@article {8333, title = {Toward SERS-based point-of-care approaches for therapeutic drug monitoring: the case of methotrexate.}, journal = {Faraday Discuss}, volume = {187}, year = {2016}, month = {2016 Jun 23}, pages = {485-99}, abstract = {

To date, in spite of their toxicity, the plasmatic concentration of most chemotherapeutic drugs is difficult to monitor in oncological patients, because their quantitative determination is expensive and time consuming. This contribution reports a first attempt for the direct quantitative determination of a chemotherapeutic drug in human serum samples by means of Surface Enhanced Raman Spectroscopy (SERS). In this study, SERS substrates constituted by Au nanoparticles deposited on paper by a simple dipping method have been used for rapid (few minutes) analysis of diluted human serum spiked with different concentrations of methotrexate, MTX. The drug concentrations were chosen in a range designed to cover typical therapeutic plasmatic values (from nanomolar to millimolar) in oncological patients, and the pertinent calibration was obtained by Partial Least-Squares Regression (PLSR). Stability selection was employed to evaluate the capability of the PLSR model to accurately predict and extract spectral variations correlated to MTX concentration. Such a quantitative determination is crucial for frequent, and hence adherent, therapeutic drug monitoring, TDM, of chemiotherapic drugs, given their heavy side effects. Its low cost, rapid response and the possibility of obtaining spectra with simple and compact instruments, make SERS particularly apt for implementing effective TDM. The promising results obtained in the analytical validation indicate which steps are to be taken on the way toward a clinical validation with real samples from oncological patients, for MTX as well as for other chemotherapeutic drugs.

}, issn = {1359-6640}, doi = {10.1039/c5fd00173k}, author = {Fornasaro, Stefano and Marta, Silvia Dalla and Rabusin, Marco and Bonifacio, Alois and Sergo, Valter} } @article {3524, title = {TNF-α SNP rs1800629 and risk of relapse in childhood acute lymphoblastic leukemia: relation to immunophenotype.}, journal = {Pharmacogenomics}, volume = {15}, year = {2014}, month = {2014 Apr}, pages = {619-27}, abstract = {

AIM: In the AIEOP-BFM ALL (Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt M{\"u}nster acute lymphoblastic leukemia) 2000 protocol, 70\% of relapsed patients had favorable prognostic features and fell within less intensive polychemotherapeutic regimens, suggesting the need for better assessing lower risk stratification.

MATERIALS \& METHODS: A novel two-phase study design selected 614 children to be genotyped for TNF-α SNP rs1800629 (-308G>A). A weighted Cox model was applied to evaluate the SNP effect on hazard of relapse, adjusting for immunophenotype, risk group, age and gender and including interaction terms.

RESULTS: Significant interaction was found with immunophenotypes (p = 0.0007, with minor allele genotypes being adverse genetic markers in B-cell acute lymphoblastic leukemia and protective ones in T-cell acute lymphoblastic leukemia), and also with risk protocols (p = 0.0041, with minor allele genotypes as prognostic factor of relapse for standard risk patients [only one T-cell acute lymphoblastic leukemia in the subgroup analyzed]).

CONCLUSION: The presence of at least one A allele in TNF-α SNP rs1800629 should suggest a closer monitoring in B-cell acute lymphoblastic leukemia standard risk patients.

}, keywords = {Adolescent, Antineoplastic Agents, Child, Child, Preschool, Drug Resistance, Neoplasm, Female, Genotype, Humans, Infant, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Phenotype, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Recurrence, Risk Assessment, Steroids, Tumor Necrosis Factor-alpha}, issn = {1744-8042}, doi = {10.2217/pgs.13.249}, author = {Franca, Raffaella and Rebora, Paola and Athanasakis, Emmanouil and Favretto, Diego and Verzegnassi, Federico and Basso, Giuseppe and Tommasini, Alberto and Valsecchi, Maria Grazia and Decorti, Giuliana and Rabusin, Marco} }