Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: Average size, polydispersity index (PdI), and Z-potential of the different formulation obtained by dynamic light scattering (DLS).

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques: Formulation

Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: TEM images of ( A ) MZ1-NPs and ( B ) MZ1-ACNPs.

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques:

Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: ( A ) Physical stability of ACNPs. ( B ) In vitro release profiles of MZ1-NPs and MZ1-ACNPs at pH 7.4. Data are expressed as mean ± s.e.m. from at least three independent experiments.

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques: In Vitro

Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: Trastuzumab vectorization increases the antitumor efficacy of MZ1-carrying nanoparticles. Cell viability (in %, referred to the DMSO vehicle) by MTT assay under treatment with control (Ctl) free MZ1, MZ1-NPs or MZ1-ACNPs in SKBR3 ( A ) and BT474 ( B ) HER2+ cell lines. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques: MTT Assay, Control

Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: MZ1-encapsulated nanoparticles do not affect cell cycle distribution in HER2+ cell lines and increase cell death by apoptosis induction in HER2+ cell lines. Distribution of cells (in % of the total) under treatment with vehicle, free MZ1, MZ1-NPs, or MZ1-ACNPs in SKBR3 ( A , C ) and BT474 ( B , D ) HER2+ cell lines, evaluated by flow cytometry. ** p < 0.01; *** p < 0.001.

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques: Flow Cytometry

Journal: Pharmaceutics

Article Title: Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

doi: 10.3390/pharmaceutics12100986

Figure Lengend Snippet: MZ1-ACNPs rendered a strong cytotoxic effect in trastuzumab, MZ1-naturally resistant cell line HCC1954. Cell viability (in %, referred to the DMSO vehicle) by MTT assay under treatment with free MZ1, MZ1-NPs, or MZ1-ACNPs. *** p < 0.001.

Article Snippet: Zinc catalyst was prepared according to literature procedures [ ]. (+)-JQ1 based PROTAC (MZ1) were purchased (high-performance liquid chromatography (HPLC) ≥98% purity) by TOCRIS Bioscience (Bristol, UK), and trastuzumab was purchased as Herceptin by ROCHE (F. Hoffmann-La Roche Ltd.).

Techniques: MTT Assay

Journal: Haematologica

Article Title: Targeting BCL2 with venetoclax is a promising therapeutic strategy for “double-proteinexpression” lymphoma with MYC and BCL2 rearrangements

doi: 10.3324/haematol.2018.204958

Figure Lengend Snippet: Characteristics of four germinal center B-cell-like diffuse large B-cell lymphoma-derived cell lines. (A) The four germinal center B-cell-like diffuse large B-cell lymphoma-derived cell lines have the MYC rearrangement. MYC is fused to IGH in BJAB, SU-DHL10, and OCI-Ly8 cells, while the IGH-BCL2 fusion was detected in SU-DHL10, Karpas231, and OCI-Ly8 cells. Fluorescence in situ hybridization analyses confirmed that SU-DHL10, Karpas231, and OCI-Ly8 are double-hit high grade B-cell lymphoma cell lines with MYC and BCL2 rearrangements. (B) Western blot analysis showed that the four lines express BCL6, MYC, BRD4, MCL1, BCL-xL, BIM, BAD, BAK, and BAX at a variety of levels. Despite the presence of the IGH-BCL2 fusion, SU-DHL10 cells failed to show BCL2 protein expression. In contrast, Karpas231 and OCI-Ly8 cells had abundant BCL2 protein, a considerable part of which is phosphorylated (pBCL2) at serine 70. The results indicate that Karpas231 and OCI-Ly8 correspond to double-hit and double-protein-expression lymphoma cells.

Article Snippet: The BCL2 inhibitor venetoclax (Selleck Chemicals, Houston, TX, USA), MCL1 inhibitor S63845 (ApexBio, Houston, TX, USA), BCL-xL inhibitor A-1155463 (Selleck Chemicals), and BRD4 inhibitor JQ-1 (Sigma-Aldrich, St. Louis, MO, USA) were dissolved with dimethyl sulfoxide (DMSO; Nacalai Tesque, Kyoto, Japan) and added to the culture medium.

Techniques: Derivative Assay, Fluorescence, In Situ Hybridization, Western Blot, Expressing

Journal: Haematologica

Article Title: Targeting BCL2 with venetoclax is a promising therapeutic strategy for “double-proteinexpression” lymphoma with MYC and BCL2 rearrangements

doi: 10.3324/haematol.2018.204958

Figure Lengend Snippet: Growth inhibitory effect and apoptotic sensitivity of the four cell lines to JQ-1 and three BH3 mimetics. (A) JQ-1 suppressed proliferation in three cell lines, but not in BJAB, in a dose-dependent manner. Venetoclax inhibited proliferation of Karpas231 and OCI-Ly8 cells even at a concentration of 20 nM, but had no effect on either BJAB or SU-DHL10 cells. S63845 showed the inhibitory effect only in SU-DHL10 cells. At nanomolar concentrations, A-1155463 failed to suppress the proliferation of any cell lines. (B) Although 50 μM of JQ-1 suppressed cell proliferation in the SU-DHL10, Karpas231, and OCI-Ly8 lines, the exposure was insufficient to induce apoptosis in Karpas231 (annexin V + 7-aminoactinomycin D + 30.3%) and OCI-Ly8 (annexin V + 7-aminoactino-mycin D + 4.4%) cells. Exposure to 200 nM of venetoclax effectively led to apoptotic changes (annexin V + ) in more than 80% of both Karpas231 and OCI-Ly8 cells. Exposure to 100 nM of S63845 induced cell death only in SU-DHL10 cells. Consistent with the results in cell proliferation assays, 1 μM of A-1155463 did not induce even modest cell death in any cell lines. DMSO: dimethyl sulfoxide.

Article Snippet: The BCL2 inhibitor venetoclax (Selleck Chemicals, Houston, TX, USA), MCL1 inhibitor S63845 (ApexBio, Houston, TX, USA), BCL-xL inhibitor A-1155463 (Selleck Chemicals), and BRD4 inhibitor JQ-1 (Sigma-Aldrich, St. Louis, MO, USA) were dissolved with dimethyl sulfoxide (DMSO; Nacalai Tesque, Kyoto, Japan) and added to the culture medium.

Techniques: Concentration Assay