2 research outputs found
Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer
When
compared with hormonal therapy alone, treatment with combined
hormone and radiation therapy (CHRT) gives improved disease-specific
survival outcomes for patients with prostate cancer; however, a significant
number of CHRT patients still succumb to recurrent disease. The purpose
of this study was to use longitudinal patient samples obtained as
part of an ongoing noninterventional clinical trial (ICORG06-15) to
identify and evaluate a potential serum protein signature of disease
recurrence. Label-free LC–MS/MS based protein discovery was
undertaken on depleted serum samples from CHRT patients who showed
evidence of disease recurrence (<i>n</i> = 3) and time-matched
patient controls (<i>n</i> = 3). A total of 104 proteins
showed a significant change between these two groups. Multiple reaction
monitoring (MRM) assays were designed for a subset of these proteins
as part of a panel of putative prostate cancer biomarkers (41 proteins)
for evaluation in longitudinal serum samples. These data revealed
significant interpatient variability in individual protein expression
between time of diagnosis, disease recurrence, and beyond and serve
to highlight the importance of longitudinal patient samples for evaluating
the use of candidate protein biomarkers in disease monitoring
Janus PEG-Based Dendrimers for Use in Combination Therapy: Controlled Multi-Drug Loading and Sequential Release
The increasing use of drug combinations to treat disease
states,
such as cancer, calls for improved delivery systems that are able
to deliver multiple agents. Herein, we report a series of novel Janus
dendrimers with potential for use in combination therapy. Different
generations (first and second) of PEG-based dendrons containing two
different “model drugs”, benzyl alcohol (BA) and 3-phenylpropionic
acid (PPA), were synthesized. BA and PPA were attached via two different
linkers (carbonate and ester, respectively) to promote differential
drug release. The four dendrons were coupled together via (3 + 2)
cycloaddition chemistries to afford four Janus dendrimers, which contained
varying amounts and different ratios of BA and PPA, namely, <b>(BA)</b><sub><b>2</b></sub><b>-G1-G1-(PPA)</b><sub><b>2</b></sub>, <b>(BA)</b><sub><b>4</b></sub><b>-G2-G1-(PPA)</b><sub><b>2</b></sub>, <b>(BA)</b><sub><b>2</b></sub><b>-G1-G2-(PPA)</b><sub><b>4</b></sub>, and <b>(BA)</b><sub><b>4</b></sub><b>-G2-G2-(PPA)</b><sub><b>4</b></sub>. Release studies in plasma showed that
the dendrimers provided sequential release of the two model drugs,
with BA being released faster than PPA from all of the dendrons. The
different dendrimers allowed delivery of increasing amounts (0.15–0.30
mM) and in exact molecular ratios (1:2; 2:1; 1:2; 2:2) of the two
model drug compounds. The dendrimers were noncytotoxic (100% viability
at 1 mg/mL) toward human umbilical vein endothelial cells (HUVEC)
and nontoxic toward red blood cells, as confirmed by hemolysis studies.
These studies demonstrate that these Janus PEG-based dendrimers offer
great potential for the delivery of drugs via combination therapy