Summary
Molecular mechanisms other than activating
KRAS
mutations should underlie the occurrence of weaker versus stronger responses to cetuximab (CTX) in EGFR-dependent carcinomas with either an ...intact
KRAS
signaling or in which
KRAS
mutations do not predict CTX efficacy. We hypothesized that
KRAS
wild-type (WT) tumor cell-line models chronically adapted to grow in the presence of CTX could be interrogated to establish if the positive predictive value of the mRNAs coding for the EGFR ligands
amphiregulin
(
AR
) and
epiregulin
(
EPI
) could be significantly altered during and/or after treatment with CTX. Gene expression analyses using real-time (kinetic) RT-PCR were performed to monitor the transcriptional evolution of EGFR ligands
EGF
,
TGFα
,
AR
,
BTC
,
EPI
,
NRG
and
HB-EGF
in experimental modes induced to exhibit acquired resistance to the mono-HER1 inhibitor CTX, the mono-HER2 inhibitor trastuzumab (Tzb) or the dual HER1/HER2 inhibitor lapatinib (LPT). Gene expression signatures for EGFR ligands distinctively related to the occurrence of unresponsiveness to CTX, Tzb or LPT, with minimal overlap between them. CTX’s molecular functioning largely depended on the overproduction of the mRNAs coding for the EGFR ligands
AR
and
EPI
. Thus, a dramatic down-regulation of
AR/EPI
mRNA expression occurred upon loss of CTX efficacy in EGFR-positive tumor cells with an intact regulation of
RAS
signaling. Unlike
KRAS
mutations, which are informative of unresponsiveness to CTX solely in mCRC, our hypothesis-generating data suggest that expression status of
AR
and
EPI
mRNAs might be evaluated as dynamic predictors of response in
KRAS
WT patients receiving any CTX-based therapy.
La formulació de propostes de treball amb controvèrsies sòcio-científiques (o CSC) implica treballar tres eixos fonamentals: la definició i proposta de dilemes rellevants, i el treball explícit de la ...lectura crítica i altres habilitats comunicatives com el debat. Es proposen criteris i estratègies de treball en aquestes tres línies i un marc general de tipus de CSC.
Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to assess whether serum FASN concentrations are altered in ...patients with chronic liver disease, and to investigate whether its measurement may be a useful tool in the clinical evaluation of this derangement.
We investigated 93 patients with chronic liver disease (14 minimal change disease, 79 steatohepatitis) and 100 control subjects. Serum FASN concentrations were measured using ELISA.
Patients had a significant increase in serum FASN concentration (p<0.001), which was specifically associated with the hepatic Knodell sub-index III of portal inflammation (p=0.019). In addition, serum FASN concentrations were significantly correlated with the circulating levels of the monocyte chemoattractant protein-1 (MCP-1) (Spearman rho=0.375; p<0.001) and type III procollagen-N-peptide (P-III-P) (Spearman rho=0.297; p<0.001).
Serum FASN concentrations are increased in patients with chronic liver impairment, and are associated with specific histological alterations and biochemical markers of portal inflammation. These data suggest that FASN measurement may contribute significantly to the evaluation of these patients.
The present study describes, for the first time, the glycosidic content of boar bulbourethral glands using lectin histochemistry. Fourteen horseradish peroxidase- or digoxigenin-labelled lectins with ...different carbohydrate specificities were used in samples obtained from 3 healthy Landrace boars. The results obtained indicate that endpiece and duct cells synthesize and secrete mainly O-glycoproteins with alpha- and beta-D-N-acetylgalactosamine, beta-D-galactose-beta(1-->3)-D-N-acetylgalactosamine, D-N-acetylglucosamine and neuraminic acid residues. Glycoproteins secreted by bulbourethral glands have a role in the protection and lubrication of the urethra. In addition, they may be also involved in the regulation of the sperm metabolic activity and in the maintenance of the structural integrity of acrosomal and plasma membranes.
Prompt inhibition of platelet aggregation is important in acute coronary syndrome and before an intervention procedure. To determine whether a single low dose of iv aspirin inhibits platelet ...aggregation, twenty-seven healthy volunteers (7 F and 20 M), mean age 43.5 years, were randomized double-blind to a single iv low dose of aspirin DL-Iysine (L-ASA) equivalent to 2mg/kg of aspirin, high dose (H-ASA) equivalent to 10mg/kg, or placebo (PI). Platelet aggregation were performed before and 1 hand 24h after drug administration, in whole blood (WB) using electrical impedance and in platelet-rich plasma (PRP) by optical light transmittance. Baseline WB platelet aggregation (Col 3 μg/mI) was the same with L-ASA, H-ASA and PI (24±5, 23±3 and 24±4rl respectively) and decreased significantly more with L-ASA and H-ASA than with PI after 1 h.(17±6, 15±7 and 21±5Ω p<0.0l)and 24h(17±7, 16±6 and 25±4Ω P<0.01).
in PRP were similar:PR Poptical aggregation (%)BeforeAfterASA1 h.24 hADP (5/LM):L-ASA73±2150±14*45±15*H-ASA65±2354±17*52±16*PI69×1872±2269±14Col (3 /Lg/ml):L-ASA64±1933±13*36±18*H-ASA60±1632±17*34±14*PI55±1356±1857±14*p<0.001 (ANOVA test) respect to PI and the baseline values
No differences in response were observed between the two doses of aspirin and no significant changes occurred between 1 and 24 hours in any group.
Effective inhibition of platelet aggregation is thus achieved within 1 hour after the administration of low-dose 2mg/kg of ivaspirin.
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