IMP dehydrogenase rod/ring structures in acral melanomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy

Theoretical - Experimental Analysis of Cellular and Primary Dendritic Spacings during Unidirectional Solidification of Sn-Pb Alloys

Structural parameters as grain size, dendritic and cellular spacings, segregated products, porosity and other phases are strongly influenced by the thermal behavior of the metal/mold system during solidification, imposing a close correlation between this and the resulting microstructure. Several unidirectional solidification studies with the objective of characterizing cellular and dendritic spacings have been developed in large scale involving solidification in steady-state heat flow. The main objective of this work is to determine the thermal solidification parameters during the cellular/dendritic transition as well as to compare theoretical models that predict cellular and primary dendritic spacings with experimental results for solidification situations in unsteady-state heat flow. Experiments were carried out in a water cooled unidirectional solidification apparatus and dilute alloys of the Sn-Pb system were used (Sn 1.5wt%Pb, Sn 2.5wt%Pb and Sn 5wt%Pb). The upper limit of the Hunt-Lu cellular growth model closely matched the experimental spacings. The lower limit calculated with the Hunt-Lu dendritic model best generated the experimental results. The cellular/dendritic transition was observed to occur for the Sn 2.5wt%Pb alloy over a range of analytical cooling rates from 0.28 K/s to 1.8 K/s