Objective: This study aims to develop a mechanistically grounded mathematical framework to quantify the time- and dose-dependent inhibitory effects of Pinus massoniana bark extract (PMBE) on BEL-7402 human hepatoma cells, advancing beyond phenomenological approaches through integration of stochastic processes and pharmacodynamic modeling. Methods: A continuous-time branching–Hill hybrid model was constructed by integrating stochastic branching-process kinetics, logistic growth constraints, and sigmoidal pharmacodynamic inhibition (Hill function). The model was calibrated using 48-hour MTT assay data across five PMBE concentrations (20–200 µg/mL) and validated against experimental inhibition rates. Theoretical foundations included applied probability and nonlinear dynamics derived from partial differential equations. Results: The model demonstrated high predictive accuracy, with a maximal inhibition rate of 0.24 at 160 µg/mL PMBE, closely matching empirical observations (0.237 ± 0.015). Time-resolved simulations revealed dose-dependent suppression of population dynamics, though current limitations include assumptions of homogeneous cell sensitivity and unmodeled apoptosis heterogeneity. Conclusion: This hybrid framework bridges stochastic cell behavior with pharmacological inhibition kinetics, providing a quantitative basis for adaptive therapy optimization in hepatocellular carcinoma. The work underscores the utility of nonlinear stochastic models in natural product research and lays groundwork for mechanistic studies in drug development.
Stereotactic radiosurgery is an effective and safe method that can help prevent the development of deep-seated or large-sized cavernomas. However, there are limited studies on familial, multiple and symptomatic cerebral cavernous malformations (CCM). The approach in these cases is not yet clear. This case is a CCM that can be confused with other brain masses and metastases, and contributes to the literature in terms of genetic transmission, management and treatment of cavernomas.
Rethinking Cancer: A New Paradigm for the Postgenomics Era is a groundbreaking book edited by leading scientists Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell, and published by MIT Press in April 27, 2021.
Background: C-Reactive Protein (CRP) is associated with cancer development, survival, and tumor recurrence. A barrier to its use is the inability to interpret changes in CRP levels. Aims: The aim of this study was to determine when a change in CRP is clinically meaningful. Methods: This was a retrospective cohort study of consecutive cancer patients. Those with a solid tumor diagnosis and at least two consecutive CRP measurements postdiagnosis were included. Subjects were divided into Baseline High CRP (bHCRP; CRP ≥ 10 mg/L) and Baseline Normal CRP groups (bNCRP; CRP < 10 mg/L), We identified appropriate CRP cut-off points for CRP levels changes; compared bHCRP and bNCRP; constructed Kaplan- Meier survival plots and Cox Proportional Hazard Model to confirm cut-off points in each group. Results: 1473 were eligible. In bHCRP group, Overall survival (OS) Mean (Standard Error) was 87(2) and 81(4) months for ≥ 50% vs < 50% CRP decrease respectively. In bNCRP group, OS was 90(3) and 105(3) months for ≥ 2x vs < 2x increase in CRP levels, respectively. These differences remained significant after adjusting for confounders. Conclusion: After a baseline normal CRP an increase of 2-fold or greater was associated with clinical and statistically significantly shorter OS. Conversely, after a baseline high CRP a 50% or greater decrease from baseline was associated with longer OS. Quantification of clinically meaningful CRP change could impact more effective CRP use as a biomarker, prognostic indicator and aid therapeutic decision making. This is especially important to reduce healthcare disparities in financially struggling healthcare systems.
