Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24⁻, CD44^+/++, CD326^−/+ and CD133/1⁻, while PANC-1 is CD24^−/+, CD44⁺, CD326^−/+ and CD133/1⁻. Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16^INK4A, but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide inter-individual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of this study was to determine the existence of any association between the main genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) and an altered risk for haematological neoplasias. A total of 160 patients and 128 controls were genotyped by means of PCR–RFLP-based assays. Mutated alleles comprising CYP2D6*4, GSTM1*0, NAT2*5A, *5B, *5C, *6 and *7 were analysed along with the wild-type alleles. The results showed a higher frequency of CYP2D6 extensive metabolizers carrying two functional alleles in the leukaemia group, when compared with controls (76.6 versus 57.0%, P = 0.008). No differences were found in the case of Hodgkin and non-Hodgkin lymphomas. Analysis of the GSTM1 and NAT2 polymorphisms failed to show an association with any of the neoplasias, although a near significant increase in fast acetylators was also found in the leukaemia group (50.0 versus 35.9%, P = 0.06). The results suggest an association of extensive metabolism with an increased risk for leukaemia, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Opposite findings presented in other studies may reflect geographical differences in the type of environmental carcinogens to which different populations are exposed.

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.