Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

Paraná Basin: Mineral resource potentials in Brazil, Uruguay, and Paraguay

The Paraná Basin is a Western Gondwanan cratonic basin that is better defined as the Paraná depositional site, since it has a diverse history as a basin. Sedimentation started in the Ordovician-Silurian, followed by extensive marine Devonian deposition. A Late Paleozoic/ Triassic facies cycle wedge was clearly built during Pangean time. The Early Cretaceous was characterized by extensive basaltic lava flows immediately before the break-up of Pangea. Following these rifting and drifting processes, the basin's structural framework was totally rebuilt, generating new depositional sites in the Late Cretaceous to Tertiary. Based on more recent data, at least two different basins may be defined during the evolution of what was once considered a unique basin. Nevertheless, even if considered as a single basin, the sedimentary pile of the Paraná Basin has considerable economic potential, until now exploited only rudimentarily, except for its groundwater resources. Aggregates, limestones, clays, industrial sands, gems, dimension stones, hydrocarbons, coal, peat, and uranium are some of the potential mineral resources of this basin. Copyright © 1997 by V. H. Winston & Son, Inc. All rights reserved

Sedimentology of a distributive fluvial system: The Serra da Galga Formation, a new lithostratigraphic unit (Upper Cretaceous, Bauru Basin, Brazil)

The Bauru Basin of SE Brazil is a large (ca. 370,000 km2) Upper Cretaceous intracratonic feature, important for its fossil remains and of particular value as a source of regional palaeoclimatic information. Historically, lithostratigraphic reconstructions have been performed mainly for successions of the central and southern parts of the basin, resulting in a lithostratigraphic scheme that is not applicable to the northernmost regions. In particular, the northeastern deposits of the Marília Formation (Serra da Galga and Ponte Alta members) reveal lithological, stratigraphic, and palaeontological differences from southeastern and northwestern counterparts (Echaporã Member). Nevertheless, these deposits are considered as a single lithostratigraphic formation in the literature. To address this problem, this study demonstrates how the northeastern deposits of the Marília Formation do not show affinity to the rest of the unit. A more suitable lithostratigraphic model is proposed for the northeastern succession as a distinct and independent unit. Lithofacies and palaeopedological analysis, combined with lithostratigraphic mapping of the northeastern deposits, reveal 11 distinct lithofacies and three pedotypes over an area of ~450 km2. Sedimentary facies and pedotypes were assigned to six interbedded architectural elements: (a) type 1 channel fill, (b) type 2 channel fill, (c) type 3 channel fill, (d) interchannels, (e) palaeosols, and (f) calcrete beds. The succession is interpreted as a distributive fluvial system with overall direction of flow to the NNW, and which developed under the influence of a semiarid climate regime. This contrasts with deposits of the southeastern and northwestern Marília Formation, previously suggested to be of fine-grained aeolian affinity with interbedded poorly channelised deposits assigned to an aeolian sand sheet environment. By revising the existing lithostratigraphic scheme for the northeastern deposits, and contrasting them with laterally equivalent strata, this work demonstrates how the previously named Serra da Galga and Ponte Alta members reveal a unique set of lithological, architectural, and genetic signatures that permits to separate them from the Marília Formation. Finally, a new lithostratigraphic classification for the unit is proposed: the Serra da Galga Formation, whose deposition relates to an ancient distributive fluvial system.Fil: Soares, Marcus Vinícius Theodoro. Universidade Estadual de Campinas; BrasilFil: Basilici, Giorgio. Universidade Estadual de Campinas; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: da Silva Marinho, Thiago. Universidade Federal do Triângulo Mineiro; BrasilFil: Martinelli, Agustín Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Marconato, André. Universidade Federal de Ouro Preto; BrasilFil: Mountney, Nigel Philip. University Of Leeds.; Reino UnidoFil: Colombera, Luca. University Of Leeds.; Reino UnidoFil: Mesquita, Áquila Ferreira. Universidade Estadual de Campinas; BrasilFil: Vasques, Julia Tucker. Universidade Estadual de Campinas; BrasilFil: Junior, Francisco Romero Abrantes. Universidade Estadual de Campinas; BrasilFil: Ribeiro, Luiz Carlos Borges. Universidade Federal Do Triangulo Mineiro; Brasi

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy

Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells

This document is the Accepted Manuscript version of the following article: Wen Li, Yuen-Ki Cheong, Hui Wang, Guogang Ren and Zhuo Yang, ‘Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells’, Neurochemical Research, Vol. 41 (4): 844-854, April 2016. The final publication is available at Springer via https://doi.org/10.1007/s11064-015-1761-4.Etidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a ‘germinal bisphosphonate’ unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P–C–P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca2+ channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca2+, are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter-reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 μM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10–100 μM TrisPP showed remarkable cell protection (78–86 %). Moreover, pre-treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca2+ overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents.Peer reviewe