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1. Treatment patterns of adjuvant interferon-alpha 2b for high-risk melanoma: a retrospective study of the Grupo Espanol Multidisciplinar de Melanoma - Prima study

Author

Espinosa, E, Soriano, V, Malvehy, J, Berrocal, A, de Prado, PM, Quindos, M, Soria, A, Marquez-Rodas, I, Palacio, I, Cerezuela, P, Lopez-Vivanco, G, Alonso, L, Samaniego, E, Ballesteros, A, Puertolas, T, Diaz-Beveridge, R, de la Cruz-Merino, L, Castro, RL, Lopez, RL, Stevinson, K, del Barrio, P, Tornamira, MV, Guillem, V, and Martin-Algarra, S

Subjects
adjuvant treatment, melanoma, tolerability, compliance, interferon-alpha 2b
Abstract

Adjuvant interferon-alpha 2b (IFN-alpha 2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-alpha 2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-alpha 2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-alpha 2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN alpha 2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN alpha 2b treatment provided a benefit consistent with that described previously. (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

Published
2016

2. α-cyanobacteria possessing form IA RuBisCO globally dominate aquatic habitats.

Author

Cabello-Yeves PJ, Scanlan DJ, Callieri C, Picazo A, Schallenberg L, Huber P, Roda-Garcia JJ, Bartosiewicz M, Belykh OI, Tikhonova IV, Torcello-Requena A, De Prado PM, Millard AD, Camacho A, Rodriguez-Valera F, and Puxty RJ

Subjects
Carbon, Carbon Dioxide, Ecosystem, Oxygenases, Ribulose-Bisphosphate Carboxylase genetics, Synechococcus genetics
Abstract

RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) is one the most abundant enzymes on Earth. Virtually all food webs depend on its activity to supply fixed carbon. In aerobic environments, RuBisCO struggles to distinguish efficiently between CO 2 and O 2 . To compensate, organisms have evolved convergent solutions to concentrate CO 2 around the active site. The genetic engineering of such inorganic carbon concentrating mechanisms (CCMs) into plants could help facilitate future global food security for humankind. In bacteria, the carboxysome represents one such CCM component, of which two independent forms exist: α and β. Cyanobacteria are important players in the planet's carbon cycle and the vast majority of the phylum possess a β-carboxysome, including most cyanobacteria used as laboratory models. The exceptions are the exclusively marine Prochlorococcus and Synechococcus that numerically dominate open ocean systems. However, the reason why marine systems favor an α-form is currently unknown. Here, we report the genomes of 58 cyanobacteria, closely related to marine Synechococcus that were isolated from freshwater lakes across the globe. We find all these isolates possess α-carboxysomes accompanied by a form 1A RuBisCO. Moreover, we demonstrate α-cyanobacteria dominate freshwater lakes worldwide. Hence, the paradigm of a separation in carboxysome type across the salinity divide does not hold true, and instead the α-form dominates all aquatic systems. We thus question the relevance of β-cyanobacteria as models for aquatic systems at large and pose a hypothesis for the reason for the success of the α-form in nature., (© 2022. The Author(s).)

Published
2022
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3. Elucidating the picocyanobacteria salinity divide through ecogenomics of new freshwater isolates.

Author

Cabello-Yeves PJ, Callieri C, Picazo A, Schallenberg L, Huber P, Roda-Garcia JJ, Bartosiewicz M, Belykh OI, Tikhonova IV, Torcello-Requena A, De Prado PM, Puxty RJ, Millard AD, Camacho A, Rodriguez-Valera F, and Scanlan DJ

Subjects
Ecosystem, Fresh Water, Proteome metabolism, Cyanobacteria genetics, Cyanobacteria metabolism, Salinity
Abstract

Background: Cyanobacteria are the major prokaryotic primary producers occupying a range of aquatic habitats worldwide that differ in levels of salinity, making them a group of interest to study one of the major unresolved conundrums in aquatic microbiology which is what distinguishes a marine microbe from a freshwater one? We address this question using ecogenomics of a group of picocyanobacteria (cluster 5) that have recently evolved to inhabit geographically disparate salinity niches. Our analysis is made possible by the sequencing of 58 new genomes from freshwater representatives of this group that are presented here, representing a 6-fold increase in the available genomic data., Results: Overall, freshwater strains had larger genomes (≈2.9 Mb) and %GC content (≈64%) compared to brackish (2.69 Mb and 64%) and marine (2.5 Mb and 58.5%) isolates. Genomic novelties/differences across the salinity divide highlighted acidic proteomes and specific salt adaptation pathways in marine isolates (e.g., osmolytes/compatible solutes - glycine betaine/ggp/gpg/gmg clusters and glycerolipids glpK/glpA), while freshwater strains possessed distinct ion/potassium channels, permeases (aquaporin Z), fatty acid desaturases, and more neutral/basic proteomes. Sulfur, nitrogen, phosphorus, carbon (photosynthesis), or stress tolerance metabolism while showing distinct genomic footprints between habitats, e.g., different types of transporters, did not obviously translate into major functionality differences between environments. Brackish microbes show a mixture of marine (salt adaptation pathways) and freshwater features, highlighting their transitional nature., Conclusions: The plethora of freshwater isolates provided here, in terms of trophic status preference and genetic diversity, exemplifies their ability to colonize ecologically diverse waters across the globe. Moreover, a trend towards larger and more flexible/adaptive genomes in freshwater picocyanobacteria may hint at a wider number of ecological niches in this environment compared to the relatively homogeneous marine system., (© 2022. The Author(s).)

Published
2022
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4. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset.

Author

Thaler J, Greil R, Gaenzer J, Eisterer W, Tschmelitsch J, Samonigg H, Zabernigg A, Schmid F, Steger G, Steinacher R, Andel J, Lang A, Függer R, Hofbauer F, Woell E, Geissler D, Lenauer A, Prager M, Van Laethem JL, Van Cutsem E, D'Haens G, Demolin G, Kerger J, Deboever G, Ghillebert G, Polus M, Van Cutsem E, RezaieKalantari H, Delaunoit T, Goeminne JC, Peeters M, Vergauwe P, Houbiers G, Humblet Y, Janssens J, Schrijvers D, Vanderstraeten E, Van Laethem JL, Vermorken J, Van Daele D, Ferrante M, Forget F, Hendlisz A, Yilmaz M, Nielsen SE, Vestermark L, Larsen J, Ychou M, Zawadi A, Zawadi MA, Bouche O, Mineur L, Bennouna-Louridi J, Dourthe LM, Ychou M, Boucher E, Taieb J, Pezet D, Desseigne F, Ducreux M, Texereau P, Miglianico L, Rougier P, Fratte S, Levache CB, Merrouche Y, Ellis S, Locher C, Ramee JF, Garnier C, Viret F, Chauffert B, Cojean-Zelek I, Michel P, Lecaille C, Borel C, Seitz JF, Smith D, Lombard-Bohas C, Andre T, Gornet JM, Fein F, Coulon-Sfairi MA, Kaminsky MC, Lagasse JP, Luet D, Etienne PL, Gasmi M, Vanoli A, Nguyen S, Aparicio T, Perrier H, Stremsdoerfer N, Laplaige P, Arsene D, Auby D, Bedenne L, Coriat R, Denis B, Geoffroy P, Piot G, Becouarn Y, Bordes G, Deplanque G, Dupuis O, Fruge F, Guimbaud R, Lecomte T, Lledo G, Sobhani I, Asnacios A, Azzedine A, Desauw C, Galais MP, Gargot D, Lam YH, Abakar-Mahamat A, Berdah JF, Catteau S, Clavero-Fabri MC, Codoul JF, Legoux JL, Goldfain D, Guichard P, Verge DP, Provencal J, Vedrenne B, Brezault-Bonnet C, Cleau D, Desir JP, Fallik D, Garcia B, Gaspard MH, Genet D, Hartwig J, Krummel Y, MatysiakBudnik T, Palascak-Juif V, Randrianarivelo H, Rinaldi Y, Aleba A, Darut-Jouve A, de Gramont A, Hamon H, Wendehenne F, Matzdorff A, Stahl MK, Schepp W, Burk M, Mueller L, Folprecht G, Geissler M, Mantovani-Loeffler L, Hoehler T, Asperger W, Kroening H, von Weikersthal LF, Fuxius S, Groschek M, Meiler J, Trarbach T, Rauh J, Ziegenhagen N, Kretzschmar A, Graeven U, Nusch A, von Wichert G, Hofheinz RD, Kleber G, Schmidt KH, Vehling-Kaiser U, Baum C, Schuette J, Haag GM, Holtkamp W, Potenberg J, Reiber T, Schliesser G, Schmoll HJ, Schneider-Kappus W, Abenhardt W, Denzlinger C, Henning J, Marxsen B, GuenterDerigs H, Lambertz H, Becker-Boost I, Caca K, Constantin C, Decker T, Eschenburg H, Gabius S, Hebart H, Hoffmeister A, Horst HA, Kremers S, Leithaeuser M, Mueller S, Wagner S, Daum S, Schlegel F, Stauch M, Heinemann V, Labianca R, Colucci G, Amadori D, Mini E, Falcone A, Boni C, Maiello E, Latini L, Zaniboni A, Amadori D, Aprile G, Barni S, Mattioli R, Martoni A, Passalacqua R, Nicolini M, Pasquini E, Rabbi C, Aitini E, Ravaioli A, Barone C, Biasco G, Tamberi S, Gambi A, Verusio C, Marzola M, Lelli G, Boni C, Cascinu S, Bidoli P, Vaghi M, Cruciani G, Di Costanzo F, Sobrero A, Mini E, Petrioli R, Aglietta M, Alabiso O, Capuzzo F, Falcone A, Corsi DC, Labianca R, Salvagni S, Chiara S, Ferraù F, Giuliani F, Lonardi S, Gebbia N, Mantovani G, Sanches E, Sanches E, Mellidez JC, Santos P, Freire J, Sarmento C, Costa L, Pinto AM, Barroso S, Santo JE, Guedes F, Monteiro A, Sa A, Furtado I, Tabernero J, Salazar R, Aguilar EA, Herrero FR, Tabernero J, Valera JS, ValladaresAyerbes M, FeliuBatlle J, Gil S, Garcia-Giron C, Vivanco GL, Salvia AS, Orduña VA, Garcia RV, Gallego J, Sureda BM, Remon J, Safont Aguilera MJ, CireraNogueras L, Merino B, Castro CG, de Prado PM, PijaumePericay C, ConstenlaFigueiras M, Jordan I, GomeReina MJ, Garcia AL, Garcia-Ramos AA, Cervantes A, Martos CF, MarcuelloGaspar E, Montero IC, Emperador PE, Carbonero AL, Castillo MG, Garcia TG, Lopez JG, Flores EG, GuillotMorales M, LlanosMuñoz M, Martín AL, Maurel J, Camara JC, Garcia RD, Salgado M, HernandezBusquier I, Ruiz TC, LacastaMuñoa A, Aliguer M, Ortiz de Taranco AV, Ureña MM, Gaspa FL, Ponce JJ, Roig CB, Jimenez PV, GalanBrotons A, AlbiolRodriguez S, Martinez JA, Ruiz LC, CentellesRuiz M, Bridgewater J, Glynne-Jones R, Tahir S, Hickish T, Cassidy J, and Samuel L

Published
2015
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