 67 staining in C33A xenografts, and suppression of the RB-E2F1 pathway was confirmed by immunohistochemical staining for CDK4, CDK6, cyclin D1 and Rb. LEE011-induced apoptosis was detected by using TUNEL assay (scale bar, 100 μm). F. The index of the antiproliferative effect, the RB-E2F1 pathway and apoptosis in HeLa xenografts did not show obvious differences. G.H.I. The biochemical indicators (ALT, AST, ALB, ALP, BUN, CR, LDH-L, CK) were detected from blood samples and the morphologic of heart, liver and kidney were studied and showed that there were no serious adverse effects in xenograft models treated with LEE011.

Article Snippet: :434.54 g/mol, HY-15777,MCE) was solubilized in 2.3013 ml of DMSO and 10 mM stock solution was made,2 mg of LEE011 powder was solubilized into 20 mM stock solution.

Techniques: In Vivo, Control, Staining, Immunohistochemical staining, TUNEL Assay

Journal: JCI Insight

Article Title: RB expression confers sensitivity to CDK4/6 inhibitor–mediated radiosensitization across breast cancer subtypes

doi: 10.1172/jci.insight.154402

Figure Lengend Snippet: ( A – C ) A GFP reporter system was used to measure relative HR repair efficiency in RB WT MCF-7 ( A ) and MDA-MB-231 ( B and C ) cells after treatment with in IC 50 concentration of palbociclib (gray), ribociclib (blue), or abemaciclib (green). A CHK1/2 inhibitor (200 nM AZD7762) was used as a positive control, and a DNAPK inhibitor (1.5 μM NU7441) was used as the negative control. For the reporter assay a 1-way ANOVA with Dunnett’s post hoc test was used to compare treatment groups to DMSO-treated cells. * P < 0.05; ** P < 0.01; *** P < 0.001, **** P < 0.0001. ( D , E , G , and H ) For RAD51 immunofluorescence, cells were pretreated for 1 hour with palbociclib, and coverslips were fixed 6 hours and 16 hours after 4 Gy radiation in RB WT MDA-MB-231 ( D ) and CAL-120 ( E ) cells, as well as RB-null MDA-MB-468 ( G ) and CAL-851 ( H ) TNBC cells. Two-tailed t tests were performed between radiation and combination treated groups at each RAD51 time point, and correction was performed for multiple comparisons. ( F and I ) Western blots were used to assess RAD51 protein expression at the same time points. All experiments represent the average of 3 independent experiments and bar graphs display the average ± SEM.

Article Snippet: Palbociclib (MilliporeSigma, PZ0199), abemaciclib (Med Chem Express, HY-16297A), and ribociclib (Med Chem Express, HY-15777A) were used to make 10 mM stocks in 100% DMSO for in vitro assays.

Techniques: Concentration Assay, Positive Control, Negative Control, Reporter Assay, Immunofluorescence, Two Tailed Test, Western Blot, Expressing

Journal: JCI Insight

Article Title: RB expression confers sensitivity to CDK4/6 inhibitor–mediated radiosensitization across breast cancer subtypes

doi: 10.1172/jci.insight.154402

Figure Lengend Snippet: ( A and B ) A eYFP reporter system was used to measure relative NHEJ repair efficiency in RB WT MDA-MB-231 ( A ) and CAL-120 ( B ) cells after treatment with palbociclib (gray), ribociclib (blue), or abemaciclib (green). The CHK1/2 inhibitor (200 nM AZD7762) was used as a negative control, and the DNAPK inhibitor (2.5 μM NU7441) was used as a positive control. ( C – F ) Cells were fixed 0.5, 6, 16, and 24 hours after RT (2 Gy) in RB WT MDA-MB-231 ( C and E ) and CAL-120 ( D and F ) cells, and cells were stained for γH2AX foci (red) and DAPI (blue). * P < 0.05; ** P < 0.01. All experiments represent the mean of n = 3 experiments. Two-tailed t tests were used to compare the RT and combination-treated groups at each γH2AX time point, and correction was performed for multiple comparisons. Original magnification, ×60.

Article Snippet: Palbociclib (MilliporeSigma, PZ0199), abemaciclib (Med Chem Express, HY-16297A), and ribociclib (Med Chem Express, HY-15777A) were used to make 10 mM stocks in 100% DMSO for in vitro assays.

Techniques: Negative Control, Positive Control, Staining, Two Tailed Test

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: The effect of fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i, palbociclib, 200 nM in the MCF-7 and T47D cell models; 5 µM in the ZR-75-1 cell model) and AKT inhibitor (AKTi, capivasertib, 500 nM in the MCF-7 cell model; 200 nM in the T47D model; 150 nM in the ZR-75-1 cell model), as single agents or in double and triple combinations, was assessed in all cell lines by crystal violet growth assay ( A , B , E , F , I and J ) and CellTiter-Blue viability assay ( C , D , G , H , K , and L ) performed over 6 days. Outgrowth of resistant colonies was investigated in MCF-7 ( M and N ) and T47D models ( O and P ) by weekly evaluation of the percentage of 48 wells at 50% or greater confluence (positive wells) over 12 weeks. Experiments were conducted in three biological replicates and data are shown as mean ± SEM. Asterisks indicate significant differences in the one-way ANOVA test at day 6 (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001, and **** p < 0.0001).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Growth Assay, Viability Assay

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: Apoptotic levels were determined by evaluating the presence of cytoplasmic nucleosomes in MCF-7 ( A ), T47D ( B ), and ZR-75-1 ( C ) cells using an ELISA cell death detection assay. Data are shown with error bars representing mean ± SEM of three biological replicates. Asterisks indicate significant differences in the one-way ANOVA test (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001, and **** p < 0.0001). D Western blot analysis of apoptosis markers in the three fulvestrant-resistant breast cancer models. Densitometry analysis of Western blot bands of cleaved-PARP was performed using ImageJ software. Data are shown as the area under the curve (AUC) normalized to loading control. E Western blot analysis of key signal transduction proteins in the three fulvestrant-resistant breast cancer models. F Western blotting analysis of p-AKT (S473) and total AKT expression in the three fulvestrant-resistant breast cancer models. Densitometry analysis of Western blot bands of p-AKT (S473) and total AKT was performed using ImageJ software. Data are shown as the area under the curve (AUC) normalized to loading control. GAPDH was used as a loading control for Western blotting analysis. For all Western blots, a representative of two biological replicates is shown. Both apoptosis assay and harvesting protein for Western blotting analysis were performed 3 days after treatment with fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i, palbociclib, 200 nM in the MCF-7 and T47D cell models; 5 µM in the ZR-75-1 cell model) and AKT inhibitor (AKTi, capivasertib, 500 nM in the MCF-7 cell model; 200 nM in the T47D model; 150 nM in the ZR-75-1 cell model).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Enzyme-linked Immunosorbent Assay, Detection Assay, Western Blot, Software, Control, Transduction, Expressing, Apoptosis Assay

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: Tumor growth curves of MCF-7 ( A ) and 182R-1 ( B ) tumors following treatment with fulvestrant (Fulv, 100 mg/Kg bodyweight; N = 7) or vehicle (castor oil, N = 8) administered subcutaneously once a week. Treatment was initiated when tumors reached 50 mm 3 and continued for 5 weeks. C Mice were sacrificed on week 5 and MCF-7 and 182R-1 tumors were excised. Tumor growth curves of 182R-1 tumors treated with CDK4/6 inhibitor (CDK4/6i, palbociclib, 50 mg/Kg bodyweight; N = 8) alone ( D ), in combination with fulvestrant (100 mg/Kg bodyweight; N = 7 and N = 10) ( D and E ), or in combination with both AKT inhibitor (AKTi, capivasertib 100 mg/Kg bodyweight) and fulvestrant (100 mg/Kg bodyweight; N = 6 and N = 10) ( D and E ), or vehicle (castor oil and 25% w/v HPB cyclodextrin; N = 8) ( D ). CDK4/6i and AKTi were administered by oral gavage once daily for 5 days a week when tumors reached 50 mm 3 ( D ) or 250 mm 3 ( E ), and treatment was continued for up to 8 weeks. Data are shown as mean tumor volume ± SEM. Asterisks indicate a significant difference in ANOVA one-way test ( D ) or two-tailed t -test ( A , B and E ) at the endpoint (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001 and **** p < 0.0001).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Two Tailed Test

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: The effect of fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i, palbociclib, 200 nM) and AKT inhibitor (AKTi, capivasertib, 250–500 nM in the MCF-7 cell model; 100 nM in the T47D cell model), as single agents or in the double and triple combination, was assessed in all cell lines by crystal violet growth assay ( A , B , E , and F ) and CellTiter-Blue viability assay ( C , D , G , and H ) performed over 6 days. Outgrowth of resistant colonies was investigated in MPF-R ( I ) and TPF-R ( J ) cells by weekly evaluation of the percentage of 48 wells at 50% or greater confluence (positive wells) over 12 weeks. Experiments were conducted in three biological replicates and data are shown as mean ± SEM. Asterisks indicate significant differences in one-way ANOVA tests at day 6 (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001, and **** p < 0.0001).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Growth Assay, Viability Assay

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: Apoptotic levels were determined by evaluating the presence of cytoplasmic nucleosomes in MCF-7 ( A ) and T47D ( B ) cell models using an ELISA cell death detection assay. Data are shown with error bars representing mean ± SEM of three biological replicates. Asterisks indicate significant differences in one-way ANOVA tests (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001, and **** p < 0.0001). C Western blot analysis of apoptosis markers in both models resistant to combined fulvestrant and CDK4/6i. Densitometry analysis of Western blot bands of cleaved-PARP was performed using ImageJ software. Data are shown as the area under the curve (AUC) normalized to loading control. D Western blot analysis of key signal transduction proteins in breast cancer cell models resistant to combined CDK4/6i and fulvestrant therapy. E Western blotting analysis of p-AKT (S473) and total AKT expression in both breast cancer models resistant to combined fulvestrant and CDK4/6i. Densitometry analysis of Western blot bands of p-AKT (S473) and total AKT was performed using ImageJ software. Data are shown as the area under the curve (AUC) normalized to loading control. GAPDH was used as a loading control for Western blotting analysis. For all Western blots, a representative of two biological replicates is shown. Both apoptosis assay and harvesting protein for Western blotting analysis were performed 3 days after treatment with fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i, palbociclib, 200 nM), and AKT inhibitor (AKTi, capivasertib, 250 nM in the MCF-7 cell model; 100 nM in the T47D cell model).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Enzyme-linked Immunosorbent Assay, Detection Assay, Western Blot, Software, Control, Transduction, Expressing, Apoptosis Assay

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: A Tumor growth curves of orthotopic MPF-R tumors treated with a CDK4/6 inhibitor (CDK4/6i, palbociclib, 50 mg/Kg bodyweight) combined with fulvestrant (Fulv, 100 mg/Kg bodyweight; N = 9) or in combination with both AKT inhibitor (AKTi, capivasertib, 100 mg/Kg body weight) and fulvestrant (Fulv, 100 mg/Kg bodyweight; N = 10), or vehicle (castor oil and 25% w/v HPB cyclodextrin; N = 10). CDK4/6i and AKTi were administered by oral gavage once daily for 5 days a week, whereas fulvestrant was administered subcutaneously once a week. Treatment was initiated when tumors reached 100 mm 3 and continued for up to 7 weeks. Mice from the control group were sacrificed and tumors excised on week 6 due to their large size, while mice from double and triple combination groups were sacrificed and tumors excised on week 7. Data are shown as mean tumor volume ± SEM. Asterisks indicate significant differences in the two-tailed t -test at the endpoint (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001, and **** p < 0.0001). B Western blot analysis of key signal transduction proteins in 3 tumors of each treatment group excised when mice were sacrificed. GAPDH was used as a loading control. A representative of two independent experiments is shown. C Tumor volumes over time of the parental PDX KCC_P_3837 untreated (blue) and treated with combined CDK4/6i palbociclib (25 mg/kg in 2.5% DMSO, 25% β-cyclodextrin, 5 days per week by oral gavage) and fulvestrant (100 mg/kg in castor oil, once weekly via subcutaneous injection) (orange), and of the derivative PDX KCC_P_3837-FPR resistant to combined palbociclib and fulvestrant (red) at the third passage of continuous exposure to combined palbociclib and fulvestrant. D Kaplan-Meier survival plot of progression of PDX KCC_P_3837-FPR (resistant to combined CDK4/6i and fulvestrant) under treatment with combined CDK4/6i and fulvestrant with or without AKTi capivasertib (100 mg/kg in 2.5% DMSO, 25% β-cyclodextrin, 5 days per week by oral gavage) ( N = 5 and N = 4, respectively). Progression was defined as tumors growing to at least 5 mm in the shortest dimension. A two-sided p- value ( p < 0.05) was calculated using log-rank testing. E , F Evaluation of metastasis area > 2500 µm 2 relative to lung area at the endpoint (6 weeks) using an experimental metastasis model. MPF-R tumors were treated with fulvestrant (100 mg/Kg body weight) combined with CDK4/6i (palbociclib, 25 mg/Kg bodyweight; N = 10), fulvestrant combined with AKTi (capivasertib, 100 mg/Kg bodyweight; N = 10), or triple combination ( N = 9). TPF-R tumors were treated with the same dosage of fulvestrant and CDK4/6i and 50 mg/Kg bodyweight of AKTi ( N = 7 in fulvestrant and CDK4/6i group, N = 10 in fulvestrant and AKTi and N = 10 in triple combination group). CDK4/6i and AKTi were administered by oral gavage once daily for 5 days a week, while fulvestrant was administered subcutaneously once a week. Treatment was initiated 3 days before injection of cells in the tail vein and continued for up to 6 weeks. Data are shown as mean ± SEM. Significant differences were evaluated by the two-tailed Mann-Whitney test. G Representative micrographs of MPF-R and TPF-R tumors in mice lungs of each treatment group showing cytokeratin expression by immunohistochemistry (scale bars, 200 µm).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Control, Two Tailed Test, Western Blot, Transduction, Injection, MANN-WHITNEY, Expressing, Immunohistochemistry

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: Clinical and pathological characteristics of ER+ breast cancer patients with advanced disease treated with combined CDK4/6i and endocrine treatment from pilot and validation cohorts according to p-AKT levels.

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques:

Journal: Nature Communications

Article Title: Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer

doi: 10.1038/s41467-021-25422-9

Figure Lengend Snippet: A Kaplan-Meier plots evaluating progression-free survival (PFS) according to p-AKT (S473) levels in ER+ metastatic lesions from a validation cohort of ER+breast cancer patients treated with combined CDK4/6i and endocrine therapy in the advanced setting. A two-sided p -value ( p < 0.05) was calculated using log-rank testing. Representative micrographs of all breast cancer metastasis sections showing low p-AKT expression (H-score < 150, B and C ) or high p-AKT expression (H-score ≥ 150, D and E ; scale bars, 100 µm).

Article Snippet: Fulvestrant (ICI 182,780, Tocris) was dissolved in ethanol 96%, AKTi capivasertib (HY-15431, MedchemExpress), CDK4/6i ribociclib succinate hydrate (HY-15777C, MedchemExpress), CDK4/6i abemaciclib (HY-16297A, MedchemExpress), and dual PI3K/mTORi gedatolisib (#HY-10681, MedchemExpress) were dissolved in DMSO (Sigma-Aldrich) and CDK4/6i palbociclib isothiocyanate (HY-A0065, MedchemExpress) was dissolved in water.

Techniques: Expressing