Vascular endothelial growth factor and tryptase changes after chemoembolization in hepatocarcinoma patients

AIM: To evaluate vascular endothelial growth factor (VEGF) and tryptase in hepatocellular cancer (HCC) before and after trans-arterial chemoembolization (TACE). METHODS: VEGF and tryptase serum concentrations were assessed from 71 unresectable HCC patients before and after hepatic TACE performed by binding DC-Beads® to doxorubicin. VEGF levels were examined for each serum sample using the Quantikine Human VEGF-enzyme-linked immuno-absorbent assay (ELISA), whereas tryptase serum concentrations were assessed for each serum sample by means of fluoro-enzyme immunoassay (FEIA) using the Uni-CAP100 tool. Differences between serum VEGF and tryptase values before and after TACE were evaluated using Student t test. Person's correlation was used to assess the degree of association between the two variables. RESULTS: VEGF levels and serum tryptase in HCC patients before TACE had a mean value and standard deviation (SD) of 114.31 ± 79.58 pg/mL and 8.13 ± 3.61 μg/L, respectively. The mean levels and SD of VEGF levels and serum tryptase in HCC patients after TACE were 238.14 ± 109.41 pg/mL and 4.02 ± 3.03 μg/L. The changes between the mean values of concentration of VEGF and tryptase before treatment and after treatment was statistically significant (P < 0.000231 and P < 0.00124, by Wilcoxon-Mann-Whitney respectively). A significant correlation between VEGF levels before and after TACE and between tryptase levels before and after TACE was demonstrated (r = 0.68, P = 0.003; r = 0.84, P = 0.000 respectively). CONCLUSION: Our pilot results suggest that the higher serum VEGF levels and the lower tryptase levels following TACE may be potential biomarkers changing in response to therapy

Pharmacokinetic and metabolism determinants of fluoropyrimidines and oxaliplatin activity in treatment of colorectal patients

Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary to develop an effective therapy adapted to the patient's molecular profile, while minimizing life-threatening toxicities. In this review, we discuss literature data, defining predictive and prognostic markers actually identified in the treatment of CRC. We analyzed predictive markers of fluoropyrimidines effectiveness, principally for 5-Fluorouracil (5-FU) and also for oral fluoropyrimidines, as thymidylate Synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), methylenetetrahydrofolate reductase (MTHFR), deoxyuridine triphosphate nucleotidohydrolase (dUTPase), micro-satellite instability. DPD represent the more studied 5-FU toxicity marker, followed by TS and OPRT. Oxaliplatin effectiveness is principally regulated by nucleotide excision repair (NER) pathway, including excision repair cross-complementation group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XDP). The major oxaliplatin toxicity marker is represented by glutathione S-transferase (GST). All these results are based principally on retrospective studies. The future challenge became to validate molecular markers and their association with clinical outcomes in prospective trials, refining technologic platforms and bioin-formatics to accommodate the complexity of the multifaceted molecular map that may determine outcome, and determining CRC patients most likely to benefit from therapeutic interventions tailored specifically for them

Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross-talk in the bone marrow of multiple myeloma patients

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor-2 (FGF2), thus inhibiting its pro-angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient-derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross-talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel(\uae) assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3-induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co-cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time- and dose-dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose-dependent manner, and impacts in vitro and in vivo FGF2-mediated MM angiogenesis. Co-cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti-angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross-talk between PCs and ECs/FBs. Copyright \ua9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd