Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant

Figure 1 Side effects are distinct from the anticancer mechanism. An exemplary case concerning taxol is depicted. TSLP: Tumor-specific lytic path; >: Greater than microbutule-disruping dose; =: Equivalent to microtubule-disrupting dose; <: Lesser than microtubule-disrupting dose; NSP: Nonspecific.

Figure 2 Structural analysis of human retinoblastoma protein. A: 3D structure of the inactive retinoblastoma protein pocket domain of retinoblastoma-1 (PDB ID: 4ELL). The model was generated using PyMol molecular graphics system, version 1.2r3pre, Schrödinger, LLC. B: Structures (or structural model) of phosphorylated retinoblastoma. The model shows the protein dimer as observed in the asymmetric crystal unit for retinoblastoma^PL–P. The structural coordinates for PDB ID 4ELL were downloaded from the NIH protein database. PyMol was used to re-enter the image of the model as shown. Rb: Retinoblastoma.

Figure 3 Nocodazole triggers hyperploid progression mediated death in retinoblastoma-mutant WERI-1 retinoblastoma cells. A DNA content flow cytometric histogram of WERI-1 cells continuously treated with nocodazole (Noc; 0.415 µmol/L) for the duration (1 d, 24 h; 4 d, 96 h) is shown. Cells (5 × 10⁵) were treated as indicated, harvested using trypsin and fixed in 70% ethanol. To determine DNA content per cell, propidium (100 Kunitz units/mL) and RNase A (50 µg/mL) were added and assayed using Beckton Dickinson flow cytometry. Persistent treatment with nocodazole led to the death of hyperploid cells induced. RB: Retinoblastoma.