Validation of absolutely quantitated Ki67 and cyclinD1 protein levels for prognosis of Luminal-like breast cancer patients.

AIMS: To translate a clinical research finding into daily clinical practice requires well-controlled clinical trials. We have demonstrated the usage of absolute quantitation of Ki67 and cyclinD1 protein levels to improve prognosis of Luminal-like patients based on overall survival (OS) analysis of a cohort of 155 breast cancer specimens (cohort 1). However, this finding is considered the D level of evidence (LOE) to require subsequent validation before it may be used in daily clinical practice. To set the stage for future clinical trials, our findings were validated through OS analysis of an independent cohort (cohort 2) of 173 Luminal-like patients. METHODS: Both Ki67 and cyclinD1 levels were measured absolutely and quantitatively using the Quantitative Dot Blot (QDB) method in cohort 2. The proposed cutoffs for both biomarkers from cohort 1 were re-evaluated in cohort 2 and in the merged cohort of 1 and 2, respectively, through univariate, multivariate and Kaplan-Meier survival analysis. RESULTS: The proposed cutoffs of 2.31 nmol/g for Ki67 and 0.44 µmol/g for cyclinD1 were validated as effective cutoffs in cohort 2 and the merged cohort through OS analysis. The combined use of both biomarkers allowed us to identify patients with both biomarker levels below the cutoffs (59.3%) with10-year survival probability (SP) of 89%, in comparison to those above the cutoffs (8.3%) with 8 year SP of 28% through OS analysis in the merged cohort. CONCLUSIONS: This study validated our findings that absolute quantitation of Ki67 and cyclinD1 allows effective subtyping of luminal-like patients. It sets the stage for prospective or prospective-retrospective clinical studies.

Intelligent Micro-/Nanorobots for Cancer Theragnostic.

Cancer is one of the most intractable diseases owing to its high mortality rate and lack of effective diagnostic and treatment tools. Advancements in micro-/nanorobot (MNR)-assisted sensing, imaging, and therapeutics offer unprecedented opportunities to develop MNR-based cancer theragnostic platforms. Unlike ordinary nanoparticles, which exhibit Brownian motion in biofluids, MNRs overcome viscous resistance in an ultralow Reynolds number (Re << 1) environment by effective self-propulsion. This unique locomotion property has motivated the advanced design and functionalization of MNRs as a basis for next-generation cancer-therapy platforms, which offer the potential for precise distribution and improved permeation of therapeutic agents. Enhanced barrier penetration, imaging-guided operation, and biosensing are additionally studied to enable the promising cancer-related applications of MNRs. Herein, the recent advances in MNR-based cancer therapy are comprehensively addresses, including actuation engines, diagnostics, medical imaging, and targeted drug delivery; promising research opportunities that can have a profound impact on cancer therapy over the next decade is highlighted.