10 research outputs found
BATE Curve in Assessment of Clinical Utility of Predictive Biomarkers
In this paper, for time-to-event data, we propose a new statistical framework for casual inference in evaluating clinical utility of predictive biomarkers and in selecting an optimal treatment for a particular patient. This new casual framework is based on a new concept, called Biomarker Adjusted Treatment Effect (BATE) curve, which can be used to represent the clinical utility of a predictive biomarker and select an optimal treatment for one particular patient. We then propose semi-parametric methods for estimating the BATE curves of biomarkers and establish asymptotic results of the proposed estimators for the BATE curves. We also conduct extensive simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrate the application of the proposed method in a real-world data set
Association of dyslipidemia with renal cell carcinoma: a 1∶2 matched case-control study.
Abnormal serum lipid profiles are associated with the risk of some cancers, but the direction and magnitude of the association with renal cell carcinoma is unclear. We explore the relationship between serum lipids and renal cell carcinoma via a matched case-control study. A 1∶2-matched case-control study design was applied, where one renal cell carcinoma patient was matched to two non-renal-cell-carcinoma residents with respect to age (±0 year) and gender. Cases (n = 248) were inpatients with a primary diagnosis of renal cell carcinoma, confirmed by pathology after operations. Controls were sampled from a community survey database matched on age and gender with cases, 2 controls for each case. Stratified Cox proportional hazard regression analysis was used to obtain hazard ratios and corresponding 95% confidence intervals of lipids level and dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol (p<0.001), LDL cholesterol (p<0.001), and HDL cholesterol (p = 0.003) are associated with decreased hazard of renal cell carcinoma, adjusting for obesity, smoke, hypertension and diabetes. However, risk caused by hTG showed no statistical significance (p = 0.263). This study indicates that abnormal lipid profile influences the risk of renal cell carcinoma
Description and comparison of clinical and biochemical characteristics of the study subjects<sup>*</sup>.
*<p>Quantitative data were presented as mean±SD, and categorical data as N (percentage);</p>†<p>P-values were obtained from univariate Cox regression.</p
Hazard ratios of plasma lipids and dyslipidemia from stratified Cox regression models.
<p>Multifactor adjustment was for obesity, smoke, hypertension, and diabetes. Black squares represent the hazard ratios, and error bars indicate the 95% confidence intervals (CIs).</p
RNA Interference against ATP as a Gene Therapy Approach for Prostate Cancer
Chemotherapeutic agents targeting energy metabolism have
not achieved
satisfactory results in different types of tumors. Herein, we developed
an RNA interference (RNAi) method against adenosine triphosphate (ATP)
by constructing an interfering plasmid-expressing ATP-binding RNA
aptamer, which notably inhibited the growth of prostate cancer cells
through diminishing the availability of cytoplasmic ATP and impairing
the homeostasis of energy metabolism, and both glycolysis and oxidative
phosphorylation were suppressed after RNAi treatment. Further identifying
the mechanism underlying the effects of ATP aptamer, we surprisingly
found that it markedly reduced the activity of membrane ionic channels
and membrane potential which led to the dysfunction of mitochondria,
such as the decrease of mitochondrial number, reduction in the respiration
rate, and decline of mitochondrial membrane potential and ATP production.
Meanwhile, the shortage of ATP impeded the formation of lamellipodia
that are essential for the movement of cells, consequently resulting
in a significant reduction of cell migration. Both the downregulation
of the phosphorylation of AMP-activated protein kinase (AMPK) and
endoplasmic reticulum kinase (ERK) and diminishing of lamellipodium
formation led to cell apoptosis as well as the inhibition of angiogenesis
and invasion. In conclusion, as the first RNAi modality targeting
the blocking of ATP consumption, the present method can disturb the
respiratory chain and ATP pool, which provides a novel regime for
tumor therapies.