|
Synergistic
Cytotoxicity and Pharmacogenetics of
Gemcitabine and Pemetrexed Combination in
Pancreatic Cancer Cell
Lines
In
the last decade, the availability of
several new active drugs has improved the
efficacy of combination regimens and
substantially increased the response rate
of refractory tumors, including pancreatic
cancer. Antimetabolites are widely used in
combination regimens because of their
activity and generally manageable
toxicities; however, several preclinical
studies have shown schedule-dependent drug
interaction . For example, gemcitabine
(2',2'-difluoro-2'-deoxycytidine) is
synergistic in vitro with cisplatin in
non-small cell lung cancer cell lines and
this interaction is most pronounced when
gemcitabine precedes this drug . Similar
results were obtained using PANC-1 and
BxPc3 pancreatic cancer cells for which
the most synergistic schedule is
gemcitabine followed by cisplatin ,
whereas additive to slightly synergistic
or antagonistic effects are observed with
gemcitabine followed by topotecan,
paclitaxel, and docetaxel in various
non-small cell lung cancer cell
lines.......
See
Full Article
|
ABCG2
Pharmacogenetics
Ethnic Differences in Allele Frequency and
Assessment of Influence on Irinotecan
Disposition
|
|
The ATP-binding
cassette (ABC) transporters represent the
largest family of transmembrane proteins
that bind ATP and use the energy to drive
the transport of various molecules across
cell membranes (1) . On the basis of the
arrangement of molecular structural
components, i.e., the nucleotide binding
domain and the topology of transmembrane
domains, human proteins are classified
into seven distinct families (ABCA to
ABCG; ref. 1 ). The ABCG subfamily
consists of several half transporters that
are generally thought to form homo- or
heterodimers to create the active
transporter (2 , 3) . Very recently, it
was reported that human ABCG2 probably
exists as a homotetramer with a
possibility of a higher form of
oligomerization (3) . The human ABCG2 gene
is located on chromosome 4q22 and encodes
a 655 amino acid polypeptide (4 , 5) . In
vitro studies have indicated that, apart
from topotecan (6 , 7) , the irinotecan
metabolites 7-ethyl-10-hydroxycamptothecin
(SN-38) and its glucuronide conjugate
SN-38G (8 , 9) are very good substrates
for ABCG2. Furthermore, overexpression of
ABCG2 reportedly .
See
Full Article
|
|
Sponsors
|
Healthcare
Professionals Resource
Center
|
|
Over
400,000 pieces of content with almost 1200
new features every month!
|
|
