RESUMO
Joint models for longitudinal and survival data (JMLSs) are widely used to investigate the relationship between longitudinal and survival data in clinical trials in recent years. But, the existing studies mainly focus on independent survival data. In many clinical trials, survival data may be bivariately correlated. To this end, this paper proposes a novel JMLS accommodating multivariate longitudinal and bivariate correlated time-to-event data. Nonparametric marginal survival hazard functions are transformed to bivariate normal random variables. Bayesian penalized splines are employed to approximate unknown baseline hazard functions. Incorporating the Metropolis-Hastings algorithm into the Gibbs sampler, we develop a Bayesian adaptive Lasso method to simultaneously estimate parameters and baseline hazard functions, and select important predictors in the considered JMLS. Simulation studies and an example taken from the International Breast Cancer Study Group are used to illustrate the proposed methodologies.
Assuntos
Algoritmos , Modelos Estatísticos , Humanos , Teorema de Bayes , Análise Multivariada , Simulação por ComputadorRESUMO
Herein, we report the rational design of a DEVD-based heptapeptide hydrogelator 1 which is susceptible to caspase-3 (CASP3), and its isomeric control hydrogelator 2 with a DEDV-based heptapeptide sequence. Self-assembly of 1 in water results in flexuous, long nanofibers to form supramolecular hydrogel I with higher mechanical strength than that of hydrogel II which is composed of rigid, short nanofibers of 2. In vitro enzymatic analysis indicated that 1 is susceptive to CASP3 while 2 is not. 3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyl tetrazolium bromide (MTT) and Western blot analyses indicated that DEDV-based hydrogelator 2 induces cell death via apoptotic pathway while the DEVD-based hydrogelator 1 minimizes cellular apoptosis induction.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Hidrogéis/farmacologia , Neoplasias Hepáticas/patologia , Fragmentos de Peptídeos/farmacologia , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Caspase 3/química , Células HeLa , Humanos , Hidrogéis/química , Neoplasias Hepáticas/tratamento farmacológico , Nanofibras/química , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/química , Células Tumorais CultivadasRESUMO
One multifunctional small molecule can undergo a natural condensation reaction under the control of reducing agent to generate amphiphilic oligomers which quickly self-assemble supramolecular nanoparticles or form crosslinked, reversibly degradable polymers.
