RESUMEN
Metallographic, X-ray diffraction and magnetometric analysis were used to study the regularities of martensitic transformation in melt-spun ribbons of a Fe - 28 wt. % Ni - 2.1 wt. % Ti - 2 wt. % Al - 0.05 wt. % C alloy. The substantial differences in volume fractions of the martensite phase in local regions of thin melt-spun ribbons of the alloy are related to the size effect of the transformation and structural inhomogeneity of the ribbons. The distribution of austenitic grain size in different local areas of melt-spun ribbons is significantly different. The principal factor for changing the completeness of the martensitic transformation is the size effect of transformation. Difference in the martensite volume fraction in local regions of a ribbon is mainly determined by the different volume fractions of ultrafine-grained (500-1000 nm) and nanosized (80-100 nm and less) initial austenite grains, in which the transformation was slowed down or completely suppressed. Other factors almost do not affect the completeness of the martensitic transformation. The strong stabilizing effect of the reverse α-γ transformation with respect to the subsequent direct γ-α transformation in the melt-spun ribbons is also related to the grain size effect.
RESUMEN
PURPOSE: Gemcitabine requires transporter proteins to cross cell membranes. Low expression of human equilibrative nucleoside transporter-1 (hENT1) may result in gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). CO-101, a lipid-drug conjugate of gemcitabine, was rationally designed to enter cells independently of hENT1. We conducted a randomized controlled trial to determine whether CO-101 improved survival versus gemcitabine in patients with metastatic PDAC (mPDAC) with low hENT1. The study also tested the hypothesis that gemcitabine is more active in patients with mPDAC tumors with high versus low hENT1 expression. PATIENTS AND METHODS: Patients were randomly assigned to CO-101 or gemcitabine, after providing a metastasis sample for blinded hENT1 assessment. An immunohistochemistry test measuring tumor hENT1 was developed. To dichotomize the population, an hENT1 cutoff value was defined using primary PDAC samples from an adjuvant trial, and a high/low cutoff was applied. The primary end point was overall survival (OS) in the low hENT1 subgroup. RESULTS: Of 367 patients enrolled, hENT1 status was measured in 358 patients (97.5%). Two hundred thirty-two (64.8%) of 358 patients were hENT1 low. There was no difference in OS between treatments in the low hENT1 subgroup or overall, with hazard ratios (HRs) of 0.994 (95% CI, 0.746 to 1.326) and 1.072 (95% CI, 0.856 to 1.344), respectively. The toxicity profiles in both arms were similar. Within the gemcitabine arm, there was no difference in survival between the high and low hENT1 subgroups (HR, 1.147; 95% CI, 0.809 to 1.626). CONCLUSION: CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome.