A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer. [PDF]
Lessons learnedThe combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate ...
Friedlander, Terence +6 more
core +1 more source
By dawn or dusk—how circadian timing rewrites bacterial infection outcomes
The circadian clock shapes immune function, yet its influence on infection outcomes is only beginning to be understood. This review highlights how circadian timing alters host responses to the bacterial pathogens Salmonella enterica, Listeria monocytogenes, and Streptococcus pneumoniae revealing that the effectiveness of immune defense depends not only
Devons Mo +2 more
wiley +1 more source
Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant. [PDF]
Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem.
Davis, Jonathan M. +2 more
core +2 more sources
Exposure–response (E–R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and ...
A. Ruiz-Garcia +14 more
semanticscholar +1 more source
The Caenorhabditis elegans DPF‐3 and human DPP4 have tripeptidyl peptidase activity
The dipeptidyl peptidase IV (DPPIV) family comprises serine proteases classically defined by their ability to remove dipeptides from the N‐termini of substrates, a feature that gave the family its name. Here, we report the discovery of a previously unrecognized tripeptidyl peptidase activity in DPPIV family members from two different species.
Aditya Trivedi, Rajani Kanth Gudipati
wiley +1 more source
Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus. [PDF]
BackgroundBevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1α levels, a resistance mechanism for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant in these tumors.
Falchook, Gerald S +9 more
core +6 more sources
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. [PDF]
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics.
A Baryshnikova +56 more
core +1 more source
The role and implications of mammalian cellular circadian entrainment
At their most fundamental level, mammalian circadian rhythms occur inside every individual cell. To tell the correct time, cells must align (or ‘entrain’) their circadian rhythm to the external environment. In this review, we highlight how cells entrain to the major circadian cues of light, feeding and temperature, and the implications this has for our
Priya Crosby
wiley +1 more source
Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition. [PDF]
Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that ...
Carter, Cameron S +3 more
core +3 more sources
Peptide‐based ligand antagonists block a Vibrio cholerae adhesin
The structure of a peptide‐binding domain of the Vibrio cholerae adhesin FrhA was solved by X‐ray crystallography, revealing how the inhibitory peptide AGYTD binds tightly at its Ca2+‐coordinated pocket. Structure‐guided design incorporating D‐amino acids enhanced binding affinity, providing a foundation for developing anti‐adhesion therapeutics ...
Mingyu Wang +9 more
wiley +1 more source

