RESUMO
This is the first report about the presence of pesticide residues in water and sediments from Chacahua-Pastoria Lagoon System in the Oaxaca Coast, Mexico. Organochlorine and organophosphate pesticides were analyzed in water and sediment samples collected during rainy and dry seasons in 2018. The pesticides extraction was carried out by 525.2 EPA and QuEChERS methods for water and sediments samples, respectively. The quantification was done by gas chromatography coupled to electron microcapture (µECD) and flame photometric (FPD) detectors. Univariate and multivariate analysis were carried out to evaluate the distribution patterns, comparing between lagoons, seasons and matrices. The spatial distribution of malathion and organochlorines in water showed the highest values near to adjacent land with some patterns differences. DDT was the most frequent in water and sediments samples, showed the highest concentrations in the Pastoria Lagoon. These results indicate the need to establish a permanent monitoring programs to implement mitigation measures.
Assuntos
Hidrocarbonetos Clorados , Praguicidas , Poluentes Químicos da Água , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Clorados/análise , México , Praguicidas/análise , Água , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib. METHODS: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437. RESULTS: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients. CONCLUSIONS: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients.